Miracle-dz/UniFAR-FTUs huggingface dataset:
PALLD mutation in a European family conveys a stromal predisposition for familial pancreatic cancer

BACKGROUND Pancreatic cancer is one of the deadliest cancers, with low long-term survival rates. Despite recent advances in treatment, it is important to identify and screen high-risk individuals for cancer prevention. Familial pancreatic cancer (FPC) accounts for 4%–10% of pancreatic cancers. Several germline mutations are related to an increased risk and might offer screening and therapy options. In this study, we aimed to identity of a susceptibility gene in a family with FPC. METHODS Whole exome sequencing and PCR confirmation was performed on the surgical specimen and peripheral blood of an index patient and her sister in a family with high incidence of pancreatic cancer, to identify somatic and germline mutations associated with familial pancreatic cancer. Compartment-specific gene expression data and immunohistochemistry were also queried. RESULTS The identical germline mutation of the PALLD gene (NM_001166108.1:c.G154A:p.D52N) was detected in the index patient with pancreatic cancer and the tumor tissue of her sister. Whole genome sequencing showed similar somatic mutation patterns between the 2 sisters. Apart from the PALLD mutation, commonly mutated genes that characterize pancreatic ductal adenocarcinoma were found in both tumor samples. However, the 2 patients harbored different somatic KRAS mutations (G12D and G12V). Healthy siblings did not have the PALLD mutation, indicating a disease-specific impact. Compartment-specific gene expression data and IHC showed expression in cancer-associated fibroblasts (CAFs). CONCLUSION We identified a germline mutation of the palladin (PALLD) gene in 2 siblings in Europe, affected by familial pancreatic cancer, with a significant overexpression in CAFs, suggesting that stromal palladin could play a role in the development, maintenance, and/or progression of pancreatic cancer. FUNDING DFG SFB 1321
Dry matter yield, nitrogen absorption, and water uptake by sweet corn under salt stress

Abstract The response to salinity differs greatly among various plant species. This study was conducted to evaluate the effects of NaCl salinity on growth of corn in terms of dry matter production and nitrogen and water uptake. Dry matter yield and N and water uptake by sweet corn (Zea mays L; cv. “Florida Stay Sweet") under normal (control) and NaCl salinized (3, 6, and 9 bars osmotic pressures) nutrient solutions were investigated in a walk‐in growth chamber. The 7‐day old seedlings were grown for 14 days in complete Hoagland solution before starting salt treatments. Then, osmotic pressures of the nutrient solutions (except the controls) were raised 1 bar every day by adding 24 mmol, 1.404 g L‐1, NaCl until the desired (3, 6, and 9 bars) salinity levels were attained. The levels of the nutrient solutions in the pots were maintained at the 2‐liter mark by addition of deionized water. The added water to each pot was recorded and considered as water absorbed by plants. Thirty days after the completion of s.
Venlafaxine reduces the striatal il6/il10 ratio and increases hippocampal GR expression in female mice subjected to chronic social instability stress

Abstract Women are twice as likely as men to develop depression and antidepressant treatment is more frequent in females. Moreover, neuroinflammatory changes related to affective disorders differ in accordance with sex. Despite this evidence, female populations have been largely omitted from preclinical experiments studying antidepressants. The aim of this work is to analyze the potential restorative effect of venlafaxine on an animal model of depression. Female CD1 mice were subjected to chronic social instability (CSI) stress for 7 weeks, and were administered venlafaxine during the last 3 weeks of the stress period. Behavioral and physiological parameters were then analyzed. Stressed mice showed a decreased sucrose preference and increased whisking behavior, and had a lower body weight, higher plasma corticosterone levels and increased hypothalamic GR expression. They also had lower levels of 5-HT, 5-HIAA and NA and a higher KYN/TRYP ratio in the hippocampus. Moreover, CSI increased striatal IL-6 mRNA expression levels. Venlafaxine treatment reduced the striatal IL-6/IL-10 ratio and increased hippocampal GR expression, although it did not reverse stress-induced behavioral changes. In conclusion, seven weeks of exposure to CSI produced depressive-like alterations in female mice. The venlafaxine treatment regimen was found to have a modest anti-inflammatory effect in the striatum and increased hippocampal GR mRNA, although it failed to redress stress-induced behavioral disturbances.
DEVELOPMENT OF VOLTAMMETRIC TECHNIQUES FOR THE DETERMINATION OF SILODOSIN IN PHARMACEUTICAL FORMULATION AT GLASSY CARBON ELECTRODE

This study related to development of rapid, simple, sensitive and cost effective electrochemical and spectrophotometric methods for quantitative determination of silodosin (SLD) in pharmaceutical formulations. The electrochemical oxidation of SLD on glassy carbon electrode (GCE) was thorougly investigated by cyclic voltammetry and differential pulse voltammetry. The effect of scan rate, pH and concentration on the peak currents were investigated under the optimized experimental conditions for quantitative determination of SLD. The oxidation peak of SLD was observed on GCE at 696.0 mV in pH 2.0 BRT by using differential pulse voltammetry. The oxidation process was observed to be irreversible and diffusion-controlled. The obtained results were statistically compared with those of first derivative UV spectrophotometric method and the differences were found as insignificant.
Effects of Slowness, Frailty, Insufficient Intake, and Delirium in Patients Following Cardiac Surgery

Supplemental digital content is available in the text. Background Slow gait, frailty, insufficient postoperative caloric intake, and delirium, although seemingly distinct, can appear simultaneously in patients who underwent cardiac surgery. Objectives The aim of this study was to evaluate how these 4 factors overlap and how they individually and cumulatively affect cardiac surgery outcomes. Methods The effects of slowness (gait speed <0.83 m/s), frailty (≥3/5 Fried criteria), insufficient postoperative intake (<800 kcal/d), and delirium (defined by the Confusion Assessment Method) on hospital length of stay (LOS) and 3-month mortality were analyzed in 308 adult patients. Results Slowness, frailty, insufficient intake, and delirium affected 27.5%, 29.5%, 31.5%, and 13.3% of participants, respectively; only 42.2% (130/308) were free from these risks. Risk overlap was prevalent, as 26.3% (n = 81) had 2 or more risk factors. The most obvious overlap was in delirium (80% of delirious participants had other risks), suggesting that delirium cannot be managed in isolation. Individually, whereas slowness was associated only with longer LOS, frailty, insufficient intake, and delirium all led to longer LOS and higher mortality. When equally weighting each risk factor to analyze their cumulative effects, LOS increased by 4.4 days (95% confidence interval, 3.0–5.7) and 3-month mortality increased by 2.6-fold (95% confidence interval, 1.4–4.6), with each risk factor added, independent of participants' educational level, body mass index, and risk for cardiac surgery (EuroSCORE II ≥6). Conclusions Because a clinical overlap of slowness, frailty, insufficient postoperative intake, and delirium was evident in patients who underwent cardiac surgery, and risk of death and longer hospital stay increased with each factor added, care should be revised to consider these overlapping factors to maximize patient outcomes.
Tissue at Risk and Ischemic Core Estimation Using Deep Learning in Acute Stroke

Deep learning models with fine-tuning lead to better performance for predicting tissue at risk and ischemic core, outperforming conventional thresholding methods. BACKGROUND AND PURPOSE: In acute stroke patients with large vessel occlusions, it would be helpful to be able to predict the difference in the size and location of the final infarct based on the outcome of reperfusion therapy. Our aim was to demonstrate the value of deep learning–based tissue at risk and ischemic core estimation. We trained deep learning models using a baseline MR image in 3 multicenter trials. MATERIALS AND METHODS: Patients with acute ischemic stroke from 3 multicenter trials were identified and grouped into minimal (≤20%), partial (20%-80%), and major (≥80%) reperfusion status based on 4- to 24-hour follow-up MR imaging if available or into unknown status if not. Attention-gated convolutional neural networks were trained with admission imaging as input and the final infarct as ground truth. We explored 3 approaches: 1) separate: train 2 independent models with patients with minimal and major reperfusion; 2) pretraining: develop a single model using patients with partial and unknown reperfusion, then fine-tune it to create 2 separate models for minimal and major reperfusion; and 3) thresholding: use the current clinical method relying on apparent diffusion coefficient and time-to-maximum of the residue function maps. Models were evaluated using area under the curve, the Dice score coefficient, and lesion volume difference. RESULTS: Two hundred thirty-seven patients were included (minimal, major, partial, and unknown reperfusion: n = 52, 80, 57, and 48, respectively). The pretraining approach achieved the highest median Dice score coefficient (tissue at risk = 0.60, interquartile range, 0.43–0.70; core = 0.57, interquartile range, 0.30–0.69). This was higher than the separate approach (tissue at risk = 0.55; interquartile range, 0.41–0.69; P = .01; core = 0.49; interquartile range, 0.35–0.66; P = .04) or thresholding (tissue at risk = 0.56; interquartile range, 0.42–0.65; P = .008; core = 0.46; interquartile range, 0.16–0.54; P < .001). CONCLUSIONS: Deep learning models with fine-tuning lead to better performance for predicting tissue at risk and ischemic core, outperforming conventional thresholding methods.
Public Opinion About Adverse Childhood Experiences: Social Stigma, Attribution of Blame, and Government Intervention

Adverse childhood experiences (ACEs) are receiving increasing attention in academic, policy, and media discourses. However, no public opinion research has focused on ACEs. We conducted a nationally representative survey of U.S. adults to address this knowledge gap. A web-based survey was conducted using the Ipsos KnowledgePanel (N = 503, completion rate = 60.5%) in fall 2019. We found that inter-personal stigma and parental blame related to ACEs were prevalent, with 25.0% of respondents unwilling to have a person with “a lot of ACEs” as a close co-worker and 65.2% believing that parents were very much to blame for the consequences of ACEs. Fifty percent of respondents believed that government intervention to prevent ACEs was very important. After adjustment for demographic characteristics, inter-personal stigma toward people with ACEs and conservative ideology were significantly associated with lower perceived importance of government intervention to prevent ACEs. Black race, Hispanic ethnicity, and female gender were significantly associated with higher perceived importance of government intervention. These findings provide an empirical foundation to inform strategies to communicate ACE science to public and policymaker audiences.
Significance of Removing Comedonecrosis as an Exclusion Criterion in Mammary Low-Risk Ductal Carcinoma In Situ Managed in an Active Surveillance Clinical Trial.

OBJECTIVES This study aims to investigate the consequences of comedonecrosis omission as an exclusion criterion of the Comparison of Operative vs Monitoring and Endocrine Therapy (COMET) trial. METHODS The clinical inclusion criteria of the COMET trial were applied on women who were mammographically screened between 2007 and 2017 and had a diagnosis of low- or intermediate-grade ductal carcinoma in situ (DCIS). The percentage of ductal diameter occupied by necrosis was calculated. RESULTS Twenty-six of 129 (20.2%) cases were upgraded. Larger calcification span correlated with upgrade (P = .02), with the best cutoff of 1.1 cm, and negative predictive value of 86%. When solely analyzing cases with no comedonecrosis (n = 76), none of the variables correlated with upgrade. Comedonecrosis was significantly correlated with upgrade to invasive carcinoma (P = .041), with the best cutoff of 53% of ductal diameter occupied by necrosis. CONCLUSIONS Results indicate that comedonecrosis and span of mammographic calcifications could be risk factors in women managed with active surveillance.
Parent-Child Role Confusion: Exploring the Role of Family Processes in the Context of Parental Depression

ABSTRACT Objective Parent-child role confusion has been shown to influence developmental outcomes for children whose parents have a history of depression; however, more research is needed to understand the pathways by which parental depression increases risk of role confusion. The current study aimed to extend previous literature by evaluating how different family processes (e.g., interparental conflict, guilt induction, family cohesion, and positive parenting practices) contribute to the development of emotional role confusion in families with a history of parental depression. Method The sample was comprised of 90 parent-child dyads (parent M age = 42, 90% female, 83.3% White; child M age = 11.51, 51.1% female, 75.6% White) participating in the control group of a randomized controlled trial. All parents had a history of depression. A longitudinal path analysis was conducted to evaluate prospective associations in the multiple mediator model. Results Findings from the current study suggest that parental depressive symptoms are not directly related to the development of parent-child emotional role confusion, but are instead indirectly related through increased interparental conflict observed by youth. Although not identified as significant mediators, guilt induction and positive parenting practices emerged as predictors of emotional role confusion. Lastly, family cohesion did not appear to influence the development of role confusion. Conclusion Findings suggest that parenting behaviors and coparenting relationship quality play important roles in the development of parent-child emotional role confusion, with interparental conflict emerging as the strongest predictor in families with a history of parental depression.
Correlation Evaluation of Functional Corticomuscular Coupling With Abnormal Muscle Synergy After Stroke

Objective: While neuroplasticity and functional reorganization during motor recovery can be indirectly reflected and evaluated by functional corticomuscular coupling (fCMC), little work has been published regarding the cortical origin of abnormal muscle synergy and compensatory mechanism in the separation movement of stroke patients. Methods: In this study, we proposed to use extended partial directed coherence (ePDC) combined with an optimal spatial filtering approach to estimate fCMC in stroke patients and healthy controls, and further established muscle synergy model (MSM) to jointly explore the modulation mechanism between cortex and muscles. Results: Compared to healthy controls, stroke patients had significantly reduced coupling strength in both descending and ascending pathway. Moreover, the MSM were abnormal with high variability and low similarity in the separation stage of stroke patients. Further exploration of the positive relationship between fCMC characteristics and MSM parameters proved the possibility of using fCMC-MSM-based correlation indicator to evaluate abnormality of the cortical related synergy movement as well as the rehabilitation level of stroke patients. Conclusion: We developed a computational procedure to evaluate the correlation between fCMC and MSM in stroke patients. Significance: This article provides a quantitative evaluation metrics based on fCMC to reveal the deficits during poststroke motor restoration and a promising approach to help patients correct abnormal movement habits, paving the way for neurophysiological assessment of neuromuscular control in conjunction with clinical scores.
Analyses of peripheral blood dendritic cells and magnetic resonance spectroscopy support dysfunctional neuro‐immune crosstalk in Tourette syndrome

Evidence supports that neurodevelopmental diseases, such as Tourette syndrome (TS), may involve dysfunctional neural‐immune crosstalk. This could lead to altered brain maturation and differences in immune and stress responses. Dendritic cells (DCs) play a major role in immunity as professional antigen‐presenting cells; changes in their frequency have been observed in several autoimmune conditions.
Impact of COVID-19 on mental health and quality of life: Is there any effect? A cross-sectional study of the MENA region

The COVID-19 pandemic is a major health crisis that has changed the life of millions globally. The purpose of this study was to assess the effect of the pandemic on mental health and quality of life among the general population in the Middle East and North Africa (MENA) region. A total of 6142 adults from eighteen countries within the MENA region completed an online questionnaire between May and June 2020. Psychological impact was assessed using the Impact of Event Scale-Revised (IES-R) and the social and family support impact was assessed with questions from the Perceived Support Scale (PSS). The IES-R mean score was 29.3 (SD = 14.8), corresponding to mild stressful impact with 30.9% reporting severe psychological impact. Most participants (45%–62%) felt horrified, apprehensive, or helpless due to COVID-19. Furthermore, over 40% reported increased stress from work and financial matters. Higher IES-R scores were found among females, participants aged 26–35 years, those with lower educational level, and participants residing in the North Africa region (p<0.005). About 42% reported receiving increased support from family members, 40.5% were paying more attention to their mental health, and over 40% reported spending more time resting since the pandemic started. The COVID-19 pandemic was associated with mild psychological impact while it also encouraged some positive impact on family support and mental health awareness among adults in the MENA region. Clinical interventions targeted towards vulnerable groups such as females and younger adults are needed.
Biological evidence to define a vitamin A deficiency cutoff using total liver vitamin A reserves

Vitamin A is a fat-soluble vitamin involved in essential functions including growth, immunity, reproduction, and vision. The vitamin A Dietary Reference Intakes (DRIs) for North Americans suggested that a minimally acceptable total liver vitamin A reserve (TLR) is 0.07 µmol/g, which is not explicitly expressed as a vitamin A deficiency cutoff. The Biomarkers of Nutrition for Development panel set the TLR cutoff for vitamin A deficiency at 0.1 µmol/g based on changes in biological response of several physiological parameters at or above this cutoff. The criteria used to formulate the DRIs include clinical ophthalmic signs of vitamin A deficiency, circulating plasma retinol concentrations, excretion of vitamin A metabolites in the bile, and long-term storage of vitamin A as protection against vitamin A deficiency during times of low dietary intake. This review examines the biological responses that occur as TLRs are depleted. In consideration of all of the DRI criteria, the review concludes that induced biliary excretion and long-term vitamin A storage do not occur until TLRs are >0.10 µmol/g. If long-term storage is to continue to be part of the DRI criteria, vitamin A deficiency should be set at a minimum cutoff of 0.10 µmol/g and should be set higher during times of enhanced requirements where TLRs can be rapidly depleted, such as during lactation or in areas with high infection burden. In population-based surveys, cutoffs are important when using biomarkers of micronutrient status to define the prevalence of deficiency and sufficiency to inform public health interventions. Considering the increasing use of quantitative biomarkers of vitamin A status that indirectly assess TLRs, i.e. the modified-relative-dose response and retinol-isotope dilution tests, setting a TLR as a vitamin A deficiency cutoff is important for users of these techniques to estimate vitamin A deficiency prevalence. Future researchers and policymakers may suggest that DRIs should be set with regard to optimal health and not merely to prevent a micronutrient deficiency.
Development and performance of CUHAS-ROBUST application for pulmonary rifampicin-resistance tuberculosis screening in Indonesia

Background and objectives Diagnosis of Pulmonary Rifampicin Resistant Tuberculosis (RR-TB) with the Drug-Susceptibility Test (DST) is costly and time-consuming. Furthermore, GeneXpert for rapid diagnosis is not widely available in Indonesia. This study aims to develop and evaluate the CUHAS-ROBUST model performance, an artificial-intelligence-based RR-TB screening tool. Methods A cross-sectional study involved suspected all type of RR-TB patients with complete sputum Lowenstein Jensen DST (reference) and 19 clinical, laboratory, and radiology parameter results, retrieved from medical records in hospitals under the Faculty of Medicine, Hasanuddin University Indonesia, from January 2015-December 2019. The Artificial Neural Network (ANN) models were built along with other classifiers. The model was tested on participants recruited from January 2020-October 2020 and deployed into CUHAS-ROBUST (index test) application. Sensitivity, specificity, and accuracy were obtained for assessment. Results A total of 487 participants (32 Multidrug-Resistant/MDR 57 RR-TB, 398 drug-sensitive) were recruited for model building and 157 participants (23 MDR and 21 RR) in prospective testing. The ANN full model yields the highest values of accuracy (88% (95% CI 85–91)), and sensitivity (84% (95% CI 76–89)) compare to other models that show sensitivity below 80% (Logistic Regression 32%, Decision Tree 44%, Random Forest 25%, Extreme Gradient Boost 25%). However, this ANN has lower specificity among other models (90% (95% CI 86–93)) where Logistic Regression demonstrates the highest (99% (95% CI 97–99)). This ANN model was selected for the CUHAS-ROBUST application, although still lower than the sensitivity of global GeneXpert results (87.5%). Conclusion The ANN-CUHAS ROBUST outperforms other AI classifiers model in detecting all type of RR-TB, and by deploying into the application, the health staff can utilize the tool for screening purposes particularly at the primary care level where the GeneXpert examination is not available. Trial registration NCT04208789.