Miracle-dz/UniFAR-FTUs huggingface dataset:
Contrasting Distribution of SARS-CoV-2 Lineages across Multiple Rounds of Pandemic Waves in West Bengal, the Gateway of East and North-East States of India

Multiple waves of infection were observed in many states in India during the coronavirus disease 2019 (COVID19) pandemic. Fine-scale evolution of major SARS-CoV-2 lineages and sublineages during four wave-window categories: Pre-Wave 1, Wave 1, Pre-Wave 2, and Wave 2 in four major states of India: Delhi (North), Maharashtra (West), Karnataka (South), and West Bengal (East) was studied using large-scale virus genome sequencing data. ABSTRACT The evolution of viral variants and their impact on viral transmission have been an area of considerable importance in this pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed the viral variants in different phases of the pandemic in West Bengal, a state in India that is important geographically, and compared the variants with other states like Delhi, Maharashtra, and Karnataka, located in other regions of the country. We have identified 57 pango-lineages in 3,198 SARS-CoV-2 genomes, alteration in their distribution, as well as contrasting profiles of amino acid mutational dynamics across different waves in different states. The evolving characteristics of Delta (B.1.617.2) sublineages and alterations in hydrophobicity profiles of the viral proteins caused by these mutations were also studied. Additionally, implications of predictive host miRNA binding/unbinding to emerging spike or nucleocapsid mutations were highlighted. Our results throw considerable light on interesting aspects of the viral genomic variation and provide valuable information for improved understanding of wave-defining mutations in unfolding the pandemic. IMPORTANCE Multiple waves of infection were observed in many states in India during the coronavirus disease 2019 (COVID19) pandemic. Fine-scale evolution of major SARS-CoV-2 lineages and sublineages during four wave-window categories: Pre-Wave 1, Wave 1, Pre-Wave 2, and Wave 2 in four major states of India: Delhi (North), Maharashtra (West), Karnataka (South), and West Bengal (East) was studied using large-scale virus genome sequencing data. Our comprehensive analysis reveals contrasting molecular profiles of the wave-defining mutations and their implications in host miRNA binding/unbinding of the lineages in the major states of India.
Stochastic collective model of public transport passenger arrival process

It is essential to understand how transit passengers arrive at stops, as it enables transit operators and researchers to anticipate the number of waiting passengers at stops and their waiting time. However, the literature focuses more on predicting the total passenger demand, rather than simulating individual passenger arrivals to transit stops. When an arrival process is required especially in public transport planning and operational control, existing studies often assume a deterministic uniform arrival or a homogeneous Poisson process to model this passenger arrival process. This study generalises the homogeneous Poisson process (HPP) to a more general non-HPP (NHPP) in which the arrival rate varies as a function of time. The proposed collective NHPP (cNHPP) simulates the passenger arrival using less time regions than the HPP, takes less time to compute, while providing more accurate simulations of passenger arrivals to transit stops. The authors first propose a new time-varying intensity function of the transit passenger arrival process and then a maximum likelihood estimation method to estimate the process. A comparison study shows that the proposed cNHPP is capable of capturing the continuous and stochastic fluctuations of passenger arrivals over time.
Sex differences in morphine sensitivity are associated with differential glial expression in the brainstem of rats with neuropathic pain

Chronic pain is more prevalent and reported to be more severe in women. Opioid analgesics are less effective in women and result in stronger nauseant effects. The neurobiological mechanisms underlying these sex differences have yet to be clearly defined, though recent research has suggested neuronal–glial interactions are likely involved. We have previously shown that similar to people, morphine is less effective at reducing pain behaviors in female rats. In this study, we used the immunohistochemical detection of glial fibrillary acidic protein (GFAP) expression to investigate sex differences in astrocyte density and morphology in six medullary regions known to be modulated by pain and/or opioids. Morphine administration had small sex‐dependent effects on overall GFAP expression, but not on astrocyte morphology, in the rostral ventromedial medulla, the subnucleus reticularis dorsalis, and the area postrema. Significant sex differences in the density and morphology of GFAP immunopositive astrocytes were detected in all six regions. In general, GFAP‐positive cells in females showed smaller volumes and reduced complexity than those observed in males. Furthermore, females showed lower overall GFAP expression in all regions except for the area postrema, the critical medullary region responsible for opioid‐induced nausea and emesis. These data support the possibility that differences in astrocyte activity might underlie the sex differences seen in the processing of opioids in the context of chronic neuropathic pain.
Clinical neuroimaging in intracerebral haemorrhage related to cerebral small vessel disease: contemporary practice and emerging concepts

ABSTRACT Introduction About 80% of all non-traumatic intracerebral hemorrhage (ICH) are caused by the sporadic cerebral small vessel diseases deep perforator arteriopathy (DPA, also termed hypertensive arteriopathy or arteriolosclerosis) and cerebral amyloid angiopathy (CAA), though these frequently co-exist in older people. Contemporary neuroimaging (MRI and CT) detects an increasing spectrum of hemorrhagic and non-hemorrhagic imaging biomarkers of small vessel disease which may identify the underlying arteriopathies. Areas covered We discuss biomarkers for cerebral small vessel disease subtypes in ICH, and explore their implications for clinical practice and research. Expert opinion ICH is not a single disease, but results from a defined range of vascular pathologies with important implications for prognosis and treatment. The terms ‘primary’ and ‘hypertensive’ ICH are poorly defined and should be avoided, as they encourage incomplete investigation and classification. Imaging-based criteria for CAA will show improved diagnostic accuracy, but specific imaging biomarkers of DPA are needed. Ultra-high-field 7 T-MRI using structural and quantitative MRI may provide further insights into mechanisms and pathophysiology of small vessel disease. We expect neuroimaging biomarkers and classifications to allow personalized treatments (e.g. antithrombotic drugs) in clinical practice and to improve patient selection and monitoring in trials of targeted therapies directed at the underlying arteriopathies.
Endoscopic and clinicopathologic features of early gastric signet ring cell carcinoma ≤20 mm: a retrospective observational study

Abstract Objectives Limited literature exists on the characteristics of early gastric signet ring cell carcinoma (GSRCC) within 20 mm. This study aimed to explore this type of cancer from several aspects, to provide guidance for early detection and intervention of GSRCC. Methods We retrospectively collected data from 24 patients diagnosed with early GSRCC ≤20 mm in Beijing Friendship Hospital from 2016 to 2021. According to tumor size, those lesions were divided into three groups: diminutive group (1–5 mm, n = 4), small group (6–10 mm, n = 12) and intermediate group (11–20 mm, n = 8). The clinicopathologic and endoscopic characteristics of GSRCC were compared among the three groups. Results Treatment strategies for lesions differed according to the size (p<.05). There were no significant differences among the three groups with regard to age, sex, Helicobacter pylori infection, tumor location and macroscopic type. Lesions were often flat type and more likely to present with discoloration, uneven color, ulceration and submucosal invasion with the increase of diameter. Almost all cases showed abnormal intervening part (IP) under magnifying endoscopy. Conclusions The location of early signet ring cell carcinoma is not specific, and the diminutive lesions are often flat. Abnormal IP may be the early endoscopic feature of early GSRCC.
Burden, anxiety and depressive symptoms in partners – course and predictors during the first two years after stroke

ABSTRACT Background Partners of patients with stroke are at high risk for burden, anxiety and depressive symptoms. Previous studies have reported contradictory results and did not investigate these three courses simultaneously. In this study we comprehensively studied the courses and predictors of burden, anxiety and depressive symptoms in partners of patients with stroke during the first two years after stroke. They were analyzed as outcomes as well as predictors for each other. Methods Six general hospitals recruited 215 patients with stroke and their partners for a longitudinal cohort study. Mixed model analyses were performed for burden (CSI), anxiety (HADS-A) and depressive symptoms (HADS-D) as time-varying outcome variables, measured at four time points during two years after stroke. Results Burden and depressive symptoms did not significantly change over time, whereas anxiety symptoms initially decreased followed by an increase. Higher burden was predicted by partners’ younger age, higher education, more symptoms of anxiety and depression, and by patients’ greater stroke severity, lower cognitive functioning and more symptoms of anxiety and depression. More anxiety symptoms were predicted by higher burden, more depressive symptoms, and lower self-efficacy of the partner. More depressive symptoms were predicted by older age, higher burden, more symptoms of anxiety, less proactive coping strategies of the partner, and more depressive symptoms of the patients. Conclusions Burden, anxiety and depressive symptoms are interrelated and become chronic in partners of patients with stroke. It is important to screen partners early after stroke to identify partners who are at risk for negative outcomes.
Cortico‐thalamocortical interactions for learning, memory and decision‐making

The thalamus and cortex are interconnected both functionally and anatomically and share a common developmental trajectory. Interactions between the mediodorsal thalamus (MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as learning and adaptive decision‐making. Cortico‐thalamocortical interactions involving other dorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these cognitive processes. Our work, and that of others, indicates a crucial influence of these interdependent cortico‐thalamocortical neural networks that contributes actively to the processing of information within the cortex. Each of these thalamic nuclei also receives potent subcortical inputs that are likely to provide additional influences on their regulation of cortical activity. Here, we highlight our current neuroscientific research aimed at establishing when cortico‐MD thalamocortical neural network communication is vital within the context of a rapid learning and memory discrimination task. We are collecting evidence of MD–prefrontal cortex neural network communication in awake, behaving male rhesus macaques. Given the prevailing evidence, further studies are needed to identify both broad and specific mechanisms that govern how the MD, anterior thalamus and pulvinar cortico‐thalamocortical interactions support learning, memory and decision‐making. Current evidence shows that the MD (and the anterior thalamus) are crucial for frontotemporal communication, and the pulvinar is crucial for frontoparietal communication. Such work is crucial to advance our understanding of the neuroanatomical and physiological bases of these brain functions in humans. In turn, this might offer avenues to develop effective treatment strategies to improve the cognitive deficits often observed in many debilitating neurological disorders and diseases and in neurodegeneration.
Developmental exposure to the brominated flame retardant DE-71 reduces serum thyroid hormones in rats without hypothalamic-pituitary-thyroid axis activation or neurobehavioral changes in offspring

Polybrominated diphenyl ethers (PBDEs) are legacy flame retardants for which human exposure remains ubiquitous. This is of concern since these chemicals can perturb development and cause adverse health effects. For instance, DE-71, a technical mixture of PBDEs, can induce liver toxicity as well as reproductive and developmental toxicity. DE-71 can also disrupt the thyroid hormone (TH) system which may induce developmental neurotoxicity indirectly. However, in developmental toxicity studies, it remains unclear how DE-71 exposure affects the offspring’s thyroid hormone system and if this dose-dependently relates to neurodevelopmental effects. To address this, we performed a rat toxicity study by exposing pregnant dams to DE-71 at 0, 40 or 60 mg/kg/day during perinatal development from gestational day 7 to postnatal day 16. We assessed the TH system in both dams and their offspring, as well as potential hearing and neurodevelopmental effects in prepubertal and adult offspring. DE-71 significantly reduced serum T4 and T3 levels in both dams and offspring without a concomitant upregulation of TSH, thus inducing a hypothyroxinemia-like effect. No discernible effects were observed on the offspring’s brain function when assessed in motor activity boxes and in the Morris water maze, or on offspring hearing function. Our results, together with a thorough review of the literature, suggest that DE-71 does not elicit a clear dose-dependent relationship between low serum thyroxine (T4) and effects on the rat brain in standard behavioral assays. However, low serum TH levels are in themselves believed to be detrimental to human brain development, thus we propose that we lack assays to identify developmental neurotoxicity caused by chemicals disrupting the TH system through various mechanisms.
A LAMP-based toolbox developed for detecting the major pathogens affecting the production and quality of the Chinese medicinal crop Aconitum carmichaelii Debx.

Aconitum carmichaelii Debeaux is a traditional Chinese medicinal herb that has been utilized for approximately two thousand years. However, as cultivation has increased, there have been more reports of A. carmichaelii infections caused by four major pathogenic fungal species, Fusarium oxysporum, F. solani, Mucor circinelloides, and Sclerotium rolfsii, resulting in increased disease incidences and limited production and quality. To detect these infections, we developed a LAMP-based toolbox in this study. The cytochrome c oxidase subunit 1 (cox1) gene, translation elongation factor-1α (EF-1α), internal transcribed spacer (ITS) regions of rDNA, and alcohol dehydrogenase 1 (ADH1) gene, respectively, were used to design species-specific LAMP primer sets for F. oxysporum, F. solani, S. rolfsii, and M. circinelloides. The results showed that the LAMP-based toolbox was effective at detecting pathogens in soil and plant materials. We also used this toolbox to investigate pathogen infection in the main planting regions of A. carmichaelii. Before harvesting, F. oxysporum, M. circinelloides, and S. rolfsii, were commonly found in the planting fields and in infected A. carmichaelii plants. Therefore, the toolbox we developed will be useful for tracking these infections, as well as for disease control in A. carmichaelii.
Dog Ownership and Risk for Alveolar Echinococcosis, Germany

Human alveolar echinococcosis is caused by the parasite Echinococcus multilocularis, and dog ownership has been identified as a risk factor. We sought to specify the factors of dog ownership underlying this risk by conducting a case–control study among dog owners in Germany. The analysis revealed an increased odds ratio of ≈7-fold for dog owners whose dogs roam unattended in fields, 13-fold for dog owners who feed their dogs organic waste daily, 4-fold for dog owners who take their dog to a veterinarian only in case of illness, and 10-fold for dog owners who have never been informed by a veterinarian about the risk for infection. The results highlight the risk for infection associated with various factors of dog ownership and the value of veterinarians informing owners about prevention.
Machine learning‐guided covariate selection for time‐to‐event models developed from a small sample of real‐world patients receiving bevacizumab treatment

Therapeutic outcomes in patients with metastatic colorectal cancer (mCRC) receiving bevacizumab treatment are highly variable, and a reliable predictive factor is not available. Progression‐free survival (PFS) and overall survival (OS) were recorded from an observational, prospective study after 5 years of follow‐up, including 46 patients with mCRC receiving bevacizumab treatment. Three vascular endothelial growth factor (VEGF)‐A and two intercellular adhesion molecule‐1 genes polymorphisms, age, gender, weight, dosing scheme, and co‐treatments were collected. Given the relatively small number of events (37 [80%] for the PFS and 26 [57%] for the OS), to study the effect of these covariates on PFS and OS, a covariate analysis was performed using statistical and supervised machine learning techniques, including Cox regression, penalized Cox regression techniques (least absolute shrinkage and selection operator [LASSO], ridge regression, and elastic net), survival trees, and survival forest. The predictive performance of each method was evaluated in bootstrapped samples, using prediction error curves and the area under the curve of the receiver operating characteristic. The LASSO penalized Cox‐regression model showed the best overall performance. Nonlinear mixed effects (NLME) models were developed, and a conventional stepwise covariate search was performed. Then, covariates identified as important by the LASSO model were included in the base NLME models developed for PFS and OS, resulting in improved models as compared to those obtained with the stepwise covariate search. It was shown that having gene polymorphisms in VEGFA (rs699947 and rs1570360) and ICAM1 (rs1799969) are associated with a favorable clinical outcome in patients with mCRC receiving bevacizumab treatment.
Natural killer cells during acute HIV-1 infection: clues for HIV-1 prevention and therapy

Despite progress in preexposure prophylaxis, the number of newly diagnosed cases with HIV-1 remains high, highlighting the urgent need for preventive and therapeutic strategies to reduce HIV-1 acquisition and limit disease progression. Early immunological events, occurring during acute infection, are key determinants of the outcome and course of disease. Understanding early immune responses occurring before viral set-point is established, is critical to identify potential targets for prophylactic and therapeutic approaches. Natural killer (NK) cells represent a key cellular component of innate immunity and contribute to the early host defence against HIV-1 infection, modulating the pathogenesis of acute HIV-1 infection (AHI). Emerging studies have identified tools for harnessing NK cell responses and expanding specialized NK subpopulations with adaptive/memory features, paving the way for development of novel HIV-1 therapeutics. This review highlights the knowns and unknowns regarding the role of NK cell subsets in the containment of acute HIV-1 infection, and summarizes recent advances in selectively augmenting NK cell functions through prophylactic and therapeutic interventions.
Proteomic Network of Antibiotic-Induced Outer Membrane Vesicles Released by Extensively Drug-Resistant Elizabethkingia anophelis

Elizabethkingia anophelis is a bacterium often associated with nosocomial infection. This study demonstrated that imipenem-induced E. anophelis outer membrane vesicles (OMVs) are immunologically relevant and crucial for bacterial survival under antibiotic stress conditions rather than being a source of antibiotic resistance. ABSTRACT Elizabethkingia anophelis, a nonfermenting Gram-negative bacterium, causes life-threatening health care-associated infections. E. anophelis harbors multidrug resistance (MDR) genes and is intrinsically resistant to various classes of antibiotics. Outer membrane vesicles (OMVs) are secreted by Gram-negative bacteria and contain materials involved in bacterial survival and pathogenesis. OMVs specialize and tailor their functions by carrying different components to challenging environments and allowing communication with other microorganisms or hosts. In this study, we sought to understand the characteristics of E. anophelis OMVs under different antibiotic stress conditions. An extensively drug-resistant clinical isolate, E. anophelis C08, was exposed to multiple antibiotics in vitro, and its OMVs were characterized using nanoparticle tracking analysis, transmission electron microscopy, and proteomic analysis. Protein functionality analysis showed that the OMVs were predominantly involved in metabolism, survival, defense, and antibiotic resistance processes, such as the Rag/Sus family, the chaperonin GroEL, prenyltransferase, and an HmuY family protein. Additionally, a protein-protein interaction network demonstrated that OMVs from imipenem-treated E. anophelis showed significant enrichments in the outer membrane, adenyl nucleotide binding, serine-type peptidase activity, the glycosyl compound metabolic process, and cation binding proteins. Collectively, the OMV proteome expression profile indicates that the role of OMVs is immunologically relevant and related to bacterial survival in antibiotic stress environments rather than representing a resistance point. IMPORTANCE Elizabethkingia anophelis is a bacterium often associated with nosocomial infection. This study demonstrated that imipenem-induced E. anophelis outer membrane vesicles (OMVs) are immunologically relevant and crucial for bacterial survival under antibiotic stress conditions rather than being a source of antibiotic resistance. Furthermore, this is the first study to discuss the protein-protein interaction network of the OMVs released by E. anophelis, especially under antibiotic stress. Our findings provide important insights into clinical antibiotic stewardship.
Draft Genome Sequence of Pseudomonas sp. Strain MWU13-2517, Isolated from a Wild Cranberry Bog in Provincetown, MA

Pseudomonas spp. are dominant in many soils, but little is known about how they interact with other members of the soil microbiome. Pseudomonas sp. strain MWU13-2516, isolated from a wild cranberry bog in Massachusetts, has predicted genes for hemolysins, usually associated with pathogens, and type 6 secretion systems. ABSTRACT Pseudomonas spp. are dominant in many soils, but little is known about how they interact with other members of the soil microbiome. Pseudomonas sp. strain MWU13-2516, isolated from a wild cranberry bog in Massachusetts, has predicted genes for hemolysins, usually associated with pathogens, and type 6 secretion systems.