Miracle-dz/UniFAR-FTUs huggingface dataset:
A Combined Immunophenotypic And Transcriptional Single-Cell Map Of First Trimester Human Fetal Liver Hematopoiesis

Knowledge of human fetal blood development and how it differs from adult is highly relevant for our understanding of congenital blood and immune disorders as well as childhood leukemia, the latter known to originate in utero. Blood production during development occurs in waves that overlap in time and space adding to heterogeneity, which necessitates single cell approaches. Here, a combined single cell immunophenotypic and transcriptional map of first trimester primitive blood development is presented. Using CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) the molecular profile of established immunophenotypic gated progenitors was analyzed in the fetal liver (FL). Classical markers for hematopoietic stem cells (HSCs) such as CD90 and CD49F were largely preserved, whereas CD135 (FLT3) and CD123 (IL3R) had a ubiquitous expression pattern capturing heterogenous populations. Direct molecular comparison with an adult bone marrow (BM) data set revealed that HSC-like cells were less frequent in FL, whereas cells with a lympho-myeloid signature were more abundant. Furthermore, an erythro-myeloid primed multipotent progenitor cluster was identified, potentially representing a transient, FL-specific progenitor. Based on the projection performed, up- and downregulated genes between fetal and adult cells were analyzed. In general, cell cycle pathways, including MYC targets were shown to be upregulated in fetal cells, whereas gene sets involved in inflammation and human leukocyte antigen (HLA) complex were downregulated. Importantly, a fetal core molecular signature was identified that could discriminate certain types of infant and childhood leukemia from adult counterparts. Our detailed single cell map presented herein emphasizes molecular as well as immunophenotypic differences between fetal and adult primitive blood cells, of significance for future studies of pediatric leukemia and blood development in general.
Glycerol‐3‐phosphate acyltransferase 6 controls filamentous pathogen interactions and cell wall properties of the tomato and Nicotiana benthamiana leaf epidermis

The leaf epidermal wall is covered by a cuticle, composed of cutin and waxes, which protects against dehydration and constitutes a barrier against pathogen attack. Cutin monomers are formed by the transfer of 16- or 18-carbon fatty acids to glycerol by glycerol-3-phosphate acyltransferase (GPAT) enzymes, which facilitates their transport to the plant surface. Here we address the dual functionality of pathogen-inducible Glycerol phosphate acyltransferase 6 (GPAT6) in controlling pathogen entry and dehydration in leaves. Silencing of Nicotiana benthamiana NbGPAT6a increased leaf susceptibility to the oomycetes Phytophthora infestans and P. palmivora, whereas stable overexpression of NbGPAT6a-GFP rendered leaves more resistant to infection. A loss-of-function mutation of the orthologous gene in tomato (Solanum lycopersicum), SlGPAT6, similarly resulted in increased susceptibility of leaves to Phytophthora infection concomitant with altered intracellular infection structure morphology. Conversely, Botrytis cinerea disease symptoms were reduced. Modulation of GPAT6 expression predominantly altered the outer cell wall of leaf epidermal cells. The impaired cell wall-cuticle continuum of tomato gpat6-a mutants resulted in increased water loss and these plants had fewer stomata. Our work highlights a hitherto unknown role for GPAT6-generated cutin monomers in controlling epidermal cell properties that are integral to leaf-microbe interactions and limit dehydration.
A Retrospective Observational Study of Problems Faced by Children and Adolescents with Cancer: A 5-year Experience from a Pediatric Psycho-Oncology Service in India

Abstract Introduction Psychological concerns are common in children and adolescents with cancer, for which they require referral to specialist services. There is a dearth of pediatric psycho-oncology services in India. There are limited studies on emotional and related distress in children. Objectives To evaluate the types of problems and associated factors in children and adolescents with cancer referred to the pediatric psycho-oncology service in a tertiary care oncology center in India. Materials and Methods A retrospective analysis of all referrals to the institution's pediatric psycho-oncology service over 5 years was performed. Patients newly referred to the service, up to 18 years of age, with a cancer diagnosis, on active disease-modifying treatment or supportive care or following up within 2 years of completion of treatment were included. Patients not on any disease-modifying treatment and receiving the best supportive care only were excluded as needs and problems would differ in this group. Patients whose medical records were incomplete were excluded too. Descriptive measures and tests of association were performed for analysis. Results Of the 278 children referred to the service in 5 years, 66.5% were males. The average age was 11 years (standard deviation [SD]: 4.5). Most children had hematolymphoid cancers (58.2%). All reported problems were mainly emotional/behavioral (59%), physical health-related (21%), and academic (14%). Male children, referred from outpatient clinics and undergoing treatment with palliative intent, had more emotional problems, but these factors were not statistically significant. Conclusion Children and adolescents with cancer had different problems, most commonly emotional/behavioral and physical health-related. Age, gender, and treatment intent were factors associated with emotional problems. Psychosocial care services for children and adolescents with cancer are necessary for low-resource settings.
Violating social distancing amid the COVID‐19 pandemic: Psychological factors to improve compliance

This study uses the theory of planned behavior as a framework to predict intentions of noncompliance with social distancing during the COVID-19 pandemic while also assessing the predictive role of intolerance of uncertainty and sociodemographic variables. A total of 2,056 Brazilian participants completed measures on attitudes, injunctive, and descriptive norms, and perceived behavioral control toward social distancing. They also answered about their political ideology, income, employment status, gender, age, and educational level. Our findings indicate that positive attitudes toward complying with physical distancing, stronger descriptive norms using ingroup members as referents, and weaker perceived behavioral control over the action of breaching social distancing predict stronger adherence. Besides, individuals who support right-wing parties, younger people, and males are more prone to noncompliance. We suggest designing interventions that foster positive attitudes toward social distancing and address the negative consequences that violating social distancing can cause to in-group members to persuade individuals to stay at home. We also discuss the need for support from prominent political figures to increase adherence to this preventive measure.
Bio‐energetic modeling of medium‐sized cetaceans shows high sensitivity to disturbance in seasons of low resource supply

Abstract Understanding the full scope of human impact on wildlife populations requires a framework to assess the population‐level repercussions of nonlethal disturbance. The Population Consequences of Disturbance (PCoD) framework provides such an approach, by linking the effects of disturbance on the behavior and physiology of individuals to their population‐level consequences. Bio‐energetic models have been used as implementations of PCoD, as these integrate the behavioral and physiological state of an individual with the state of the environment, to mediate between disturbance and biological significant changes in vital rates (survival, growth, and reproduction). To assess which levels of disturbance lead to adverse effects on population growth rate requires a bio‐energetic model that covers the complete life cycle of the organism under study. In a density‐independent setting, the expected lifetime reproductive output of a single female can then be used to predict the level of disturbance that leads to population decline. Here, we present such a model for a medium‐sized cetacean, the long‐finned pilot whale (Globicephala melas). Disturbance is modeled as a yearly recurrent period of no resource feeding for the pilot whale female and her calf. Short periods of disturbance lead to the pre‐weaned death of the first one or more calves of the young female. Higher disturbance levels also affect survival of calves produced later in the life of the female, in addition to degrading female survival. The level of disturbance that leads to a negative population growth rate strongly depends on the available resources in the environment. This has important repercussion for the timing of disturbance if resource availability fluctuates seasonally. The model predicts that pilot whales can tolerate on average three times longer periods of disturbance in seasons of high resource availability, compared to disturbance happening when resources are low. Although our model is specifically parameterized for pilot whales, it provides useful insights into the general consequences of nonlethal disturbance. If appropriate data on life history and energetics are available, it can be used to provide management advice for specific species or populations.
TAM receptors in cardiovascular disease

Abstract The TAM receptors are a distinct family of three receptor tyrosine kinases, namely Tyro3, Axl, and MerTK. Since their discovery in the early 1990s, they have been studied for their ability to influence numerous diseases, including cancer, chronic inflammatory and autoimmune disorders, and cardiovascular diseases. The TAM receptors demonstrate an ability to influence multiple aspects of cardiovascular pathology via their diverse effects on cells of both the vasculature and the immune system. In this review, we will explore the various functions of the TAM receptors and how they influence cardiovascular disease through regulation of vascular remodelling, efferocytosis and inflammation. Based on this information, we will suggest areas in which further research is required and identify potential targets for therapeutic intervention.
Targeted metabolite profiling to gain chemometric insight into Indian pomegranate cultivars and elite germplasm.

BACKGROUND Pomegranate fruit is an excellent source of bioactive polyphenolics, known to contribute significantly to human health. India is the largest producer of pomegranate in the world and produces the finest quality fruit with highly desirable consumer traits such as soft seeds, low acidity, and attractive fruit and aril color. Knowledge of the extent of variation in key metabolites (sugars, organic acids, phenolics, and anthocyanins) is key to selecting superior genotypes for germplasm improvement. Relevant information with respect to Indian genotypes is scarce. The present study therefore aims to evaluate quantitatively important metabolites in some cultivars and elite germplasm of pomegranate in India. RESULTS Identification and quantification of primary and secondary metabolites such as sugars, organic acids, vitamin C, polyphenolics, and anthocyanins were conducted using a liquid chromatography - mass spectrometry (LC-MS) platform. Fructose and citric acid were the predominant sugar and organic acid, respectively. Wild genotypes had significantly higher concentrations of organic acids, antioxidant activity, and phenolics, namely punicalagin, ellagic acid, sinapic, and ferulic acid. CONCLUSION Cyanidin and delphinidin derivatives of anthocyanins were more abundant in red aril commercial genotypes. Results suggest that wild-sour accessions represent a rich source of polyphenolics that can be utilized in future breeding programs to breed healthier varieties, food supplements, and pharmaceutical products. © 2019 Society of Chemical Industry.
Evaluating a New International Risk-Prediction Tool in IgA Nephropathy.

Importance Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. Objective To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and Participants We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and Measures Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. Results The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R2D (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and Relevance In this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.
Elective colectomy after acute diverticulitis: an international comparison

Routine elective colectomy after acute diverticulitis is not recommended, yet significant numbers are still being performed. Amidst global concern over the rising costs of surgery and the value of healthcare, acute diverticulitis is a disease that is amenable to optimization of strategies for operative intervention. We aim to compare rates of elective colectomy after acute diverticulitis in the USA, England and Australia.
Allosensitization after transplant failure: the role of graft nephrectomy and immunosuppression – a retrospective study

There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re‐transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NX−, n = 48). Sera were assessed for HLA‐A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months. The NX+ group showed a higher rate of donor specific antibody (DSA) and non‐DSA human leukocyte antigen (HLA) antibody production at all the time points. Multivariable analysis showed that nephrectomy was a strong, independent risk factor for the development of DSAs after 12 and 24 months (P = 0.005 and 0.008). In the NX− group, low tacrolimus levels correlated with DSA formation (AUC 0.817, P = 0.002; best cut‐off level 2.9 ng/ml). Analysis with a standardized pool of UK donors showed a more difficult grade of HLA matchability following nephrectomy compared with the NX− group. Nephrectomy is followed by the long‐term production of DSA and non‐DSA HLA antibodies and negatively impacts on the chances of finding a HLA‐compatible kidney. Tacrolimus levels ≥3 ng/ml are protective against the development of allosensitization and could facilitate re‐transplantation in the NX− group.
Neurodevelopmental outcome following prenatal diagnosis of a short corpus callosum

Data regarding the neurodevelopmental outcome of fetal short corpus callosum (CC) diagnosed according to standard reference charts is scarce. The purpose of this study was to assess whether the finding is related to neurodevelopmental delay, and to examine reclassification to normal fetal CC length using CC length/EFW ratio.
Psychosocial Factors in Painful Diabetic Neuropathy: A Systematic Review of Treatment Trials and Survey Studies.

OBJECTIVE Diabetes mellitus is associated with a number of complications that can adversely impact patients' quality of life. A common and often painful complication is painful diabetic neuropathy. The aims of this study were to systematically review and summarize evidence from studies of psychological treatments and psychosocial factors related to painful diabetic neuropathy and assess the methodological quality of these studies. METHODS Electronic databases, related reviews, and associated reference lists were searched. Summaries of participants' data relating to the efficacy of psychological treatments and/or to associations between psychosocial factors and outcomes in painful diabetic neuropathy were extracted from the included studies. The methodological quality of included studies was assessed using two standardized quality assessment tools. RESULTS From 2,921 potentially relevant titles identified, 27 studies were included in this systematic review. The evidence suggests that depression, anxiety, sleep, and quality of life are the most studied variables in relation to pain outcomes in painful diabetic neuropathy and are consistently associated with pain intensity. The magnitude of the associations ranged from small to large. CONCLUSIONS Research into psychosocial factors in painful diabetic neuropathy is unexpectedly limited. The available evidence is inconsistent and leaves a number of questions unanswered, particularly with respect to causal associations between variables. The evidence reviewed indicates that depression, anxiety, low quality of life, and poor sleep are associated with pain in painful diabetic neuropathy. The disproportionate lack of research into psychological treatments for painful diabetic neuropathy represents a significant opportunity for future research.
A gamified mobile application for first-year student orientation to promote library services

This study proposes a mobile application as a new approach for first-year student orientation to promote knowledge of library services using the gamification concept. The application is based on mobile devices with GPS to locate students, allowing them to catch, collect, and battle monsters around the library with questions on library service instructions. To evaluate the learning effectiveness of the approach, we performed a comparative experiment in which the control group used e-learning, while the experimental group used the mobile application of the CMU Journey. We evaluated the pre-and post-test scores, delayed 1-month post-test scores, and intrinsic motivation based on the IMI questionnaire. The results demonstrated that the preference for gamified experience among students can enhance knowledge retention and intrinsic motivation compared to other groups.
Development and validation of a clinical model for preconception and early pregnancy risk prediction of gestational diabetes mellitus in nulliparous women

Implementation of dietary and lifestyle interventions prior to and early in pregnancy in high risk women has been shown to reduce the risk of gestational diabetes mellitus (GDM) development later in pregnancy. Although numerous risk factors for GDM have been identified, the ability to accurately identify women before or early in pregnancy who could benefit most from these interventions remains limited. As nulliparous women are an under-screened population with risk profiles that differ from their multiparous counterparts, development of a prediction model tailored to nulliparous women may facilitate timely preventive intervention and improve maternal and infant outcomes. We aimed to develop and validate a model for preconception and early pregnancy prediction of gestational diabetes mellitus based on clinical risk factors for nulliparous women. A risk prediction model was built within a large California birth cohort including singleton live birth records from 2007–2012. Model accuracy was assessed both internally and externally, within a cohort of women who delivered at University of Iowa Hospitals and Clinics between 2009–2017, using discrimination and calibration. Differences in predictive accuracy of the model were assessed within specific racial/ethnic groups. The prediction model included five risk factors: race/ethnicity, age at delivery, pre-pregnancy body mass index, family history of diabetes, and pre-existing hypertension. The area under the curve (AUC) for the California internal validation cohort was 0.732 (95% confidence interval (CI) 0.728, 0.735), and 0.710 (95% CI 0.672, 0.749) for the Iowa external validation cohort. The model performed particularly well in Hispanic (AUC 0.739) and Black women (AUC 0.719). Our findings suggest that estimation of a woman’s risk for GDM through model-based incorporation of risk factors accurately identifies those at high risk (i.e., predicted risk >6%) who could benefit from preventive intervention encouraging prompt incorporation of this tool into preconception and prenatal care.