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En Diciembre del 2019, surgió el nuevo Coronavirus, SARS- COV-2 en China, dando un giro a la historia mundial convirtiéndose en un brote pandémico, que ha provocado 112 521 610 casos y 2 495 881muertes hasta finales de Febrero del 2021 (1), afectando a todos los países a nivel mundial. Los estudios realizados en las pandemias pasadas de SARS y MERS, determinaron que, durante la primera fase, con la finalidad de disminuir la transmisión, la incidencia de casos y la tasa de mortalidad fue imprescindible la implementación de políticas de salud pública como cuarentenas domiciliarias, aislamiento de personas vulnerables y distanciamiento social (2,3); y además, una estrategia vital que demostró prevenir el pánico y contener el brote, que consistía en la provisión de información oportuna, clara y correcta. Al no ser una de las tareas prioritarias, se ha dado lugar a uno los enemigos más letales, que hoy en día enmarca otra crisis dentro de la pandemia por SARS-COV-2, la llamada infodemia o sobreabundancia en el volumen de la información real y falsa, entre rumores, teorías conspirativas, discursos estigmatizantes, y productos pseudocientíficos (4), cuyas consecuencias han afectado a toda la población a nivel mundial, vulnerando especialmente a un grupo del que poco se habla, y que constituye nuestra población de estudio y análisis, los niños. |
To retrieve the list of biomedical literature associated with ROS and diabetes, PubMed was queried using ("Reactive Oxygen Species"[MeSH] AND "Diabetes Mellitus"[MeSH]). This query yielded 1,154 articles as of April 27, 2009. SciMiner, a web-based literature mining tool , was used to retrieve and process the abstracts and available full text documents to identify targets (full text documents were available for approximately 40% of the 1,154 articles). SciMiner-identified targets, reported in the form of HGNC [HUGO (Human Genome Organization) Gene Nomenclature Committee] genes, were confirmed by manual review of the text. |
Additionally, Rømer Thomsen et al. reported no statistically significant relationship between PVG and every impulsivity dimension such as urgency, lack of premeditation, lack of perseverance, and sensation seeking. Similarly, Deleuze et al. showed no difference between PVG group and health control group (in this same impulsivity dimensions examined by Rømer Thomsen et al. . Bargeron and Hormes reported a higher level of attentional and motor impulsivity among gamers with PVG compared to gamers without PVG. However, they no found the difference between groups in non-planning impulsivity. |
The broad differences in vegetation composition, aridity levels and topography characterizing each of these eight zones together influence the carbon and nitrogen isotope composition of the floral base of the foodweb. This is further reflected in the isotope composition of herbivorous consumers, in this case grazing and browsing livestock97–99. In order to distinguish the contribution of 13C enriched or 13C depleted agricultural cereals to pastoralist diets from foodstuffs that derive from steppe food resource pools, which include milk and meat products obtained from livestock grazing on 13C enriched C4 and water-stressed C3 graze, we used independent isotope reference sets that measure isotope variation in local foodwebs using δ13C and δ15N values of livestock that are spatially and temporally congruent to the human sample set. The δ13C and δ15N values of pastoralists whose dietary intake draws heavily from animal products should closely track those of domesticated herbivores alongside a trophic fractionation factor of + 3–6‰ in δ15N100–102 and +1‰ in δ13C103,104, represented by positive regression lines similar to those exhibited by co-occurring livestock ingesting local floral resources. Conversely, pastoralist diets characterized by a sustained consumption of 13C enriched millet or 13C depleted barley and wheat no longer track herbivores and instead exhibit significantly different regression lines from co-occurring livestock indicating consumption of dietary resources typically not available on steppe landscapes. |
The GOLD (Protein Ligand Docking Software) software v5.8.1 (CCDC; Cambridge, UK; http://www.ccd.cam.ac.uk. Archived on 28 November 2019) was applied to dock ligands into the binding site of the receptors. For each compound and receptor, 30 binding poses were generated without any constraints. In bees cases, the centroid of the binding site was defined using the coordinates of the crystallographic complexes, 2NXX in the case of EcR monomer (#C24 of P1A: x = 29.069, y = 6.239, z = 8.576) and 1FM6 in the case of USP monomer (#C10 of 9CR: x = 17.688, y = 14.021, z = 14.525), while in the human case was used 1FM6 for RXRα (#C10 of 9CR: x = 17.688, y = 14.021, z = 14.525) and 4QE6 in the case of FXR (#C13 of JN3: x = 10.872, y = 15.018, z = 11.917). Side chain flexibility was allowed for the amino acids: EcR: Glu17, Thr52, Lys93, Phe437, Tyr114; USP: Val30, Ile33, Thr37, Lys39, Leu91, Thr93, Ile110, Leu201, Phe202; RXRα: Phe436, His435, Phe439, Leu436; FXR: Met265, Met290, His294, Phe336, Phe350, Tyr369, Met450, Trp454, Trp469. For the genetic algorithm run, a maximum number of 100,000 operations were performed on a population of 100 individuals with a selection pressure of 1.1. The number of islands was set to 5 and the niche size was set to 2. The default GOLD Score fitness function was applied for performing the energetic evaluations. The distance for hydrogen bonding was set to 2.5 Å and the cut-off value for the van der Waals calculation to 4.0 Å. For ligand flexibility options, flip pyramidal N, flip amide bonds, and flip ring corners were allowed. After that, all the poses generated by GOLD were rescored using the scoring functions Chem Score and Hint Score (HINT, Hydropathic INTeraction) with the aim to obtain a consensus. |
The antimalarial efficacy of sulfa drugs was discovered in 1940s. They inhibit the malarial parasites multiplication and development by blocking nucleic acid synthesis (28). In 1950, pyrimethamine was firstly invented by George Hitchings and his comrades at Burroughs Wellcome in the United States. At its primary period of synthesis, it was synthesized as an anticancer agent, and then approved as a drug for the treatment of malaria disease in Britain in 1951 (29). Pyrimethamine and other sulfa drug sulfadoxine differently act on folic acid synthesis. Combination of them could synergistically improve the antimalarial efficacy between them. |
A protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database (http://string-db.org; version 10.0), with a minimum interaction score cutoff of 0.4 (7). Cytoscape (version 3.7.2) was used for visualization of the interaction networks (8). The MCODE plug-in was used to construct key clustering modules (MCODE score > 5, degree cutoff = 2, node score cutoff = 0.2, max depth = 100, and k-score = 2). |
The premature secretion of estradiol increases the growth rate and accelerates bone maturation, which can shorten the growing period, and it may cause reduced adult height (AH). Treatment with gonadotropin-releasing hormone (GnRH) analog blocks the pituitary-ovarian axis, thereby preventing the secretion of estradiol, slowing the bone age (BA) progression and preserving growth potential. This action has been demonstrated in the evolving forms of idiopathic central precocious puberty in girls . However, in two randomized studies on girls with onset of puberty at 7.5-8.5 yr and at 8.4-10 yr , the AHs were similar between the untreated patients and the patients treated with GnRH analog. In a previous study on girls with advanced puberty , we demonstrated that the AHs of untreated patients and patients treated with GnRH analog were similar between the two groups. Furthermore, the participants’ AHs were similar to their target heights (TH) and were significantly below their heights at age 4 yr, as expressed by the standard deviation score (SDS). The AH was below the TH by more than 5 cm in 7/40 (17.5%) girls, 5 of whom were untreated and 2 of whom were treated. Determining the risk of reduced AH as a result of advanced puberty is of crucial importance because the age limit that is used to define central precocious puberty has decreased over time . |
本次调查人群对肺癌筛查的意识较好，能接受每年1次筛查的比例达到了80.3%；人群筛查所能承受的费用从免费到几千元不等，有效调查人数1, 624人，缺失9人，65.4%的调查对象能承受的筛查费用在500元以内，仅有25.2%的人群能承受500至1, 000的筛查检费用，能承担1, 000以上的调查对象则更少，仅有8.8%（表 5）。为分析肺癌筛查意愿的影响因素，我们将接受2年以上筛查的人群设为1，接受1年1次和2年1次体检的人群设为0，进行多因素logistic分析，结果表明性别、家庭收入、肺癌知晓情况以及教育程度是调查对象筛查意愿的影响因素（表 6）。 |
Stakeholders will ensure that the scope, key research areas and dissemination of the findings are directly informed by the priorities and interests of practitioners, people with dementia and carers, and their representatives. This approach was used by the National Institute for Clinical Excellence and Social Care Institute for Excellence guidelines and methods developed by other studies and complex reviews . Ethical permissions have been received for this part of the research (National Research Ethics Service Committee East of England, Cambridge Central, reference: 13/EE/0040). Written informed consent for participation in the study will be obtained from all participants. |
Thus, we also modified ancTRIM5αV1:Q to compare the impact of each of the cercopithecine V1 adaptations, including the V1:G and V1:G+20 variants, which we refer to as ancTRIM5αV1:G and ancTRIM5αV1:G+20. The 20 amino-acid insertion recreates the original duplication (that is, the duplicated sequences are identical) without the additional diversification seen in extant TRIM5α orthologs. We also generated ancTRIM5α derivatives with the additional V1-patch modifications found in Papionini species (ancTRIM5αV1:SFP and ancTRIM5αV1:TFP) and their predicted evolutionary intermediates (ancTRIM5αV1:QFQ, ancTRIM5αV1:PFP)(Fig 2 and S1 Fig). |
It is well known that when retardation in the uterus growth occurs, a delay or reduction in skeletal ossification and, in some cases, increases in minor skeletal variations is often present. This is observed with test agents that exert their effects through maternal toxicity . Agents known to interfere directly with fetal nutrition, growth factors, and other developmental processes may also induce growth retardation by a direct effect on the fetus . Under some circumstances, the induction of skeletal variations such as supernumerary and wavy ribs is considered the result of maternal toxicity or stress rather than a direct toxic effect on the conceptus . |
The A-graded SLR by Ip et al. (22), concluded that breastfeeding was associated with significant reduction in AOM, although only four of the five cohort studies included in the meta-analysis had clear definitions on feeding practices. For the final analysis infant feeding was dichotomized into two groups; exclusive breastfeeding and partial/mixed feeding vs. exclusive artificial feeding. Pooled adjusted OR of risk for AOM when comparing ever breastfed with never breastfed was 0.77 (95% CI: 0.64, 0.91). Comparing exclusively breastfed infants for 3 or 6 months compared with never breastfed gave a pooled adjusted OR 0.50 (95% CI: 0.36, 0.70). Results were conflicting for GI and the 16 studies (12 prospective cohort, two retrospective cohort, two case-control) included in a meta-analysis were graded B and suffered from various methodological flaws. For LRI a meta-analysis was done including seven cohort studies, the relative risk (RR) of hospitalization due to LRTI <1 year in those exclusively breastfed 4 months or more compared with formula-fed infants was 0.28 (95% CI: 0.14, 0.54). |
La universalidad de la cobertura médica de calidad está fuertemente correlacionada con la proporción de personas de menos de 60 años dentro de las personas fallecidas (r=-0,92, p<0,01). Los países que tienen una mejor universalidad de la cobertura médica tienen una baja proporción de personas jóvenes o de mediana edad dentro de las personas fallecidas (figura 2). Todos los países de proporción alta o intermediar de personas jóvenes o de mediana edad obtuvieron una calificación inferior al 82/100 (Índice de cobertura efectiva de los servicios de salud), incluyendo los Estados Unidos. Por el otro lado, todos los países con una baja proporción de personas jóvenes o de mediana edad tuvieron una calificación superior al 84 (cuadro 1). Los tres países que tuvieron las calificaciones más bajas fueron Guatemala, Honduras y Ucrania, es decir los tres países con la proporción de personas jóvenes o de mediana edad más alta. |
In Anbetracht der Eindeutigkeit der Studienlage, die die hohe Wirksamkeit der Gliflozine bei Patienten mit HFrEF belegt, wurde jüngst Empagliflozin die Zulassung von der EMA für dieses Indikationsgebiet erteilt. Außerdem wurde Dapagliflozin als erster Vertreter der SGLT2-Inhibitoren vom G-BA (Gemeinsamer Bundesausschuss) ein beträchtlicher Zusatznutzen über alle Patientengruppen der DAPA-HF-Studie bescheinigt. |
LGP as a new restrictive method for treatment of morbid obesity has shown acceptable results during its evolution since 12 years ago. The complications were not more than other methods; and costs were far less than any other bariatric surgery. The final result of weight loss was almost the same as other restrictive techniques . However, the wide range of weight loss resulted from different methods of restrictive bariatric surgery means the main reason of weight loss is not just a specific technique; but also could be mostly the patient’s motivation to keep appropriate lifestyle . |
CCL2 is not only released from bone marrow cells but also from SMCs, endothelial cells, and other tissues 9, 25. To investigate which source of CCL2 plays the most important role in neointima formation due to VPC migration chimeric mouse models were created. Wild‐type bone marrow was transplanted into an irradiated CCL2−/− mouse to form a CCL2 chimera. Conversely, a wild‐type chimeric mouse model was prepared by transplanting CCL2−/− mouse bone marrow cells into an irradiated wild‐type mouse. The levels of CCL2 in serum of peripheral blood were measured using a murine CCL2 ELISA kit. In the wild‐type chimeric mouse model, the level of CCL2 in peripheral blood was increased despite transplantation with CCL2−/− bone marrow when compared to a nontransplanted wild‐type mouse control, indicating that CCL2 is mostly released from nonbone marrow tissue. In contrast, the level of CCL2 was increased in CCL2−/− mice with transplanted wild‐type bone marrow cells, but to a much lesser extent, indicating that only a small proportion of CCL2 is released from bone marrow derived cells (Fig. 7A). Data from HE stained sections showed that neointima lesion area correlated with the CCL2 level in blood (Fig. 7B, 7C). These results support the observations that CCL2 induced VPC migration contributes to neointima formation. |
Fig. 5The effect of vegetation height on the number of small blue eggs per flowerhead. Points represent individual flowerheads in 2006 (green), 2007 (red), 2008 (blue), and 2020 (purple), and are semi-transparent so that overlapping points appear darker. Solid lines represent predicted values from the best fitting model, as assessed by AIC, with other significant effects held at their means. Dashed lines show standard errors. Though years are shown separately for clarity, data were fitted together in regression models. (Color figure online) |
Our results may contribute to the understanding of breast cancer causation and aid in risk stratification. However, weight gain would not provide a strategy for long‐term risk reduction because weight and weight gain are positively associated with risks of postmenopausal breast cancer, several other types of cancer, and other adverse health outcomes.46, 47 Additionally, obese women diagnosed with breast cancer tend to have worse outcomes than leaner women, independent of their menopausal status.48 |
Als das EAP-Konzept Anfang der 1970er-Jahre in der Bundesrepublik bekannt wurde, war „süchtiges Trinken als besondere Form des Alkoholismus“ 1968 gerade erst vom Bundessozialgericht als behandlungsbedürftige Krankheit anerkannt worden. Schon 1975 wurde der erste Stufenplan in einer Betriebsvereinbarung festgeschrieben. Statt der ursprünglich vorgesehenen frühen Intervention bei Alkoholproblemen wurde allerdings in den hiesigen Konzepten häufig erst ein Eingreifen bei Symptomen der Alkoholkrankheit empfohlen [4, 7]. Ohne eindeutige Diagnose schränkte das die Handlungssicherheit der Personalverantwortlichen erheblich ein. |
We now define some auxiliary variables that will be used for defining these matrices. First, we let n and m be equal to the length of R and S(6, 1′), respectively, and F(α, β) be the total number of times that state α transfers to state β, where α and β are in {M, X, Y, D1, D2, end, start}. For example, F(M, X) is equal to the number of times a gap follows a match in all the alignments obtained by Barkan et al. . Let G(i, j, k) be equal to the total number times the ith amino acid pair is witnessed binding to nucleotide j in a k-type PPR sequence. Lastly, we let γ and η be a set of pseudo-counts used for determining the probabilities for T and A, respectively. We define γ(i, j) for all possible i and j, where i and j are states in the pair hidden Markov model. The variables γ and η are similarly defined. |
MO instigated the production of the paper with MB and wrote 60% of the text with IG helping with a review of the relevant scientific literature as well as the proofreading of the paper. MB contributed 15% to the general development of concepts and wrote the section on nutrient and light limitation. AW led the section on modeling with contributions from AF and AL, 15% in total. RS provided 10% of the supporting text. IB created the diagrams. AB-P helped develop a coherent and consistent narrative in the paper. |
Chronic kidney disease (CKD) can cause fluid retention, mainly due to reduced glomerular filtration of sodium and activation of the renin-angiotensin system. Many patients with stage 3–5 CKD present fluid retention, which may lead to a higher cardiovascular risk via several pathways1–4. First, fluid retention is related to hypertension in CKD patients and salt sensitivity of blood pressure increases with decreasing kidney function5. Hypertension associated with fluid retention in CKD patients often requires multiple medications6. Second, fluid retention causes endothelial oxidative stress and release of inflammatory mediators, which have been demonstrated to increase the cardiovascular risk7. In order to control fluid retention, salt restriction is essential. Therefore, the Japanese Society of Nephrology recommends restricting the salt intake to <6 g/day for CKD patients8, whereas the Kidney Diseases Improving Global Outcomes (KDIGO) guidelines recommend <5 g/day9. |
As described in more detail in the Supplementary Methods, TiO2 samples (Princeton Scientific) are first cleaned by sonicating in IPA for 5 min. The samples are then transferred to a high-vacuum chamber and baked in an alumina-coated molybdenum boat (Mathis) at ∼1,200 °C for 90 min. Next, plasmonic nanostructures are fabricated using standard e-beam lithography techniques. Structures were written in 8 × 10 arrays in poly-methyl-methacrylate (PMMA A4 495K, MicroChem) and developed for 60 s in a 1:3 solution of methyl-iso-butyl-ketone:isopropanol solution. Different device types (for example, Au Schottky, Au Ohmic, Al Ohmic) were fabricated on the same substrate by sequential evaporation and shadow masking. Au films were deposited at 0.5 Å s−1; Al films were deposited at 0.7 Å s−1; and Ti films were deposited at 1 Å s−1. The base pressure for all evaporations was 5.0 e−7 Torr or better. Liftoff was performed at 60 °C in PG Remover solution (MicroChem). Finally, a large Ti contact pad was deposited and the sample was mounted onto a glass microscope slide using cyanoacrylate. |
AQP2 состоит из 271 аминокислоты с молекулярной массой 28 837 Да, в своем составе имеет N- и С-концевые домены, три экстрацеллюлярные петли, две интрацеллюлярные петли и шесть трансмембранных доменов. AQP2 регулирует реабсорбцию воды в ответ на стимуляцию AVP. При уменьшении объема плазмы или повышении ее осмоляльности в нейрогипофизе секретируется AVP и, связываясь с рецептором AVPR2 в собирательных трубочках почек, увеличивает внутриклеточную концентрацию циклического аденозинмонофосфата. Данный процесс стимулирует транспортировку AQP2 к апикальной плазматической мембране и ингибирует его интернализацию, опосредованную эндоцитозом. Как результат, происходит накопление AQP2 в апикальной плазматической мембране, что позволяет воде двигаться по осмотическому градиенту через мембрану в интерстиций, а затем в кровоток . |
As presented in Table 5 Section B, using data from the full sample (i.e., not only participants who endorsed previous ALEs), reexperiencing one or more ALEs showed evidence of potentiating reductions in Neuroticism, such that reexperiencing was associated with an incremental 0.21 and 0.19 unit decrease in Neuroticism between baseline and post (p = 0.003), and baseline and follow-up (p = 0.009), respectively. Reexperiencing one or more severe ALEs similarly showed evidence of potentiating reductions in Neuroticism between baseline and post (B = 0.012, p = 0.031). Lastly, reexperiencing an additional ALE event type (represented by the Reexperiencing Index moderator) was associated with an incremental 0.06 unit decrease in Neuroticism between baseline and post (p = 0.004), and 0.05 between baseline and follow-up (p = 0.022). |
Images of the microstructure performance of LLZO powder were taken with a scanning electron microscope (SEM) Tescan MAIA3 (Tescan, Brno, Czech Republic) with secondary electron detection. Bruker XFlash 6–10 (Bruker, Karlsruhe, Germany) was used for energy-dispersive X-ray spectroscopy (EDS). |
The hierarchical model also permits quantification of heterogeneity between studies for each measure, reflecting how much the studies differ from one to another over and above mere measurement error. Such differences would be attributable to unmodeled differences between the studies’ respective methods (e.g., instruction emphasis on speed vs. accuracy, time of day, etc.) or sample populations (e.g., age range, socioeconomic status, etc.). Accounting for this heterogeneity is one of the primary benefits of the hierarchical model employed here, and this modeling choice is validated to the degree that the posterior distribution on the heterogeneity parameter is shifted away from zero. Figure 6 depicts posterior distributions on heterogeneity for both the intercept and the difference between groups for each measure, revealing credibly non-zero heterogeneity for all intercepts as well as the difference between groups on mean RT, while zero heterogeneity remains relatively credible for the difference between groups on alerting, orienting, and executive network scores. |
In August 2016, someone called “Tom Elvis Jedusor” (the French name for Voldemort in Harry Potter) posted a link to a text file on the IRC Channel describing a cryptocurrency protocol with a different approach from BitCoin. This article titled ‘Mimblewimble’ addressed some privacy concerns and the ability of compressing the transaction history of the chain without loss of validity verification. Since this document left some questions open, in October 2016 Andrew Poelstra published a paper where he describes, in more detail, the design of a blockchain based on Mimblewible. In 2019, the first two practical implementations were launched: Grin and Beam. In what follows, we shall first describe the main features of their design and will compare them with our model. Then, we shall discuss features that set apart Grin from Beam. |
Voor de gestratificeerde analyses is het totale aantal diagnoses van meerdere weken genomen (maximaal vier opeenvolgende weken), omdat de aantallen per week te weinig inzicht kunnen geven in de trends van diverse subgroepen. De aantallen zijn hier ook weer vergeleken met het aantal diagnoses in week 2 tot en met 5. Voor de uitsplitsing naar tumorsoort is gekozen voor een indeling op algemene hoofdgroep, met uitzondering van kanker in de mondholte/orofarynx en hematologische maligniteiten. Voor andere kankersoorten werden de aantallen per week bij verdere opsplitsing te klein om trends te kunnen weerspiegelen. |
Despite improved operative technique and postoperative rehabilitation, the outcomes of intrasynovial flexor tendon repair are highly variable [1–5]. The most commonly manifested complications of tendon repair are gap formation, repair-site failure, and adhesion formation between the repaired tendon and synovial sheath . Typically, complications are noted within the initial few weeks following suture repair and depend, to a considerable extent, on the initial biomechanical properties of the repair . Improving the biomechanical properties of repaired tendon is central to reducing the incidence of tendon rupture and gap formation, and for facilitating early controlled mobilization. |
Actuellement, il est décrit dans la littérature deux critères majeurs à la TDM basés sur l'histologie et la physiologie qui permettent une approche entre les adénomes bénins des masses surrénaliennes malignes. Il s'agit du contenu lipidique de la masse qui représente la différence anatomique entre les adénomes et les masses malignes et la densité qui représente la différence physiologique. En effet, les adénomes sont riches en matières grasses intracytoplasmiques et ont donc une faible densité au scanner. Si la densité est inférieure à dix unités Hounsfield (UH) sur une acquisition réalisée avant injection de contraste, on peut considérer la masse comme un adénome bénin. La mise en évidence de la graisse dans la lésion est en général suffisante pour arrêter les investigations [2, 9]. A l′inverse, les masses surrénaliennes malignes ou les métastases ont peu de graisses intracytoplasmiques et par conséquent ont une densité élevée sans injection de produit de contraste au scanner. Ces faits sont corroborés dans une étude quantifiant les matières grasses des glandes surrénales. Elle avait montré l'existence d'une forte corrélation entre la teneur riche en matières grasses des glandes surrénales et une faible atténuation à la TDM avec la perte de signal au déplacement chimique à l'imagerie par résonance magnétique . |
Psychische Erkrankungen wie Angst, Angst und Depression gemischt sowie somatoforme Störungen haben somatische Erkrankungen im Ranking der häufigsten Krankheitsbilder der Österreicher 2019 abgelöst. Laut OECD und europäischer Kommission 2018 („Gesundheit auf einen Blick“) wurde bereits 2014 festgehalten, dass psychische Erkrankungen rund 3,5 % des österreichischen Bruttoinlandsproduktes (BIP), somit 11 Mrd. Euro Kosten und größtes individuelles und familiäres Leid erzeugen . Dieser Betrag hat sich bis 2019 auf 4,3 % des BIP, somit 13,9 Mrd. Euro gesteigert. Im Rahmen der COVID-19-Folgeerkrankungen wird eine aktuelle weitere Steigerung um 20 % der genannten Krankheitsbilder in ersten Erhebungen sichtbar. |
Plasmid libraries were electroporated into the E. coli T7 expression strain C41(DE3) (Lucigen, Middleton WI) and grown to mid-log phase. We were careful to maintain the diversity represented in the plasmid library by accepting only high efficiency of transformation (typically >1010 individual transformants) at this step. Coat protein expression was induced by the addition of IPTG (1 mM) for three to five hours and bacteria were collected by centrifugation and the pellet was stored at -20°C overnight. Bacteria were lysed in SCB buffer (50 mM Tris, pH 7.5, 100 mM NaCl) by addition of 10 μg/ml of lysozyme, sonicated and purified from bacterial debris by centrifugation. The supernatant was treated with 10 units/mL of DNaseI and the VLPs were purified away from contaminating bacterial proteins by size exclusion chromatography using sepharose CL-4B resin (Sigma-Aldrich, St. Louis MO) as previously described . Fractions that contained VLPs were combined and precipitated by the addition of ammonium sulfate at 50% saturation. Precipitated VLPs were collected by centrifugation, solubilized in SCB buffer and dialyzed in SCB overnight (Slide-a-lyzer cassettes 20K MWCO, Millipore). |
To investigate the roles of circRNAs in the radiotherapy of lung cancer, we performed RNA-seq and analyzed the expression profiles of circRNAs in non-irradiated and irradiated A549 lung cancer cells (sequences were deposited in the Gene Expression Omnibus under dataset code GSE124396; www.ncbi.nlm.nih.gov/geo). A total of 1875 dysregulated circRNAs were identified in irradiated A549 cells (Fig. 1a). The hierarchical clustering heatmap suggested that the expression levels of circRNAs were clustered and distinguishable (Supplementary Fig. S1a). The clonogenic survival assay showed that the 4 Gy dose of radiation treatment significantly reduced the proliferation ability of A549 cells (Supplementary Fig. S1b). In addition, the category and chromosomal localization of circRNAs were also identified (Fig. 1b, c). Based on the STEM and ANOVA analysis, 230 circRNAs showed an upregulated or downregulated trend in A549 cells treated with different doses (0, 2, or 4 Gy) of radiation (|fold change | ≥ 2.0, P < 0.05). Of these, the first 15 downregulated and 15 upregulated circRNAs are represented in Fig. 1d and listed in Table S1. Through integrated analysis of junction reads and logCPM by edgeR, we selected and validated 10 circRNAs using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) (Fig. 1e and Table S2). The results showed that hsa_circ_0001460 (termed circNEIL3) was the most significantly downregulated circRNA in the LUAD cells treated with either 0, 2, or 4 Gy of radiation, respectively (Fig. 1a, e).Fig. 1The circRNA expression profile workflow in the irradiated LUAD cells.a Flow chart for identifying and validating circRNAs in A549 cells. b Distribution map of circRNAs based on chromosome location. c Distribution map of circRNAs based on category. d Heatmap showing the top 15 most upregulated and top 15 most downregulated circRNAs in A549 cells treated with either 0, 2, or 4 Gy radiation, respectively. e Ten most representative circRNAs verified using RT-qPCR. |
Our observations that excellent flocculation and removal of cyanobacteria can be achieved without effects on the zeta potential when low dose of flocculants and a ballast are used, seems contradictory to a plethora of studies that have reported less negative zeta potentials are critical for attractive van der Waals forces to overcome the repulsive electrostatic forces of negative zeta potentials and thus to promote particles aggregation [25, 26, 53–55]. However, the charge neutralization or the electrical double layer compression are not the only forces in flocculation, but also inter-particle bridging can promote strong flocculation even when the zeta potential is low . In addition to bridging, other flocculation mechanism that does not involve changes in charge and plays a role here is sweeping. In this process the cells are entrapped by large flocks formed due to polymeric precipitation or the formation of insoluble large metal hydroxide . We postulate that the variety of monomeric and polymeric Al complexes possibly formed in our experiments around the neutral pH values led to inter-particle bridging and not necessarily the impairment of the zeta potential. Likewise, for chitosan at circumneutral pH, bridging would be the main mechanism in flocculation . Similar observations have been made for chitosan and kaolinite/bentonite where inter-particle bridging made neutralizing the surface charge of particles unnecessary . At neutral pH and without major effects on the low negative zeta potentials, low doses of chitosan (1–2 mg L-1) caused strong water clearing due to bridging flocculation . |
Zaobserwowano zjawisko konsekwentnego trwania rodziców w podjętej w oddziale noworodkowym decyzji odroczenia szczepienia lub zaniechania go w ogóle. Do 6. miesiąca życia dziecka 80% pierwotnie uchylających się rodziców zrealizowała program szczepień ochronnych. 20% rodziców nadal nie podejmuje takiej decyzji. Wszystko wskazuje na to, że będzie to decyzja trwała. |
The time-series decompositions of the diarrhoea case numbers show clear seasonal patterns with the major peak in June and a declining trend until 2013, but with a resurgence in 2014 (Fig. 4). The map of standardised morbidity ratios (SMR) by districts show that higher cases of diarrhoea is observed in the central part of Bhutan (Fig. 5).Fig. 4Decomposed total diarrhoea time-series. Data presented as incidence rates per 10,000 population Fig. 5Raw standardised morbidity ratios for diarrhoea by district of Bhutan for the study period 2003–13 |
Notably, there were no abrupt changes in the NW morphology associated with the increase in V/III ratio by 1.5 times and subsequent catalytic droplet consumption at the second NW growth stage—NW tapering angle mostly keeps constant along the NW length. This indicates that the interface area between the catalytic droplet and the GaP NW top facet, which determines the NW diameter, remains constant despite the catalytic droplet consumption. |
Given our observations that IL-36β enhances antiviral immunity in keratinocytes in a STAT1/2 dependent manner (Fig. 4d, e) and it induces IFNAR expression (Fig. 5 and Supplementary Fig. 4), we further tested whether the antiviral activity promoted by IL-36β was dependent upon signaling through IFNAR. In human keratinocytes, in which expression of IFNAR1 or IFNAR2 was eliminated using CRISPR-Cas9 gene editing, higher HSV-1 replication was observed when cells were not treated with IL-36β (Fig. 8a, b). Importantly, in IFNAR1 deficient cells IL-36β no longer protected against infection and IL-36β did not induce Mx1 expression either (Fig. 8a). Similar observations were made when IFNAR2 was deleted (Fig. 8b). Analyses using mouse primary keratinocytes and neutralizing antibodies directed against the mouse IFNARs revealed similar outcomes (Fig. 8c). Hence, the antiviral state induced by IL-36β is dependent upon both IFNAR1 and IFNAR2 in both human and mouse cells.Fig. 8IL-36β induced antiviral state is dependent upon IFNAR. a Human keratinocytes were transfected with control (Ctrl) or IFNAR1 gRNA/Cas9 expression plasmids, treated with IL-36β and infected with HSV-1. b Control (Ctrl) or IFNAR2 gRNA/Cas9 expression plasmid transfected human keratinocytes were treated with IL-36β and infected with HSV-1. a, b Levels of ICP4, Mx1, IFNAR1, IFNAR2, and GAPDH were determined using western blotting and ImageJ analyses. c Mouse primary keratinocytes were treated with IL-36β as indicated, incubated with neutralizing antibodies against IFNAR or isotype matched Ig and infected with HSV-1. Levels of ICP4, Mx1 and GAPDH were determined using western blotting and ImageJ analyses. a–c Quantitative data are shown as means ± SD. *p < 0.05 (one-way ANOVA, n = 2 biologically independent samples per treatment group). Each red dot represents a single data point. Source data are provided as a Source Data file |
In our opinion, fasting-induced mild oxidative stress response primes the skeletal muscle to better withstand oxidative stress, which normally occurs during physiological contraction and/or regular physical activity. Thus, this Nrf2-driven antioxidant mechanism could change the set point of stresses and/or points to adaptive transcriptional program buffering future stressors, leading to beneficial effects on health and lifespan. |
The Jaya algorithm was developed based on the thought that, during each iteration, the solution for a given problem should move toward the best solution and avoid the worst solution. Considering a general optimization problem, it is assumed that at any iteration i, the number of design variables is N and the population size is M. If pm,n(i)≜pi,m,n is the value of the n-th (n=1,2,⋯,2N) variable for the m-th (m=1,2,⋯,M) candidate during the i-th iteration, then this value is updated according to the following formula. (11)pi,m,n′=pi,m,n+r1(pi,best,n−|pi,m,n|)−r2(pi,worst,n−|pi,m,n|), where pi,best,n is the value of the n-th parameter for the best solution and pi,worst,n is the value of the n-th parameter for the worst solution in the population. Moreover, pi,m,n′ is the new value of pi,m,n, and r1 and r2 are two random numbers whose values are in the range of , respectively. The term “r1(pi,best,n−|pi,m,n|)” indicates that the solution tries to move towards the best solution, and the term “−r2(pi,worst,n−|pi,m,n|)” shows that the solution tries to avoid the worst solution. The two random numbers r1 and r2 provide the Jaya algorithm with the ability to perform a random search within the search space, theoretically ensuring that the algorithm can converge to the global optimal solution. In addition, the exploration capability of the Jaya algorithm is further improved by utilizing the absolute value of the candidate solution. pi,m,n′ is accepted if the function value it produces is better. Let Pi,m={pi,m,n}n=12N, Pi,m′={pi,m,n′}n=12N, and J(·) be the fitness evaluation function; then, it can be expressed as (12)Pi+1,m=Pi,m′,ifJ(Pi,m′)>J(Pi,m)Pi,m,ifJ(Pi,m′)⩽J(Pi,m) |
The IL-23/IL-17 axis is also involved in the pathogenicity of PsA . In addition to AS, polymorphisms in IL23R are a risk factor for PsA . The frequency of Th17 cells is increased in PsA synovial fluid . Celis et al. found an association between higher IL-23A mRNA expression and synovial lymphoid angiogenesis, and that IL-23A mRNA expression significantly correlates with swollen joint count and CRP in PsA patients . In addition, Raychaudhuri et al. showed that IL-17 induces MMP-3 and proinflammatory cytokines such as IL-6 from cultured FLS with PsA patients . Furthermore, IL-22/IL-22R could be a therapeutic target for the treatment of PsA . |
The experimental data presented in this research displays the utility of using sophisticated mathematical modelling of flow dynamics across a spectrum of predefined and selected conditions. This allows one to describe response behaviors that are not limited to the known and unknown characteristics that may be present in a specific subgroup of human or animal subjects. However, despite the comprehensiveness of the modelling, the current findings were not verified in–vivo. Encompassing the complexity of human physiological responses may remain elusive to mathematical models, and hence, such findings should be regarded as hypothesis generating and should pave the way for subsequent in–vivo validation studies. It should be noted, that despite these known limitations, the mathematical basis for the modelling is well validated from previous publications. A limitation in the design of the current modeling includes lack of consideration for percussion waves. The impact of percussion waves on MG across the spectrum of valvular stenoses and LV elastances is yet to be fully elucidated. The input variables for the modeling were derived from prior publications and uses an average sized middle-aged male as reference. The extrapolation to different genders, body surface areas and ages is thought to be a reasonable assumption but will need future validation. Finally, the work should be regarded as hypothesis generating using idealized conditions, that requires external validation in in-vivo studies. |
The patients in this group, 334 patients (38.6%) were smokers. 305 patients had not coronary artery disease. In this group, 9 patients (3%) in the age group 30-40 years, 67 patients (22%) in the age group 40-50 years, 111 patients (36.4%) in the age group 50-60 years and 118 patients (38.7%) in group older than 60 years. 57% (174 patients) in the group was female and 43% (131 patients) were male. 4.6% (13 patients) of the patients in this group were using drugs, of which 4 patients (30.8%) orally, 8 patients (61.5%) fumigation and one patient (7.7%) with other methods. In this group, 17.7% (54 patients) was with diabetes and 46.9% (143 patients) were patients with hypertension. In this group, 75 patients (24.6%) were smokers. |
Houve uma redução de 49,6% no número absoluto de pacientes com doenças cardiovasculares atendidos no setor de emergência. Um estudo italiano obteve resultados semelhantes ao avaliar apenas as internações hospitalares por infarto agudo do miocárdio durante uma semana em comparação a uma semana equivalente em 2019.10 Outro estudo, realizado nos EUA, observou um redução de até 48% nas taxas semanal de hospitalização por infarto agudo do miocárdio durante o período da pandemia de COVID-19.11 Embora a redução do número absoluto observada em nosso estudo seja semelhante à de outros dados internationais, não houve alteração no percentual de pacientes com doenças cardiovasculares atendidos no setor de emergência durante o surto de COVID-19. |
AS, anastomotic biliary stricture, CMV cytomegalovirus, EBV Epstein-Barr virus, HHV human herpesvirus, ERC endoscopic retrograde cholangiopancreatography, HSV herpes simplex virus, LT liver transplantation, MELD model of end-stage liver disease, NAS non-anastomotic biliary stricture, VZV varicella-zoster virus |
The imaging feature common to all 22 cases was iliac bone destruction of various forms; 8 cases were accompanied by soft tissue masses of varying sizes, and 2 cases exhibited needle periosteal reaction. Pathology results showed seven disease types: 8 cases of neuroblastoma iliac bone metastasis, 7 cases of bone eosinophilic granuloma, 2 cases of Ewing's sarcoma, 2 cases of osteomyelitis, 1 case of bone cyst, 1 case of bone fibrous dysplasia, and 1 case of non-Hodgkin's lymphoma. |
The dissipation inequality is even simpler in the isothermal situation (178)pI+σ:D+−Bα:αt+−Dβ:βt≥0.The linear solution to the dissipation inequality is obtained in the same manner as in the case of a single internal variable:(179)pI+σαtβt=LD(−Bα)(−Dβ), where (180)L=L11L12L13L21L22L23L31L32L33, with the same condition concerning the positive semidefiniteness of the matrix L as for the single internal variable case. As a result, the constitutive relationship for stress is depicted as (181)pI+σ=L11D+L12(−Bα)+L13(−Dβ).Evolution equations for internal variables α and β take the form (182)αt=L21D+L22(−Bα)+L23(−Dβ), (183)βt=L31D+L32(−Bα)+L33(−Dβ).Both the constitutive relationship (181) and the evolution equations are coupled. The internal variables α and β are dual, as shown by Equations (182) and (183). |
The dust phase following sapropel S6 formation is weaker than one would expect based on the insolation and the monsoon index (Fig 6). This can be attributed to the generally cooler glacial boundary conditions, which dampen the intensity of African summer monsoon rainfalls , thus preventing the establishment of extensive lake and river systems and associated biomes. Changing wind systems cannot be responsible for the different patterns, because the regional wind direction and strength during glacial periods were not significantly different from that during interglacial periods . |
La prise en charge des accidents vasculaires cérébraux ischémiques (AVCi) est une urgence absolue et doit être réalisée en priorité dans des unités neuro-vasculaires. Le traitement repose en premier lieu sur la thrombolyse intraveineuse après réalisation d’une imagerie par résonnance magnétique qui objective l’AVCi. En milieu isolé ou dans les pays non pourvus de telles structures, le traitement est souvent symptomatique. La thrombolyse intraveineuse pourra être réalisée uniquement dans des cas exceptionnels après avoir éliminé des contre-indications à ce traitement en évaluant scrupuleusement le rapport bénéfices/risques et seulement après concertation auprès d’un médecin neurologue habitué à gérer les urgences neuro-vasculaires. |
HBV ist ein umhülltes Virus. Die Hülle wird aus den 3 Hüllproteinen LHBs („large hepatitis B virus surface antigen“), MHBs („middle hepatitis B virus surface antigen“) und SHBs („small hepatitis B virus surface antigen“) aufgebaut und umgibt das Nucleocapsid, das aus dem Core-Protein aufgebaut ist. Das Nucleocapsid beherbergt das partiell doppelsträngige zirkuläre ca. 3,2 kB große DNA-Genom. Das HBV-Genom umfasst 4 verschiedene offene Leserahmen. Diese codieren für die HBV-Polymerase (P), die viralen Hüllproteine (LHBs, MHBs und SHBs – in ihrer Gesamtheit als HBsAg bezeichnet), das regulatorische X Protein (HBx) sowie für das Capsid (HBcAg) bzw. dessen sekretorische Variante (HBeAg). |
Eine Experimentalaufgabe, die ein breites Beanspruchungsspektrum in Versuchspersonen zuverlässig und reproduzierbar induzieren kann, muss so entwickelt werden, dass sich aufeinanderfolgende Teilaufgaben in der induzierten Beanspruchung signifikant unterscheiden. Ansonsten kann ein physiologisches Messsystem keinen Unterschied detektieren. Aus den Ergebnissen der drei Studien und den Anforderungen, die Belastung gezielt zu variieren und Wiedererkennungseffekte zu minimieren (vgl. Städtler 1998), lassen sich die folgenden drei Bedingungen an die Reihenfolge der Aufgabenkombinationen ableiten:Aufeinanderfolgende Teilaufgaben sollen sich in der Buchstabenfrequenz unterschieden.Dieselbe Teilaufgabe soll in der Experimentalaufgabe nicht wiederholt werden.Aufeinanderfolgende Teilaufgaben sollen sich in der Nebenaufgabe unterschieden. |
Na última década, a antiagregação plaquetária múltipla foi considerada fundamental para o sucesso do tratamento das SCA. A ativação e a agregação plaquetária ocorre por vias distintas, o que demanda que a antagonização por fármacos antiplaquetários contemple todas as vias envolvidas. Desse modo, o tratamento atual antiplaquetário é feito com dois ou três fármacos combinados17 (Quadro 1). |
A Trainable Weka Segmentation was utilized to provide a cheaper alternative to tools such as CHAMP for scene segmentation. The constructed pixel level classifier produced excellent segmentations for the single images as shown in Table 5. However, segmentation results from full slide pap-smear images required more pre-processing before feature extraction. TWS has been used in many studies and its accuracy is largely dependent on the accuracy of training the pixel level classifier [27, 65, 66]. Increasing the training sample as reported by Maiora et al. could improve the performance of the classifier. TWS’s capability to produce good segmentation is due to its pixel level classification where each pixel is assigned to a given class. However, the poor performance to segment the whole slide would be attributed to the small dataset used for building the segmentation classifier, as this was a manual process that involved annotation by an experienced cytopathologist. Feature selection played an important role in this work since it eliminated features that increased error in the classification algorithm. Eighteen out of the twenty-nine extracted features were selected for classification purpose. It was noted that most of the features that added noise to the classifier were cytoplasmic features. This could be attributed to the difficulty in separating the cytoplasm from the background as opposed to the nucleus, which is darker . Increasing the number of clusters during feature selection reduced the fuzziness exponent. This implies that increasing the number of clusters reduces the defuzzification error computed by the defuzzification method presented in this paper, which is based on Bayesian probability to generate a probabilistic model of the membership function for each data point and apply the model to the image to produce the classification information. An optimal number of 25 clusters was attained and overtraining occurred when too many clusters (above 25) were used. This is due to the defuzzification method used whose density measure works against overfitting by giving smaller clusters less influence than larger clusters. The overall accuracy of the tool could be attributed to the fuzzy membership that is assigned to each class, and the relevance of the nucleus features selected. |
Ondanks dat er nog sprake is van een leercurve blijkt dat het goed mogelijk is om transprostatische implantaten te plaatsen onder lokale anesthesie. Dit maakt de kosten lager zonder dat dit ten koste gaat van de kwaliteit van de behandeling en er wordt minder gebruikgemaakt van schaarse operatiekamer en/of sedatiecapaciteit. |
末次随访时间为2012年7月20日。随访内容为患者的临床资料，包括年龄、TNM分期、体力状况、吸烟状况、转移部位、接受治疗情况及疗效。主要观察指标为患者靶向药物治疗失败后的生存时间。其中血癌胚抗原（carcinoembryonic antigen, CEA）检测方法：靶向药物治疗失败后至挽救性治疗前，采集患者空腹静脉血4 mL，采用Luminax仪器用电化学发光免疫法检测血清CEA水平，严格按仪器和试剂说明书操作，以10.0 ng/mL为正常值上限。随访时间为从靶向药物治疗失败后化疗的开始时间到患者死亡日期。 |
Pyruvate and lactate are the end products of glycolysis and major substrates for the tricarboxylic acid (TCA) cycle. They constitute critical branch points in cellular metabolism, lying at the intersection of catabolic pathways with anabolic pathways for lipid synthesis, amino acid biosynthesis, and gluconeogenesis. Indeed, dysregulated carbon metabolism becomes emerging hallmarks of diabetes, obesity, and cancer1–3. Under aerobic conditions, glucose was generally assumed to be fully catabolized to carbon dioxide in cells via the concerted action of glycolysis and the TCA cycle. However, in recent years, there is an increased awareness of the metabolic flexibility, in which glycolysis and the TCA cycle are uncoupled, thus allowing independent cell-specific regulation of both processes4. Notably, circulating lactate was recently demonstrated to be a major source of carbon for the TCA cycle both in normal and cancerous tissues5, highlighting the physiological significance of monocarboxylate transport. |
Avaliamos o balanço de amostras do banco de dados completo, calculando diferenças padronizadas e utilizando o teste χ2Omnibus. Com base nos resultados da regressão logística simples, pareamos os grupos utilizando o método do escore de propensão, considerando duas covariáveis: número de óvulos maduros e idade da mulher. Assim, pareamos os casos na proporção de 1:2 dos ciclos nos Grupos Freeze-all e a Fresco. Essa seleção de casos foi realizada pelo método do vizinho mais próximo ( nearest-neighbor ); para cada transferência no Grupo Freeze-all , selecionamos duas transferências no Grupo a Fresco, com o escore de propensão mais próximo. Os resultados das transferências em fase de clivagem e blastocisto foram analisados separadamente. |
In addition, we have explicit evidence from coding of the narratives that 94 % of the respondents intended to regulate the internal feeling states of the targets as well as their outward expression of laughter. Those individuals who did not explicitly state a goal of regulating the internal feeling state of the target tended to have the goal of regulating the target’s emotional expression (i.e., making the person laugh), but we cannot determine conclusively whether or not they had the goal of regulating the internal feeling state of the target.3 |
We further investigated how the performance of ASSET relates to various other parameters of the SSEs, such as the number of its sequential synchronous events composing the SSE, the number of neurons in each synchronous event, and the total number of observed neurons. SSEs were statistically more significant and therefore easier to detect when they involved a larger fraction of the total neurons. However, they could be retrieved even when employing sub-optimal parameters such as a kernel length smaller than the length of the DS, given that the SSE involved enough neurons. In contrast, the method did not detect spatio-temporal patterns, i.e. a special case of SSE where each event is composed by a single spike only. Spatio-temporal patterns in a more general sense (with different time intervals between spikes) were suggested as signatures of synfire chain activity in data of low numbers of simultaneously recorded neurons [40, 46, 47]. |
In the AR tracking evaluation, all of the participants responded to the question (Q1) whether each system was useful (Table 1). Some of the comments in free text were as follows: “I was attracted by the specimens through the AR guide” or “The AR information facilitated my understanding of the diseases.” The AR system itself seemed to have been favorably accepted as a useful tool. |
Vorhandene Hyperkeratosen, Beläge und nekrotisches Gewebe sollten mechanisch entfernt werden. Beim scharfen Debridement zeigte eine Studie einen Vorteil gegenüber der einer Standardtherapie. Ein enzymatisches Debridement brachte im Vergleich zu Hydrogel keinen Vorteil. Studien zur Madentherapie sind mit einem hohen Bias verbunden und somit ist keine Beurteilung hinsichtlich eines Zusatznutzen möglich . Auch Wundauflagen mit Wirkstoffen inklusive Silber zeigten keinen eindeutigen vorteilhaften Nutzen. Ein Cochrane Review aus dem Jahre 2017 bestätigt lediglich, dass antimikrobielle Wundauflagen die Heilungsrate verbessern könnten. Der Evidenzgrad ist jedoch niedrig . |
ATP6V0d2 is involved in the function of important lysosomal enzymes, such as cathepsin D (CTSD), whose cleavage into mature forms depends on this V-ATPase subunit isoform. Inhibition of CTSD activity was demonstrated to either increase or decrease cholesterol intracellular levels depending on the studied models and a definitive participation of CTSD in cholesterol homeostasis remains to be established. Sphingolipid metabolism is also likely to be disturbed by ATP6V0d2 knock-down: β-glucocerebrosidase (GCase), whose activity is decreased in ATP6V0d2-KD macrophages and is responsible for breaking down glucosylceramide into ceramide , is also implicated in CTSD processing [60, 61], and α-galactosidase (α-Gal), whose activity is increased in ATP6V0d2-KD macrophages, participates in the production of glucosylceramide . Hence, in addition to a 40% decrease in intracellular cholesterol levels, ATP6V0d2-KD macrophages could accumulate glucosylceramide (glucocerebroside) in detriment to ceramide and its incorporation into macrophage membranes. The data therefore indicate that ATP6V0d2 participates in lysosomal metabolic processes involved in the homeostasis of important membrane components, such as cholesterol and ceramide, which ultimately interfere in the biogenesis of pathogen-containing vacuoles in macrophages. |
Then, we further evaluated the relationships between SMOC1 expression and prognosis in 33 cancer types from the TCGA project in GEPIA2. The impact of SMOC1 expression on the survival of these 33 cancer types is presented in Figure 2A (OS) and 2B (disease-free survival). Notably, survival of LGG and LUAD were also significantly correlated with SMOC1 expression. Higher expression of SMOC1 was correlated with better survival of LGG (OS, HR = 0.43, p-value = 3.3e-06; disease-free survival, HR = 0.58, p-value = 0.0005) (Figure 2C) but worse survival of LUAD (OS, HR = 1.4, p-value = 0.043) (Figure 2D). No correlation was observed between SMOC1 expression and the survival probability of GBM (Supplementary Figure S1A). |
This was a retrospective record-based study of all cases of poisoning that were presented to the ED of JOOTRH from January 2011 to December 2016. Data was collected from charts of patients who were admitted at JOOTRH due to acute poisoning. A pre-structured proforma was used to extract data from treatment records of patients diagnosed with poisoning. Relevant files were reviewed for the year of poisoning, gender, age, place of residence, religion, marital and occupational status. The nature and motive of poisoning, the period of hospitalization, initial/final diagnosis, time lapse before treatment, and the types of poison, were also recorded. Data on the route of exposure, clinical presentation, laboratory findings, management, and outcome of poisoning, were also included. |
Résultats de la troisième journée: la totalité des personnes présentes à cette journée était persuadée que l'impact de cette formation sur leurs travaux sera « assez 68% » voire « très important 31%» et plus de 95% ont estimé qu'elle a permis d'améliorer leurs connaissances dans les différents thèmes traités. |
When WT and BRAF-mutant hECTs were subjected to uniaxial stretch testing on a physiologic muscle bath apparatus, the slope of the resulting diastolic stress-strain curve yielded an apparent Young’s modulus for the passive tissue that was higher on average in BRAF-mutant hECTs (0.164±0.264 kPa, n = 4) compared to WT tissues (0.036±0.019 kPa, n = 4) (Fig 4C). Note that the large standard deviation in the BRAF-mutant hECTs is due to one particularly stiff tissue. Consequently, although the power of the data was not sufficient to achieve statistical significance, the trend suggests the observed changes in diastolic force in the BRAF-mutant hECTs may partly reflect an elevated passive stiffness of the mutant cardiac tissues, which is a common characteristic of HCM. |
Unlike protein-coding genes, where function can be inferred by identification of known regulatory motifs, structural prediction, or orthology to other genes, there are no established rules for predicting the function of lncRNAs. Based on the premise that genes that show correlated expression profiles may be under a common regulatory architecture and therefore potentially share a common role, we investigated lncRNAs situated in trans relative to the differentially expressed protein-coding genes with focus on lncRNAs correlated to Arc and the most significantly differentially expressed protein-coding genes, Arc, Mapk4, Dbc1, Tet3, Pim1, and Pmepa1 (Figure 5). By applying this method, we found 34 lncRNAs highly correlated (p < 0.05 and Pearson correlation coefficient > 0.75). The corresponding lncRNA include XLOC_047519 corresponding to a lncRNA upstream of Tmem150c (Figure S6A), XLOC_139362 corresponding to the lincRNA Tunar (Figure S6B), and XLOC_055591 corresponding to a lncRNA overlapping, but not sharing any exons with, LOC306079, which does not show any sign of differential expression (Figure S6C). Tunar (TCL1 Upstream Neural Differentiation-Associated RNA), or in human TUNA (Figure S5B), was recently shown to be evolutionary conserved and required for neuronal differentiation (Lin et al., 2014). Deregulation of TUNA in the striatum has been suggested to be part of the pathophysiology of Huntington's disease. The present findings implicate Tunar in neuronal activity-dependent synaptic plasticity in the adult brain, however, these observations need to be tested further. In light of increasing numbers of lncRNAs with demonstrated roles in regulation, we propose that the lncRNAs described in this study may represent important targets for future biological studies in understanding the molecular mechanisms underlying LTP. |
Abnormalities in mineral metabolism, in particular hyperphosphatemia, frequently observed in chronic renal disease, have emerged as a key regulator of vascular calcification and been considered risk factors for cardiovascular mortality in this population6 , 7. NO is a cell-signaling molecule with multiple roles, including the regulation of vascular tone and neurotransmission8 , 9. NO is produced by most cells of the body and its substrate is the L-arginine, which under the effect of nitric oxide synthase (NOS) generates L-citrulline and NO10. The NO synthesized by endothelial cells is crucial in maintaining vascular health and preventing the development of vascular diseases11. NOS presents two isoforms: the constitutive (cNOS) and the inducible (iNOS); the latter can be induced by agents as lipopolysaccharide (LPS) from several bacteria and inhibited by aminoguanidine (AG)12. NOS expression has been detected in vivo and in vitro in osteoblastic cell lineage13 and there is evidence that the production of NO may have an important role in the regulation of osteoblast metabolism14. |
A cirurgia convencional para tratamento do pseudoaneurisma de aorta abdominal associado à pancreatite é definida como o padrão-ouro em pacientes instáveis2. Nos casos em que há estabilidade hemodinâmica, o tratamento ideal é controverso, devido ao pequeno número de casos relatados3. Em todos os relatos identificados na literatura, a opção terapêutica adotada foi a correção por técnica aberta com exclusão do pseudoaneurisma e interposição de prótese sintética. |
As can be anticipated, acoustic-phonetic parameters that are under a lower orthogonal relation—as the relation between speech and articulation rates, and f 0 median and f 0 baseline)—tend to co-vary. Conversely, less inter-dependent parameters tend to contribute differently to the overall statistical model being tested, given their higher orthogonal association (i.e., higher degree of independence). Such logic may explain why the combination of f 0 base value and vowel duration, or f 0 median and vowel duration resulted in better discriminatory performance when compared to the combinations between f 0 base value and f 0 median, for instance (see Table 3). It was also noted that combining F1 and F2 to either f 0 base value or f 0 median did not result in an expressive change in system performance. |
Hughes (1962) prägte den Begriff dirty work für Formen von Arbeit mit geringem Prestige. In der Organisations- und Managementforschung wurden unterschiedliche Formen von Stigmatisierung im Kontext von dirty work untersucht. Dabei wird dirty work als spezifische Form von Stigmatisierung interpretiert, die sich auf die Ausübung von Arbeit bezieht. Ashforth und Kreiner (1999, 2013, 2014) differenzieren unterschiedliche Formen des öffentlich wahrgenommenen Makels, auf dessen Basis eine Arbeit als dirty stigmatisiert sein kann. Als „morally tainted work“ (Ashforth und Kreiner 2014, S. 82) gilt Arbeit, die von der gesellschaftlichen Mehrheit als moralisch fragwürdig oder anstößig wahrgenommen wird, etwa Prostitution oder das Ausführen der Todesstrafe. In der umfangreichen Forschungsliteratur zu Stigmatisierung im Allgemeinen sowie zu dirty work im Speziellen wurde eine Vielzahl an Reaktionsweisen auf Stigmatisierung auf der Mikroebene diskutiert. Stigmareaktionen unterscheiden sich nach Grund, Art und kulturellem Kontext des Stigmas (vgl. Lamont et al. 2012, S. 44). Häufig wird dabei zwischen aktiven und reaktiven (LeBel 2008; Link und Phelan 2001, S. 378) sowie zwischen individuellen und gruppenbezogenen (Miller und Kaiser 2001, S. 83) Reaktionsweisen unterschieden. Zu der Vielzahl der untersuchten konkreten Reaktionsweisen gehören beispielsweise die Abwehr negativer Attribuierungen (Claire et al. 2016), das Verheimlichen von Stigmata (Goffman 1967; Bursell 2012), das Vermeiden von Konfrontation (Miller und Kaiser 2001; LeBel 2008) oder das Fokussieren auf nicht-stigmatisierende Aspekte des eigenen Lebens oder der Arbeit (Ashforth und Kreiner 2013; Miller und Kaiser 2001). Als besonders relevant für die Entstigmatisierung werden in der sozialwissenschaftlichen Forschungsliteratur aktive, konfrontierende Reaktionen benannt (vgl. Lamont et al. 2013, S. 133; Fleming et al. 2011). Diese umfassen insbesondere Versuche, die kulturellen Ideen der Stigmatisierenden oder das öffentliche Bild der Stigmatisierten zu ändern (Claire et al. 2016; Meisenbach 2010). Hierbei spielen unter anderem sozialer Aktivismus (vgl. LeBel 2008; Lamont et al. 2012, S. 43), das Ziehen vorteilhafter Vergleiche (Meisenbach 2010, S. 280f.) und Aufklärungsarbeit (Fleming et al. 2011), aber auch verschiedene Formen des reframing eine Rolle. Beim reframing versuchen Akteure, die kulturelle Bedeutung einer Handlung oder Situation zu ändern, um dem Stigma entgegenzuwirken (Ashforth und Kreiner 2013; Miller und Kaiser 2001), etwa indem es als ungerechtes Vorurteil gedeutet wird. |
Neste estudo demonstramos de forma ampla e numérica os desfechos dos mecanismos da impunidade do crime violento grave no Brasil. Por exemplo, o Monitor da violência relatou que em 2018, dentre os 1.195 crimes violentos ocorridos em uma semana aleatória no país, apenas 39% dos agressores foram identificados e 2% tiveram alguma condenação no prazo de 316 dias estabelecido pelo Judiciário20,21. |
The mean BCVA significantly improved from 0.45 ± 0.22 LogMAR at baseline to 0.38 ± 0.15 LogMAR after 12 months of treatment (p < 0.001). Moreover, the mean CMT significantly reduced from 508.07 ± 99.78 μm at baseline to 277.04 ± 65.23 μm (p < 0.001) after 12 months of treatment. (Figure 1) The average time from intravitreal DEX injection to anti-VEGF was 4.33 ± 1.13 months (range 3-8). The total number of injections was 4.79 ± 1.35. |
No significant differences were observed between groups at pre-training for 1RM, MBIF or isokinetic peak torque at any of the measurement velocities. Changes in 1RM at post-training are shown in Table 1. All four training groups showed significant increases (p = 0.000) in 1RM at mid- and post-training with the post-training increases in normalised 1RM ranging between 8 and 13 %. Figure 2 shows the differences in the normalised 1RM improvements for four training groups. In terms of effect size, the STR regimens demonstrated a large effect compared to those reported for the HYP regimen. Whilst the effect sizes for the CL-1 and CL-2 regimens were largely similar when calculated for the normalised 1RM changes, the CL-2 demonstrated a larger effect than the CL-1 regimen for the absolute 1RM changes.Table 1Changes in 1RM back squat strength during and following the training periodPrePostPre-post change (kg)ES95 % CIDynamic strength 1RM (kg) STR120.56 ± 13.96135.83 ± 13.64*15.28 ± 1.95HYP 1.10613.34–16.66 HYP124.29 ± 24.01135.36 ± 24.81 *11.07 ± 2.440.4538.14–13.29 CL-1134.72 ± 21.88150.56 ± 23.78*15.83 ± 3.540.69315.75–19.80 CL-2121.39 ± 21.36138.61 ± 20.85*17.22 ± 2.32HYP 0.81612.71–18.40 1RM (kg/BM) STR1.55 ± 0.151.73 ± 0.16*0.19 ± 0.04HYP 1.1610.15–0.21 HYP1.64 ± 0.341.70 ± 0.30*0.12 ± 0.040.1870.08–0.20 CL-11.60 ± 0.281.77 ± 0.29*0.17 ± 0.040.5880.13–0.20 CL-21.59 ± 0.331.79 ± 0.35*0.21 ± 0.03HYP 0.5960.19–0.24Fig. 2Pre- to post-training percentage changes in 1RM back-squat strength. Asterisks significant difference from the HYP regimen (p < 0.05) |
Activity level was measured indirectly by self reported maximal walking capacity. This is a rough measure and validity is a potential issue, because there is no guarantee that a patient really uses his capacity to the full extent. We emphasize that self reported activity has been used before and there are reports about correlation of self reported and objectively measured activity levels . Even though our stratification resembles to that of the University of California Los Angeles activity score, it has not been tested against pedometer measurement. However, our simple activity measure via walking capacity yielded an important factor in statistical analysis. It should be noted that our measure of activity was not correlated to age, which stands in line with previous reports . |
In 2014, nearly one in four adults in the United States was diagnosed with a mental illness (National Institutes of Mental Health1). Treatment for many of these illnesses is hampered by limited efficacy of the medications and patient noncompliance due to intolerable side effects. To address this need, the National Institutes of Mental Health has launched an initiative to research these illnesses from all levels, ranging from genomic to behavioral. Dubbed the Research Domain Criteria (RDoC), this initiative proposes to complement top-down understanding of these diseases, beginning with human behavior, with bottom-up research by understanding the molecular and cellular causes of these disorders. |
Na podstawie wyników badań opracowano w wielu krajach rekomendacje, zgodnie z którymi stosowanie preparatów emoliencyjnych zostało włączone do pierwszej linii postępowania w atopowym zapaleniu skóry u dzieci i dorosłych pacjentów. W zależności od przebiegu choroby mogą one być aplikowane w monoterapii lub w połączeniu z miejscowo stosowanymi glikokortykosteroidami (terapia przerywana) bądź inhibitorami kalcyneuryny (terapia proaktywna). |
As a result, the P&S model had a good capability of predicting the UCS of CTB with different types of tailings, different curing ages, and different mixing proportioning settings. In the future, the accuracy and robustness of the prediction model will be further improved as the size of the dataset continues to grow. This could be helpful to assist the CTB design process with a high efficiency and accuracy. |
The UK health care system, National Health Service, is funded from taxation to provide comprehensive health care coverage available to all legally registered UK residents. Data on COVID-19 status were obtained from Public Health England covering the period from 16 March 2020 up to 26 April 2020. During this period, testing was restricted to those with symptoms in hospital (https://biobank.ndph.ox.ac.uk/showcase/field.cgi?id=40100); thus, our outcome represents hospitalizations for severe COVID-19. The data cover England only; thus, participants residing in Scotland and Wales were removed from our analytical sample. Biological samples from combined nose/throat swabs were used to perform COVID-19 testing, with real-time PCR in accredited laboratories (14). |
Parts of the frozen (− 80 °C) livers from rats treated with 0, 5, 10 or 20 ppm NVP were thawed in formalin (specifically 4% formaldehyde in sodium phosphate buffer pH 7) and left therein for fixation at least 7 days. Subsequently the livers were cut into approximately 4 mm-thick slices, which were dehydrated in increasingly concentrated ethanol (70–100%), washed in xylene and then transferred into fluid paraffin. The livers were put into kassettes with the parts which were foreseen for cutting toward the bottom, the kassettes filled with paraplast (melting point 58–62 °C) and the material left for hardening. From the embedded livers 3- to 6 µm-thick slices were cut by a rotation microtome, then stretched (in a water bath at 45 °C), transferred to a slide and dried overnight at 50 °C. Subsequently the slices were stained with HE and covered with Pertex. The slices were then microscopically evaluated. Structural changes were classified into severity grades 0, 1, 2 and 3. |
Fig 4 gives us two pieces of information that are important for our analysis going forward. First, we observe that statically-linked networks can store elastic energy, since g0 ≔ σ21(t → ∞) > 0, while all of the energy dissipates in transiently-linked networks. Second, both permanent and dynamic networks have multiple relaxation timescales, as most of the stress (≈ 80% for dynamic networks) relaxes over the first 0.2 s or so, with the remaining part taking seconds to relax. In Fig 4, we show a two-timescale decay curve that approximately, but not exactly, matches the decay of the stress in both statically- and transiently-linked networks. Given that one of the time constants is on the order 0.1 s and the other is on the order 1 s, Fig 4 demonstrates that both slow and fast timescales exist in cross-linked networks. Our rheological experiments will give more precise estimates for the individual timescales, but it is worth noting that the dissipation of all of the stress over a O(1)s timescale implies that the longest timescale in the system cannot be much longer than five seconds. This is not surprising since the filament turnover time is of this order, but is in sharp contrast to modeling studies without turnover, where stress takes hundreds of seconds to dissipate (Fig. 4). |
Рассмотрим результаты апробации русской версии опросника PHPQoL в фокусной группе больных ПГПТ. В целом опросник был понятен и не вызывал трудностей в заполнении у подавляющего большинства пациентов. Опросники были заполнены полностью в подавляющем большинстве случаев: пропущенных данных на всем массиве — 0,7%; 86,2% больных ответили на все вопросы опросника, что сопоставимо с данными, полученными при использовании оригинальной версии опросника (88%; S. Webb и соавт., 2016). Полученные результаты свидетельствуют о высоком качестве данных и хорошей заполняемости опросника. |
Cropping system mostly observed in DR Congo was intercropping pattern (90%) where yam is mostly intercropped with other arable crops. Approximately 10% of the farmers practice sole cropping system (Table 6). At the province and territory level, similar trend of results was obtained except for Bumba territory where the gap between these two cropping systems was significantly reduced. In this territory, over 40% of the farmers practice sole cropping system for yams as compared to other territories where less than 15% of the farmers were observed.Table 6Cultural practices in yam farming.CategoryBas-Uélé ProvinceMongala ProvinceTshopo ProvinceTotal n = 540Bambesa n = 90Buta n = 90Bumba n = 90Lisala n = 90Kisangani n = 90Isangi n = 90Cropping system (%)Intercropping10010056.6710088.8995.5690.18Sole cropping––43.33–11.114.449.82Staking (%)Positive response25.5611.1110061.1174.4475.5657.96Negative response74.4488.8938.8925.5624.4442.04n = 23n = 10n = 90n = 55n = 67n = 68n = 313Staking period (%)After 1 month10010094.4410010010099.07After 2 months–––––––After 3 months––5.56–––0.93After 4 months–––––––Staking type (%)Trellis–––––––Individual100100100100100100100Group–––––––Staking material (%)Wooden stick100100100100100100100Bamboo stick–––––––Others–––––––Harvest signature (%)–––––––≤ 25% leaf senescence–––––––50% leaf senescence–––––––100% leaf senescence100100100100100100100Number of harvest (%)Once100100100100100100100Twice–––––––Activity after harvest (%)Storage10010075.5688.8985.5682.2288.71Sold directly––24.4411.1114.4417.7811.30 |
The characterization of the LIDAR was performed pointing the LASER to a moving target and measuring the duty cycle (δ) of the PWM signal. The sensor was fixed at one end of a graduated ruler while the target could move freely anywhere from 10 to 90 cm. The distance was measured directly from the ruler, with a resolution of 0.5 mm and the pulse width was measured using a universal counter, model PM6669 from Philips (Amsterdam, Netherlands). Figure 5 presents the obtained results. |
In both the models, we assumed a negative binomial model to represent the annual frequency of the tornadoes in each state. The negative binomial model is appropriate for counts data and is a generalization of the Poisson regression model that accounts for overdispersion. The models are structured using a hierarchical Bayesian regression framework that allows the pooling of information across selected states. |
We determined the Km and kcat of PDCoV Mpro to be 56.6 ± 1.9 µM and 0.030 ± 0.009 s−1, respectively (Table 3). This Km value is close to that of HCoV-NL63 Mpro (50.8 ± 3.4 µM) and TGEV Mpro (61 ± 5 µM), lower than that of mouse hepatitis virus A59 (MHV-A59) Mpro (77 ± 5 µM), HCoV-HKU1 Mpro (83.2 ± 13.3 µM), SARS-CoV Mpro (129 ± 7 µM) and IBV Mpro (139 ± 15 µM), and higher than that of HCoV-229E Mpro (29.8 ± 0.9 µM) and FIPV Mpro (13.5 ± 1.8 µM) (Table 3). Structural analysis showed that the substrate-binding pocket of PDCoV Mpro shares several features in common with Mpros from CoVs in the other three genera, especially the S1, S2 and S4 subsites. The key residues at these sites are almost completely conserved (Figure 2). The N3 is a peptidomimetic inhibitor designed against various Mpros, such as those from SARS-CoV, HCoV-229E and FIPV . Therefore, we deduced that the Michael acceptor and peptidomimetic inhibitor N3 may inhibit PDCoV Mpro. An enzymatic assay showed that N3 inactivated PDCoV Mpro. The calculated Ki and k3 were 11.98 ± 0.13 µM and 72.91 ± 7.05 (10−3 s−1), respectively. The k3 is approximately 23-fold larger than that of SARS-CoV Mpro, which indicates that N3 inactivates PDCoV Mpro faster than it does SARS-CoV. |
Jennifer and Michael are expecting their first child in the summer. Arthur has been diagnosed with dementia and although Mabel is able to care for him, she relies on her family for support. The pandemic has highlighted the vulnerability of both Mabel and Arthur, who are now shielded because of their ages and health conditions, following the guidance and directive by the government. |
Les calcifications discales sont constituées d'une pâte molle contenant des cristaux d'hydroxyapatite de calcium. Elles touchent le nucleus pulposus, et plus rarement la totalité du disque vertébral . Depuis sa première description en 1924 par Baron , chez l'enfant, à cette date on compte plus de 300 cas décrits dans la littérature . Environ 100 cas de formes symptomatiques et environ 15% de formes asymptomatiques . Leur fréquence globale est encore mal connue. Les cas rapportés restent exclusivement ceux des enfants à peau dite blanche . L'étiologie des calcifications discales n'est pas connue de nos jours. Aucun facteur prédisposant n'est attribué à cette pathologie. Plusieurs facteurs ont été incriminés comme le traumatisme , l'infection , la cause auto-immune l'hypervitaminose D et les chondrocalcinoses sont parfois incriminées. Même si ces facteurs n'ont pas été retrouvés chez nos 2 patients, leur étiologie reste en général inconnue [4, 7] mais chez les enfants, les hyperparathyroïdies et l'hémochromatose sont tout aussi souvent citées dans les étiologies. L'âge moyen de leur survenue est de sept à huit ans avec des extrêmes de sept jours de vie à 20 ans. Il existe une légère prédominance masculine . Les C.D.I symptomatiques peuvent survenir à n'importe quel niveau du rachis, avec une très nette prédominance à l'étage cervical. L'espace le plus touché est C6-C7. Les C.D.I asymptomatiques se situent essentiellement à l'étage thoracique . Les symptômes les plus souvent retrouvés, regroupent des douleurs cervicales, des dorsalgies, une diminution de la mobilité rachidienne, une contracture, une raideur para-vertébrale pouvant être responsable d'un torticolis, une fièvre modérée, qui représentent 75% des cas Alors que les formes asymptomatiques 25% des cas, sont des découvertes d'examen systématique en particulier à l'occasion de radiographie pulmonaire . Dans l'anamnèse, on met en évidence dans les jours précédents une notion de traumatisme dans 30% des cas, ou une infection respiratoire haute dans environ 15 % des cas, mais il semble que cette association reste purement fortuite. |
Integrins are key regulators of epithelial-mesenchymal transition (EMT), a phenomenon that increases cancer cell motility and invasiveness . The complex reprogramming of gene expression required for down-regulation of epithelial-specific genes and up-regulation of mesenchymal phenotype genes requires integrin signaling, as evinced by the requirement for α3β1 integrin for TGFβ1-stimulated Smad signaling to promote EMT . EMT also requires changes in cell adhesion and expression of specific integrins, such as down-regulation of β4 integrin upon stimulation of epithelial cells with TGFβ1 during EMT . Specific integrins also control the activity and localization of matrix metalloproteases to facilitate invasive migration, such as the control of matrix metalloproteases 9 (MMP9) by αvβ3 integrin in MDA-MB-435 breast cancer cells . Modulation of integrin function also contributes to angiogenesis, and controls the contribution of stromal cells within the tumour microenvironment to cancer cell growth . |
A proper stoichiometric ratio of Orai1 to STIM1 is required for optimal SOCE function. Overexpression of Orai1 alone has been found to decrease SOCE in some cell types including HEK-293, HeLa and A549 . Recent crystallization study revealed a hexametric structure for the functional Orai channel through coupling with STIM1, and provided evidence to support the model that the optimal Orai1/STIM1 for maximal SOCE activation is 2:1. However, variations in the ratios of Orai1 expression to STIM1 expression and in the functional properties of SOCE are reported for different cell types. Any perturbation in the stoichiometry may have significant consequence on SOCE properties and intracellular Ca2+ oscillations, and likely tumor progression. Any perturbation in stoichiometry may have significant consequences for the properties of the channel, for the manifestation of intracellular Ca2+ oscillations, and for tumor progression. An unexpected finding in the present study was the observed increase in Orai1 expression with no increase in STIM1 expression in ESCC tumor tissues (Fig. 1, and Fig. S1). In addition, knockdown of STIM1 in KYSE-150 cells appeared to have no effect on SOCE activity (Supplementary Fig. S3). These findings support two possibilities: 1) the expression of STIM1 is so abundant in esophageal epithelial cells and thus it is sufficient to cope with the regulatory needs even in the case of significant elevated expression of Orai1 in esophageal cancer cells; 2) STIM1 is not sufficient to support the regulatory needs so that some Orai1 channels may escape coupling with STIM1. Further studies will warrant the differentiation of the two mechanisms. While the present report is in preparation, Wang et al identified distinct Orai1-coupling domains in STIM1 and STIM2, which determines the efficacy of coupling between STIM2 and Orai1 as well as whether it contains store-dependent agonist properties. And our data showed that the expression of STIM2 was elevated in ESCC cells compared to that in HET-1A cells. It applauses the possibility that STIM2 may replace STIM1 to couple with Orai1 in cancer cells. Clearly, more studies are urgent to address these following important questions: 1) is uncoupling regulated in response to different cellular requirements in cancer cells and how does regulation occur? 2) are additional factors required for coupling of STIMs with Orai1 and/or for regulation of Orai1 channel gating in ESCC as compared to normal esophageal epithelial cells? 3) does Orai1-STIM2 complex control intracellular Ca2+ oscillations and tumor progression in ESCC? |
Om in kaart te brengen of de variabelen onderling zowel binnen de domeinen (eetgedrag, leefstijl en sociaal-emotionele gezondheid), als tussen de domeinen samenhangen, zijn correlatiecoëfficiënten berekend binnen het cohort vóór de coronacrisis (in fig. 1 en in digitaal aanvullende content tab. S1 boven de diagonaal) en binnen het cohort tijdens de eerste lockdown (in fig. 1 en in digitaal aanvullende content tab. S1 onder de diagonaal). |
During the past decades, studies have demonstrated that different probiotic bacteria strains could exert antioxidant capacity in different ways. However, few reviews regarding the basis for the antioxidant mechanisms of probiotics have been found. Thus, the following sections provide an overview of the existing knowledge on the oxygen resistant mechanisms of various probiotic strains (Figure 2). |
The GFDL AM3 model with anthropogenic emissions held constant captures much of the observed interannual variability in median ozone (r2=0.56; Fig. 2a) and in the frequency of high-ozone events in WUS surface air (r2=0.57; Fig. 2b), lending confidence in its ability to relate the observed variability to specific processes. The model attributes much of the observed interannual variability to fluctuations in the stratospheric influence, with O3Strat fluctuations explaining 43% of the observed and 74% of the total simulated variability. In contrast, the role of Asian pollution7 and wildfires on interannual variability during spring is minimal (Supplementary Fig. 5). Model deficiencies in representing the complex ozone chemistry in fire plumes32 are of minor importance in spring when wildfires are less frequent than summer. |
The anatomical structure of the heart is complex, and sonogram genres are disparate. Therefore, it is particularly necessary to manage the recognition and functional evaluation of the cardiac structure in different models. However, there are numerous standardized sections of echocardiography. Patients without abnormalities have to undergo 10–20-section scans. Occasional slight angle differences among sections cause extreme difficulties in identification of various sections for physicians with insufficient experience and qualifications, resulting in failure to provide accurate and standardized analysis. It typically takes at least 1 to 2 years for a sonographer to grasp the basic echocardiography principles and methods of operation. In China, many grassroots regions cannot afford the labor cost of training echocardiography physicians. Therefore, two-dimensional (2D) ultrasound data sets from more than 500 patients and 7,000 videos were gathered from research performed in 2018. A classification model was then constructed using the method of convolutional neural networks by dividing them into seven groups of various cardiac views. The model’s classification accuracy reached 98% . Likewise, researchers from the University of California, San Francisco used echocardiographic images from 267 patients to classify static and dynamic original images using deep learning approaches and to build an automatic section recognition model with classification criteria from 15 standard sections. The outcome showed that recognition accuracy achieved 97.8%, while physician recognition accuracy was approximately 70.2–83.5% . Rapid standard section recognition with AI technology can somewhat shorten the evaluation time and enhance detection ability as well as novice accuracy. This technology has the potential to be applied in specialized non-echocardiography or emergency departments, which would advance operational efficiency. It can also be extended to the grassroots regions where echocardiography physician resources for standardized inspection and quality control are scarce. |
Recently, the assessment of the expression and role of a circulating factor, growth differentiation factor 11 (GDF11), has provided conflicting results [32, 33]. The results from the first study implied that circulating GDF11 levels decline with aging and showed that the treatment of old mice with recombinant GDF11 improved muscle regeneration after injury . A subsequent study showed that GDF11 levels do not decline with aging and that administration of recombinant GDF11 protein does not affect repair of old muscle . The reasons for the discrepancies are discussed elsewhere . |
Der plötzliche Bewusstseinsverlust und die nachgewiesenen Krampfpotenziale bei einer Patientin ohne Epilepsie in der Vorgeschichte beweisen, dass die Sauerstoffversorgung des Gehirns zeitweise kompromittiert war. Wir gehen daher davon aus, dass sich die Gabe von Hemopure® auf den weiteren Verlauf positiv ausgewirkt hat, auch wenn die effektive, Met-Hb-bereinigte Hb-Wert-Steigerung nur 0,4–0,8 g/dl ausmachte. Dies entsprach jedoch initial einer Steigerung der Sauerstoffbindungskapazität des Blutes um 33 %. |
Bei EMAH-Patienten dürfen neben den vitientypischen Aspekten jedoch im Rahmen der Abklärung der akuten Herzinsuffizienz nicht die sonst üblichen Ursachen einer kardialen Dekompensation vernachlässigt werden, insbesondere mit zunehmendem Alter der Patienten. Es ist immer auch beispielsweise an eine Lungenembolie, Myokardischämie (besonders bei TGA und Zustand nach Arterial-switch-Operation, Abb. 3), Sepsis, akutes Lungenversagen durch eine Pneumonie oder an eine Perikardtamponade zu denken. |
Oligonucleotide sequences. The table shows the sequences of all the oligonucleotides used in the different assays (ChIP, gel shift assays and Q-PCR). The corresponding species (human or mouse) is indicated as well as the orientation of oligonucleotides i.e. sense/forward (fwd) or reverse (rev). The name of the target (promoter, binding site or mRNA) is also presented. |