Miracle-dz/UniFAR-FTUs huggingface dataset:
Insight on the Genetics of Atrial Fibrillation in Puerto Rican Hispanics

Non-Hispanic whites present with higher atrial fibrillation (AF) prevalence than other racial minorities living in the mainland USA. In two hospital-based studies, Puerto Rican Hispanics had a lower prevalence of atrial fibrillation of 2.5% than non-Hispanic Whites with 5.7%. This data is particularly controversial because Hispanics possess a higher prevalence of traditional risk factors for developing AF yet have a lower AF prevalence. This phenomenon is known as the atrial fibrillation paradox. Despite recent advancements in understanding AF, its pathogenesis remains unclear. In this study, we compared a genetic dataset of Puerto Rican Hispanics to 111 SNP known to be associated with AF in a large European cohort and determine if they are associated with AF susceptibility in our cohort. To achieve this aim, we performed a secondary analysis of existing data using the following two studies: (1) The Pharmacogenetics of Warfarin in Puerto Ricans study and the (2) A Genomic Approach for Clopidogrel in Caribbean Hispanics, and assess for the presence of European SNPs associated with AF from the genome-wide association study of 1 million people identifies 111 loci for atrial fibrillation. We used data from 555 cardiovascular Puerto Rican Hispanic patients, consisting of 486 control and 69 cases. We found that the following SNPs showed significant association with AF in PHR: rs2834618, rs6462079, rs7508, rs2040862, and rs10458660. Some of these SNPs are proteins involved in lysosomal activities responsible for breaking ceramides to sphingosines and collagen deposition around atrial cardiomyocytes. Furthermore, we performed a machine learning analysis and determined that Native American admixture and heart failure were strongly predictive of AF in PHR. For the first time, this study provides some genetic insight into AF's mechanisms in a Puerto Rican Hispanic cohort.
Nonalcoholic Fatty Liver Disease and Cardiovascular Diseases: The Heart of the Matter

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent cause of liver disease worldwide, comprising a plethora of conditions, ranging from steatosis to end-stage liver disease. Cardiovascular disease (CVD) has been associated with NAFLD and CVD-related events represent the main cause of death in patients with NAFLD, surpassing liver-related mortality. This association is not surprising as NAFLD has been considered a part of the metabolic syndrome and has been related to numerous CVD risk factors, namely, insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease, and type 2 diabetes. Moreover, both NAFLD and CVD present similar pathophysiological mechanisms, such as increased visceral adiposity, altered lipid metabolism, increased oxidative stress, and systemic inflammation that could explain their association. Whether NAFLD increases the risk for CVD or these diagnostic entities represent distinct manifestations of the metabolic syndrome has not yet been clarified. This review focuses on the relation between NAFLD and the spectrum of CVD, considering the pathophysiological mechanisms, risk factors, current evidence, and future directions.
Effect of Oral Administration with Lactobacillus plantarum CAM6 Strain on Sows during Gestation-Lactation and the Derived Impact on Their Progeny Performance

Background To evaluate the biological response of the sows and their offspring with oral administration of Lactobacillus plantarum CAM6 in breeding sows, a total of 20 Pietrain breeding sows with three farrowings and their descendants were used, randomly divided into two groups of 10 sows each. Treatments included a basal diet (T0) and basal diet +10 mL biological agent containing 109 CFU/mL L. plantarum CAM6 (T1). No antibiotics were used throughout the entire experimental process of this study. Results The L. Plantarum CAM6 supplementation in sows' feeding did not affect (P > 0.05) the reproductive performance of the sows; however, the number of deaths for their offspring before weaning (P ≤ 0.05) decreased. In addition, the oral administration of Lactobacillus plantarum CAM6 in sows increased (P ≤ 0.05) the content of lactose, nonfat solids, mineral salts, and the density of sows' milk, with a decrease in milk fat. Moreover, the probiotic feed orally to the sows improved the body weight (P ≤ 0.05) and reduced the diarrhea incidence of their offspring (P ≤ 0.05). Also, the probiotic administration of sows changed (P ≤ 0.05) the serum concentration of Na+, pCO2, and D-β-hydroxybutyrate and increased (P ≤ 0.05) the leukocytes, lymphocytes, and platelets in their piglets. Conclusion Oral administration of Lactobacillus plantarum CAM6 in breeding sows improved body weight, physiological status, and the health of their offspring. And preparing the neonatal piglets physiologically is of great importance to the pig farming industry which could decrease the operational cost and medication (especially antibiotics) consumption of the pig producers.
Evaluation of Hippo Pathway and CD133 in Radiation Resistance in Small-Cell Lung Cancer

Although the Hippo pathway and CD133 have been reported to play pertinent roles in a variety of cancer, knowledge about their contribution to radiation resistance in small-cell lung cancer (SCLC) is limited. In this first-of-a-kind study, we have reported the expression of key Hippo pathway proteins in SCLC patients by immunohistochemical staining. We assessed the involvement of yes-associated protein 1 (YAP1) in radiation resistance by Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, we analysed the impact of CD133 on radiotherapy for SCLC. The mammalian Ste20-like serine/threonine kinase 2(MST2), pMST2, and pYAP1 in the Hippo pathway were not significantly associated with the disease stage and survival time in patients with SCLC. However, the pYAP1 expression showed some significance in the “YAP/TAZ subgroup” of SCLC patients. The proportion of CD133 in the SCLC cells was controlled by the YAP1 expression. The CD133 and YAP1 levels were significantly correlation with each other in tissues of SCLC patients. We sorted and isolated the CD133+ and CD133−cells in H69 and found that the cell surface glycoprotein may be associated with the radiation resistance of SCLC.In summary, we have firstly reported the expression of key Hippo pathway proteins in SCLC patients. Furthermore, we also identified that CD133 may be controlled by the expression of YAP1 in the Hippo pathway and that CD133 may be associated with the radiation resistance of SCLC.
W196 and the β-Hairpin Motif Modulate the Redox Switch of Conformation and the Biomolecular Interaction Network of the Apoptosis-Inducing Factor

The human apoptosis-inducing factor (hAIF) is a moonlight flavoprotein involved in mitochondrial respiratory complex assembly and caspase-independent programmed cell death. These functions might be modulated by its redox-linked structural transition that enables hAIF to act as a NAD(H/+) redox sensor. Upon reduction with NADH, hAIF undergoes a conformational reorganization in two specific insertions—the flexible regulatory C-loop and the 190-202 β-harpin—promoting protein dimerization and the stabilization of a long-life charge transfer complex (CTC) that modulates its monomer-dimer equilibrium and its protein interaction network in healthy mitochondria. In this regard, here, we investigated the precise function of the β-hairpin in the AIF conformation landscape related to its redox mechanism, by analyzing the role played by W196, a key residue in the interaction of this motif with the regulatory C-loop. Mutations at W196 decrease the compactness and stability of the oxidized hAIF, indicating that the β-hairpin and C-loop coupling contribute to protein stability. Kinetic studies complemented with computational simulations reveal that W196 and the β-hairpin conformation modulate the low efficiency of hAIF as NADH oxidoreductase, contributing to configure its active site in a noncompetent geometry for hydride transfer and to stabilize the CTC state by enhancing the affinity for NAD+. Finally, the β-hairpin motif contributes to define the conformation of AIF's interaction surfaces with its physiological partners. These findings improve our understanding on the molecular basis of hAIF's cellular activities, a crucial aspect for clarifying its associated pathological mechanisms and developing new molecular therapies.
Insecticide resistance selection and reversal in two strains of Aedes aegypti

Background: Laboratory reared mosquito colonies are essential tools to understand insecticide action. However, they differ considerably from wild populations and from each other depending on their origin and rearing conditions, which makes studying the effects of specific resistance mechanisms difficult. This paper describes our methods for establishing multiple resistant strains of Aedes aegypti from two colonies as a new resource for further research on metabolic and target site resistance. Methods: Two resistant colonies of Ae. aegypti, from Cayman and Recife, were selected through 10 generations of exposure to insecticides including permethrin, malathion and temephos, to yield eight strains with different profiles of resistance due to either target site or metabolic resistance. Resistance ratios for each insecticide were calculated for the selected and unselected strains. The frequency of kdr alleles (F1534C and V1016I) in the Cayman strains was determined using TaqMan assays. A comparative gene expression analysis among Recife strains was conducted using qPCR in larvae (CCae3A, CYP6N12, CYP6F3, CYP9M9) and adults (CCae3A, CYP6N12, CYP6BB2, CYP9J28a). Results: In the selected strain of Cayman, mortality against permethrin reduced almost to 0% and kdr became fixated by 5 generations. A similar phenotype was seen in the unselected homozygous resistant colony, whilst mortality in the susceptible homozygous colony rose to 82.9%. The Recife strains showed different responses between exposure to adulticide and larvicide, with detoxification genes in the temephos selected strain staying similar to the baseline, but a reduction in detoxification genes displayed in the other strains. Conclusions: These selected strains, with a range of insecticide resistance phenotypes and genotypes, will support further research on the effects of target-site and/or metabolic resistance mechanisms on various life-history traits, behaviours and vector competence of this important arbovirus vector.
Transport and diffusion calculations on MRI-generated data

In this study we analyze the limits of the diffusion approximation to the Boltzmann transport equation for photon propagation in the human brain. Two dimensional slices through the head are obtained with the method of magnetic resonance imaging (MRI). Based on these images we assign optical properties to different regions of the brain. A finite- difference transport/diffusion code is then used to calculate the fluence throughout the head. Differences between diffusion and transport calculations occur especially in void-like spaces and regions where the absorption coefficient is comparable to the reduced scattering coefficient.
Laboratory intercomparison of marine particulate digestions including Piranha: a novel chemical method for dissolution of polyethersulfone filters

The US GEOTRACES program will generate marine particulate trace metal data over spatial scales and depth resolutions never before sampled. In preparation for these analyses, we conducted a four laboratory intercomparison exercise to determine our degree of intercalibration and to examine how several total digestion procedures perform on marine particles collected on polyethersulfone (PES, Pall Supor) filters. In addition, we present a new chemical method for complete dissolution of PES filters using a combination of sulfuric acid and hydrogen peroxide called Piranha reagent that can be conducted using minimal specialized equipment. Intralaboratory subsampling variability across 142 mm particulate matter filters, for subsamples representing approximately 10 L filtered seawater, was measured at an element‐dependent 1% to 9% (RSD: 1δ/x-, %), whereas interlaboratory variability accounted for an additional 5% to 42% variability. Lab‐ and element‐specific trends in recoveries are discussed, though all digestion methods tested appear to completely solubilize particulate material. We recommend rigorous determination of digest‐acid and/or filter process blanks, as some particulate elements (namely Pb and Zn) have natural abundances that approach blank values.
Nanocomposite of SWNTs and SnO2 fabricated by soldering process for ammonia gas sensor application

We introduce a simple method to fabricate an ammonia gas sensor with a nanocomposite of single‐walled carbon nanotubes (SWNTs) and SnO2. The nanocomposite showed a semiconducting property. With exposure to ammonia gas, the electrical resistance of the nanocomposite sensor increases rapidly. It was found that the sensor can detect the concentration of NH3 down to the 10 ppm level at room temperature. The sensor exhibited a fast response time of less than 100 s and good sensing response and recovery. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Higher tolerance of a novel lipase from Aspergillus flavus to the presence of free fatty acids at lipid/water interface

The main objective of this work was to identify novel lipases of industrial interest. In this paper, Aspergillus flavus lipase (AFL) was isolated from the traditional tannery of Fez city in Morocco; it kept its stability even in the presence of high concentrations of detergent from 0 to 10 mM sodium deoxycholate (NaDC). Bile salts showed no inhibitory effect on the lipolytic activity, whereas the calcium salts showed a stimulating action on the lipase activity. Unlike most of the lipases which were quickly denatured at the lipid/water interface, the accumulation of free fatty acids at the oil/water interface did not affect the activity of the enzyme which effectively hydrolyzed the emulsified olive oil even in the absence of bile salts. Furthermore, AFL was more active on long chain triacylglycerols than on short chain triacylglycerols. This study allowed us to prove that AFL had the interfacial activation phenomenon. A 3D structure model of AFL was built and we have concluded that the ratio hydrophobic surface/hydrophilic surface was 51% versus 50%; it could be responsible for a higher tolerance to the presence of free fatty acids at lipid/water interface. Key words: Aspergillus flavus lipase (AFL), detergent, interfacial activation, free fatty acids, model.
Loneliness and the onset of new mental health problems in the general population: a systematic review

Background Loneliness is associated poor health including premature mortality. There are cross sectional associations with depression, anxiety, psychosis and other mental health outcomes. However, the direction of causation is unclear and clarifying the evidence from longitudinal studies is a key step in understanding this relationship. Aims We synthesized evidence from longitudinal studies investigating the relationship between loneliness and new onset of mental health problems, in the general population. Method We systematically searched six electronic databases, unpublished sources and hand-searching of references, up to March 2020. We conducted a meta-analysis of eight independent cohorts, and narrative synthesis of the remaining studies. Results We included 20 studies, of which the majority focused on depression. Our narrative synthesis concluded that loneliness at baseline is associated with subsequent new onset of depression. The few studies on anxiety also showed an association. Our meta analysis found a pooled adjusted odds ratio of 2.33 (95% C.I. 1.62 to 3.34) for risk of new onset depression in adults who were often lonely compared with people who were not often lonely. This should be interpreted with caution given evidence of heterogeneity. Most of the studies were in older adults. Conclusion Loneliness is a public mental health issue. There is growing evidence it is associated with the onset of depression and other common mental health problems. Future studies should explore its impact across the age range, look beyond depression, and explore the mechanisms involved.
A prediction model for COVID-19 prevalence based on demographic and healthcare parameters in Iran

Coronavirus Disease 2019 (COVID-19) pandemic has become the greatest threat to global health in only a matter of months. Iran struggling with COVID-19 coincidence with Nowruz vacations has led to horrendous consequences for both people and the public health workforce. Modeling approaches have been proved to be highly advantageous in taking appropriate actions in the early stages of the pandemic. To this date, no study has been conducted to model COVID-19 to investigate the impact of disease factors, especially after travel restrictions in Iran. In this study, we exploited the opportunities that Artificial neural networks offer to investigate contributing factors of early-stage coronavirus spread via generating a model to predict daily confirmed cases in Iran. We collected publicly available data of confirmed cases in 24 provinces from April 4, 2020, to May 2, 2020, with a list of explanatory factors. The factors were checked separately for any linear associations and to train and validate a multilayer perceptron network. The accuracy of the models was evaluated, the R2 scores were 0.842 for population distribution, 0.822 for health index, and 0.864 for the population in the provinces. Our results suggest the significant impact of the mentioned factors on disease spread in the time of travel restrictions when the vacation ended. Accordingly, this information can be implicated in assessing the risk of epidemics and future policy makings in this area.
Sequencing Data of North American SARS-CoV-2 Isolates Shows Widespread Complex Variants

Several new variants of the SARS-CoV-2 have been isolated in the United States, Mexico, and Canada. Many of the variants contain single variants of functional significance (e.g. S: N501Y increases transmissibility). To study the occurrence and co-circulation of these variants, we have developed an easy-to-use dashboard at https://janieslab.github. io/sars-cov-2.html. We created a multiple sequence alignment workflow and processing script to generate a variant dataset, which populates this dashboard. We then use the features of the dashboard, such as visualization of the single and complex nucleotide variants geospatially and in a color-coded matrix format. Users also interact with the dashboard to filter the underlying data to regions of interest and or variants of interest. The user can export reports based on the desired filters, which we intend to be used for regionally specific pandemic response. We find in Genbank, an isolate from Massachusetts containing [(S: Q677H), (ORF3a: Q57H), (M: A85S), (N: D377Y)] collected on September 11, 2020. Moreover, we find that many viral isolates bear a marker of increased transmissibility (S: N501Y) in linkage with at least one variant of concern isolated from Ohio also range across the Untied States and stretch from British Columbia, Canada to Mexico. When we analyze co-circulation of more complex variant constellations with (S: N501Y), we note that the Upper Midwest and Northeast United States contain these isolates. In summary, the viral variants that have raised concern in a few US States in recent reports are widespread. Based on the increase in the proportion of variant viruses being sampled and some empirical evidence in the United Kingdom, South Africa, and Ohio, these variants are likely to lead to increased transmission of SARS-CoV-2 across North America in the coming months.
Baseline functional connectivity in resting state networks associated with depression and remission status after 16 weeks of pharmacotherapy: A CAN-BIND Report

Understanding the neural underpinnings of major depressive disorder (MDD) and its treatment could improve treatment outcomes. While numerous studies have been conducted, findings are variable and large sample replications scarce. We aimed to replicate and extend altered functional connectivity findings in the default mode, salience and cognitive control networks (DMN, SN, and CCN respectively) associated with MDD and pharmacotherapy outcomes in a large, multi-site sample. Resting-state fMRI data were collected from 129 patients and 99 controls through the Canadian Biomarker Integration Network in Depression (CAN-BIND) initiative. Symptoms were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS). Connectivity was measured as correlations between four seeds (anterior and posterior DMN, SN and CCN) and all other brain voxels across participants. Partial least squares, a multivariate statistical technique, was used to compare connectivity prior to treatment between patients and controls, and between patients reaching remission early (MADRS smaller than 10 within 8 weeks), late (MADRS smaller than 10 within 16 weeks) or not at all. We replicated previous findings of altered connectivity in the DMN, SN and CCN in patients. In addition, baseline connectivity of the anterior/posterior DMN and SN seeds differentiated patients with different treatment outcomes. Weaker connectivity within the anterior DMN and between the anterior DMN and the SN and CCN characterised early remission; stronger connectivity within the SN and weaker connectivity between the SN and the DMN and CCN was related to late remission, of which the weaker SN - anterior DMN connectivity might specifically be associated with remission to dual pharmacotherapy; and connectivity strength between the posterior DMN and cingulate areas distinguished all three groups, with early remitters showing the strongest connections and non-remitters the weakest. The stability of these baseline patient differences was established in the largest single-site subsample of the data. Our replication and extension of altered connectivity within and between the DMN, SN and CCN highlighted previously reported and new differences between patients with MDD and controls, and revealed features that might predict remission prior to pharmacotherapy.
Multinational Prevalence of Neurological Phenotypes in Patients Hospitalized with COVID-19

OBJECTIVE: Neurological complications can worsen outcomes in COVID-19. We defined the prevalence of a wide range of neurological conditions among patients hospitalized with COVID-19 in geographically diverse multinational populations. METHODS: Using electronic health record (EHR) data from 348 participating hospitals across 6 countries and 3 continents between January and September 2020, we performed a cross-sectional study of hospitalized adult and pediatric patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test, both with and without severe COVID-19. We assessed the frequency of each disease category and 3-character International Classification of Disease (ICD) code of neurological diseases by countries, sites, time before and after admission for COVID-19, and COVID-19 severity. RESULTS: Among the 35,177 hospitalized patients with SARS-CoV-2 infection, there was increased prevalence of disorders of consciousness (5.8%, 95% confidence interval [CI]: 3.7%-7.8%, pFDR<.001) and unspecified disorders of the brain (8.1%, 95%CI: 5.7%-10.5%, pFDR<.001), compared to pre-admission prevalence. During hospitalization, patients who experienced severe COVID-19 status had 22% (95%CI: 19%-25%) increase in the relative risk (RR) of disorders of consciousness, 24% (95%CI: 13%-35%) increase in other cerebrovascular diseases, 34% (95%CI: 20%-50%) increase in nontraumatic intracranial hemorrhage, 37% (95%CI: 17%-60%) increase in encephalitis and/or myelitis, and 72% (95%CI: 67%-77%) increase in myopathy compared to those who never experienced severe disease. INTERPRETATION: Using an international network and common EHR data elements, we highlight an increase in the prevalence of central and peripheral neurological phenotypes in patients hospitalized with SARS-CoV-2 infection, particularly among those with severe disease.