Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Acute Kidney Injury Subphenotypes with Differing Molecular Signatures and Responses to Vasopressin Therapy

Rationale: Currently, no safe and effective pharmacologic interventions exist for acute kidney injury (AKI). One reason may be that heterogeneity exists within the AKI population, thereby hampering the identification of specific pathophysiologic pathways and therapeutic targets. Objective: The aim of this study was to identify and test whether AKI subphenotypes have prognostic and therapeutic implications. Methods: First, latent class analysis methodology was applied independently in two critically ill populations (discovery [n = 794] and replication [n = 425]) with AKI. Second, a parsimonious classification model was developed to identify AKI subphenotypes. Third, the classification model was applied to patients with AKI in VASST (Vasopressin and Septic Shock Trial; n = 271), and differences in treatment response were determined. In all three populations, AKI was defined using serum creatinine and urine output. Measurements and Main Results: A two‐subphenotype latent class analysis model had the best fit in both the discovery (P = 0.004) and replication (P = 0.004) AKI groups. The risk of 7‐day renal nonrecovery and 28‐day mortality was greater with AKI subphenotype 2 (AKI‐SP2) relative to AKI subphenotype 1 (AKI‐SP1). The AKI subphenotypes discriminated risk for poor clinical outcomes better than the Kidney Disease: Improving Global Outcomes stages of AKI. A three‐variable model that included markers of endothelial dysfunction and inflammation accurately determined subphenotype membership (C‐statistic 0.92). In VASST, vasopressin compared with norepinephrine was associated with improved 90‐day mortality in AKI‐SP1 (27% vs. 46%, respectively; P = 0.02), but no significant difference was observed in AKI‐SP2 (45% vs. 49%, respectively; P = 0.99) and the P value for interaction was 0.05. Conclusions: This analysis identified two molecularly distinct AKI subphenotypes with different clinical outcomes and responses to vasopressin therapy. Identification of AKI subphenotypes could improve risk prognostication and may be useful for predictive enrichment in clinical trials.
Odonata: Who They Are and What They Have Done for Us Lately: Classification and Ecosystem Services of Dragonflies

Odonata (dragonflies and damselflies) are well-known but often poorly understood insects. Their phylogeny and classification have proved difficult to understand but, through use of modern morphological and molecular techniques, is becoming better understood and is discussed here. Although not considered to be of high economic importance, they do provide esthetic/spiritual benefits to humans, and may have some impact as predators of disease vectors and agricultural pests. In addition, their larvae are very important as intermediate or top predators in many aquatic ecosystems. More recently, they have been the objects of study that have yielded new information on the mechanics and control of insect flight.
p53 Phosphomimetics Preserve Transient Secondary Structure but Reduce Binding to Mdm2 and MdmX

The disordered p53 transactivation domain (p53TAD) contains specific levels of transient helical secondary structure that are necessary for its binding to the negative regulators, mouse double minute 2 (Mdm2) and MdmX. The interactions of p53 with Mdm2 and MdmX are also modulated by posttranslational modifications (PTMs) of p53TAD including phosphorylation at S15, T18 and S20 that inhibits p53-Mdm2 binding. It is unclear whether the levels of transient secondary structure in p53TAD are changed by phosphorylation or other PTMs. We used phosphomimetic mutants to determine if adding a negative charge at positions 15 and 18 has any effect on the transient secondary structure of p53TAD and protein-protein binding. Using a combination of biophysical and structural methods, we investigated the effects of single and multisite phosphomimetics on the transient secondary structure of p53TAD and its interaction with Mdm2, MdmX, and the KIX domain. The phosphomimetics reduced Mdm2 and MdmX binding affinity by 3–5-fold, but resulted in minimal changes in transient secondary structure, suggesting that the destabilizing effect of phosphorylation on the p53TAD-Mdm2 interaction is primarily electrostatic. Phosphomimetics had no effect on the p53-KIX interaction, suggesting that increased binding of phosphorylated p53 to KIX may be influenced by decreased competition with its negative regulators.
Development of an instrument measuring user satisfaction of the human-computer interface

This study is a part of a research effort to develop the Questionnaire for User Interface Satisfaction (QUIS). Participants, 150 PC user group members, rated familiar software products. Two pairs of software categories were compared: 1) software that was liked and disliked, and 2) a standard command line system (CLS) and a menu driven application (MDA). The reliability of the questionnaire was high, Cronbach's alpha=. 94. The overall reaction ratings yielded significantly higher ratings for liked software and MDA over disliked software and a CLS, respectively. Frequent and sophisticated PC users rated MDA more satisfying, powerful and flexible than CLS. Future applications of the QUIS on computers are discussed.
Elevated Transforming Growth Factor-β2 in the Aqueous Humor: A Possible Explanation for High Rate of Capsular Contraction Syndrome in High Myopia

Purpose. The purpose of the study was to elucidate the role of transforming growth factor-beta 2 (TGF-β2) in the development of high myopic capsular contraction syndrome. Methods. Nineteen cases of capsular contraction syndrome, including 14 with high myopia, were collected, and their clinical data were reviewed. Aqueous humor and anterior capsular membranes were obtained during capsulotomy. Hematoxylin-eosin and immunohistochemical staining with anti-TGF-β2 antibody were performed on capsular membranes. TGF-β2 levels in aqueous humor were assayed using ELISA and western blot. Results. High myopia was significantly associated with the incidence of capsular contraction syndrome (odds ratio: 14.74, P < 0.001, 95% CI: 5.29–41.05). Histopathological analysis revealed proliferation of fibroblast-like lens epithelial cells on the shrunken anterior capsule, labeled with TGF-β2 antibodies. ELISA and Western blot showed higher levels of TGF-β2 in aqueous humor of patients with capsular contraction syndrome and high myopia. Conclusions. High myopia is a risk factor for capsular contraction syndrome. Elevated TGF-β2 levels in high myopic cataract patients may play an important role in the pathogenesis of capsular contraction syndrome.
Family-related Disparities in College Enrollment across the Great Recession

The economic crisis of the Great Recession in the late 2000s had implications for the intergenerational transmission of inequality within families. Studying patterns of college enrollment across the Great Recession among U.S. youth from diverse family contexts provides insight into how economic volatility can either compound or undercut the advantages that some parents can give their children. Although college enrollment among 18- to 21-year-olds did not decline during or after the Great Recession, analyses of the National Longitudinal Survey of Youth 1979–Young Adult cohort revealed that this general trend subsumed variability by family history, local economic conditions, and age. Histories of family stability and sufficiency were associated with higher odds of college enrollment over time and across age, but this advantage was largest during the Recession in high-unemployment communities. These results illuminate how life course consequences of early family life can fluctuate with volatility and opportunity in the broader economy.
Association of Functional Movement Screen and Y-Balance Test Scores With Injury in High School Athletes

Abstract Lisman, P, Hildebrand, E, Nadelen, M, and Leppert, K. Association of functional movement screen and Y-Balance Test scores with injury in high school athletes. J Strength Cond Res 35(7): 1930–1938, 2021—The purpose of this study was to determine the association between functional movement screen (FMS) and Y-Balance Test (YBT) performance and lower extremity injury in a sample of male high school athletes. A total of 124 high school football (n = 89), lacrosse (n = 25), and baseball (n = 10) players underwent FMS and YBT before the start of their competitive seasons. Time loss lower extremity injury incidence data were tracked by each team's certified athletic trainer and used for analysis. Receiver operating characteristic (ROC) curves were calculated to determine the optimal cutpoints for FMS composite score (CS) and YBT measures, including CS and reach distance asymmetry for anterior, posteromedial, and posterolateral directions, for predicting injury. No cutpoints on the ROC curves maximized sensitivity and specificity; therefore, FMS CS and YBT measures (CS and asymmetry) were analyzed as continuous variables. Logistic regression models adjusted for age and sport revealed no significant associations between FMS CS and lower extremity injury (odds ratio [OR] = 0.99; 95% confidence interval [CI] = 0.83–1.20). Similar findings were found for YBT asymmetry in all directions (ORs ranged from 0.98 to 1.08) and CS (OR = 0.99; 95% CI = 0.95–1.04). There were also no significant associations between the presence of asymmetry and low score (score of 1) on any individual FMS test and injury. Overall, FMS and YBT were not associated with increased risk of lower extremity injury in this sample of high school athletes. These findings do not support the use of FMS and YBT as stand-alone injury risk assessments in high school athletes.
Declining Mortality in Patients With Acute Respiratory Distress Syndrome: An Analysis of the Acute Respiratory Distress Syndrome Network Trials

Objectives: There has been multiple advances in the management of acute respiratory distress syndrome, but the temporal trends in acute respiratory distress syndrome–related mortality are not well known. This study aimed to investigate the trends in mortality in acute respiratory distress syndrome patients over time and to explore the roles of daily fluid balance and ventilation variables in those patients. Design: Secondary analysis of randomized controlled trials conducted by the Acute Respiratory Distress Syndrome Network from 1996 to 2013. Setting: Multicenter study involving Acute Respiratory Distress Syndrome Network trials. Patients: Patients with acute respiratory distress syndrome. Interventions: None. Measures and Main Results: Individual patient data from 5,159 acute respiratory distress syndrome patients (excluding the Late Steroid Rescue Study trial) were enrolled in this study. The crude mortality rate decreased from 35.4% (95% CI, 29.9–40.8%) in 1996 to 28.3% (95% CI, 22.0–34.7%) in 2013. By adjusting for the baseline Acute Physiology and Chronic Health Evaluation III, age, ICU type, and admission resource, patients enrolled from 2005 to 2010 (odds ratio, 0.61; 95% CI, 0.50–0.74) and those enrolled after 2010 (odds ratio, 0.73; 95% CI, 0.58–0.92) were associated with lower risk of death as compared to those enrolled before 2000. The effect of year on mortality decline disappeared after adjustment for daily fluid balance, positive end-expiratory pressure, tidal volume, and plateau pressure. There were significant trends of declines in daily fluid balance, tidal volume, and plateau pressure and an increase in positive end-expiratory pressure over the 17 years. Conclusions: Our study shows an improvement in the acute respiratory distress syndrome-related mortality rate in the critically ill patients enrolled in the Acute Respiratory Distress Syndrome Network trials. The effect was probably mediated via decreased tidal volume, plateau pressure, and daily fluid balance and increased positive end-expiratory pressure.
Base excision repair deficiency signatures implicate germline and somatic MUTYH aberrations in pancreatic ductal adenocarcinoma and breast cancer oncogenesis

We report a case of early-onset pancreatic ductal adenocarcinoma in a patient harboring biallelic MUTYH germline mutations, whose tumor featured somatic mutational signatures consistent with defective MUTYH-mediated base excision repair and the associated driver KRAS transversion mutation p.Gly12Cys. Analysis of an additional 730 advanced cancer cases (N = 731) was undertaken to determine whether the mutational signatures were also present in tumors from germline MUTYH heterozygote carriers or if instead the signatures were only seen in those with biallelic loss of function. We identified two patients with breast cancer each carrying a pathogenic germline MUTYH variant with a somatic MUTYH copy loss leading to the germline variant being homozygous in the tumor and demonstrating the same somatic signatures. Our results suggest that monoallelic inactivation of MUTYH is not sufficient for C:G>A:T transversion signatures previously linked to MUTYH deficiency to arise (N = 9), but that biallelic complete loss of MUTYH function can cause such signatures to arise even in tumors not classically seen in MUTYH-associated polyposis (N = 3). Although defective MUTYH is not the only determinant of these signatures, MUTYH germline variants may be present in a subset of patients with tumors demonstrating elevated somatic signatures possibly suggestive of MUTYH deficiency (e.g., COSMIC Signature 18, SigProfiler SBS18/SBS36, SignatureAnalyzer SBS18/SBS36).
Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions

ABSTRACT Three phase II randomized trials evaluated the safety/immunogenicity of two formulations of live-attenuated tetravalent dengue virus (TDEN) vaccine in dengue-endemic (Puerto Rico, Thailand) and non-endemic (US) regions (NCT00350337/NCT00370682/NCT00468858). We describe cell-mediated immune (CMI) responses; safety and humoral responses were reported previously. Participants received two doses of vaccine or control (placebo or the precursor live-attenuated TDEN vaccine) 6 months apart. Selected US participants received a booster 5–12 months post-dose 2. Evaluated subsets of the per-protocol cohorts included 75 primarily dengue virus (DENV)-unprimed US adults, 69 primarily flavivirus-primed Thai adults, and 100 DENV-primed or DENV-unprimed Puerto Rican adults/adolescents/children. T-cell responses were quantified using intracellular cytokine staining (ICS; DENV-infected cell-lysate or DENV-1/DENV-2 peptide-pool stimulation) or IFN-γ ELISPOT (DENV-2 peptide-pool stimulation). Memory B-cell responses were quantified using B-cell ELISPOT. Across populations and age strata, DENV serotype-specific CD4+ T-cell responses were slightly to moderately increased (medians ≤0.18% [ICS]), DENV-2–biased, and variable for both formulations. Responses in unprimed subjects were primarily detected post-dose 1. Response magnitudes in primed subjects were similar between doses. Multifunctional CD8+ T-cell responses were detected after peptide-pool stimulation. T-cell responses were mostly directed to DENV nonstructural proteins 3 and 5. Memory B-cell responses were tetravalent, of low-to-moderate magnitudes (medians ≤0.25%), and mainly observed post-dose 2 in unprimed subjects and post-dose 1 in primed subjects. A third dose did not boost CMI responses. In conclusion, both formulations of the live-attenuated TDEN vaccine candidate were poorly to moderately immunogenic with respect to B-cell and T-cell responses, irrespective of the priming status of the participants. Abbreviation ATP: according-to-protocol; ICS: Intracellular Cytokine Staining; NS3: Nonstructural protein 3; ELISPOT: Enzyme-Linked ImmunoSpot; JEV: Japanese encephalitis virus; PBMC: peripheral blood mononuclear cells
Noninvasive Assessment of Cerebral Perfusion and Oxygenation in Acute Ischemic Stroke by Near-Infrared Spectroscopy

Background: In acute stroke patients, there is a need for noninvasive measurement to monitor blood flow-based therapies. We investigated the utility of near-infrared spectroscopy (NIRS) to determine cerebral perfusion in these patients. Methods: Eleven patients were investigated within 1.4 ± 2.2 days after onset of an ischemic middle cerebral artery infarction by monitoring the kinetics of an intravenous bolus of indocyanine green (ICG). For ICG kinetics, bolus peak time, time to peak (TTP = time between 0 and 100% ICG maximum), maximum ICG concentration, rise time (time between 10 and 90% ICG maximum), slope (maximum ICG/TTP), and blood flow index (BFI = maximum ICG/rise time) were obtained. Perfusion-weighted MRI (PWI) and NIRS measurements were performed within 24 h, and the interhemispherical differences of TTP values were compared. Results: Stroke patients showed an increased bolus peak time (p < 0.02), TTP (p < 0.01), and rise time (p < 0.01), whereas slope (p < 0.01) and BFI (p < 0.01) were diminished at the site of infarction as compared to the unaffected hemisphere. The interhemispherical differences of TTP as measured by PWI and NIRS were closely correlated (r = 0.86). Conclusions: Noninvasive measurements of cerebral ICG kinetics by NIRS provide a useful means of detecting cerebral perfusion deficits in patients with acute stroke, which correlate well with those obtained by PWI.
Theaflavin 3,3′‐digallate reverses the downregulation of connexin 43 and autophagy induced by high glucose via AMPK activation in cardiomyocytes

Theaflavin 3,3′‐digallate (TF3), is reported to protect cardiomyocytes from lipotoxicity and reperfusion injury. However, the role of TF3 in the protection of high‐glucose injury is still poorly understood. This study investigated the protective effects of TF3 on gap junctions and autophagy in neonatal cardiomyocytes (NRCMs). NRCMs preincubated with high glucose were coincubated with TF3. The expression of connexins and autophagy‐related proteins was determined. The functioning of gap‐junctional intercellular communication (GJIC) was measured by a dye transfer assay. Adenosine monophosphate‐activated protein kinase (AMPK) activity was determined by western blot. Moreover, AMPK was activated with aminoimidazole‐4‐carboxamide‐1‐β‐d‐ribofuranoside (AICAR) or inhibited by AMPKα small interfering RNA (siRNA) to explore the role of AMPK in the modulation of connexin 43 (Cx43) and autophagy. Meanwhile, autophagy was activated or blocked to observe the change in Cx43 expression. It was found that the protein expression of Cx43 and autophagy‐related proteins was increased in a TF3 dose‐ and time‐dependent manner under high glucose. TF3 also recovered the reduced GJIC function induced by high glucose concentrations. TF3 activated phosphorylated AMPK in a time‐dependent way. AMPKα siRNA abrogated the protection of TF3, while AICAR showed similar results compared to the TF3 treatment. Meanwhile, autophagy activation caused decreased Cx43, while cotreatment with baf A1 enhanced Cx43 expression further compared with the TF3 treatment alone under high glucose. We concluded that TF3 partly reversed the inhibition of Cx43 expression and autophagy induced by high glucose in NRCMs, partly by restoring AMPK activity. Inhibition of autophagy might be protective by preserving Cx43 expression in NRCMs stimulated by high glucose.
Correlation between human leukocyte antigen-G expression and clinical parameters in oral squamous cell carcinoma.

BACKGROUND Human leukocyte antigen-G (HLA-G) is a tumor-associated molecule, whose expression may help the cancer cells to escape the immune response. AIMS The aim of this study was to evaluate the diagnostic value of HLA-G level in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS A total of 52 patients who had definite pathological diagnosis and 20 cases of healthy controls were enrolled in this clinical trial. Immunohistochemisty (IHC) and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis were considered for HLA-G identification and multilevel validations. Statistical analysis was performed using SPSS and statistical significance was determined at P < 0.05. RESULTS IHC results demonstrated that the expression of HLA-G in OSCC was strongly positive and the rate of positive expression was 55.77% (29/52), but the expression of HLA-G in healthy controls was negative (0/20). Furthermore, RT-PCR results showed that the positive expression rate of HLA-G messenger RNA was weak in healthy controls, but strong in OSCC. Besides, HLA-G expression in the tumors was significantly correlated with histological grade. CONCLUSIONS Our results suggested that HLA-G is associated with the prognosis of OSCC and may serve as a novel therapeutic target.
Participatory farm diversification and nutrition education increase dietary diversity in Western Kenya

Abstract Our study assessed the effectiveness of a community‐based participatory approach in increasing micronutrient adequacy of diets of women and young children through agricultural activities and nutrition education in Vihiga County, Western Kenya. Outcome indicators include the mean dietary diversity score (DDS), the percentage of women and children reaching minimum dietary diversity (MDD), and micronutrient adequacy (mean adequacy ratio). The project consisted of(a) a diagnostic survey covering agrobiodiversity and nutrition, (b) participatory development of activities to improve nutrition, (c) a baseline survey covering dietary intakes, (d) participatory implementation of the developed activities, and (e) an endline survey covering dietary intakes. The diagnostic survey was conducted in 10 sublocations of Vihiga County, which were pair‐matched and split into five intervention and five control sublocations. The intervention sublocations developed activities towards improving nutrition. Before implementation, a baseline survey collected the dietary intake data of 330 women–child pairs in the intervention and control sublocations. To support the activities, communities received agriculture and nutrition training. After 1 year of implementation, an endline survey collected dietary intake data from 444 women–child pairs in the intervention and control sublocations. Impact was assessed using the difference‐in‐difference technique. Highly significant positive impacts on children's mean DDS (treatment effect = 0.7, p < 0.001) and on the share of children reaching MDD (treatment effect = 0.2, p < 0.001) were shown. Higher dietary diversity can be explained by the development of subsistence and income‐generating pathways and increased nutrition knowledge. Participatory farm diversification and nutrition education were shown to significantly increase dietary diversity of young children in Western Kenya.