Miracle-dz/UniFAR-FTUs huggingface dataset:
Stroke and HIV‐associated neurological complications: A retrospective nationwide study

There is an increased risk of stroke and other neurological complications in human immunodeficiency virus (HIV) infected patients with no large population‐based studies in the literature. We aim to evaluate the prevalence of stroke, HIV‐associated neurological complications, and identify risk factors associated with poor outcomes of stroke among HIV admissions in the United States. In the nationwide inpatient sample with adult HIV hospitalizations, patients with primary cerebrovascular disease (CeVDs) and HIV‐associated neurological complications were identified by ICD‐9‐CM codes. We performed a retrospective study with weighted analysis to evaluate the prevalence of stroke and neurological complications and outcomes of stroke among HIV patients. We included 1,559,351 HIV admissions from 2003 to 2014, of which 22470 (1.4%) patients had CeVDs (transient ischemic attack [TIA]: 3240 [0.2%], acute ischemic stroke [AIS]: 14895 [0.93%], and hemorrhagic stroke [HS]: 4334 [0.27%]), 7781 (0.49%) had neurosyphilis, 29,925 (1.87%) meningitis, 39,190 (2.45%) cytomegalovirus encephalitis, 4699 (0.29%) toxoplasmosis, 9964 (0.62%) progressive multifocal leukoencephalopathy, and 142,910 (8.94%) epilepsy. There is increased overall prevalence trend for CeVDs (TIA: 0.17%–0.24%; AIS: 0.62%–1.29%; HS: 0.26%–0.31%; pTrend < .0001) from 2003 to 2014. Among HIV admissions, variables associated with AIS were neurosyphilis (odds ratio: 4.38; 95% confidence interval: 3.21–5.97), meningitis (4.87 [4.10–5.79]), and central nervous system tuberculosis (6.72 [3.85–11.71]). Toxoplasmosis [4.27 [2.34–7.76]), meningitis (2.91 [2.09–4.06)], and cytomegalovirus encephalitis (1.62 [1.11–2.37]) were associated with higher odds of HS compared to patients without HS. There was an increasing trend of CeVDs over time among HIV hospitalizations. HIV‐associated neurological complications were associated with the risk of stroke, together with increased mortality, morbidity, disability, and discharge to long‐term care facilities. Further research would clarify stroke risk factors in HIV patients to mitigate adverse outcomes.
Bayesian estimation of cell type–specific gene expression with prior derived from single-cell data

When assessed over a large number of samples, bulk RNA sequencing provides reliable data for gene expression at the tissue level. Single-cell RNA sequencing (scRNA-seq) deepens those analyses by evaluating gene expression at the cellular level. Both data types lend insights into disease etiology. With current technologies, scRNA-seq data are known to be noisy. Constrained by costs, scRNA-seq data are typically generated from a relatively small number of subjects, which limits their utility for some analyses, such as identification of gene expression quantitative trait loci (eQTLs). To address these issues while maintaining the unique advantages of each data type, we develop a Bayesian method (bMIND) to integrate bulk and scRNA-seq data. With a prior derived from scRNA-seq data, we propose to estimate sample-level cell type–specific (CTS) expression from bulk expression data. The CTS expression enables large-scale sample-level downstream analyses, such as detection of CTS differentially expressed genes (DEGs) and eQTLs. Through simulations, we show that bMIND improves the accuracy of sample-level CTS expression estimates and increases the power to discover CTS DEGs when compared to existing methods. To further our understanding of two complex phenotypes, autism spectrum disorder and Alzheimer's disease, we apply bMIND to gene expression data of relevant brain tissue to identify CTS DEGs. Our results complement findings for CTS DEGs obtained from snRNA-seq studies, replicating certain DEGs in specific cell types while nominating other novel genes for those cell types. Finally, we calculate CTS eQTLs for 11 brain regions by analyzing Genotype-Tissue Expression Project data, creating a new resource for biological insights.
Sequence of αPD-1 relative to local tumor irradiation determines the induction of abscopal antitumor immune responses

The magnitude of antitumor abscopal effects is determined by the sequence of checkpoint blockade in relation to local tumor irradiation. Order of immunotherapy matters Immune checkpoint blockade is clinically successful in various cancer types, yet many treated patients recur; thus, determining effective combination therapies that induce systemic antitumor immunity is crucial. Immune checkpoint blockade combined with local radiation can improve antitumor responses, but it remains unclear how the sequence of these therapies alters efficacy. Here, Wei et al. used mouse tumor models to demonstrate that treatment with anti–PD-1 after stereotactic body radiation therapy (SBRT) elicited superior systemic antitumor immunity, abscopal effects, and protection compared with anti–PD-1 given before SBRT. These data correlated to improved intratumoral CD8+ T cell responses and decreased CD8+ T cell death in local and distant tumors. This work provides preclinical rationale for giving anti–PD-1 after SBRT in patients with cancer. Although radiotherapy has been used for over a century to locally control tumor growth, alone it rarely induces an abscopal response or systemic antitumor immunity capable of inhibiting distal tumors outside of the irradiation field. Results from recent studies suggest that combining immune checkpoint blockades to radiotherapy may enhance abscopal activity. However, the treatment conditions and underlying immune mechanisms that consistently drive an abscopal response during radiation therapy combinations remain unknown. Here, we analyzed the antitumor responses at primary and distal tumor sites, demonstrating that the timing of αPD-1 antibody administration relative to radiotherapy determined the potency of the induced abscopal response. Blockade of the PD-1 pathway after local tumor irradiation resulted in the expansion of polyfunctional intratumoral CD8+ T cells, a decrease in intratumoral dysfunctional CD8+ T cells, expansion of reprogrammable CD8+ T cells, and induction of potent abscopal responses. However, administration of αPD-1 before irradiation almost completely abrogated systemic immunity, which associated with increased radiosensitivity and death of CD8+ T cells. The subsequent reduction of polyfunctional effector CD8+ T cells at the irradiated tumor site generated a suboptimal systemic antitumor response and the loss of abscopal responses. Therefore, this report maximizes the potential synergy between radiotherapy and αPD-1 immunotherapy, information that will benefit clinical combinations of radiotherapy and immune checkpoint blockade.
COVID-19-Related Occupational Burnout and Moral Distress among Nurses: A Rapid Scoping Review.

Background The COVID-19 pandemic is placing unprecedented pressure on a nursing workforce that is already under considerable mental strain due to an overloaded system. Convergent evidence from the current and previous pandemics indicates that nurses experience the highest levels of psychological distress compared with other health professionals. Nurse leaders face particular challenges in mitigating risk and supporting nursing staff to negotiate moral distress and fatigue during large-scale, sustained crises. Synthesizing the burgeoning literature on COVID-19-related burnout and moral distress faced by nurses and identifying effective interventions to reduce poor mental health outcomes will enable nurse leaders to support the resilience of their teams. Aim This paper aims to (1) synthesize existing literature on COVID-19-related burnout and moral distress among nurses and (2) identify recommendations for nurse leaders to support the psychological needs of nursing staff. Methods Comprehensive searches were conducted in Medline, Embase and PsycINFO (via Ovid); CINAHL (via EBSCOHost); and ERIC (via ProQUEST). The rapid review was completed in accordance with the World Health Organization Rapid Review Guide. Key Findings Thematic analysis of selected studies suggests that nurses are at an increased risk for stress, burnout and depression during the ongoing COVID-19 pandemic. Younger female nurses with less clinical experience are more vulnerable to adverse mental health outcomes.
Emotion and humor as misinformation antidotes

Many visible public debates over scientific issues are clouded in accusations of falsehood, which place increasing demands on citizens to distinguish fact from fiction. Yet, constraints on our ability to detect misinformation coupled with our inadvertent motivations to believe false science result in a high likelihood that we will form misperceptions. As science falsehoods are often presented with emotional appeals, we focus our perspective on the roles of emotion and humor in the formation of science attitudes, perceptions, and behaviors. Recent research sheds light on how funny science and emotions can help explain and potentially overcome our inability or lack of motivation to recognize and challenge misinformation. We identify some lessons learned from these related and growing areas of research and conclude with a brief discussion of the ethical considerations of using persuasive strategies, calling for more dialogue among members of the science communication community.
Knowledge, preventive behaviors and risk perception of the COVID-19 pandemic: A cross-sectional study in Turkish health care workers

The coronavirus disease 2019 (COVID-19) outbreak spread to over 100 countries with a total of 100,000 cases during the first week of March 2020. Health care workers, as those on the frontline of the COVID-19 pandemic, are more susceptible to infection. Inadequate related knowledge and preventive behaviors among health care workers might lead to delayed treatment and result in the rapid spread of the infection. Therefore, this study evaluated the knowledge of health care workers with regard to COVID-19. A cross-sectional study was conducted from June 10–18, 2020. Participants were general practitioners, specialists, and nurses working at the forefront of the pandemic. Their knowledge, preventive behaviors, and risk perceptions concerning COVID-19 were evaluated using an online questionnaire created by our medical specialists. The questionnaire consisted of 29, 5, and 4 items about COVID-19 knowledge, preventive behaviors, and risk perceptions, respectively. A total of 251 health care workers completed the questionnaire. The mean age of the participants was 33.88±8.72 years old, and the sample consisted of 68 males (27.08%) and 183 females (72.91%). While there was no difference between the percentage of correct answers given by female and male participants to knowledge-based questions (p>0.05), the percentage of correct answers to the questions on preventive behaviors was significantly higher in female participants than in males (p<0.001). The overall average percentages of correct responses were 91.66% for knowledge-based questions and 85.96% for preventive behavior questions. The scores for knowledge-based questions were higher for medical specialists, whereas nurses scored higher on preventive behavior questions. Government hospital staff showed a significant difference in preventive behaviors compared to that of university hospitals (p<0.05). In addition, there was a positive correlation between knowledge scores and preventive behaviors. Although all the participants (100%) knew that contracting COVID-19 can lead to death, only 66.93% of them were willing to get vaccinated themselves. The knowledge level of health care workers concerning COVID-19 was above 90%, but the level of competence in terms of preventive behaviors was found to be low, especially in males.
An equine tendon model for studying intra-tendinous shear in tendons that have more than one muscle contribution

Human Achilles tendon is composed of three smaller sub-tendons and exhibits non-uniform internal displacements, which decline with age and after injury, suggesting a potential role in the development of tendinopathies. Studying internal sliding behaviour is therefore important but difficult in human Achilles tendon. Here we propose the equine deep digital flexor tendon (DDFT) and its accessory ligament (AL) as a model to understand the sliding mechanism. The AL-DDFT has a comparable sub-bundle structure, is subjected to high and frequent asymmetric loads and is a natural site of injury similar to human Achilles tendons. Equine AL-DDFT were collected and underwent whole tendon level (n=7) and fascicle level (n=7) quasi-static mechanical testing. Whole tendon level testing was performed by sequentially loading through the proximal AL and subsequently through the proximal DDFT and recording regional strain in the free structures and joined DDFT and AL. Fascicle level testing was performed with focus on the inter-sub-bundle matrix between the two structures at the junction. Our results demonstrate a significant difference in the regional strain between the joined DDFT and AL and a greater transmission of force from the AL to the DDFT than vice versa. These results can be partially explained by the mechanical properties and geometry of the two structures and by differences in the properties of the interfascicular matrices. In conclusion, this tendon model successfully demonstrates that high displacement discrepancy occurs between the two structures and can be used as an easy-access model for study intra-tendinous shear mechanics at the sub-tendon level.
Seroprevalence of SARS-CoV-2 following the largest initial epidemic wave in the United States: Findings from New York City, May 13-July 21, 2020

Abstract Background New York City (NYC) was the U.S. epicenter of the Spring 2020 COVID-19 pandemic. We present seroprevalence of SARS-CoV-2 infection and correlates of seropositivity immediately after the first wave. Methods From a serosurvey of adult NYC residents (May 13-July 21, 2020), we calculated the prevalence of SARS-CoV-2 antibodies stratified by participant demographics, symptom history, health status, and employment industry. We used multivariable regression models to assess associations between participant characteristics and seropositivity. Results Seroprevalence among 45,367 participants was 23.6% (95% CI, 23.2%-24.0%). High seroprevalence (>30%) was observed among Black and Hispanic individuals, people from high poverty neighborhoods, and people in health care or essential worker industry sectors. COVID-19 symptom history was associated with seropositivity (adjusted relative risk=2.76; 95% CI, 2.65-2.88). Other risk factors included sex, age, race/ethnicity, residential area, employment sector, working outside the home, contact with a COVID-19 case, obesity, and increasing numbers of household members. Conclusions Based on a large serosurvey in a single U.S. jurisdiction, we estimate that just under one-quarter of NYC adults were infected in the first few months of the COVID-19 epidemic. Given disparities in infection risk, effective interventions for at-risk groups are needed during ongoing transmission.
Real-World Data (RWD) on the 3-Year Follow-Up Outcomes of Different CNS Prophylaxis Strategies Across CNS-IPI Risk Groups in Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

PURPOSE CNS relapse in patients with diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis with a median survival of about 2.5 months. Data demonstrating best prophylactic strategy remain controversial and need further definition. PATIENTS AND METHODS We present data of 110 patients with DLBCL treated with standard systemic therapy divided into four groups based on primary CNS prophylaxis strategy and CNS International Prognostic Index (IPI) risk categories. We compared their 3-year CNS relapse rate and overall survival in each group. RESULTS The CNS prophylaxis strategy consisted of intrathecal (IT) methotrexate (MTX) in group 1, high-dose (HD) MTX in group 2, combination IT and HD MTX in group 3, and IT and/or HD MTX with intensive chemotherapy in group 4. At 3 years, CNS relapse rate was 8.6% (4/46), 8.3% (1/12), 4.8% (2/42), and 18% (2/11) in groups 1-4 (P = .64), respectively. According to CNS IPI, the CNS relapse rate was 16.6%, 10.1%, and 0% in high-, intermediate-, and low-risk groups, respectively. The 3-year overall survival rate was 69%, 75%, 80%, and 45% in groups 1-4 (P = .71), respectively. CONCLUSION Our study while did not find statistical significance did indicate a lower incidence of CNS relapse with the addition of systemic HD MTX to IT MTX in the high-risk DLBCL population.
Enhancing clinical and immunological effects of anti-PD-1 with belapectin, a galectin-3 inhibitor

Background PD-1/PD-L1 engagement and overexpression of galectin-3 (Gal-3) are critical mechanisms of tumor-induced immune suppression that contribute to immunotherapy resistance. We hypothesized that Gal-3 blockade with belapectin (GR-MD-02) plus anti-PD-1 (pembrolizumab) would enhance tumor response in patients with metastatic melanoma (MM) and head and neck squamous cell carcinoma (HNSCC). Methods We performed a phase I dose escalation study of belapectin+pembrolizumab in patients with advanced MM or HNSCC (NCT02575404). Belapectin was administered at 2, 4, or 8 mg/kg IV 60 min before pembrolizumab (200 mg IV every 3 weeks for five cycles). Responding patients continued pembrolizumab monotherapy for up to 17 cycles. Main eligibility requirements were a functional Eastern Cooperative Oncology Group status of 0–2, measurable or assessable disease, and no active autoimmune disease. Prior T-cell checkpoint antibody therapy was permitted. Results Objective response was observed in 50% of MM (7/14) and and 33% of HNSCC (2/6) patients. Belapectin+pembrolizumab was associated with fewer immune-mediated adverse events than anticipated with pembrolizumab monotherapy. There were no dose-limiting toxicities for belapectin within the dose range investigated. Significantly increased effector memory T-cell activation and reduced monocytic myeloid-derived suppressor cells (M-MDSCs) were observed in responders compared with non-responders. Increased baseline expression of Gal-3+ tumor cells and PD-1+CD8+ T cells in the periphery correlated with response as did higher serum trough levels of pembrolizumab. Conclusions Belapectin+pembrolizumab therapy has activity in MM and HNSCC. Increased Gal-3 expression, expansion of effector memory T cells, and decreased M-MDSCs correlated with clinical response. Further investigation is planned.
Multilevel Deep-Aggregated Boosted Network to Recognize COVID-19 Infection from Large-Scale Heterogeneous Radiographic Data

In the present epidemic of the coronavirus disease 2019 (COVID-19), radiological imaging modalities, such as X-ray and computed tomography (CT), have been identified as effective diagnostic tools. However, the subjective assessment of radiographic examination is a time-consuming task and demands expert radiologists. Recent advancements in artificial intelligence have enhanced the diagnostic power of computer-aided diagnosis (CAD) tools and assisted medical specialists in making efficient diagnostic decisions. In this work, we propose an optimal multilevel deep-aggregated boosted network to recognize COVID-19 infection from heterogeneous radiographic data, including X-ray and CT images. Our method leverages multilevel deep-aggregated features and multistage training via a mutually beneficial approach to maximize the overall CAD performance. To improve the interpretation of CAD predictions, these multilevel deep features are visualized as additional outputs that can assist radiologists in validating the CAD results. A total of six publicly available datasets were fused to build a single large-scale heterogeneous radiographic collection that was used to analyze the performance of the proposed technique and other baseline methods. To preserve generality of our method, we selected different patient data for training, validation, and testing, and consequently, the data of same patient were not included in training, validation, and testing subsets. In addition, fivefold cross-validation was performed in all the experiments for a fair evaluation. Our method exhibits promising performance values of 95.38%, 95.57%, 92.53%, 98.14%, 93.16%, and 98.55% in terms of average accuracy, F-measure, specificity, sensitivity, precision, and area under the curve, respectively and outperforms various state-of-the-art methods.
Influence of Soil Variation on Diosgenin Content Profile in Costus speciosus from Indo‐Gangetic Plains

Costus speciosus is a rich source of commercially important compound Diosgenin, distributed in different regions of India. The present investigation was aimed to quantify diosgenin through High Performance Thin Layer Chromatography in 34 germplasms of Costus speciosus and also to identify the superior sources and to correlate the macronutrients of rhizospheric soil. The starch content varied in microscopic examination and correlated inversely (r=−0.266) with diosgenin content. Findings revealed that the extraction process with acid hydrolysis yielded higher diosgenin content (0.15–1.88 %) as compared to non‐hydrolysis (0.009–0.368 %) procedure. Germplasms from Uttar Pradesh (NBCS‐4), Jharkhand (NBCS‐39) and Bihar (NBCS‐2) were identified as elite chemotypes based on hierarchical clustering analysis. The phosphorous content of respective rhizospheric soil correlated positively (r=0.742) with diosgenin content. Findings of present study are useful to identify the new agrotechniques. The elite germplasms can also be used as quality planting material for large scale cultivation in order to assure a sustained supply to the herbal drug industry.
DNA methylation and brain dysmaturation in preterm infants

Preterm birth is associated with dysconnectivity of structural brain networks and is a leading cause of neurocognitive impairment in childhood. Variation in DNA methylation (DNAm) is associated with early exposure to extrauterine life but there has been little research exploring its relationship with brain development. Using genome-wide DNA methylation data from saliva of 258 neonates, we investigated the impact of gestational age on the methylome and performed functional analysis to identify enriched gene sets from probes that contributed to differentially methylated probes (DMPs) or regions (DMRs). We tested the hypothesis that variation in DNAm could underpin the association between preterm birth and atypical brain development by linking DMPs with measures of white matter connectivity derived from diffusion MRI metrics: peak width of skeletonised mean diffusivity (PSMD), fractional anisotropy (PSFA) and neurite density index (PSNDI). Gestational age at birth was associated with widespread differential methylation, with genome-wide significant associations observed for 8,870 CpG probes (p<3.6x10-8) and 1,767 differentially methylated regions. Functional analysis identified 14 enriched gene ontology terms pertaining to cell-cell contacts and cell-extracellular matrix contacts. Principal component analysis of probes with genome-wide significance revealed a first principal component (PC1) that explained 23.5% of variance in DNAm, and this was negatively associated with gestational age at birth. PC1 was associated with PSMD ({beta}=0.349, p=8.37x10-10) and PSNDI ({beta}=0.364, p=4.15x10-5), but not with PSFA ({beta}=-0.035, p=0.510); these relationships mirrored the imaging metrics associations with gestational age at birth. Gestational age at birth has a profound and widely distributed effect on the neonatal saliva methylome. Enriched gene ontology terms related to cell-cell contacts reveal pathways that could mediate the effect of early life environmental exposures on development. Finally, associations between differential DNAm and image markers of white matter tract microstructure suggest that variation in DNAm may provide a link between preterm birth and the dysconnectivity of developing brain networks that characterises atypical brain development in preterm infants.