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In animal experiments, GPRC6a–/– alloSCT recipients had increased GVHD morbidity and mortality. GPRC6a, a G protein coupled receptor, was previously found to be activated by increased extracellular Ca2+ levels leading to an increase in the intracellular Ca2+ concentration, triggering the activation of i.a. the NLRP3 inflammasome and caspase-1, mediated through the phosphatidyl inositol/Ca2+ pathway. Activation of the NLRP3 inflammasome via DAMPs has already been shown to be connected to GVHD severity (7, 19). In preclinical models, inhibition of the NLRP3 inflammasome lead to improved GVHD morbidity and delayed GVHD-induced mortality (5–7). Interestingly, when using NLRP3 deficient mice, this effect was only prominent when deficiency was present in alloSCT recipients, not in donors (6). In patients, recipient single nucleotide polymorphisms of NLRP3 were found connected to the incidence of acute GVHD grades 2–4 (20). While the role of NLRP3 was studied in GVHD, potential upstream immune regulatory functions of GPRC6a are unknown. Results in GPRC6a–/– mice showing reduced inflammatory response and reduced inflammasome activation in a mouse model of carrageenan-induced footpad swelling (4), suggested that GPRC6a deficiency may also lead to reduced GVHD-associated inflammation as seen in GVHD studies analyzing the NLRP3 inflammasome. However, our data contradicts these findings, as GPRC6a deficiency in alloSCT recipients was associated to increased acute GVHD. As GPRC6a is located upstream from the NLRP3 inflammasome, influence on other pathways is likely, potentially leading to differing results. In addition, GPRC6a is widely expressed throughout the body and can recognize multiple ligands next to Ca2+, e.g., L-α-amino acids as L-arginine or L-lysin, zinc, testosterone or osteocalcin acting as positive or negative allosteric modulators (9, 21). The wide tissue expression and multiple activators of GPRC6a, let assume a wide range of functions and the entire scope of GPRC6a functions is not yet known. In line, experimental data from GPRC6a–/– mice show a diversity in physiological and pathophysiological functions, mainly involving a role in inflammation, endocrine functions and metabolism. However, functional phenotyping of these mice is enclosed by disparities, e.g., in glucose and fat or bone metabolism (9, 22). Whereas one group found glucose intolerance and insulin resistance as well as osteopenia and impaired osteoblast mediated bone formation in GPRC6a–/– mice (22), other groups could not detect such phenotypes (23, 24). This underlines the possibility that besides the Ca2+ mediated GPRC6a signaling, other signaling pathways contribute to the observed phenotype in our GVHD model.
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Aspects professionnels (Tableau 2): S’agissant de type de tâches à accomplir dans le service, nous constatons que chez les aides-soignants et nettoyeurs 42,5% ont été atteint par la TB alors que chez les autres (médecin, infirmier et laborantin) seuls 10,8% l’ont été. La comparaison de ces deux fréquences montre une relation statistiquement significative entre le type de tâches et le fait de contracter de la TB (p=0,0000012). Les aides-soignants et nettoyeurs courent un risque multiplié par 7 d’être atteints de la TB par rapport aux autres professions (OR=7,13; 3,34-15,19).
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These criteria were revised in 2011 by the National Institute on Ageing and Alzheimer’s Association (NIA-AA) workgroup to incorporate scientific knowledge accumulated to date . Based on neuroimaging techniques and cerebrospinal fluid (CSF) analysis, AD pathology biomarkers, such as Aβ deposition in the brain, Aβ42 and pathologic tau level in CSF, have been added to clinical criteria. The observation that AD pathological events (neurofibrillary tangles) can be present in the absence of any clinical symptoms has also been taken into account building a basis for distinguishing between preclinical and clinical stages of AD. The course of the disease has been divided into three stages on the basis of both degree of cognitive impairment and AD biomarker profiles , namely: preclinical stage, characterized by normal cognitive ability; prodromal stage, characterized by mild cognitive impairment; and the dementia stage, characterized by functional impairment. The separate diagnostic recommendations have been formulated for each stage [12–14]. The clinical criteria of cognitive functions are still a basis for diagnosis, whereas biomarker information provides additional supportive evidence and is proposed to be used in clinical research and trials .
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In the model, the reduction of the incidence of CIN 3 cases in the entire female population is vividly shown and at the same time allows a deep insight into the age groups of particular interest. The influences of HPV vaccination on the development of CIN 3 as well as the influences of the two secondary prevention mechanisms—cytology alone and co-testing—can be identified separately on the same age distribution curve. In the model-based analysis, it becomes apparent that after a temporary increase in CIN 3 incidence in the time period from 2020 to 2022, a sharp decrease in the incidence of these lesions as a precursor to invasive cervical cancer should be seen, especially in the 2nd round 2023–2025 of the new cervical cancer screening program.
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Following treatment with siRNAs or engineered S. Typhimurium, the viability of B16F10 melanoma cells was assessed using a trypan blue dye exclusion assay and lactate dehydrogenase (LDH) assay. The exclusion of trypan blue dye by viable cells was evaluated within the grid of a hemocytometer. Cell survival rate was calculated as the number of viable cells divided by the total number of cells. A minimum of 200 cells were counted. To evaluate plasma membrane damage, LDH assays were performed by measuring the release of LDH from the cytosol into the culture medium, using a CytoTox 96 non-radioactive Cytotoxicity Assay kit (Promega, Madison, WI, USA) in accordance with the manufacturer’s protocols. LDH activity was determined by measuring the conversion of a tetrazolium salt into a red formazan product using an ELISA reader at 492 nm. Treatment-induced LDH release was calculated as a percentage of the total LDH activity found in the culture medium.
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Além de interferir na produção de óxido nítrico, o ácido úrico também pode ser responsável pela sua degradação. Embora, em concentrações fisiológicas, o ácido úrico tenha efeito antioxidante e seja, portanto, um fator de proteção endotelial, a elevação nos níveis séricos faz com que assuma um papel pró-oxidante, pois sua via de formação pela xantina oxidase produz espécies reativas de oxigênio e peróxido de hidrogênio, que, em excesso, irão reagir com o óxido nítrico endotelial e formar o peroxinitrito, importante agente oxidante.27
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The lncRNA/mRNA coexpression network constructed using the cytoscape program for the CK10 group. The lncRNAs and mRNAs with Pearson correlation coefficients ≥ 0.99 or ≤ −0.99 were selected to draw the regulatory network using the cytoscape program. In gene-coexpression networks, each gene corresponds to a node. Two genes are connected by an edge, indicating a strong correlation. Within the network analysis, a degree is the simplest, most important measure of the centrality of a gene within a network and determines the relative importance. A degree is defined as the number of directly linked neighbors. In the network, the node size indicates the node degrees and the number represents the number of directly linked neighbours that are associated with each color. Therefore, the larger the node size suggested the targeted lncRNA or mRNA could directly linked with more neighboring genes.
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Фолликулостимулирующий гормон (ФСГ) после связывания c собственными рецепторами на клетках Сертоли стимулирует мембраносвязанную аденилатциклазу (mAC), которая активирует цАМФ-зависимую протеинкиназу А (cAMP/PKA) и далее фактор транскрипции CREB (cAMP response element-binding protein). В 2000 г. Chen et al. клонировали новый тип аденилатциклазы, названный растворимой аденилатциклазой (sAC). Он заметно отличается от mAC тем, что чувствителен к HCO3– и кальцию и представляет собой альтернативный способ активации cAMP/PKA. Этой же группой ученых было продемонстрировано, что CFTR участвует во входе HCO3– в клетки Сертоли для запуска cAMP-зависимой транскрипции и, в конечном итоге, обеспечения сперматогенеза. Дефекты CFTR могут приводить к недостаточности ФСГ-опосредованной внутриклеточной передачи сигнала и, как следствие, экспрессии генов сперматогенеза . Так, отсутствие синтеза CFTR у пациентов с необструктивной азооспермией отличается дефицитом фосфорилирования CREB, его суммарной экспрессии в клетках Сертоли . Вопрос о факторах прогноза по угнетению гаметогенеза с возрастом у мужчин с мутациями CFTR требует изучения (рис. 4).
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When lysates made from various murine tissues were separated by SDS-PAGE and immunostained with a commercially available pan C antibody (Figure 1A), a 40 kDa band was detected in all tissues. In addition to this ubiquitously expressed band a weaker band of 47 kDa was detected, that seemed to be restricted to lymphoid tissues, as it could only be detected in lymph nodes, spleen and thymus. No expression was detected in brain, heart, lung, liver, kidney and skeletal muscle.
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Differentially accumulated proteins (DAPs) were considered as those displayed a fold change >1.3 or <0.77 in relative abundance and a p value < 0.05. Compared with UP, 389, 189, and 307 protein species exhibited a differentially accumulated pattern, with 179, 102, and 156 protein species up-accumulated and 210, 87, and 151 protein species down-accumulated in PC, PI, and NA, respectively (Figure 3A, Table S2).
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The time course of rod microglia emergence and resolution in most diseases is poorly understood since clinical cases are usually based on a single post-mortem histological observation. Nevertheless, in a rat model of transient ischemic attack obtained experimentally, with the middle cerebral artery occlusion, rod microglia were found in the penumbra area of the ipsilateral cortex already 10 min after the insult, and at 24 or 48 h of reperfusion . On the contrary, in our experiments rod microglia was no longer evident in CA1 SP or SR 36 h after OGD, when frank neuronal damage and degeneration of CA1 SP were evident. Our data can be explained considering that the 30 min OGD is a very strong insult and confirm the findings by Graeber and Mehraein who determined that rod microglia can only form when the tissue is preserved and not completely damaged after the insult. Indeed, 36 h after OGD, when most of CA1 pyramidal neurons were damaged, the density of rod microglia was very low, while microglia cells were mainly amoeboid and were phagocytosing HDN neurons in both the outer and inner SP layers. Our data indicate that in 12 h the scenario completely changed, and most of microglia assumed an amoeboid phagocytic phenotype. These results are in accordance with Graeber and Mehraein , who described that when the tissue is highly damaged and with extensive neuronal necrosis, microglia acquire the morphology of activated, phagocytic cells. Until recently, activated microglia was classified in M1, proinflammatory, and M2, anti-inflammatory, states . Nevertheless, this classification is too simplistic and does not correspond to the many different microglia phenotypes found in the brain . Indeed, it is now more and more evident that many microglia activation states may exist, not related merely to the type of insult and the time course of the disease progression, but dependent upon the CNS area in which microglia cells are located . In this scenario, it is not surprising that microglia located in two contiguous hippocampal areas, CA1 and CA3, react in a different way to the same simil-ischemic insult, responding to internal cues, independent from the environment or from the insult. The areas CA3 and CA1 of the hippocampus are considered as a continuum since they are contiguous and interconnected via the Schaffer collaterals. Nevertheless, they respond differently to ischemic insults. The CA1 pyramidal neurons are among the most vulnerable , as demonstrated in experimental animal models of hypoxia or ischemia (reviewed by ), and in patients . Although it is still not completely understood how and why these two areas of the hippocampus are differently affected by the same ischemic event, some new data start to shed some light onto the possible mechanisms. The modifications that ischemia brings about not only in neurons but also in microglia, or astrocytes, and their interrelationships can be envisaged as one of the causes of the different responses of CA1 and CA3 neurons to the same ischemic insult. Our data may help to better understand these different responses. We found that, at 24 h after OGD, higher neuronal vulnerability was paralleled by rod microglia formation in CA1. On the contrary, in CA3 where most of pyramidal neurons did not show signs of damage, in parallel no rod microglia was formed. Furthermore, after NIR-laser application, a physical stimulus known to protect neurons after OGD , no rod microglia were found in CA1. Although from our data it is not possible to discriminate which came first, the presence of neuronal damage was always accompanied by rod microglia formation. From all our results it is possible to envisage that rod microglia do not have a protective role towards neuronal damage caused by an ischemic insult, at least in CA1 hippocampus.
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Per quanto non esistano evidenze specifiche nel caso dell’infezione da COVID-19, è comunque auspicabile che un adeguato controllo venga raggiunto in assenza di ipoglicemia, perché sia glicemie elevate che glicemie troppo basse sono state correlate a esiti peggiori in caso di patologie acute intercorrenti nella persona con diabete [15–17].
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O presente estudo mostrou que existem pelo menos 29 escalas de avaliação de dor em RN disponíveis em publicações científicas da área de neonatologia, sendo 13 unidimensionais e 16 multidimensionais, que contemplam RNPT e RN a termo, em situações de dor aguda e prolongada.
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y proponía a los Cabildos varias soluciones 10: establecer horas y sitios de trabajo; determinar la ración de comida, diferenciando entre casados y solteros; definir el tipo de vestuario, la periodicidad de cambio y su calidad, y consolidar los castigos que debían imponerse, con lo que debía aumentar la productividad y disminuirse las “alteraciones sociales” asociadas:
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To confirm that the significant inhibition in biofilm formation by Mg2+ ions is not a result of toxicity to bacterial cells, we tested the effect of different concentrations of Mg2+ ions on bacterial growth. As shown in Supplementary Figure 1, the growth curve analysis suggests about very little effect of the Mg2+ ions on bacterial growth at the tested concentrations; hence, the mode of action of Mg2+ ions is apparently specific to inhibition of biofilm formation.
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An organism cannot avoid all damage caused by ROS, so systems that repair damaged proteins and lipids are needed (fig. 2a). Methionine sulfoxide reductase A (MsrA) and methionine sulfoxide reductase B (MsrB), which have independent evolutionary origins (Delaye et al. 2007), both restore oxidized methionine residues. Our analyses showed that different Fornicata lineages acquired both proteins through independent LGT events. In the MsrA phylogenetic tree, Giardia clustered with Firmicute sequences (with good support), whereas S. salmonicida clustered (with low support) within Mycoplasma (supplementary fig. 19, Supplementary Material online). The phylogenetic tree of K. bialata showed it clustering within Proteobacteria with low support (supplementary fig. 20, Supplementary Material online).
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W dalszych badania nad genetycznym uwarunkowaniem otyłości stosowano trzy różne metody poszukiwań. Pierwszą było typowanie genów kandydackich związanych z regulacją metabolizmu w oparciu o badania na zwierzętach lub in vitro. Weryfikacja wytypowanych genów polega na porównaniu częstości występowania mutacji danego genu w grupie osób z daną cechą (w tym przypadku otyłością) a występowania mutacji danego genu w grupie osób zdrowych. Ten sposób był z powodzeniem stosowany w identyfikacji genów odpowiadających za powszechne choroby i cechy złożone. Jednak w przypadku otyłości nie uzyskano zadawalających rezultatów, mimo przebadania ponad 200 genów związanych z regulacją apetytu, metabolizmem glukozy i tłuszczów oraz rozwojem tkanki tłuszczowej .
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Second, the strong-linked nodes (SN) and the weak-linked nodes (WN) are selected from NS, denoting proteins in NS closely and weakly related with disease proteins in S, where a strong-linked node is defined as the protein having a connective similarity with S larger than 0.99, and a weak-linked node is defined as the protein when it has a connective similarity with S smaller than the average value in NS. Note that, the connective similarity ranges from 0 to 1, and the average value of connective similarity is always smaller than 0.99. Thus, there is no intersection between the strong-linked nodes (SN) and the weak-linked nodes (WN). Third, the network G is changed to G new by adding or removing several links associated with the strong-linked or weak-linked nodes, according to the suggested network adjustment strategy. The network adjustment strategy includes two key operators, i.e., adding and removing links, which are designed as follows.1) Adding link operator: For a strong-linked node p′ ∈ SN, we check whether a link needs to be added between p′ and the node in S which is not connected with p′ in the current network. Let S1′={pi1,…,pir}⊆S and S2′=S/S1′ be the two sets of nodes which are connected and not connected to node p′. For each node pie∈S2′ , a link between node p′ and node pie is added into the current network when ss(p′,pie)>φ1 . This means that a link is added if the semantic similarity ss(p′,pie) between p′ and node pie is larger than φ 1, where φ 1 is the mean semantic similarity between p′ and each node in S1′ .
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Several in vitro experiments have shown that IL-7 and IL-15 can induce TN cells to expand into memory T cell subsets and, compared with IL-2, these cytokines are beneficial for preserving the phenotype of TSCM cells [108–110]. A clinical trial showed that IL-7 and IL-15 could produce prolonged survival of CAR T cells exposed to repeated serial antigen stimulation . Moreover, it has been demonstrated in mice that CD19 CAR–modified TSCM cells facilitate efficient homing to the secondary lymphoid organs and proliferate continuously in vivo [108, 110]. In an in vitro study, researchers confirmed that a short period of CD3/CD28 costimulation (48 h) increased the percentages of TSCM cells within the CD4+ and CD8+ subsets when the cells were cultured with IL-7/IL-15 and that adding IL-21 to the culture further increased the number of TSCM cells (Fig. 4b). However, whether IL-7 and IL-21 play a positive role in expansion is controversial. A study by Darya Alizadeh et al demonstrated that IL-15 preserved the TSCM phenotype by reducing mTORC1 activity but the addition of IL-7 and/or IL-21 reduced the benefits of IL-15 on the CAR T cell phenotype and antitumor activity . Thus, this area remains to be further studied. In addition, the ratio of CD4+:CD8+ CAR T cells can remain stable in culture medium with added IL-7 and IL-1 5.
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These peptides were obtained from interalpha trypsin, chitin synthase, peroxisomal hydratase–dehydrogenase–epimerase, and phosphoenolpyruvate carboxykinase. In general, these proteins are produced when the fungus undergoes a mechanism of adaptation to the intracellular environment, in order to survive in a latent state . The low-oxygen environment allows the fungus to survive via metabolic adaptation, thereby enabling the fungus to evade intracellular defense mechanisms while remaining protected by the endosome. To stay into the endosome, the fungus inhibits the phagolysosome maturation, lyses the host cell, detoxifies oxidative or nitrosative reagents, and uses different metabolic pathways to obtain energy from the available nutrients . This mechanism is characterized by interactions between the fungus and host molecules and with the components of the cellular matrix, thereby causing delays in immune response induction . Despite efforts required for fungal evasion, infected macrophages can act as antigen-presenting cells APCs, and can process and present antigens to TCD4+ cells. Recognition promotes the differentiation of TCD4+ cells into auxiliary T (Th1) cells, which when activated secrete IFN-γ, further activating the microbicidal function of alveolar macrophages and stimulating the presentation of antigens at the infected sites .
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A–C. Scatter plot showing that the number of Macrophage scavenger receptor B (Msr-B)-positive macrophages/microglia was comparable between rolipram-treated and control animals. Control n = 9, rolipram n = 9; ANOVA: p > 0.1; control = 146.8 ± 27.97, rolipram = 124.5 ± 18.23. Representative images of sections stained by in situ hybridization for Msr-B 14 days post lesion induction.
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Co ciekawe, odmowy szczepień ochronnych z reguły nie dotyczą noworodków przedwcześnie urodzonych. Wydaje się, że dłuższy kontakt rodziców z personelem medycznym oraz obserwacja długiego i często skomplikowanego procesu zdrowienia dziecka wytwarza pewien poziom ufności, sprzyjający akceptacji zaszczepienia dziecka. U długo hospitalizowanych wcześniaków także następne szczepienia (DTaP+ HIB+PCV) sąw wielu oddziałach neonatologicznych wykonywane w szpitalu. Jak wykazano w naszym poprzednim badaniu, przyjęcie takiej taktyki sprzyja zarówno realizacji szczepień ochronnych jak i terminowości ich wykonania . Mimo to ponad połowa oddziałów neonatologicznych na Mazowszu nie wprowadziła szczepień ochronnych wcześniaków do procedur realizowanych podczas hospitalizacji . Tymczasem, u noworodków przedwcześnie urodzonych z istniejącymi czynnikami podwyższającymi ryzyko wystąpienia zdarzeń niepożądanych, wykonanie szczepień w szpitalu jest szczególnie uzasadnione .
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Le traitement de la tuberculose pelvienne est essentiellement médical (Table 1). Selon l'Organisation Mondiale de la Santé et l'American Thoracic Society recommandent un traitement pendant 6 mois reparti en une quadrithérapie intensif (isoniazide, rifampicine, Ethambutol, pyrazinamide) pendant deux mois, puis un traitement d'entretien pendant 4 mois par une bithérapie quotidienne (isoniazide, rifampicine) .
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Scaffold design then moved to the second phase, in which bioactive glass has been used as a scaffold in bone tissue engineering . Kargozar and colleagues used a combination of bioactive glass/gelatin (BaG/Gel) scaffolds, aiming for a highly porous structure, which is considered ideal for bone substitution. A comprehensive physiochemical analysis showed that the structure had an intact, 3D porous microstructure with interconnected pores. It was also shown that the properties were very close to those of natural spongy bone . They demonstrated that neovascularization was significantly better in the UC-MSC-seeded scaffold when compared to the BM-MSC-seeded scaffold, indicating that the BaG/Gel scaffold is MSC type-dependent. A study by Todeschi and colleagues used hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP), or a mixture of the two as the scaffold. They showed that a significantly higher number of blood vessels were present in the UC-MSC-seeded implants .
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In addition to severe respiratory complications, which can rapidly progress to coma in some children, influenza-associated neurological complications are more severe in children and are the leading cause of influenza death [12, 14, 15]. Until now, the pathogenesis of influenza-associated neurological complications is still unclear. Autopsy of these patients showed necrosis and epithelial hemorrhage of thalamus and posterior cerebral cap of pons, pale myelin sheath in white matter of brain and cerebellum, and no clear obstruction of vascular endothelium and peripheral vascular edema . Due to the acute onset of influenza-associated neurological diseases, severe brain dysfunction can occur quickly. The treatment time window is tight. Before the symptoms of nervous system appear, the children’s respiratory system disorder is not prominent or even no respiratory system performance, and lack of early warning indicators. Although immunization can reduce its incidence to a certain extent , most children are not actively vaccinated. Once the patient developed into an Influenza-associated neurological disease, treatment is extremely difficult, and some children develop cardiopulmonary failure within a short period of time. Many children have undergone cardiopulmonary resuscitation before admission, and showed pupil light loss or even brain herniation after admission, the brain failure will soon appear even if with active treatment. Even if they survived, some children will still have serious neurological complications. The mortality rate of acute necrotizing encephalopathy is 31.8%, and only 10% of patients make a full recovery, with many more surviving as neurological sequelae. The neurological sequelae recover very slowly and some patients received unacceptable long-term rehabilitation . Therefore, effective treatment of influenza-associated neurological disease, especially acute necrotizing encephalopathy is a problem that we urgently need to solve. In this study, we found that the mortality of children in the CBP group was lower than that of the non-CBP group, and the neurological coma score (Glasgow score), PCIS score and PIM-2 score were improved compared with the non-CBP group. This suggests that CBP is associated with a reduction in mortality.
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Le syndrome occlusif clinique est marqué par les douleurs abdominales aigues initialement localisées, puis permanentes et généralisées, un tableau d'hypovolémie est évocateur dans 56% des cas . La radiographie de l'abdomen sans préparation peut montrer occasionnellement les caractéristiques d'une double occlusion à boucle fermée avec des niveaux hydro-aériques sigmoïdiens dans le quadrant supérieur droit, et d'autres de type grêlique pouvant être latéralisées à gauche [2, 4, 10], le plus souvent elle montre un volvulus sigmoïdien ou une occlusion grêlique isolée. Le scanner abdominopelvien confirme l'occlusion sigmoïdienne et iléale, permet de chercher outre les signes de l'ischémie intestinale, des signes caractéristiques du NIS, le tour de spire est plus volumineux que dans un volvulus isolé du sigmoïde, portant les vaisseaux mésentériques supérieurs et inférieurs , cet aspect pourrait s'expliquer par le fait que les deux volvulus se superposent . La rétention des matières dans le colon proximal non distendu et la disposition radiaire des anses grêliques orientent le diagnostic selon Hashimoto et al . L'association de la déviation médiale du colon descendant et du mesocœcum, avec aspect effilé et pointu de leurs bord internes, convergeant vers des tours de spires est très caractéristique du nœud iléo-caecal [3, 10, 12], cet aspect est dû d'une part à l'attraction du péritoine pariéto-colique gauche et du mésocoecum vers le centre du NIS, et d'autre part à l'effet de masse des anses grêles dilatées . Le NIS est associé à une mortalité élevée nécessitant un diagnostic précoce, une prise en charge chirurgicale adaptée et rapide, le traitement est basé sur la résection-anastomose ou la colostomie si les segments intestinaux sont nécrosés, la détorsion et la sigmoïdopexie est recommandée dans les rares cas où il n'y a pas de nécrose .
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On the other hand, iNKT cells from MS patients seemed to not respond to stimulation with α-GalCer, either by proliferation or by the production of IFN-γ , a similarly weaker proliferation was observed by others . This was, however, contradicted by a study of Gigli et al., who observed a significant increase in IFN-γ, IL-4 and IL-5 production by α-GalCer-stimulated iNKT after IFN-β treatment . The effect of IFN-β was mediated by dendritic cells—direct addition of IFN-β to cell culture completely blocked cytokine secretion in iNKT cells . Blocking the activity of phosphodiesterase with non-selective inhibitor ibudilast promoted a significant increase in iNKT percentage among T cells in RR-MS patients as well as promoting a general Th2-shift in Th cells in peripheral blood .
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In der ersten Schlussfolgerung wird festgestellt, dass die Affektion auf ein bestimmtes Ereignis zurückgeführt werden kann und daher nicht angeboren war. Eine Frau habe den Patienten am Hals gewürgt, woraufhin ein defectus (potentiae) coeundi (Fehlen der Fähigkeit zum Beischlaf) eingetreten sei. Da die Werke der Natur Bewegung sind, sei die ablatio potentiae coeundi ein permanenter Verlust an Bewegung. Bewegung vollziehe sich immer prozesshaft und nie plötzlich. Reichart schlussfolgert, dass die Frau einen Zauber (maleficium) bewirkt habe, der auf die Natur gewirkt habe.
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A multi-responsive hydrophilic ABCBA-type pentablock terpolymer, consisting of poly(ethylene glycol), poly(N-isopropylacrylamide), and poly(methacrylic acid), PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA, were synthesized according to the following four steps: (1) preparation of RAFT agent (CTA); (2) preparation of macromolecular chain transfer agent, CTA–PEG–CTA; (3) synthesis of triblock copolymer (PNIPAM-b-PEG-b-PNIPAM); (4) synthesis of pentablock terpolymer (PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA) to achieve dual-responsive hydrophilic polymers.
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We first determined the expression patterns of LIN28B in non-small cell lung cancer (NSCLC) tissues. After measuring the expression levels of the LIN28B protein in seven pairs of NSCLC tissues and corresponding normal adjacent tissues via Western blotting (the clinical features of these tissue samples are listed in Table S1), we observed that the LIN28B protein levels were significantly higher in the cancer tissues (Fig. 1A and B). Subsequently, we performed quantitative RT-PCR to measure the expression levels of LIN28B mRNA in the same 7 pairs of cancerous and noncancerous tissues. It was observed that the LIN28B mRNA levels did not differ significantly between the cancerous and noncancerous tissues (Fig. 1C). The disparity between the LIN28B protein and mRNA levels in NSCLC strongly suggests that a post-transcriptional mechanism is involved in the regulation of LIN28B. Additionally, we found that the expression levels of let-7 were conspicuously decreased in the cancer tissues compared with those in normal adjacent tissues (Fig. 1D), which is consistent with the previous findings that Lin28B blocks the maturation of let-7 miRNAs101112.
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The PI/MH(lim) and the MMI/MH(lim) cohorts included a pre-clinical humanities curriculum that was limited to the first year of medical school. The third cohort (MMI/MH(ext)) participated in an extensive and comprehensive three-year pre-clinical curriculum.
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The ability of SN4 laccase to oxidize several phenolic and non-phenolic substrates viz. ABTS, SGZ, guaiacol, pyrogallol, α-naphthol, PPD, resorcinol, DMP, catechol, L-DOPA and tyrosine was determined, at different pH values ranging from 1.0–10.0 [1.0–2.0 (0.1 M KCl-HCl buffer), 2.5–3.5 (0.1 M glycine-HCl buffer), 4.0–5.5 (0.1 M acetate buffer), 6.0–7.5 (0.1 M phosphate buffer), 8.0–9.0 (0.1 M tris-HCl buffer) and 9.5–10.0 (0.1 M carbonate-bicarbonate buffer)]. The relative rate of oxidation for each substrate (at their optimum pH) was compared using the enzyme activity with DMP as 100%.
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We begin by considering the accuracy of structure modeling different conformations. Table 2 and Supplementary Table S3 report accuracy of centroids of the three largest clusters (‘C1’, ‘C2’, and ‘C3’) compared to the two or three experimentally verified conformations (in rows) for each sequence. We consider that Rsample correctly identified a conformation if the accuracy is higher than 80% and the identified structure is not closer to any other known conformation. In the case of the FMN riboswitch, we lower the accuracy criterion to 70% considering that it is an artificially designed sequence (49), i.e. it is not known in biology, and its secondary structure has not been independently verified. Out of the total of 20 experimentally known conformations for the six sequences, using no SHAPE restraints identifies only 13 conformations correctly, our prior method with SHAPE restraints, ‘Pseudo ΔG’, identifies just 12 correctly, but Rsample identifies a remarkable 18 conformations correctly. RNAsc (32) and RNAprobing (31) correctly identify 12 and 13 conformations respectively (Supplementary Table S3), thus performing similarly to our prior method with the Pseudo ΔG SHAPE restraints (21).
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There is a strong relationship between geographic distance and annual amplitude among cities, indicating that cities located in close proximity to one another experience similar mortality amplitudes from year-to-year (Fig. 6). This relationship is highly statistically significant (p = 0.000) with an r-squared of 0.219. It appears as if this relationship is not completely linear, with both logarithmic (r-squared = 0.294) and third-order polynomial (r-squared = 0.308) trends providing better fits. Interestingly, the relationship between distance and the annual timing of the mortality peak is even more striking, indicating that cities located near each other experience similar dates of maximum mortality (Fig. 7). This relationship is also highly significant (p = 0.000) with an r-squared value of 0.265. The strong relationship in year-to-year timing of the seasonal mortality peak is particularly surprising given that the “dual peak” signature discussed earlier would weaken these results considerably. Clearly, there is a strong regional homogeneity in amplitude and timing within the cities’ annual mortality curves.
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Como a redução da eosinofilia no escarro está relacionada com uma resposta clínica e funcional positiva aos corticosteroides, nossos resultados apoiam a recomendação de que se deve aumentar a dose de corticosteroides quando a asma se torna descontrolada.( 8 , 21 ) Em uma análise de regressão múltipla, ten Brinke et al.( 23 ) constataram que o fator mais importante potencialmente relacionado com obstrução persistente do fluxo aéreo na asma grave foi uma proporção de eosinófilos no escarro > 2% (OR ajustada = 7,7). No entanto, existem indivíduos com asma não controlada que não apresentam eosinofilia no escarro. Ainda não se determinou se esse subgrupo é menos sensível aos corticosteroides.
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Die Relevanz der MRT wird durch die Zusammenhänge von Bildgebung und Kognition deutlich. MRT-Korrelate für kognitive Dysfunktionen sind die T2-Läsionslast, die kortikale Läsionslast und die kortikale Dicke sowie die globale und fokale Hirnatrophie [8, 9, 53]. Bestimmte Läsionslokalisationen bergen ein höheres Risiko für kognitive Defizite. Auch welche kognitive Domäne beeinträchtigt ist, wird von der Läsionslokalisation bzw. dem Verteilungsmuster mitbestimmt. Läsionen in der weißen Substanz sind maßgeblich für die kognitive Verarbeitungsgeschwindigkeit verantwortlich, Läsionen der tiefen grauen Substanz (z. B. im Hippokampus) sind häufig mit Gedächtnisdefiziten assoziiert .
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Urinary microalbumin (UMb) was measured based on particle-enhanced turbidimetric inhibition immunoassay (PETINIA) using Dimension® clinical chemistry system (Siemens, New York, NY, USA). In the presence of human albumin-bound particle reagent (PR), albumin present in the sample competes for monoclonal antibody (mAb) and reduces the rate of PR—mAb aggregation. Therefore, the rate of aggregation is inversely proportional to albumin concentration in urine samples. The rate of aggregation was measured using bichromatic turbidimetric reading at 340 nm (assay range: 1.3 °C 100 mg/L). UMb level was later used to calculate ACR and participants with higher ACR (≥30 mg/g Cr) were retested after 3 months of initial collection. Ion-exchange high-performance liquid chromatography (HPLC) was used for the measurement of HbA1c using Bio-Rad D-10TM.
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CBF genes, also named DREB genes, belong to AP2/ERF gene family . CBF/DREB1 genes have been studied in various plant species, such as Arabidopsis thaliana, Oryza sativa, soybean (Glycine max), Chrysanthemum, Vitis vinifera, Malus domestica, Prunus persica and Prunus mume . There are six CBF/DREB1 genes in the model plant Arabidopsis, CBF3/DREB1A regulates many genes related to cold response, and hormone metabolism . DREB1 (AtCBF1–3) and DREB2 also function in the signal pathway under low-temperature conditions . The transgenic plants overexpressing AtCBF1 and 3 show strong tolerance to cold stresses . Unlike AtCBF1–3, the expression of AtCBF4 is induced by abscisic acid (ABA) and is not influenced by low temperatures . What’s more, DDF1 and DDF2 (AtCBF5 and AtCBF6) are induced by salinity stress, which is connected to gibberellic acid (GA) levels and results in dwarfism and delayed flowering . Cold hardiness has also been observed when a PpCBF from peach (Prunus persica) is overexpressed in apple . In peach, there are five CBF genes, which are highly induced by 4 °C in leaves and this depends on specific CBF gene . For other species, such as Triticum aestivum and O. sativa, the dwarf phenotype is observed in transgenic plants .
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The reeling length was measured to evaluate the reel-ability of the silk filament from the silkworm cocoon. It was the length of reeled silk filament until the occurrence of the first breakage. The reeling length was calculated from the reeling velocity and reeling time associated with this breakage.
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原发性气管肿瘤的临床评估包括局部肿瘤的评估、明确病理及分期。影像学检查可以确定局部肿瘤的精确位置、范围和浸润程度。由于气管前后有纵隔组织及骨骼影的重叠,气管肿瘤在普通胸片上多为阴性。直接数字化X线摄影术(direct digital radiography, DDR)或高千伏正侧位片是显示腔内肿瘤有效而又简便的方法。这种方法所获图像较透亮、层次感强,但欠清晰。CT由于密度分辨率高,能较清楚地显示肿瘤向腔外侵犯纵隔组织、纵隔淋巴结转移情况等。随着螺旋CT的产生及图像后处理软件的成熟,例如通过CT仿真内镜(CT virtual endoscopy, CTVE)、表面遮盖显示(shaded surface display, SSD)、MPR等技术处理,所获图像能多方位显示气管肿瘤。MRI摄影形成的冠状面、矢状面、横断面三维图像对显示气管肿瘤及肿瘤与周围组织的关系比其它检查方法更清楚、更全面。
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The synthesis was based on the published protocol . The free-base 5,10,15,20-tetraphenyl-2-(benzimidazol-2-yl)-porphyrin (73 mg, 0.1 mmol), InCl3 (110 mg, 0.5 mmol) and NaOAc (410 mg, 5 mmol) were refluxed in AcOH (5 mL) for 1.5 h. The conversion was monitored by TLC, and the reaction was continued until the starting porphyrin was completely consumed. After cooling to ambient temperature, the reaction mixture was diluted with CHCl3 (50 mL) and extracted with water (50 mL). The organic phase was separated, evaporated to dryness and applied to a column packed with silica gel in CHCl3. The column was eluted with CHCl3/MeOH mixtures (0→6% of MeOH) containing 0.2% of Et2NH. The fraction of the target complex was eluted with 3→6% of MeOH in CHCl3 and evaporated to provide 96 mg (96%) of the chloroindium(III) complex, which was subsequently used in the next synthetic step.
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Despite its brittleness and low capacity to bear tensile stress , ordinary concrete is the most frequently used building material in the world. Concrete is almost always reinforced by some kind of steel elements (e.g., bars, stirrups, meshes) when used for construction to counteract its brittleness. Over the last 50 years, steel fibre has become a more and more popular type reinforcement for concrete. Currently, steel fibre reinforced concrete (SFRC) is one of the main building materials . SFRC is characterized by higher tensile, shear and flexural strength , better performance when exposed to elevated temperatures and lower shrinkage than ordinary concrete of similar composition. Usually, steel fibre is arranged randomly but evenly in the SFRC volume. Nevertheless, in some circumstances, irregularity in the fibre distribution may occur. These irregularities in fibre spacing significantly affect its properties. The homogeneous spacing of randomly oriented fibre within a structural element is crucial for guaranteeing proper structural performance with a satisfactory degree of repeatability . Many attempts are being made to study fibre spacing using different destructive and non-destructive methods. The most successful methods are X-ray tomography and cross-section analysis . Both methods give very precise results but are not feasible in common in-situ test scenarios. The simplicity of a conducted test and affordability of used equipment are two main factors influencing the practicability and popularity of a testing method. In many cases, construction companies already have apparatuses dedicated for non-destructive testing (NDT) location of steel bars in existing concrete structures. Harnessing such apparatuses for the assessment of steel fibre volume and spacing would be the most practical and sustainable solution. In the authors’ opinion, two existing NDT techniques, electromagnetic induction and radar-based techniques, have the potential for testing SFRC. The inductive technique was proven as a robust and simple non-destructive method to assess the content and the distribution of steel fibre. Nevertheless, there is still a necessity to define its accuracy. The equations for the conversion of the inductance into fibre volume and spacing are also needed. Multiple attempts have also been made to use radar-based technique for the similar assesment of SFRC. The fundamental differences between electromagnetic induction and radar technologies are the detectability of objects of different materials and the dependency on the properties of the base material. Using the induction technology, only ferrous materials can be detected. Radar techniques allow the detection of objects of different materials, including ferrous and non-ferrous metals, water-filled pipes, voids, etc. . Moreover, the radar-based technique can be applied not only to detect location of reinforcement, but also to assess moisture in reinforced concrete .
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Para reduzir a possibilidade de confundimento, optou-se por trabalhar com um grupo controle comparável ao grupo de intervenção. A única região do estado de São Paulo que atendeu aos critérios estabelecidos, ou seja, não ter o Samu implementado durante o período de análise e apresentar valores de covariáveis semelhantes aos da região do Grande ABC, foi a região da Baixada Santista.
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Eerder onderzoek heeft laten zien dat er ook in Nederland mensen zijn met een verminderde voedselzekerheid [9, 10]. Er is echter nog geen informatie beschikbaar over de ervaren impact van de COVID-19-crisis op voedselzekerheid in de Nederlandse context. Wel is er vooral in de grote steden een trend te zien van een toenemend beroep op voedselbankgebruik sinds het begin van de COVID-19-crisis. In december 2020 was het voedselbankgebruik met 7,2% gestegen in vergelijking met 2019. De toename was het grootst in Noord-Holland en Rotterdam . De urgentie van deze kwestie is het kabinet niet ontgaan en in maart en november 2020 is extra financiële ondersteuning voor de voedselbanken beschikbaar gesteld. Hoewel voedselbankgebruik een indicatie kan geven van het aantal mensen dat verminderde toegang tot voeding heeft, blijkt uit zowel internationaal als nationaal onderzoek dat voedselbankgebruik geen accurate indicator is voor een verminderde voedselzekerheid: veel mensen die een verminderde voedselzekerheid ervaren, maken om verschillende redenen geen gebruik van de voedselbank [12, 13]. Het is daarom belangrijk om voedselbankgebruik niet als indicator te gebruiken voor het in kaart brengen van de mate van voedselzekerheid in Nederland.
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The current study demonstrates the potential for blastocysts of differing sex to produce dimorphic signals in the form of miRNAs, which can collectively impose changes in transcripts of maternal cells. Endometrial cell internalization of miRNAs, and subsequent upregulation of PGR is a remarkable display of the potential for miRNAs to function as signaling molecules during preimplantation development and allows for a new perspective on understanding the preparation of maternal cells for interaction with blastocysts, which already contain inherent differences due to their sex. Male and female embryo dimorphism in miRNA production allows for future discovery of invaluable biomarkers of embryo signaling, and understanding the potential roles of miRNAs in preimplantation development blastocyst-to-mother communication.
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Outcomes included fatal and nonfatal self-harm, certainly including some instances of self-harm without suicidal intent. Self-harm with and without suicidal intent cannot be distinguished using ICD-10-CM coding of nonfatal events or ICD-10 coding of fatal events.
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In recent years, genomic selection (GS) and high-throughput phenotyping (HTP) have emerged as potential technologies for improving breeding efficiency (Furbank and Tester 2011; Cabrera-Bosquet et al. 2012; Crossa et al. 2017). In GS, genome-wide marker effects are estimated for a “training set” of lines that has been phenotyped and genotyped (Meuwissen et al. 2001). Those estimates are then applied to selection candidates prior to phenotyping to predict trait values, which may reduce the time and cost of testing breeding lines. While GS was initially developed to predict within individual environments, recent studies have extended the genomic best linear unbiased prediction (GBLUP) model to accommodate G×E interactions. Burgueño et al. (2012), Heslot et al. (2013), Jarquín et al. (2014), López-Cruz et al. (2015), and Pérez-Rodríguez et al. (2017) reported increases in prediction accuracies with extended models relative to single-environment analyses.
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Deglutition is one of the principal physiological functions of the oral cavity. Pressure from the tongue during deglutitive motion may contribute to the equilibrium that maintains tooth position . It has long been debated whether abnormal patterns of orofacial muscle function, including tongue and lip postures, influence or create dental malocclusion, or conversely, whether malocclusion is the cause of abnormal tongue posture and function . Therefore, deglutitive tongue function is of substantial interest not only to those in the dentistry field (orthodontists, dentists, and dental hygienists) but also to speech-language pathologists [3, 4] and other professionals working in the orofacial area.
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+30.5 (c 0.5, MeOH); 1H NMR (600 MHz, CDCl3) δ 9.22 (s, 1H), 6.96 (s, 1H), 4.17–4.09 (m, 1H), 3.76–3.67 (m, 1H), 3.49–3.38 (m, 2H), 3.36–3.31 (m, 1H), 2.13–2.04 (m, 1H), 1.97–1.81 (m, 2H), 1.78–1.69 (m, 1H), 1.46 (s, 9H), 1.30 (s, 9H) ppm; 13C NMR (151 MHz, CDCl3) δ 182.3, 157.3, 80.6, 57.4, 55.9, 53.7, 47.5, 29.9, 28.5, 24.0, 22.2 ppm; IR (ATR): 3307, 2973, 1653, 1159, 1237, 1058 cm−1; HRMS (m/z): [M + Na]+ calcd for C15H29N3O3S2, 386.1543; found, 386.1543; [M + H]+ calcd, 364.1729; found, 364.1722.
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SOX2是一种转录因子并且对胚胎和神经干细胞严格调控,在肺上皮细胞的发展中发挥关键作用。RNA干扰敲除SOX2可减少细胞增殖,抑制SOX2比PIK3CA和TP63对细胞生长的影响更大。SOX2过表达可导致细胞迁徙、锚定和独立生长,而SOX2基因敲除则可影响细胞生长。SOX2过度表达可导致小鼠模型广泛增生和癌变,有证据表明,SOX2扩增可能只是一个“启动事件”,需要下游信号通路进一步改变才能驱动癌变。目前没有SOX2抑制剂在临床试验中使用。FGFR1是FGFR家族的受体酪氨酸激酶的成员,通过PI3K/AKT、RAS/MAPK激活下游信号传导,促使肿瘤生长、迁徙和血管生成等。在肺鳞癌的FGFR1扩增比腺癌常见,约20%肺鳞癌具有FGFR1扩增,在细胞株和小鼠模型抑制FGFR1显示可抑制细胞生长和诱导凋亡。FGFR1基因突变非常罕见。FGFR抑制剂正在研发中,多为多靶点TKIs,可针对除FGFR1外的其他靶点。针对FGFR1扩增肺鳞癌的多个临床研究正在进行中。PI3K-AKT通路在许多癌症的存活和增殖起着核心作用,PIK3CA扩增及突变在肺癌均已确定,扩增可导致PI3K通路细胞信号激活。有多个PI3K抑制剂正在开发中,特异性地针对PI3K/MTOR、panPI3K等。临床前数据表明,PIK3CA激活突变对PI3K通路抑制剂最为敏感,PI3K抑制剂与其他信号通路抑制剂联合应用的研究正在积极进行中。体细胞PTEN基因缺失、突变和PTEN失活,如甲基化或小分子RNA沉默失活,可出现在多种癌症。无论是腺癌和鳞状细胞,PTEN表达下降或不表达发生率均高达70%,肺鳞癌PTEN基因突变高于腺癌(10.2% vs 1.7%)。虽然缺乏确切的数据,但是PTEN基因丢失肺癌可能对PI3K途径抑制剂更敏感,PI3K抑制剂治疗PTEN丢失患者的临床试验正在进行中。由于缺乏针对肺鳞癌驱动基因有效的靶向治疗药物,且多数尚在临床研究初期,多为Ⅰ期、Ⅱ期临床研究,所以目前肺鳞癌分子分型并未给临床带来更多的获益。
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In addition to eamA, Kang et al. discovered RhtA, an endosomal transporter protein encoded by the rhtA gene that effluxes isotopes and threonine with broad substrate specificity and accelerates ALA production in E. coli . Following this, RhtA frequently functions as a non-specific transporter and plays a crucial role in the efficient production of ALA by E. coli as an extracellular . In addition, many scholars have also introduced E. coli rhtA into Corynebacterium glutamicum as a more efficient and cost-effective strategy for producing extracellular ALA than E. coli . Conversely, in the future, it may be possible to reduce ALA secretion to the extracellular compartment by down-regulating rhtA expression in E. coli, thereby enhancing the intracellular ALA titer and favoring heme production.
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Entgegen der häufig beschriebenen Manifestation der mykotischen Paecilomyces-Infektion im hinteren Hornhautstroma sahen wir 2 Fälle mit oberflächlichen Hornhautinfiltraten.Es wird die Bedeutung eines zeitnahen Hornhautscrapings bei Kontaktlinsenträgern mit oberflächlichen Hornhautinfiltraten oder verzögerter Wundheilung/Epithelirregularitäten deutlich.Durch das prompte Einleiten einer antimykotischen Therapie mit Voriconazol können so eine Ausbreitung in das tiefe Stroma und eine intraokuläre Invasion verhindert werden.
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(A) Image data results; (B) Text data results. Colour shaded regions represent 95% confidence interval with respect to mean percentage of model estimates lying within Δ clusters of the true cluster number (corresponding coloured line). Legend: solid RED–complete linkage, L2 (Euclidean) norm; segmented MAGENTA–complete linkage, L1 (Manhattan) norm; short-long segmented YELLOW–Ward’s method; solid GREEN–single linkage, L2 norm; segmented BLUE–single linkage, L1 norm.
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Mentioned internal opportunities for Holocue improvement mainly comprised modality of cues and patient-tailoring cues. In the current version of the Holocue application the choice was limited to four pre-made types of visual cues. In a future Holocue application, users should be able to adjust more settings, including opting for auditory cues, to better tailor the cues to their needs and desires. Furthermore, future studies should test more settings (e.g., walking with both 2D and 3D cues, varying intercue distance) per individual to better understand gait-modifying and FOG-alleviating effects of various cue characteristics and assess the practical feasibility of the Holocue application (e.g., monitor adverse events, such as falls, and explore the possibilities for independent use). Participants saw potential in Holocue, but indicated that mixed-reality headsets need to improve with respect to comfort and mixed-reality field of view. Participants indeed stated that they had trouble with stepping onto or over cues (see Supplementary Material 2), for which unnatural head postures were required to see the nearby holographic cues during the targeted step or crossing maneuver. As such, the small mixed-reality field of view thus limited the action relevance of holographic cues and their immediate effect on FOG, which could also have played a role in previous studies showing null effects with related technology and cueing applications (19, 27, 30, 31). Interestingly, mixed-reality field of view and wearer comfort have allegedly already strongly improved with the latest generation of mixed-reality headsets, such as HoloLens 2 and Magic Leap 1 and 2. These technological advancements offer external opportunities for Holocue improvement, which will likely increase the usability, patient-friendliness, experienced usefulness and potential efficacy of Holocue, especially when combined with the valuable internal opportunities for improvement we discovered with potential end-users.
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Prof. Grust erklärt in seinen Videos wirklich sehr gut und man merkt, dass er dieses Thema sehr gerne lehrt! Das motiviert natürlich nochmal ein bisschen mehr. Er ist einer der einzigen Dozenten, die sehr schnell die Umstellung auf digitale Medien (toll) hinbekommen hat,
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It is evident from Equation (61) that the time ratio τ0/τi linearly depends on two dimensionless magnitudes: the linear parameter ratio L/li and the rate ratio V0i/V. In a similar way, τ0/τr depends on L/lr and V0r/V. Once L>>li at a fixed rate ratio V0i/V or V<<V0i at a fixed linear parameter ratio L/li, the thermodynamic system tends to local equilibrium. Otherwise (L≤li at a fixed rate ratio or V≥V0i at a fixed linear parameter ratio), the latter is non-equilibrium. Similar regularities are observed for parameters of the chemical reaction.
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纳入的13个随机对照试验中,仅5个研究[12, 16, 18, 22, 24]采用了充分的随机方法,其中1个研究采用了最小化随机法,2个研究[12, 22]采用了分层随机法,2个研究[18, 24]的随机序号在试验中心产生。3个研究[16, 18, 24]采用了正确的分配隐藏方法,分别是试验中心电话[16, 18]和试验中心传真。有研究显示即使用了正确的随机方法,但如果未对随机序列进行有效隐藏,依然会在纳入患者时产生选择性偏倚,影响研究结果的真实性。本研究中大部分指标,如完全缓解、部分缓解、生活质量改善、皮疹/痤疮、疲劳等均为主观测量指标,其真实的测量结果依赖于该指标测量人员是否实施正确的盲法,以降低或避免由此造成的实施和测量偏倚。但纳入的13个随机对照试验中,仅3个研究明确说明在试验过程中使用了双盲法,且均未告知具体的施盲对象。因此,不排除其存在一定的实施和测量偏倚。此外,除干预措施外的基础药物治疗以及药物剂量在各研究之间存在一定的差异,均可能对该研究结果产生一定的影响。
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Altogether, this study demonstrates that mammalian Ssu72 can mediate tissue-specific transcriptional activity by regulating reciprocal phosphorylation of CTD both in vitro and in vivo. It also shows that Ssu72 deficiency can cause aberrant Pol II pausing and elongation defects during the transcriptional cycle, with diversity dependent upon the cell type based on gene transcription.
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The schematic of the designed NRPL is shown in Fig. 2, and a total number of 32 concentric nanorings are included to reconstruct the wavefront. The width of the nanoring for the desired phase modulation range from 10 to 100 nm. The aimed focal length f 0 is 1300 nm (2 λ 0). To efficiently utilize the MIM waveguide model, the minimum diameter of the innermost nanoring is set to be 800 nm. Furthermore, to avoid the focal shift as discussed in our previous work , the total phase difference is as large as 10π, with a predicted numerical aperture (NA) of 0.96. As a result, the theoretical Rayleigh diffraction limit, calculated by 0.61 λ 0/NA , is 413 nm (~0.64 λ 0).Fig. 2Schematic of the NRPL. a The incident light normally illuminates the lens. b Structural parameters of the lens. The coordinate values of the red triangles represent the radius r and width w of the corresponding nanoring
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Het netwerk ‘Zicht op Buiten’ is bezig om maatschappelijke bewustwording te creëren door tijdens de Buitenspeelweek van 2021 een webinar te organiseren voor alle beleidsadviseurs. In het najaar volgt een webinar voor ouders en onderwijs. Maar het netwerk heeft hulp nodig bij de volgende stappen. Wat kunnen we nog meer doen om gezond gedrag (2 uur per dag buiten zijn en gezond beeldschermgebruik) te promoten?
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Les autres études ont trouvé une prévalence de 7,1% dans les pays industrialisés, et de 10% à 15% dans les pays en voie de développement [2, 12, 13]. Seule l’étude réalisée au service de réanimation polyvalente du CHU HASSAN II, a trouvé une incidence supérieure à celle de notre étude de 38,42%. Ceci se justifie par le nombre de dispositifs invasifs en réanimation . Les autres ont trouvées une faible incidence de 2,9% et (2,6%) . Les infections les plus fréquentes sont les infections urinaires chez les patientes sondées, les infections du site opératoire après une césarienne, les endométrites et les infections de l’épisiotomie [12, 14]; conformément à nos résultats qui approuvent: les infections urinaires (65,5%), de sites opératoires (22%) après césarienne.
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Le calendrier vaccinal du Programme élargi de vaccination (PEV) avait été suivi par 62,86% des patients alors que pour les vaccins spécifiques EUVAX/ENGERIX, ACT-HIB, TYPHIM IV, seulement par 6 patients (17,14%). En dépit du traitement médical suivi par tous nos 35 patients fait des antibiotiques pendant une période d´au moins 4 semaines et des antalgiques, un traitement chirurgical avait été appliqué chez 10 patients (28,58%) ayant consisté en une séquestrectomie pour 6 malades et incision-drainage articulaire pour les 4 patients avec arthrites suppurées et les 25 patients restants (71,42%) étaient traités orthopédiquement par un matériel plâtré; et le traitement de fond à l´hydroxyurée suivi par uniquement 5 patients (14,28%). La répartition des patients en fonction de l´âge et du type d´infection ostéo-articulaires montre la prédilection de l´ostéomyélite chez les patients âgés de 6 à 10 ans avec 8 cas, l´arthrite plus dans la tranche d´âge de 21 à 25 ans avec 2 cas et l´ostéite également chez les moins de 5 ans avec 3 cas. La différence statistique est significative (p = 0,0326).
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Due to the bone defects of the anterior column, unstable vertebrae tilt was observed in the preoperative model under the upright position and flexion and extension conditions. All the surgical constructs restored the stability of the damaged thoracic spine. Compared with the preoperative model, ROM of the four surgical models were reduced under all loading conditions (Figure 5I). Compared with M+P, ROM increased slightly in B+P. Compared with the other three constructs, M+P−T8 had the largest ROM in the upright and extension conditions.
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尽管全身系统性治疗的发展非常成功,但是肺癌手术仍然是最有效的治疗策略,也是唯一可能根治疾病的手段。那么新辅助(术前)治疗比如化疗和放疗都被证实有效,到目前为止,ICI在新辅助治疗阶段的使用还非常有限。然而在肿瘤免疫治疗的这个大背景下,新辅助免疫治疗可能有更突出的优势:当原发肿瘤还在的时候,抗原的暴露会极大增强肿瘤特异性T细胞反应的程度和持续时间。在这篇综述中,我们会讨论一部分临床前研究以及免疫新辅助治疗临床研究结果,并探讨其可能的作用机制。我们还会特别指出新辅助免疫治疗的潜在危险和一部分需要解决的问题。
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The NTU network has shown its ability to work as an on-site EEW system and provide near-real-time shakemaps during recent events. Hsieh et al. (2014) discussed the performance of the P-Alert network during the two earthquakes of 27 March (ML 6.1) and 2 June (ML 6.3) 2013 that occurred in central Taiwan. The working of this network during the Meinong earthquake of 5 February 2016 was discussed by Wu et al. (2016) . The Meinong earthquake was an inland earthquake that occurred in Southern Taiwan and caused more than 117 fatalities. A detailed shakemap was generated by the NTU network within two minutes of the earthquake’s occurrence and the high shaking regions observed in the maps agreed with the damage locations. The individual instrument also provided 4–8 s of on-site warning time before PGA arrival (Figure 6), which is crucial for the locations situated in the blind zone of regional warning. The instruments recorded high PGA values (497 gals) in the epicentral region. Using PGA and PGV shakemaps, it was observed that the highly damaged areas were in high PGV (>17 cm/s) regions.
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A 28-year-old male presented to the emergency department (ED) with a chief complaint of right hip pain following a restrained motor vehicle accident (MVA). The patient had a past medical history significant for resection of right carotid body paraganglioma approximately ten years prior. At that time, the patient presented to the primary care clinic with complaints of severe generalized headaches, syncopal episodes, and associated blurry vision. Initial complaints of non-tender, right-sided neck mass resulted in a biopsy, at that time diagnosed as a benign lymph node. Upon continued symptoms, he was eventually referred to the oncology clinic for follow up for his neck mass. After a subsequent biopsy of the lesion, a carotid body paraganglioma was diagnosed and excised, and he was treated with two months of radiation without chemotherapy.
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In the present study, we sought to analyze and compare the prognostic features of biliary NENs based on a relatively large number of cases collected from the SEER database and to develop an elaborate nomogram to predict 3-year and 5-year overall survival (OS) rates based on significant prognostic factors. Further, we carried out external validation for this prediction model using our hospital database.
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Infine, è utile ricordare che, al di là della persona con diabete noto ricoverata per infezione da COVID-19 in ambito ospedaliero, frequenti possono essere i riscontri di iperglicemia non nota probabilmente svelati dalla condizione di stress acuto e quelli conseguenti all’uso, sempre più diffuso e sempre più precoce per il trattamento di questi soggetti, di steroidi.
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34. DESENDER K, DEKONINCK W, BAERT L, GROOTAERT P, J-P MAELFAIT, 2004. “In de ban van de ring’. Inventarisatie van een aantal invertebratengroepen op de bermen, de taluds en de restgronden van de R0 (Ring van Brussel en een voorstel tot monitoring. Rapport ENT.2004.01. i.o.v. AMINAL, cel NTMB, KBIN, Brussel, 61 pp.
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MN and apoptosis in each sample were determined by morphological assessment of nuclei stained with 4′,6-diamidino-2-phenylindole, dihydrochloride (DAPI) (see Section 2.3 for detailed methods). Representative images of MN and apoptosis are shown in Figure 1.
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Las células endoteliales se utilizaron en los pases 1 y 2. En platos de 24 pozos, se adicionaron 5 x 105 células endoteliales de vena de cordón umbilical humano por pozo y se estimularon por 24 horas con 10 % de suero de los grupos de mujeres del estudio, para determinar su efecto sobre la producción de especies reactivas del oxígeno intracelulares, anión superóxido mitocondrial y lipoperoxidación de membrana por citometría de flujo.
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Triple-sense codon lines were generated in a similar manner. In this case the double-sense codon lines were crossed to a different single-sense codon line to generate trans-heterozygotes with three different sense codons. In this case not all combinations produced viable trans-heterozygotes and in some cases trans-heterozygotes were viable but gave no potential recombinant males. Successful combinations were FT58-63 (AM)/FT60 (S), FT60-63 (SM)/FT62 (L), and FT58-60 (AS)/FT63 (M), which generated the lines FT58-60-63 (ASM) and FT60-62-63 (SLM). These lines were screened by crossing to nos-vp16-GAL4 virgins and compared with the double-sense codon lines as described above (Elliott et al., 2014b).
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For each species we used separate single-factor (two treatment levels: protein deprived and protein fed) multivariate analyses of variance (MANOVAs) and Fisher’s Least Significant Difference post-hoc analyses to determine whether the mean (± 1 standard error): (1) mechanical properties (ultimate strength, extensibility, toughness, and Young’s modulus), (2) nanostructures (L, 2θ FWHM of the (200) and (120) diffraction peaks and amorphous halo, I200/ I120, Xc, and fc), (3) mole compositions of glutamine, serine, proline, glycine, and alanine, and (4) spidroin (MaSp1a, MaSp1b, MaSp2a, and MaSp2b) expression. We used additional univariate (treatment) ANOVAs to individually compare the MaSp1a, MaSp1b, MaSp2a, and MaSp2b 2-ΔΔCT values between treatments for each species. We log10 or arcsine (amino acid composition data) transformed any data that failed Levene’s heterogeneity tests.
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Pedicle screws are frequently used in spine surgeries, and their use is expected to increase as the number of spinal fusion surgeries is rapidly increasing [1–4]. Pedicle screw fixation is beneficial in achieving mechanical stabilization during bony fusion. However, inadvertent perforation of pedicle screws into the spinal canal can sometimes be fatal . It can lead to neurologic injury or unsatisfactory degrees of stabilization [6, 7]. The rate of pedicle screw malpositioning ranges from 0 to 25%, depending on the case’s degree of complexity and the surgeon’s level of experience [8–12]. Safe and accurate instrumentation of pedicle screws is important, and this technique is one of the major skills that a trainee in spine surgery has to learn and acquire.
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PKD-1 regulates collagen I-induced vascular morphogenesis via modulating GSK3β activity and integrin α(2)β(1) trafficking (Shin et al., 2012), whereas PKD-1-mediated integrin αvβ3 trafficking contributes to the angiogenic process by integrating and coordinating EC activity (di Blasio et al., 2010). These studies suggest that this kinase mediates the bidirectional communication between VEGFR and integrins. Furthermore, PKD-1 regulates VEGF-mediated host inflammatory responses and could lead to inflammatory angiogenesis. PKD-1 signaling is associated with VEGF-induced expression of proinflammatory cytokines via VEGFR2 including interleukin (IL)-6, CXC chemokines IL-8, and growth-related oncogene-alpha (GRO-alpha; Hao et al., 2009a). Additionally, PKD-1 interacts with heat shock proteins (HSPs) to regulate angiogenesis. PKC-mediated PKD-1 signaling regulates VEGF-induced HSP 27 phosphorylation at phosphorylation site serine 82 and tubulogenesis in HUVECs (Evans et al., 2008). Recently, PKD-1 was shown to activate endothelial nitric oxide synthase and orchestrate mammalian vascular tone through phosphorylation, concomitantly increasing NO synthesis. Inhibition of the kinase activity in mice abolishes VEGF-induced vasodilatation, indicating that PKD-1 is the key to transducing VEGF signaling for VEGF-induced vasodilatation (Aicart-Ramos et al., 2014). These studies suggest that PKD-1 signaling may regulate EC cross-talking with other cell types, such as vascular smooth muscle cells, via producing signaling molecules in the tissue microenvironments. Interestingly, the isoform PKD2 also regulates proliferation and migration in HUVECs, the two important process of angiogenesis, and this may be mediated by modulation of the expression of VEGFR-2 and fibroblast growth factor receptor-1 (Hao et al., 2009b).
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As the battery market dramatically increases due to the electrification of the transportation sector in the world, the effective recycling of LiBs at any cost is very important to protect the environment. The commonly used methods of direct recycling, which enable recoveries of valuable materials like Li, Co, and Ni, are pyrometallurgy and hydrometallurgy , where most pyrometallurgical methods are not able to recover Li . Li is recovered as LiCO3 in China and South Korea and used for cathode compounds . Compared to pyrometallurgy, hydrometallurgy has numerous advantages such as the ability to process different types of waste batteries simultaneously, lower process temperatures, the possibility of use on a small industrial scale, a significant reduction in the emission of potential pollutants, and the high efficiency of recovering valuable metals. These contribute to its wide applications in industry and laboratory studies . Nevertheless, even after the selective recovery step, some Li and Co and all other metals remain in the solutions and require proper management, which is a tremendous technological challenge due to the solution’s properties (very low pH) and polymetallic composition. Thus, an efficient and environmentally friendly process of valuable materials recovery and separation is needed .
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The baseline assessment included collecting demographic variables including age, race/ethnicity, marital and employment status, income, education, smartphone ownership, use of other health apps, and use of mental health services, including use of medications and psychotherapy. We collected information on mental health status using PHQ-9 for depression and SDS to assess self-reported disability. PHQ-9 rates the presence and severity of depressive symptoms across 9 items, with higher scores signifying more severe symptomatology (range 0-27). This is a reliable and well-validated screening instrument that is responsive to depression treatment outcomes over time and is included in the US Preventive Services Task Force recommendations for depression screening in adults . PHQ-9 has been translated into several languages; we used both the original English language form and the validated Spanish translation . The baseline PHQ-9 demonstrated good internal consistency in our sample (Cronbach alpha=.85, 95% CI 0.83-0.87).
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We detected 83,176 SSRs, and the most abundant type of SSR motifs are dinucleotide repeats mainly of (TG/GT/AC/CA)n (48.8%) (Fig. 2). About 38.5% of the SSRs are mononucleotide repeats mainly of (A/T)n. Primers were successfully designed for 44,101 SSRs. For the purpose of molecular marker development, complex SSRs [e.g., (TTC)7(TTA)7, (CG)6catg(CA)6] and those with a motif unit size less than two nucleotides were removed. As a result, 18,670 SSR primers were obtained (Additional file 5: Table S4). The SSRs identified in our study may be useful for developing molecular markers to detect the genetic structure among populations of S. yangi.Fig. 2Distribution of SSR motifs. The different color bars represent different repeat types (repeat number ranges of SSR motif unit)
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Data are expressed as mean ± SEM. Behavioral and cognitive performance measures for were analyzed using ANOVAs or repeated-measures ANOVAs. In the case of repeated-measures ANOVA, sphericity was tested and Greenhouse–Geisser corrections were used when appropriate. For the percent time spent exploring the novel and familiar objects, paired t-tests were used. Statistical significance was determined using an error probability level of p < 0.05. As we a priori expected sex-dependent effects, the behavioral and cognitive data were analyzed separately in females and males with donor genotype as a fixed factor. When appropriate, a Dunnett’s post hoc test was conducted with the WT genotype as the set comparison. Data were analyzed using SPSS Statistics for Windows (Version 25, Armonk, NY: IBM Corp., Chicago, IL, United States) and Graphpad Prism software (San Diego, CA, United States).
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In this work, we chose to demonstrate our approach by modeling competition over a limited ribosomal pool as this is currently the most studied intracellular model in the field, mainly due to the fact that most of its parameters can accurately be estimated from experimental data. It is important to emphasize the fact that due to the competition on limited cellular resources such as ribosomes and tRNAs, even a small intracellular circuit (e.g., 1–3 genes) can affect the entire cell and should be engineered based on a whole-cell model.8−11 This is specifically true when the expression levels of the circuit need to be high and induce huge load on the host. We would like to emphasize the fact that translation consumes more than 75% of the energy in the cell;44−53 thus, it is not surprising that translation is an important aspect in such cases.
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En la segunda ronda, cada miembro fue contactado de nuevo por correo electrónico, y se le solicitaron dos o tres recomendaciones para su correspondiente grupo de actores clave. Cada recomendación se acompañó de una justificación, con sus referencias bibliográficas, con un límite aproximado de 200 palabras. Las recomendaciones se construyeron teniendo en cuenta publicaciones previas al respecto y la experiencia de los expertos en sus propias instituciones o en otras distintas. Esto permitiría obtener las mejores recomendaciones posibles por cada grupo clave de interés.
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A novel cell line was developed to monitor retinoic acid signaling (RA) that is useful in multiple cell lines. The activation of retinoic acid signaling was studied during embryogenesis and post-MI. There is shown that RA signaling is activated mainly in fibroblasts post-MI and that downregulation of RA leads to allegedly larger infarcts with greater scar is shown. Classic responses to select RA downstream effectors is shown. The studies are well written. Technical issues include the lack of a risk area assessment in the infarct studies, making the assertion that infarct size is increased an unsubstantiated assertion. Cellular studies are performed with exogenous RA that show that activation of RA gene programs occurs.
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The N-terminal domain (just after the cleaved-off signal peptide, residues 24–63; ND) has a very compact core stabilized by a unique arrangement of three tightly packed disulfide bridges (Figure 2a) . The N-terminal glutamine (Q24) is post-translationally modified to a pyroglutamate . The domain’s orientation is stabilized via several polar as well as hydrophobic contacts with TY and CD. The disulfide bonding pattern is I–IV, II–VI, and III–V (Cys residues sequentially numbered from I to VI) which is clearly different from the canonical I–III, II–IV, and V–VI linkage found in EGF-like domains . Likewise, the spacing between cysteine residues alongside the polypeptide chain differs between EGF-like domains and EpCAM ND. However, the ND does share disulfide linkage with some other small cysteine-rich domains, like the CFC domain of human cripto , and is with regard to fold most similar to the disulfide-free WW-type domains found in various proteins like formin-binding protein 3, dystrophin and NEDD, still, all these combined structural aspects are not found in any other protein of known structure, thereby classifying the structure of EpCAM N-terminal domain as unique. Domains of this type, also called cysteine-rich microdomains (size up to 40 aa residues), are often involved in protein–protein interactions, an example is a well-known EGF–EGFR interaction , and are also considered as therapeutic scaffolds with a very stable central core . Interestingly, the ND of EpCAM is targeted by the vast majority of anti-EpCAM monoclonal antibodies (mAbs) raised up to now, perhaps due to its high exposure at the membrane-distal tip of the molecule, as discussed in the following section. In contrast, the anti-EpCAM mAbs targeting the TY or CD are rare .
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Although the time of lineage diversification of maternal inherited chlorotypes was substantially delayed compared with that of bi-parental inherited ribotypes, the geographical distribution of the chlorotypes was fairly similar to that of the ribotypes, strongly supporting the last two waves of the colonisation (Fig. 1b). The distribution ranges of the ribotypes from clade II and chlorotypes from clade iii suggest that the second wave of A. squarrosum colonisation might have spread to all deserts and sandy lands in the Asian interior, dated to ~1.1 Ma. This time of colonisation is consistent with Xixiabangma glaciation (~0.8–1.17 Ma), and during this period, the EAWM were significantly intensified and thus could have greatly induced the expansion of these temperate deserts30. Compared with the second wave of colonisation, the third wave occurred more locally and recently, as the crown age of clade III was dated to ~0.67 Ma (Fig. 2b, point “F”), consistently with the Naynayxungla Glacial Period (~0.5–0.72 Ma)30. Because the new habitat was a prerequisite for the colonisation of this pioneer desert plant, these three waves of colonisation strongly suggest that the temperature deserts of the Asian interior underwent at least two significant expansions as a consequence of the glacial cycles, and the global cooling significantly contributed to the stepwise drying of the Asian interior as suggested in previous studies2431.
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2. Non sono soggette all’autorizzazione dell’autore le attività indicate nell’articolo 64-quinquies poste in essere da parte dell’utente legittimo della banca di dati o di una sua copia, se tali attività sono necessarie per l’accesso al contenuto della stessa banca di dati e per il suo normale impiego; se l’utente legittimo è autorizzato ad utilizzare solo una parte della banca di dati, il presente comma si applica unicamente a tale parte.
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Основную проблему для терапии представляют штаммы K. pneumoniae, поскольку именно они являются полирезистентными (см. табл. 5). Анализ 57 штаммов K. pneumoniae на наличие генов бета-лактамаз семейств blaSHV, blaTEM, blaCTX и бета-лактамаз семейства OXA (blaOXA-2, blaOXA-10, blaOXA-23, blaOXA-24, blaOXA-48 и blaOXA-58) выявил гены первых трех семейств и ген blaOXA-48 . Ген blaSHV присутствовал у 84 % амбулаторных штаммов K. pneumoniae со слабовыраженной резистентностью (табл. 3, 6) и у 100 % резистентных штаммов как от амбулаторных, так и от госпитализированных больных (см. табл. 4–6). Ген blaTEM отсутствовал у чувствительных к антибиотикам штаммов от амбулаторных больных, но был обнаружен у 80 % резистентных штаммов от амбулаторных больных и лишь у 40 % штаммов от госпитализированных пациентов (см. табл. 4–6). Наличие blaSHV и/или blaTEM не всегда сочеталось с резистентностью к исследованным бета-лактамам, поэтому они не могут быть корректными маркерами резистентности, в отличие от blaCTX и blaOXA-48 (см. табл. 4 и 5), выявление которых может быть использовано для быстрого определения продукции БЛРС и резистентности к карбапенемам соответственно.
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Cav3 associates strongly with unstressed internal membranes. Shows DIC and fluorescent images of an excised patch from a cell expressing Cav3-GFP pressed against coverslip. Cav3-GFP laden vesicles fill the space beneath the dome suggesting Cav3-GFP can readily associate with unstressed membranes.
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Kras+/LSL-G12D, Notch1fl/fl, Notch2fl/fl, Pdx1-Cre and Keratin5-Cre transgenic mice have been described before , , , , . Mice were interbred to obtain Pdx1-Cre;Kras+/LSL-G12D (Pdx1-Cre;Kras), Pdx1-Cre;Kras+/LSL-G12D;Notch1fl/fl (Pdx1-Cre;Kras;N1ko), Pdx1-Cre;Kras+/LSL-G12D;Notch2fl/fl (Pdx1-Cre;Kras;N1ko), Keratin5-Cre;Notch1fl/fl (K5N1ko) and Keratin5-Cre;Notch2fl/fl (K5N2ko) mice. Previously described reporter strains LSL-ROSA26R-LacZ, Notch1-GFP and Notch2lacZ , , , , were used as indicated in the text. All animals were of mixed C57BL/6J;129SV background. Animal care and experimental protocols were conducted in accordance with German animal protection laws and approved by the Institutional Animal Care and Use Committee at the Technical University of Munich.
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the potential function tends to a constant, zero in our case, value10\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \varphi (z)\to 0\kern0.36em , $$\end{document}φz→0,
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Die Interaktivität und Anpassung der Vorträge an das neue Format blieb bis auf wenige Vorschläge – wie es z. B. das Format Fishbowl aufgrund seiner Struktur vorgibt – den Präsentierenden überlassen. Daraus resultierten überwiegend klassische, z. T. sogar vollständig voraufgezeichnete Vorträge (d. h. in der Regel Screencasts). Solche On-demand-Inhalte bieten von vornherein keine Interaktivität. „Echte“, sprachliche Interaktivität mit dem Publikum war im Kongress daher nur bedingt gegeben, sie kann durch die moderierten Chat-Funktionen auch nur teilweise kompensiert werden. Ein „ständiges Rederecht für alle Teilnehmenden“ stellt keine Option dar, da dann ggf. ohne Rücksicht auf andere gleichzeitig gesprochen wird. Konkrete Forderungen und Hilfestellungen bei der Nutzung interaktiver Möglichkeiten, moderner Präsentationen, in Echtzeit ausgewertete Publikums-Polls o. Ä. sind sinnvolle Optimierungen digitaler Session-Formate. Diese sind bei der inhaltlichen und v. a. technischen Planung der Veranstaltung zu berücksichtigen und sollten Präsentierenden als moderne Optionen offeriert werden. Hier ist die Aussage der M‑Events Cross Media GmbH von Bedeutung, wonach bislang nur wenige Kongresse dieser Größenordnung ein vergleichbares, geschweige denn höheres Maß an Interaktivität boten.
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In this study, the authors asked whether the presence of a CL was associated with changes in inpatient teams’ clinical questioning, as measured by the number of questions asked and answered, the time spent asking and answering questions, and the quality of questions asked during rounds. Furthermore, we explored changes in inpatient team members’ self-reported ability, comfort, and confidence in searching the literature and applying evidence-based practices.
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Le cancer du col de l'utérus est la malignité du tractus génital féminin la plus fréquente dans les pays en voie de développement et demeure l'une des principales causes de mortalité dues au cancer chez la femme en Afrique Sub-saharienne [1–3]. Au Gabon, ce cancer est généralement diagnostiqué à un stade clinique avancé où l'indication radio-chirurgicale s'impose avec toutes les conséquences psychosociales et économiques qui en découlent . Ainsi, entre 1984-1993, le cancer du col de l'utérus représentait 26.3% de l'ensemble des cancers féminins avec une survie à 5 ans de moins de 50% . Les infections à papillomavirus humain (HPV) sont fréquentes et sexuellement transmissibles. Les souches oncogéniques, à haut risque (HR-HPV), sont les principaux facteurs de risque du cancer du col de l'utérus. La durée de l'infection par des HR-HPV a été associée au développement de lésions précancéreuses intra-épithéliales transitoires, persistantes ou évoluant en cancer [6, 7]. On évalue à une dizaine d'années la période qui sépare les premières anomalies cytologiques de l'apparition éventuelle d'un cancer infiltrant. Les vaccins préventifs, actuellement disponibles sur le marché, ciblent particulièrement les HR-HPV 16 et 18 . Cependant, l'immunodépression et les infections sexuellement transmissibles potentialiseraient l'action des souches oncogènes du HPV . D'autres facteurs tels qu'une parité élevée et des conditions socioéconomiques défavorisées participent également au développement des dysplasies cervicales . Le cancer du col de l'utérus peut être prévenu par le dépistage et le traitement des lésions précancéreuses . Une femme subissant un dépistage du cancer du col, entre 30 et 40 ans, verrait son risque de développer le cancer du col de l'utérus réduit de 25 à 36% . En Occident, les programmes de dépistage des lésions précancéreuses sont essentiellement basés sur la cytologie, à savoir la réalisation du frottis cervico-vaginal (FCV). Ainsi, la morbidité et la mortalité dues au cancer du col de l'utérus dans les pays industrialisés sont en nette diminution du fait du dépistage systématique par FCV. Dans les pays en voie de développement (PVD), l'absence de programme de dépistage systématique est principalement à l'origine de la forte incidence du cancer du col de l'utérus observée dans la population féminine. En effet, la pauvreté, le faible niveau d'instruction et l'insuffisance de personnel qualifié rendent difficiles la mise en oeuvre de ce type de programmes [13, 14]. L'inspection visuelle du col de l'utérus après application d'acide acétique (IVA) et/ou de solution de Lugol (IVL) est une approche de dépistage du cancer du col de l'utérus simple, abordable et particulièrement adaptée aux réalités des PVD . L'IVA/IVL présente l'avantage de dépister des lésions précancéreuses et cancéreuses opérables du col avec une sensibilité comparable et parfois meilleure à celle du FCV. Selon des études africaines, la sensibilité du test IVA/IVL varierait de 79 à 97% avec une spécificité se situant entre 87 et 96% [16, 17]. Récemment, à Libreville, plusieurs médecins spécialistes ont été formés à la technique IVA/IVL couplée à la colposcopie en vue de vulgariser le dépistage du cancer du col sur l'ensemble du territoire gabonais. Ainsi, le but de cette étude est d’évaluer les performances des tests IVA/IVL et FCV, en les comparant à l'histologie, dans la détection des lésions du col utérin au Gabon. Nous souhaitons également apprécier la maîtrise de la technique IVA/IVL par un médecin spécialiste nouvellement formé.
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In conclusion, using data from a community-based influenza surveillance system in Israel, we estimated VE of inactivated influenza vaccine in the Israeli population for the first time. Our study suggests that VE may vary by season, by influenza type and subtype as well as by age. Our results, and those of others, support the need for continued efforts of estimating influenza VE, both in outpatient and inpatient settings. These efforts are necessary in order to better understand the factors that affect influenza VE and to optimise vaccine composition and use. Timely VE estimates are of paramount importance for the yearly decision regarding influenza vaccine composition.
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La durée moyenne d'hospitalisation était de 11,7 ± 12,1 jours chez les patients infectés avec des extrêmes de 3 et 45 jours. Les patients non infectés avaient une durée moyenne d'hospitalisation de 4,7 ± 3,1 jours avec des extrêmes de 2 et 25 jours.La durée moyenne d'hospitalisation était plus longue chez les patients infectés (pTableau 3).
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Cauzele HA sunt numeroase, însă pentru scopul acestui articol vor fi discutate doar cazurile de HA primară care au ca factor etiologic consecințele unei diete nesănătoase, și anume: (1) diabetul zaharat provocat de către aportul excesiv de alimente ce conțin zahăr sau făină albă (2) responsivitatea crescută la catecolamine a persoanelor sensibile la sare dată de aportul crescut de alimente ce conțin cantități mari de NaCl, și (3) ateroscleroza provocată de aportul crescut de alimente ce conțin cantități mari de lipide .
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The asset index was derived from household asset ownership indicators using multiple correspondence analysis (MCA) (see Multiple Correspondence Analysis and Related Methods for a detailed discussion of the methodology of MCA) to derive the weights. This multidimensional approach to measuring SES is based on seminal work in the development economics literature and is increasingly used in welfare analysis and poverty targeting studies . The initial validation study of the asset index (using data from developing countries Indonesia, Nepal and Pakistan) produced internally coherent results which showed distinct separations across different SES households (poor, middle and rich) for each asset. The index was also robust to the assets included and was comparable with output and poverty levels across countries.
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However, a paired t-test showed on the number of cookies eaten and desired indicated that only participants in the control condition ate the desired amount of cookies, t(64) = -0.11, p = .911, d = -0.02 with dependency-corrected effect size , whereas participants in the depletion condition ate significantly more cookies than they wanted, t(62) = 4.41, p = .001, d = 0.67. Importantly, these results did not substantially change when the analyses were controlled for gender and for how often and how willingly the participants eat cookies in general. However, when gender was entered as a factor that could interact with ego depletion and goal deviation, the three-way interaction was significant, F(1, 122) = 5.25, p = .022, ηp2 = .04. Post-hoc analyses revealed that the two-way interaction was only significant for men, F(1, 44) = 5.22, p = .022, ηp2 = .11, but not women, F(1, 76) = 0.70, p = .402, ηp2 = .01.
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To facilitate in vivo studies, proteins with fewer transmembrane segments (<2) and high solubilities were prioritized for purification. First, TMHMM v.2.0 was used to predict the number of transmembrane segments and 52 proteins were shortlisted. Then, SoDoPE servers were used to filter the proteins based on solubility prediction, with 31 proteins showing a >0.5 probability of solubility being selected for further analysis (Supplementary Table S3).
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A Hispanic male patient in his mid‐50s presented with chronic rhinosinusitis symptoms including postnasal drainage, facial pressure, and nasal congestion. He was treated with maximal medical therapy including 21 days of oral antibiotic therapy and intranasal steroids and had persistent symptoms at a follow‐up visit. Post‐treatment imaging demonstrated mucosal thickening in the maxillary and ethmoid sinuses consistent with chronic rhinosinusitis. The computed tomography (CT) of the sinuses also demonstrated an unusual supraseptal ethmoid sinus cell pneumatizing into the area between the superior aspect of the midnasal septum and the ethmoid roof. Figure 1A illustrates an axial CT view of the left supraseptal ethmoid cell. Figure 1B illustrates a sagittal CT view of the left supraseptal ethmoid cell. Figure 1C shows a coronal view of the supraseptal ethmoid cell with right greater than left maxillary and ethmoid mucosal thickening indicative of chronic rhinosinusitis. Figure 1D,E illustrates more anterior coronal CT slices demonstrating mucosal thickening indicative of chronic maxillary and ethmoid rhinosinusitis. Figure 1F demonstrates a coronal CT image showing the left anterior ethmoid artery running horizontally across the superior aspect of the left anterior ethmoid sinuses anterior and lateral to the left supraseptal cell. The patient was counseled on the risks, benefits, and alternatives of functional endoscopic sinus surgery and elected to proceed with surgery.
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The leaf functional traits have been well investigated in terrestrial plants, and the photosynthesis rate, leaf weight per area and leaf life span of >2,000 species of plants have been recorded (Wright et al., 2004). The authors proposed a LES and claimed that there was a typical trade-off between leaf functional traits that leaves with high photosynthesis rate are featured low life span and low leaf MPA (Wright et al., 2004). To our knowledge, this study is the first attempt to systematically analyze the leaf functional traits in submerged freshwater macrophytes. The low leaf MPA and high photosynthesis rate of the Ottelia leaves fit well with LES and placed in the spectrum of the quick return on nutrient and biomass investment. Accordingly, the leaf life span of Ottelia was expected to be short as other submerged species (Hemminga et al., 1999; Yamamoto et al., 1999; Kamermans et al., 2001). In addition, Cornwell et al. (2010) revealed the predominant influence of plant functional traits on decomposition rates at a global scale. Based on our findings on functional traits of Ottelia populations, the decomposition rate and carbon turnover of these populations should be very fast, similar to Potamogeton crispus (Wang et al., 2016), and thus a fast carbon cycling was expected for the Ottelia-dominated karst freshwaters. However, our results, together with Yin et al. (2017), indicated that all the species or varieties of the genus Ottelia in China could use bicarbonate as inorganic carbon supply though there was variation among the populations. Similar like Potamogeton lucens (Prins et al., 1982), the Ottelia leaves were expected with polarity of pH between the adaxial and abaxial side, but with much broader leaves probably stronger effects on the polarity. Therefore, the calcium precipitation (as CaCO3) on the surfaces of Ottelia leaves could bring abundant carbon burial when the macrophytes were dominant producers and thus strongly affect the carbon cycling. Thirdly, high diel acidity changes >10 μequiv g-1 FW were found even at high inorganic carbon supply, which is potentially inducible CAM feature similar with that O. alismoides showed in Shao et al. (2017). A dense macrophyte bed with strong CAM capacity could also affect the pH of water column at night (Keeley, 1983). Consequently, the changes of pH have a strong effect on the inorganic carbon species in the water column and other primary producers, e.g., periphyton on the leaves (Maberly, 1996; Hao et al., 2017). In summary, the role of Ottelia populations on the carbon cycles in the karst freshwaters warrants further studies.
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