Miracle-dz/UniFAR-FTUs huggingface dataset:
Methotrimeprazine exerts antiviral and neuroprotective effects in Japanese encephalitis virus infection through activation of adaptive ER stress and autophagy

Japanese encephalitis virus (JEV) is the leading global cause of virus-induced encephalitis. Its pathogenesis is driven by a combination of neuronal cell death and neuroinflammation. We hypothesized that pharmacological upregulation of autophagy could exert a neuroprotective antiviral effect, and tested a panel of forty-two FDA-approved drugs that were shown to induce autophagy. Four drugs were tested in the JE mouse model based on in vitro protective effects on neuronal cell death, inhibition of viral replication, and anti-inflammatory effects in microglial cells. The antipsychotic phenothiazines Methotrimeprazine (MTP) and Trifluoperazine (TFP) showed a significant survival benefit with reduced virus titers in the brain, prevention of blood-brain barrier (BBB) breach, and inhibition of neuroinflammation. Both drugs were potent mTOR-independent autophagy flux inducers. Mechanistically MTP inhibited SERCA channel functioning, thereby resulting in rise in cytosolic calcium levels, and induction of a unique adaptive ER stress response. In virus infected drug treated cells, there was a strong transcriptional downregulation of type I interferon and interferon-stimulated genes and upregulation of cholesterol metabolic pathway genes. The drugs exerted an autophagy-dependent antiviral effect at the level of JEV protein translation/replication complex formation in diverse cell types. Inhibition of inflammatory cytokine/chemokine release from mouse microglial cells was partly autophagy-dependent. Our study suggests that MTP exerts a combined antiviral and anti-inflammatory effect in JEV infection, and has therapeutic potential to be repurposed for JE treatment.
Polarized vesicle transport requires AP-1-mediated recruitment of KIF13A and KIF13B at the trans-Golgi network

Neurons are polarized cells that require accurate membrane trafficking to maintain distinct protein complements at dendritic and axonal membranes. The Kinesin-3 family members KIF13A and KIF13B are thought to mediate dendrite-selective transport, but the mechanism by which they are recruited to polarized vesicles and the differences in the specific trafficking role of each KIF13 have not been defined. We performed live-cell imaging in cultured hippocampal neurons and found that KIF13A is a dedicated dendrite-selective kinesin. KIF13B confers two different transport modes, both dendrite- and axon-selective transport. Both KIF13s are maintained at the trans-Golgi network by interactions with the heterotetrameric adaptor protein complex AP-1. Interference with KIF13 binding to AP-1 resulted in disruptions to both dendrite- and axon- selective trafficking. We conclude that AP-1 is the molecular link between the sorting of polarized cargoes into vesicles and the recruitment of kinesins that confer polarized transport.
The role of plasmids in the gut microbiome during the first year of life

Plasmids are extrachromosomal self-replicating genetic elements that play a key role in bacterial ecology and evolution by shuttling diverse host-beneficial traits between bacteria. However, our understanding of plasmids is still limited, particularly in the human gut microbiota, and little is known about how they are acquired and become established in infants. In this study, we explored a longitudinal fecal metagenomic dataset obtained from 98 Swedish children who were followed during their first year of life. For this, we developed a bioinformatics pipeline for the complete sequence assembly and annotation of plasmids, together with the identification of plasmid contigs. We found that gut plasmids in these children were extremely diverse, particularly in the first four months of life, and this diversity decreased with maturation of the gut microbiota. Members of genera Bacteroides and Bifidobacterium were identified as major hosts of transmissible plasmids and important hubs of horizontal gene transfer in the early human gut microbiota. Additionally, we discovered that plasmids played a substantial role in expanding the gene repertoires of their bacterial hosts: approximately a quarter of unannotated plasmid genes were found only on plasmids and not on chromosomes. Together, our results provide the first characterization of the early acquisition and development of plasmids in the infant gut microbiome. Their diversity and abundance in the first months of life could benefit a variable and rapidly proliferating microbiota by providing increased adaptability in a highly competitive environment.
How Interactions During Viral-Viral Coinfection Can Shape Infection Kinetics

Respiratory virus infections are a leading cause of disease worldwide with multiple viruses detected in 20-30% of cases and several viruses simultaneously circulating. Some infections with viral copathogens have been shown to result in reduced pathogenicity while other virus pairings can worsen disease. The mechanisms driving these dichotomous outcomes are likely variable and have only begun to be examined in the laboratory and clinic. To better understand viral-viral coinfections and predict potential mechanisms that result in distinct disease outcomes, we first systematically fit mathematical models to viral load data from ferrets infected with respiratory syncytial virus (RSV) followed by influenza A virus (IAV) after 3 days. The results suggested that IAV reduced the rate of RSV production while RSV reduced the rate of IAV infected cell clearance. We then explored the realm of possible dynamics for scenarios not examined experimentally, including different infection order, coinfection timing, interaction mechanisms, and viral pairings. IAV coinfection with rhinovirus (RV) or SARS-CoV-2 (CoV2) was examined by using human viral load data from single infections together with murine weight loss data from IAV-RV, RV-IAV, and IAV-CoV2 coinfections to guide the interpretation of the model results. Similar to the results with RSV-IAV coinfection, this analysis showed that the increased disease severity observed during murine IAV-RV or IAV-CoV2 coinfection was likely due to slower clearance of IAV infected cells by the other viruses. On the contrary, the improved outcome when IAV followed RV could be replicated when the rate of RV infected cell clearance was reduced by IAV. Simulating viral-viral coinfections in this way provides new insights about how viral-viral interactions can regulate disease severity during coinfection and yields testable hypotheses ripe for experimental evaluation.
Risks and Moderators of Mental Health and Illness

Building on eHealth literacy and mental health literacy, this cross-sectional survey study examined associations between eMental health literacy (the degree to which individuals obtain, process, and understand basic mental health information online to inform mental health-related decisions), perceived barriers to mental healthcare, and psychological distress. Data were collected online for 247 older adults in the United States. Higher eMental health literacy was associated with fewer perceived barriers to mental healthcare, in models conceptualizing psychological distress as an outcome of eMental health literacy and barriers to care (intrinsic, β = 0.36, p < .001; extrinsic, β = 0.24, p = .002) and as a covariate of eMental health literacy (intrinsic, β = 0.33, p = .001; extrinsic, β = 0.24, p = .003). Continued research and replication of findings are needed to better understand the potential role of eMental health literacy in reducing barriers to mental health services in later life.
Functional connectivity in northern swamp deer (Rucervus duvaucelii duvaucelii) population across a fragmented, human-dominated landscape along Gangetic Plains of north India: implications for conservation in non-protected areas

The Indian subcontinent has witnessed disproportionate declines in large mammalian herbivore communities. The northern swamp deer ( Rucervus duvaucelii duvaucelii ) exemplifies the conservation challenges of typical non-protected area species, where apart from distribution status other ecological information is limited for the upper Gangetic basin population. We combined elements of radio-telemetry and conservation genetics to evaluate dispersal patterns, population connectivity and assess genetic variation and inbreeding status of this population living across a highly human-dominated area. We genetically identified 266 unique swamp deer and further analyses revealed presence of two spatially-admixed genetic lineages with moderate heterozygosity (H_o=0.51, SD = 0.10) and low inbreeding (F_IS = 0.128) status. Multidisciplinary evidence suggests that the small, isolated grassland patches between Jhilmil Jheel Conservation Reserve (JJCR) and Hastinapur Wildlife Sanctuary (HWLS) are highly preferred by swamp deer during migrations and are genetically connected. The southern part of the area in HWLS showed early signatures of genetic discontinuity that require immediate conservation attention. We hypothesized that the human settlement history of this landscape, river dynamics and species’ ability to negotiate various pressures and disperse has helped to maintain such connectivity. While these signatures are encouraging for this small, isolated cervid population, careful management interventions are required to ensure the integrity and functionality of this landscape. We recommend a scientifically robust population estimation approach across this landscape and multi-stakeholder-driven strategies to augment population and habitat recovery, combat poaching, plantation and riverscape management to ensure long-term survival of this species.
Generalized wavelet frames

The main purpose of this paper is to discuss generalized wavelet frames (GWF), which is based on fractional Fourier transform and wavelet frames. By analyzing Fourier transformation of the mother wavelets, we show several sufficient conditions and necessary conditions for GWF of L 2( R ). At last, when the parameters are selected by a = 2 and b = 1 as a special condition, a necessary and sufficient condition is given for tight GWF.
Simulation of Extreme New Zealand Precipitation Events. Part II: Mechanisms of Precipitation Development

Abstract The extreme precipitation event that occurred on 27 December 1989 over the South Island of New Zealand was simulated using the DAR hydrostatic mesoscale model nested within the ECMWF analyses. The model simulated nearly half of the peak observed rainfall for this storm (greater than 700 mm) and captured the location and timing of the intense precipitation. The heavy precipitation developed while a deep layer of moist subtropical air along a cold front ascended the high terrain of the South Island. The intense orographic ascent was associated with a low-level jet core with wind speeds of over 20 m s−1 ahead of the cold front. An upper-level trough and jet streak entrance region were also present upstream of the South Island during the event, aiding the ascent over the mountains and deepening the layer of moist air. The air crossing the mountain was nearly saturated throughout the troposphere and had only weak moist vertical stability near the cold front. Almost all of the simulated precipitation f.
Potential of Molecular Culture in Early Onset Neonatal Sepsis Diagnosis: A Proof of Principle Study

Delay in the time-to-positivity of a peripheral blood culture (PBC), the gold standard for early onset neonatal sepsis (EOS) diagnosis, has resulted in excessive use of antibiotics. In this study, we evaluate the potential of the rapid Molecular Culture (MC) assay for quick EOS diagnosis. In the first part of this study, known positive and spiked blood samples were used to assess the performance of MC. In the in vivo clinical study, the second part of this study, all infants receiving antibiotics for suspicion of EOS were included. At initial EOS suspicion, a blood sample was collected for PBC and MC. MC was able to detect bacteria present in the spiked samples even when the bacterial load was low. In the clinical study, MC was positive in one infant with clinical EOS (Enterococcus faecalis) that was not detected by PBC. Additionally, MC was positive in two infants without clinical sepsis (Streptococcus mitis and multiple species), referred to as contamination. The other 37 samples were negative both by MC and PBC. MC seems to be able to detect bacteria even when the bacterial load is low. The majority of MC and PBC results were comparable and the risk for contamination and false positive MC results seems to be limited. Since MC can generate results within 4 h following sampling compared with 36–72 h in PBC, MC may have the potential to replace conventional PBC in EOS diagnostics in order to guide clinicians on when to discontinue antibiotic therapy several hours after birth.
Anthropogenic Forcing Decreased Concurrent Soil Drought and Atmospheric Aridity in the Historical Period 1850–2013

As awareness of the importance of anthropogenic climate change has increased, attention is being focused on “compound extremes,” such as co‐occurring soil drought (low amounts of soil moisture, SM) and atmospheric aridity (high vapor‐pressure deficits, VPD), because of the disproportionate impacts of such extreme conditions on natural and societal systems. Few advances, however, have been made in isolating the net effect of anthropogenic forcing on the occurrence of such compound extremes. Nine Earth System models (ESMs) under natural‐only and fully‐forced simulations from Phase 6 of the Coupled Model Intercomparison Project (CMIP6) indicated that the presence of anthropogenic forcing in the historical period 1850–2013 weakened the coupling between SM and VPD and thus decreased the frequency of compound drought and aridity globally. The anthropogenically induced decrease in the strength of land–atmospheric feedbacks, which offset the drying trend effects of global warming by countering the expected natural correlation between SM and VPD, appears to have been responsible for the relative rarity of concurrent drought and aridity in the historical period. We also modeled independently the anthropogenic forcings of aerosols and greenhouse gases (GHGs) to further highlight that the widespread weakening of land–atmospheric feedbacks may have been associated primarily with the cooling effects induced by increases in anthropogenic emissions of aerosols, because the increase in intensity and frequency of compound drought and aridity that might have been expected from rising GHG concentrations was widely counter‐balanced until very recently by an aerosol‐driven cooling, particularly for the middle and high latitudes of the Northern Hemisphere. This finding indicates that the trade‐off between these two main anthropogenic forcings may determine future patterns of concurrent drought and aridity in a changing climate. If global emissions of anthropogenic aerosols decrease in the future, as expected, our results imply a renewed strengthening of land–atmospheric feedbacks, and thus an intensification of concurrent drought and aridity.
Clinical Characteristics and In-Hospital Outcomes in Patients with Iliopsoas Abscess: A Multicenter Study

(1) Background: Iliopsoas abscess (IPA) is usually overlooked due to its nonspecific symptoms and signs. The resulting delayed diagnosis and treatment can increase morbidity and mortality. The purpose of the present study was to identify the risk factors for the unfavorable outcomes associated with IPA. (2) Methods: We included patients who presented to the emergency department and were diagnosed with IPA. The primary outcome was in-hospital mortality. Variables were compared, and the associated factors were examined with Cox proportional hazards model. (3) Results: Of the 176 patients enrolled, IPA was of primary origin in 50 patients (28.4%) and of secondary origin in 126 (71.6%). Skeletal origin was the most common source of secondary IPA (n = 92, 52.3%). The most common pathogens were Gram-positive cocci. Eighty-eight (50%) patients underwent percutaneous drainage, 32 (18.2%) patients underwent surgical debridement, and 56 (31.8%) patients received antibiotics. Multivariate analyses indicated that age > 65 (year) (HR = 5.12; CI 1.03–25.53; p = 0.046), congestive heart failure (HR = 5.13; CI 1.29–20.45; p = 0.021), and platelet < 150 (103/μL) (HR = 9.26; CI 2.59–33.09; p = 0.001) were significant independent predictors of in-hospital mortality in Model A, while the predictors in Model B included age > 65 (year) (HR = 5.12; CI 1.03–25.53; p = 0.046) and septic shock (HR = 61.90; CI 7.37–519.46; p < 0.001). (4) Conclusions: IPA is a medical emergency. Our study reported that patients with advanced age, congestive heart failure, thrombocytopenia, or septic shock had a significantly higher risk of mortality, and the recognition of the associated factors may aid in risk stratification and the determination of the optimal treatment plan for IPA patients.
Ultrashort-pulse laser processing of transparent materials: insight from numerical and semi-analytical models

Interaction of ultrashort laser pulses with transparent materials is a powerful technique of modification of material properties for various technological applications. The physics behind laser-induced modification phenomenon is rich and still far from complete understanding. We present an overview of our models developed to describe processes induced by ultrashort laser pulses inside and on the surface of bulk glass. The most sophisticated model consists of two parts. The first part solves Maxwell’s equations supplemented by the rate and hydrodynamics equations for free electrons. The model resolves spatiotemporal dynamics of free-electron population and yields the absorbed energy map. The latter serves as an initial condition for thermoelastoplastic simulations of material redistribution. The simulations performed for a wide range of irradiation conditions have allowed to clarify timescales at which modification occurs after single laser pulses. Simulations of spectrum of laser light scattered by laser-generated plasma revealed considerable blueshifting which increases with pulse energy. To gain insight into temperature evolution of a glass material under the surface irradiation conditions, we employ a model based on the rate equation describing free electron generation coupled with the energy equations for electrons and lattice. Swift heating of electron and lattice subsystems to extremely high temperatures at fs timescale has been found at laser fluences exceeding the threshold fluence by 2-3 times that can result in efficient bremsstrahlung emission from the irradiation spot. The mechanisms of glass ablation with ultrashort laser pulses are discussed by comparing with the experimental data. Finally, a model is outlined, developed for multi-pulse irradiation regimes, which enables gaining insight into the roles of defects and heat accumulation.
Stability analysis for seed yield of chickpea (Cicer arietinum L.) genotypes by experimental and biological approaches

A range of environmental factors restricts the production of chickpea; therefore, introducing compatible cultivars to a range of environments is an important goal in breeding programs. This research aims to find high-yielding and stable chickpea genotypes to rainfed condition. Fourteen advanced chickpea genotypes with two control cultivars were cultivated in a randomized complete block design in four regions of Iran during 2017–2020 growing seasons. The first two principal components of AMMI explained 84.6 and 10.0 % of genotype by environment interactions, respectively. Superior genotypes based on simultaneous selection index of ASV (ssiASV), ssiZA, ssiDi and ssiWAAS were G14, G5, G9 and G10; those based on ssiEV and ssiSIPC were G14, G5, G10 and G15 and those based on ssiMASD were G14, G5, G10 and G15. The AMMI1 biplot identified G5, G12, G10 and G9 as stable and high-yielding genotypes. Genotypes G6, G5, G10, G15, G14, G9 and G3 were the most stable genotypes in the AMMI2 biplot. Based on the harmonic mean and relative performance of genotypic values, G11, G14, G9 and G13 were the top four superior genotypes. Factorial regression indicated that rainfall is very important at the beginning and end of the growing seasons. Genotype G14, in many environments and all analytical and experimental approaches, has good performance and stability. Partial least squares regression identified genotype G5 as a suitable genotype for moisture and temperature stresses conditions. Therefore, G14 and G5 could be candidates for introduction of new cultivars.
Prevalence and Complications of Subclinical and Overt Hypothyroidism in Pregnancy at North Indian Tertiary Care Center

Background: Thyroid disorders are one of the commonest endocrine problems among pregnant women. It is often argued that it is not only overt, but subclinical thyroid dysfunction also has similar adverse effects on maternal and fetal outcomes. There is a huge deficiency of data from the Indian population to assess the prevalence of thyroid dysfunction in pregnancy. This study aimed to determine the prevalence of thyroid disorders in pregnancy and their impact on obstetrical outcomes in the Indian population. The study also had the objective of finding a correlation between maternal and fetal thyroid-stimulating hormone (TSH) levels in hypothyroid pregnancies. Materials and Methods: Around 1055 pregnant women in the first and second trimesters were enrolled in the study. A detailed history was noted and general examinations were done. Apart from routine obstetrical investigations, TSH level estimation was done. If the TSH level was deranged, then free T4 (fT4) and free T3 (fT3) levels were also estimated. Furthermore, 50 hypothyroid and euthyroid pregnant women from the same cohort were followed till delivery. Their obstetrical and perinatal outcomes were noted. Results: The prevalence of thyroid dysfunction was 36.5% in this study, which was quite high in the population. Moreover, hypothyroid groups were prone to have pregnancy-induced hypertension (P = 0.03), intrauterine growth restriction (P = 0.05), and preterm delivery (P = 0.04) as compared to control. Cesarean section rate for fetal distress was significantly higher among pregnant hypothyroid women (P = 0.05). Neonatal respiratory distress and low appearance, pulse, grimace, activity, and respiration (APGAR) () scores were significantly more in the hyperthyroidism group (P = 0.04 and P = 0.02, respectively). Maternal TSH was significantly correlated with hemoglobin levels, HbA1c, and systolic blood pressure. Conclusions: Significant adverse effects on maternal and fetal outcomes were seen emphasizing the importance of routine antenatal thyroid screening.