Miracle-dz/UniFAR-FTUs huggingface dataset:
Human invariant natural killer T cells promote tolerance by preferential apoptosis induction of conventional dendritic cells

Graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. We recently showed in murine studies and in vitro human models that adoptively transferred invariant natural killer T (iNKT) cells protect from GvHD and promote graft-versus-leukemia effects. The cellular mechanisms underlying GvHD prevention by iNKT cells in humans, however, remain unknown. In order to study relevant cellular interactions, dendritic cells (DC) were either generated from monocytes or isolated directly from blood of healthy donors or GvHD patients and co-cultured in a mixed lymphocyte reaction (MLR) with T cells obtained from healthy donors or transplantation bags. Addition of culture-expanded iNKT cells to the MLR-induced DC apoptosis in a cell contact-dependent manner, thereby preventing T-cell activation and proliferation. Annexin V/propidium iodide staining and image stream assays showed that CD4+CD8–, CD4–CD8+ and double negative iNKT cells are similarly able to induce DC apoptosis. Further MLR assays revealed that conventional DC (cDC) but not plasmacytoid DC (pDC) could induce alloreactive T-cell activation and proliferation. Interestingly, cDC were also more susceptible to apoptosis induced by iNKT cells, which correlates with their higher CD1d expression, leading to a bias in favor of pDC. Remarkably, these results could also be observed in GvHD patients. We propose a new mechanism how ex vivo expanded human iNKT cells prevent alloreactivity of T cells. iNKT cells modulate T-cell responses by selective apoptosis of DC subsets, resulting in suppression of T-cell activation and proliferation while enabling beneficial immune responses through pDC.
Level of Organochlorine Pesticide in Prediabetic and Newly Diagnosed Diabetes Mellitus Patients with Varying Degree of Glucose Intolerance and Insulin Resistance among North Indian Population

Background Organochlorine pesticides (OCPs) exposure may induce an endocrine disruption which may lead to the risk of developing diabetes through alteration and disturbance of glucose metabolism, insulin resistance, and destruction of β-cells. The present study determines the recent trend of OCPs residue in blood samples and their association with the known risk factors responsible for developing the risk of diabetes among the North Indian population. Methods Blood sample of 300 patients (100 each of normal glucose tolerance [NGT], prediabetes and newly detected diabetes mellitus [DM]) between the age group of 30 to 70 years were collected. OCPs residue in whole blood samples was analyzed by using gas chromatography equipped with a 63Ni selective electron capture detector. Results Significantly higher levels of β-hexachlorocyclohexane (HCH), dieldrin, and p,p’-dichloro-diphenyl-dichloroethylene (DDE) were found in the prediabetes and newly detected DM groups as compared to NGT group. Insulin resistance showed to be significantly positive correlation with β-HCH and dieldrin. Also, fasting and postprandial glucose levels were significantly positively correlated with levels of β-HCH, dieldrin, and p,p’-DDE. Further, when OCPs level was adjusted for age and body mass index (BMI), it was found that β-HCH, dieldrin, and p,p’-DDE levels in blood increases the risk of diabetes by 2.70, 2.83, and 2.55 times respectively. Moreover, when we adjust OCPs level based on BMI categories (BMI <23, ≥23, and ≤25, and >25 kg/m2); β-HCH and p,p’-DDE showed a significant risk of developing newly detected DM with BMI >25 and ≥23 and ≤25 kg/m2. Conclusion The OCPs level present in the environment may be responsible for biological, metabolic, and endocrine disruptions within the human body which may increase the risk of developing newly detected DM. Hence, OCPs exposure can play a crucial role in the etiology of diabetes.
Understanding drivers of family planning in rural northern India: An integrated mixed-methods approach

Background Family planning is a key means to achieving many of the Sustainable Development Goals. Around the world, governments and partners have prioritized investments to increase access to and uptake of family planning methods. In Uttar Pradesh, India, the government and its partners have made significant efforts to increase awareness, supply, and access to modern contraceptives. Despite progress, uptake remains stubbornly low. This calls for systematic research into understanding the ‘why’—why people are or aren’t using modern methods, what drives their decisions, and who influences them. Methods We use a mixed-methods approach, analyzing three existing quantitative data sets to identify trends and geographic variation, gaps and contextual factors associated with family planning uptake and collecting new qualitative data through in-depth immersion interviews, journey mapping, and decision games to understand systemic and individual-level barriers to family planning use, household decision making patterns and community level barriers. Results We find that reasons for adoption of family planning are complex–while access and awareness are critical, they are not sufficient for increasing uptake of modern methods. Although awareness is necessary for uptake, we found a steep drop-off (59%) between high awareness of modern contraceptive methods and its intention to use, and an additional but smaller drop-off from intention to actual use (9%). While perceived access, age, education and other demographic variables partially predict modern contraceptive intention to use, the qualitative data shows that other behavioral drivers including household decision making dynamics, shame to obtain modern contraceptives, and high-risk perception around side-effects also contribute to low intention to use modern contraceptives. The data also reveals that strong norms and financial considerations by couples are the driving force behind the decision to use and when to use family planning methods. Conclusion The finding stresses the need to shift focus towards building intention, in addition to ensuring access of trained staff, and commodities drugs and equipment, and building capacities of health care providers.
Protein kinase Cα regulates the nucleocytoplasmic shuttling of KRIT1

ABSTRACT KRIT1 is a scaffolding protein that regulates multiple molecular mechanisms, including cell–cell and cell–matrix adhesion, and redox homeostasis and signaling. However, rather little is known about how KRIT1 is itself regulated. KRIT1 is found in both the cytoplasm and the nucleus, yet the upstream signaling proteins and mechanisms that regulate KRIT1 nucleocytoplasmic shuttling are not well understood. Here, we identify a key role for protein kinase C (PKC) in this process. In particular, we found that PKC activation promotes the redox-dependent cytoplasmic localization of KRIT1, whereas inhibition of PKC or treatment with the antioxidant N-acetylcysteine leads to KRIT1 nuclear accumulation. Moreover, we demonstrated that the N-terminal region of KRIT1 is crucial for the ability of PKC to regulate KRIT1 nucleocytoplasmic shuttling, and may be a target for PKC-dependent regulatory phosphorylation events. Finally, we found that silencing of PKCα, but not PKCδ, inhibits phorbol 12-myristate 13-acetate (PMA)-induced cytoplasmic enrichment of KRIT1, suggesting a major role for PKCα in regulating KRIT1 nucleocytoplasmic shuttling. Overall, our findings identify PKCα as a novel regulator of KRIT1 subcellular compartmentalization, thus shedding new light on the physiopathological functions of this protein. Summary: A novel role for PKC signaling in triggering Ser/Thr phosphorylation and regulating nucleocytoplasmic shuttling of KRIT1, a major protein with pleiotropic functions associated with human diseases.
Interactions of a zwitterionic thiophene-based conjugated polymer with surfactants

In this paper we investigate the optical and structural properties of a zwitterionic poly[3-(N-(4-sulfonato-1-butyl)-N,N-diethylammonium)hexyl-2,5-thiophene] (P3SBDEAHT) conjugated polyelectrolyte (CPE) and its interaction in water with surfactants, using absorption, photoluminescence (PL), electrical conductivity, molecular dynamics simulations (MDS) and small-angle X-ray scattering (SAXS). Different surfactants were studied to evaluate the effect of the head group and chain length on the self-assembly. PL data emphasize the importance of polymer–surfactant electrostatic interactions in the formation of complexes. Nevertheless, conductivity and MDS data have shown that nonspecific interactions also play an important role. These seem to be responsible for the spatial position of the surfactant tail in the complex and, eventually, for breaking-up P3SBDEAHT aggregates. SAXS measurements on P3SBDEAHT-zwitterionic cocamidopropyl betaine (CAPB) surfactant complexes showed a specific structural organization of the system. The CAPB surfactant promotes a structural transition from pure P3SBDEAHT 3-dimensional aggregates (radius of gyration ∼85 A) to thick cylindrical aggregates (∼20 A) where all CAPB molecules are associated with the polymer. For molar ratios (in terms of the polymer repeat unit) >1 the SAXS interference maximum of the complexes resembles that of pure CAPB thus suggesting ongoing phase segregation in the formation of a “pure” CAPB phase.
Role of PVT1 polymorphisms in the glioma susceptibility and prognosis

Background Genetic factors play a crucial role in the glioma risk and prognosis of glioma patients. To explore the role of plasmacytoma variant translocation 1 (PVT1) polymorphism in the susceptibility and survival of glioma in the Chinese Han population, we conducted a case-control study. Methods The three single-nucleotide polymorphisms (SNPs) in PVT1 were genotyped using Agena MassARRAY from 575 patients with glioma and 500 healthy controls. We used the χ2 test to analyze the differences in distribution of allele and genotype between the cases and controls. Odds ratio and 95% confidence interval (CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The effects of polymorphisms and clinical features on survival of glioma patients were evaluated using the log-rank test, Kaplan–Meier and Cox regression analysis. Results We found that rs13255292 was associated with a decreased risk of glioma in the recessive model in overall or male; and rs4410871 was significantly associated with an increased the risk of glioma in age ≤40 years old or female. Moreover, the extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients. However, the gender, age, tumor grade, radiotherapy and PVT1 polymorphisms have no effect on prognosis of glioma patients. Conclusions Our results indicated that PVT1 polymorphisms (rs13255292 and rs4410871) were associated with glioma susceptibility, but have no effect on prognosis of glioma patients. Further studies with large samples are required to confirm the results.
Semaphorin 3E Promotes Susceptibility to Leishmania major Infection in Mice by Suppressing CD4+ Th1 Cell Response

Key Points Sema3E suppresses CD11C+ cells and T cell functions during L. major infection. The deficiency of Sema3E leads to enhanced resistance to L. major infection. Visual Abstract Protective immunity to cutaneous leishmaniasis is mediated by IFN-γ–secreting CD4+ Th1 cells. IFN-γ binds to its receptor on Leishmania-infected macrophages, resulting in their activation, production of NO, and subsequent destruction of parasites. This study investigated the role of Semaphorin 3E (Sema3E) in host immunity to Leishmania major infection in mice. We observed a significant increase in Sema3E expression at the infection site at different timepoints following L. major infection. Sema3E-deficient (Sema3E knockout [KO]) mice were highly resistant to L. major infection, as evidenced by significantly (p < 0.05–0.01) reduced lesion sizes and lower parasite burdens at different times postinfection when compared with their infected wild-type counterpart mice. The enhanced resistance of Sema3E KO mice was associated with significantly (p < 0.05) increased IFN-γ production by CD4+ T cells. CD11c+ cells from Sema3E KO mice displayed increased expression of costimulatory molecules and IL-12p40 production following L. major infection and were more efficient at inducing the differentiation of Leishmania-specific CD4+ T cells to Th1 cells than their wild-type counterpart cells. Furthermore, purified CD4+ T cells from Sema3E KO mice showed increased propensity to differentiate into Th1 cells in vitro, and this was significantly inhibited by the addition of recombinant Sema3E in vitro. These findings collectively show that Sema3E is a negative regulator of protective CD4+ Th1 immunity in mice infected with L. major and suggest that its neutralization may be a potential therapeutic option for treating individuals suffering from cutaneous leishmaniasis.
Association of GBA Genotype With Motor and Functional Decline in Patients With Newly Diagnosed Parkinson Disease

Objective To establish the significance of glucocerebrosidase gene (GBA) carrier status on motor impairment in a large cohort of patients with incident Parkinson disease (PD). Methods Three European population-based studies followed 528 patients with PD from diagnosis. A total of 440 with genomic DNA from baseline were assessed for GBA variants. We evaluated motor and functional impairment annually using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) sections. Differential effects of classes of GBA variants on disease progression were evaluated using mixed random and fixed effects models. Results A total of 387 patients with idiopathic disease (age at baseline 70.3 ± 9.5 years; 60.2% male) and 53 GBA carriers (age at baseline 66.8 ± 10.1 years; 64.2% male) were included. The motor profile of the groups was clinically indistinguishable at diagnosis. GBA carriers showed faster annual increase in UPDRS scores measuring ADL (1.5 point per year, 95% confidence interval [CI] 1.1–2.0) and motor symptoms (2.2 points per year, 95% CI 1.3–3.1) compared to noncarriers (ADL, 1.0 point per year, 95% CI 0.9–1.1, p = 0.003; motor, 1.3 point per year, 95% CI 1.1–1.6, p = 0.007). Simulations of clinical trial designs showed that recruiting only GBA carriers can reduce trial size by up to 65% compared to a trial recruiting all patients with PD. Conclusion GBA variants are linked to a more aggressive motor disease course over 7 years from diagnosis in patients with PD. A better understanding of PD progression in genetic subpopulations may improve disease management and has direct implications for improving the design of clinical trials.
lncRNAs in development and differentiation: from sequence motifs to functional characterization

ABSTRACT The number of long noncoding RNAs (lncRNAs) with characterized developmental and cellular functions continues to increase, but our understanding of the molecular mechanisms underlying lncRNA functions, and how they are dictated by RNA sequences, remains limited. Relatively short, conserved sequence motifs embedded in lncRNA transcripts are often important determinants of lncRNA localization, stability and interactions. Identifying such RNA motifs remains challenging due to the substantial length of lncRNA transcripts and the rapid evolutionary turnover of lncRNA sequences. Nevertheless, the recent discovery of specific RNA elements, together with their experimental interrogation, has enabled the first step in classifying heterogeneous lncRNAs into sub-groups with similar molecular mechanisms and functions. In this Review, we focus on lncRNAs with roles in development, cell differentiation and normal physiology in vertebrates, and we discuss the sequence elements defining their functions. We also summarize progress on the discovery of regulatory RNA sequence elements, as well as their molecular functions and interaction partners. Summary: This Review discusses advances in the field of lncRNA functions in animal development and physiology, with a particular focus on regulatory RNA sequence motifs.
Parent‐reported Autism Diagnostic Stability and Trajectories in the Longitudinal Study of Australian Children

This study aimed to explore the stability of parent‐reported diagnosis of Autism Spectrum Disorder (ASD) and factors influencing the trajectories in two cohorts from the prospective Longitudinal Study of Australian Children (LSAC). Parent‐reported ASD diagnosis was collected for children from 6 years of age in a Birth cohort and 10 years of age in a Kinder cohort; allowing for exploration of diagnostic stability at age 6, 8, 10, and 12 years (Birth cohort) and 10, 12, 14, 16 years (Kinder cohort). Children were grouped based on persisting, desisting, inconsistent and late (diagnosis after 6 years—Birth cohort; after 10 years—Kinder) subgroups over four timepoints. Multinomial logistic regression explored predictors of diagnostic trajectories; generalized estimating equations examined trajectories of emotional and behavioral problems. Of 66 Birth cohort children parent‐reported to have ASD at age 6, with data at all four time points, 14% did not at 12 years; of 73 Kinder cohort children at age 10 years, 26% no longer had parent‐reported ASD at 16 years. Children with late diagnoses showed increasing trajectories of emotional and behavioral problems, while children with persisting or desisting diagnoses showed decreasing trajectories. Between 86% and 74% had a reported ASD diagnosis after 6 years. Findings indicate that children with ASD need services and supports that can adapt to their changing needs, which may be increasing, decreasing or different. This has implications for the provision of services and funding.
Geographic Distribution of Mental Health Problems Among Chinese College Students During COVID-19 Pandemic: Cross-Sectional, Online Survey Study.

BACKGROUND Since the outbreak of novel coronavirus disease 2019 (COVID-19), college students' mental health problems had drawn attention. OBJECTIVE We aim to estimate the prevalence of anxiety and depressive symptoms among college students in different geographical areas in China during the COVID-19 pandemic. METHODS A nationwide cross-sectional survey was conducted in 16 provinces or municipalities among Chinese college students from Feb 4 to Feb 12, 2020. An online survey was adopted to collect information, including demographics, perceived risk of infection, attitudes toward epidemic and control, and mental health status. Anxiety symptom was assessed by the Generalized Anxiety Disorder Scale (GAD-7); depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9). A total of 11 787 participants were involved in the current study. The Chi-square test was used to compare the percentage of the perceived risk of infection and attitude toward the COVID-19 between different geographic locations. The binary logistic models were used to identify associations between associations of geographic location and mental health problems after controlling for covariates. RESULTS A total of 11 787 participants were analyzed in the current study (response rate: 79.7%). The prevalence of anxiety, depressive symptoms were 17.8% (95%CI: 17.1%-18.5%) and 25.9% (95%CI: 25.1%-26.7%) for college students. After controlling for covariates, geographically speaking, current living in Wuhan was positively associated with anxiety symptoms (current living OR=1.69, 95%CI: 1.23-2.31, and depressive symptoms (current living OR=1.45, 95%CI: 1.21-1.89) compared with other areas. However, there is no difference in college location. Living or travel history in Wuhan last month was also positively associated with anxiety symptoms (OR=1.79, 95%CI: 1.51-2.31) and depressive symptoms (OR=1.62, 95%CI: 1.41-1.85). Both anxiety and depression were more prevalent among college students who reported with high perceived the infection risk of him/herself (χ2= 220.46 for anxiety, χ2=131.79 for depression; both P < .001) and family members (χ2=197.52 for anxiety, χ2=136.06 for depression; both P < .001). The prevalence of anxiety and depression were highest in college students who reported with very worry about the infection of her/himself (χ2=285.77 for anxiety, χ2=186.10 for depression; both P < .001), and community members(χ2=178.46 for anxiety, χ2=119.60 for depression; both P < .001). The prevalence of anxiety and depression were highest in college students who had a pessimistic attitude toward the COVID-19 epidemic (χ2=444.61 for anxiety, χ2=355.95 for depression; both P<.001) and control (χ2=154.02 for anxiety, χ2=124.84 for depression; both P< .001). CONCLUSIONS During the COVID-19 pandemic, mental health problems among Chinese college students were widespread and geographically diverse. Our results provide further insight into developing targeted intervention strategies.
Understanding primary care physician perspectives on recommending HPV vaccination and addressing vaccine hesitancy

ABSTRACT HPV vaccination rates have improved in recent years, but remain suboptimal in the United States. Physician recommendation is associated with increased uptake; however, specific strategies used by physicians to recommend the vaccine and address hesitancy are underexplored. We iteratively conducted qualitative in-depth interviews with family medicine and pediatrics/adolescent medicine physicians recruited from four primary care settings (federally qualified health centers and hospital-affiliated practices) within a large academic-hospital system in New Jersey. Interviews aimed to understand factors influencing physician recommendations. Transcripts were analyzed iteratively using a team-based, thematic content analysis approach. All physicians reported strong support for HPV vaccination, intention to recommend for target age groups, and providing factsheets to parents. Many physicians used electronic medical records and/or the state immunization registry for monitoring vaccinations, but few were able to report their own clinic-level rates. The majority said they needed to overcome both hesitancy for at least 10–30% of parents and misinformation from the internet. Most cited having their own children vaccinated for HPV as a first-line strategy for addressing parental hesitancy. Other strategies included using data or professional authority to address safety concerns, linking HPV to cervical cancer, highlighting only needing two doses if vaccinated younger, and normalizing the vaccine. While our findings indicate physicians are knowledgeable about HPV vaccination and recommend it to parents, strategies to overcome parental hesitancy varied. Physician, clinic, and health-system-based strategies need to be adopted to overcome parental hesitancy for HPV vaccination.