syedzayyan/paper_mill_benchmark huggingface dataset:
Search and visualization of gene-drug-disease interactions for pharmacogenomics and precision medicine research using GeneDive.

Understanding the relationships between genes, drugs, and disease states is at the core of pharmacogenomics.Two leading approaches for identifying these relationships in medical literature are: human expert led manual curation efforts, and modern data mining based automated approaches.The former generates small amounts of high-quality data, and the latter offers large volumes of mixed quality data.The algorithmically extracted relationships are often accompanied by supporting evidence, such as, confidence scores, source articles, and surrounding contexts (excerpts) from the articles, that can be used as data quality indicators.Tools that can leverage these quality indicators to help the user gain access to larger and high-quality data are needed.Approach we introduce gene dive, a web application for pharmacogenomics researchers and precision medicine practitioners that makes gene, disease, and drug interactions data easily accessible and usable.Gene dive is designed to meet three key objectives: (1) provide functionality to manage information-overload problem and facilitate easy assimilation of supporting evidence, (2) support longitudinal and exploratory research investigations, and (3) offer integration of user-provided interactions data without requiring data sharing.Results gene dive offers multiple search modalities, visualizations, and other features that guide the user efficiently to the information of their interest.To facilitate exploratory research, gene dive makes the supporting evidence and context for each interaction readily available and allows the data quality threshold to be controlled by the user as per their risk tolerance level.The interactive search-visualization loop enables relationship discoveries between diseases, genes, and drugs that might not be explicitly described in literature but are emergent from the source medical corpus and deductive reasoning.The ability to utilize user's data either in combination with the gene dive native datasets or in isolation promotes richer data-driven exploration and discovery.These functionalities along with gene dive's applicability for precision medicine, bringing the knowledge contained in biomedical literature to bear on particular clinical situations and improving patient care, are illustrated through detailed use cases.Conclusion gene dive is a comprehensive, broad-use biological interactions browser.The gene dive application and information about its underlying system architecture are available at gene dive docker image is also available for download at this url, allowing users to (1) import their own interaction data securely and privately; and (2) generate and test hypotheses across their own and other datasets.

Journal: Journal of biomedical informatics (2021)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Distribution of chimeric antigen receptor-modified T cells against CD19 in B-cell malignancies.

The unprecedented efficacy of chimeric antigen receptor t (car-t) cell immunotherapy of cd19+b-cell malignancies has opened a new and useful way for the treatment of malignant tumors.Nonetheless, there are still formidable challenges in the field of car-t cell therapy, such as the biodistribution of car-t cells in vivo.Methods nalm-6, a human b-cell acute lymphoblastic leukemia (b-all) cell line, was used as target cells.Car-t cells were injected into a mice model with or without target cells.Then we measured the distribution of car-t cells in mice.In addition, an exploratory clinical trial was conducted in 13 r/r b-cell non-hodgkin lymphoma (b-nhl) patients, who received car-t cell infusion.The dynamic changes in patient blood parameters over time after infusion were detected by q pcr and flow cytometry.Results car-t cells still proliferated over time after being infused into the mice without target cells within 2 weeks.However, car-t cells did not increase significantly in the presence of target cells within 2 weeks after infusion, but expanded at week 6.In the clinical trial, we found that car-t cells peaked at 7-21 days after infusion and lasted for 420 days in peripheral blood of patients.Simultaneously, mild side effects were observed, which could be effectively controlled within 2 months in these patients.Conclusions car-t cells can expand themselves with or without target cells in mice, and persist for a long time in nhl patients without serious side effects.Trial registration the registration date of the clinical trial is may 17, 2018 and the trial registration numbers is nct03528421 .

Journal: BMC cancer (2021)
Publication types: Journal Article
Who does what to whom? graph representations of action-predication in speech relate to psychopathological dimensions of psychosis.

Graphical representations of speech generate powerful computational measures related to psychosis.Previous studies have mostly relied on structural relations between words as the basis of graph formation, i.e., connecting each word to the next in a sequence of words.Here, we introduced a method of graph formation grounded in semantic relationships by identifying elements that act upon each other (action relation) and the contents of those actions (predication relation).Speech from picture descriptions and open-ended narrative tasks were collected from a cross-diagnostic group of healthy volunteers and people with psychotic or non-psychotic disorders.Recordings were transcribed and underwent automated language processing, including semantic role labeling to identify action and predication relations.Structural and semantic graph features were computed using static and dynamic (moving-window) techniques.Compared to structural graphs, semantic graphs were more strongly correlated with dimensional psychosis symptoms.Dynamic features also outperformed static features, and samples from picture descriptions yielded larger effect sizes than narrative responses for psychosis diagnoses and symptom dimensions.Overall, semantic graphs captured unique and clinically meaningful information about psychosis and related symptom dimensions.These features, particularly when derived from semi-structured tasks using dynamic measurement, are meaningful additions to the repertoire of computational linguistic methods in psychiatry.

Journal: Schizophrenia (Heidelberg, Germany) (2022)
Publication types: Journal Article
Synergistically designed antireflective cover for improving wide-angle photovoltaic efficiencies.

We demonstrated that a well-designed nanopatterned cover improves photovoltaic efficiency across a wide range of incident angles (θ).A nanopatterned cover was created using an integrated ray-wave optics simulation to maximize the light absorption of the surface-textured si photovoltaic device.A hexagonally arranged nanocone array with a 300 nm pitch was formed into a polymer using nanoimprinting, and the nanostructured polymer was then attached to a glass cover with an index-matching adhesive.Angle-resolved current density-voltage measurements on si photovoltaic devices showed that the nanopatterned glass cover yielded a 2-13% enhancement in power conversion efficiency at θ = 0-60°, which accounted for its broadband antireflective feature.We performed all-season-perspective simulations based on the results of the integrated ray-wave optics simulations and solar altitude database of south korea, which validated the sustainability of the developed nanopatterned cover during significant seasonal fluctuations.

Journal: Optics express (2022)
Publication types: Journal Article
Prevalence of allergic diseases among Korean adolescents during the COVID-19 pandemic: comparison with pre-COVID-19 11-year trends.

During the coronavirus disease 2019 (covid-19) pandemic, emergency department utilization and hospitalization rates for allergic diseases declined and the severity of allergies among admitted patients was low.This study aimed to determine the prevalence of allergic diseases among adolescents and the changes in trend during the covid-19 pandemic compared with those during the preceding 11 years.Subjects and methods we analyzed data from the nationwide web-based self-report korea youth risk behavior survey.From 2009 to 2020, adolescents aged 13-18 years participated in the survey.The survey period was divided into pre-pandemic periods i (2009-2011), ii (2012-2014), iii (2015-2017), and iv (2018-2019) and the pandemic period (period v, 2020).The current prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic morbidity (having at least one of the three conditions) and changes in the prevalence before and during the covid-19 pandemic were analyzed.Results data of 787,043 participants were analyzed after weighting the study population (mean age, 15.1 years; males, 52.3%).The prevalence of asthma, allergic rhinitis, atopic dermatitis, and allergic morbidity was 2.1%, 18.4%, 6.8%, and 23.6%, respectively.The prevalence of allergic morbidity increased between periods i and iv but declined significantly from periods iv to v.From periods i to iv, the prevalence of asthma decreased, the prevalence of allergic rhinitis increased, and the prevalence of atopic dermatitis remained unchanged.During period v, the prevalence of all three conditions decreased.Conclusions it is necessary to update management measures and develop relevant policies in response to the altered prevalence of allergic diseases since the outbreak of covid-19.

Journal: European review for medical and pharmacological sciences (2022)
Publication types: Journal Article
Increased fatty acid metabolism attenuates cardiac resistance to β-adrenoceptor activation via mitochondrial reactive oxygen species: A potential mechanism of hypoglycemia-induced myocardial injury in diabetes.

The mechanism of severe hypoglycemia (sh)-induced cardiovascular disease in diabetes remains unknown.Our previous study found that sh inhibits cardiac function and lipid metabolism in diabetic mice.Conversely, in nondiabetic mice, sh does not induce cardiac dysfunction but promotes cardiac lipid metabolism.This study aims to clarify the effect of increased fatty acid metabolism on the resistance of cardiomyocytes to β-adrenoceptor activation during hypoglycemia in diabetes.Results revealed that cardiomyocytes with enhanced lipid metabolism were more vulnerable to damage due to β-adrenoceptor activation, which presented as decreased cell viability, disorder of mitochondrial structure, dissipation of mitochondrial membrane potential, dysfunction of mitochondrial oxidative phosphorylation, nonapoptotic damage, and accumulation of ros and calcium from mitochondria to cytoplasm, all of which were partially reversed by mitochondrial antioxidant mito-tempo.The sh-induced cardiac dysfunction, and reduction of myocardial energy metabolism in diabetic mice were rescued by mito-tempo.Our findings indicate that high fatty acid metabolism crippled cardiac resistance to β-adrenoceptor hyperactivation, with mitochondrial ros playing a pivotal role in this process.Reducing mitochondrial ros in diabetes could disrupt this synergistic effect and prevent poor cardiac outcomes caused by sh.

Journal: Redox biology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
20S proteasomes secreted by the malaria parasite promote its growth.

Mature red blood cells (rbcs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite plasmodium falciparum (pf), in particular.Pf, while growing inside its natural host, the human rbc, secretes multipurpose extracellular vesicles (evs), yet their influence on this essential host cell remains unknown.Here we demonstrate that pf parasites, cultured in fresh human donor blood, secrete within such evs assembled and functional 20s proteasome complexes (ev-20s).The ev-20s proteasomes modulate the mechanical properties of naïve human rbcs by remodeling their cytoskeletal network.Furthermore, we identify four degradation targets of the secreted 20s proteasome, the phosphorylated cytoskeletal proteins β-adducin, ankyrin-1, dematin and epb4.1.Overall, our findings reveal a previously unknown 20s proteasome secretion mechanism employed by the human malaria parasite, which primes rbcs for parasite invasion by altering membrane stiffness, to facilitate malaria parasite growth.

Journal: Nature communications (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Single-cell gene fusion detection by scFusion.

Gene fusions can play important roles in tumor initiation and progression.While fusion detection so far has been from bulk samples, full-length single-cell rna sequencing (sc rna-seq) offers the possibility of detecting gene fusions at the single-cell level.However, sc rna-seq data have a high noise level and contain various technical artifacts that can lead to spurious fusion discoveries.Here, we present a computational tool, sc fusion, for gene fusion detection based on sc rna-seq.We evaluate the performance of sc fusion using simulated and five real sc rna-seq datasets and find that sc fusion can efficiently and sensitively detect fusions with a low false discovery rate.In a t cell dataset, sc fusion detects the invariant tcr gene recombinations in mucosal-associated invariant t cells that many methods developed for bulk data fail to detect; in a multiple myeloma dataset, sc fusion detects the known recurrent fusion ig h-whsc1, which is associated with overexpression of the whsc1 oncogene.Our results demonstrate that sc fusion can be used to investigate cellular heterogeneity of gene fusions and their transcriptional impact at the single-cell level.

Journal: Nature communications (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Characterization of a Nigerian Lumpy Skin Disease Virus Isolate after Experimental Infection of Cattle.

Lumpy skin disease virus (lsdv), together with sheeppox virus and goatpox virus, belong to the genus capripoxviruswithin the family poxviridae.Collectively, they are considered the most serious poxvirus diseases of agricultural livestock.Due to their severe clinical course and consequent loss of production, as well as high mortality of naïve small and large ruminant populations, they are known to have a significant impact on the economy and global trade restrictions of affected countries.Therefore, all capripox diseases are classified as notifiable under the guidelines of the world organization of animal health (oie).Since the 1970s, several outbreaks of lsd have been recorded in nigeria.Until now, only a little information on the virus strains leading to the reported outbreaks have been published, dealing mainly with the phylogenetic relationship of those strains and the description of field outbreaks.During the present study, we experimentally infected cattle with a low-passage nigerian lsdv strain isolated from a skin sample of lsd positive cattle in nigeria in 2018.Clinical, molecular and serological data indicate that this lsdv isolate is highly pathogenic in cattle since it induced a severe clinical course and approximately 33% mortality in naïve holstein friesian cattle after experimental infection.

Journal: Pathogens (Basel, Switzerland) (2021)
Publication types: Journal Article
Antibacterial Activity of Silver Nanoflake (SNF)-Blended Polysulfone Ultrafiltration Membrane.

The aim of this research was to study the possibility of using silver nanoflakes (snfs) as an antibacterial agent in polysulfone (psf) membranes.Snfs at different concentrations (0.1, 0.2, 0.3 and 0.4 wt.%) were added to a psf membrane dope solution.To investigate the effect of snfs on membrane performance and properties, the water contact angle, protein separation, average pore size and molecular weight cutoffs were measured, and water flux and antibacterial tests were conducted.The antimicrobial activities of the snfs were investigated using escherichia colitaken from river water.The results showed that psf membranes blended with 0.1 wt.% snfs have contact angles of 55°, which is less than that of the pristine psf membrane (81°), exhibiting the highest pure water flux.Molecular weight cutoff values of the blended membranes indicated that the presence of snfs does not lead to enlargement of the membrane pore size.The rejection of protein (egg albumin) was improved with the addition of 0.1 wt.% snfs.The snfs showed antimicrobial activity against escherichia coli, where the killing rate was dependent on the snf concentration in the membranes.The identified bacterial colonies that appeared on the membranes decreased with increasing snf concentration.Psf membranes blended with snf, to a great degree, possess quality performance across several indicators, showing great potential to be employed as water filtration membranes.

Journal: Polymers (2022)
Publication types: Journal Article
Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (pdac) is a very lethal disease, with minimal therapeutic options.Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation.We investigated phosphorylated kinases as target in pdac.Methods mass spectrometry-based phosphotyrosine proteomic analysis on pdac cell lines was used to evaluate active kinases.Pathway analysis and inferred kinase activity analysis was performed to identify novel targets.Subsequently, we investigated targeting of focal adhesion kinase (fak) in vitro with drug perturbations in combination with chemotherapeutics used against pdac.Tyrosine phosphoproteomics upon treatment was performed to evaluate signaling.An orthotopic model of pdac was used to evaluate the combination of defactinib with nab-paclitaxel.Results pdac cell lines portrayed high activity of multiple receptor tyrosine kinases to various degree.The non-receptor kinase, fak, was identified in all cell lines by our phosphotyrosine proteomic screen and pathway analysis.Targeting of this kinase with defactinib validated reduced phosphorylation profiles.Additionally, fak inhibition had anti-proliferative and anti-migratory effects.Combination with (nab-)paclitaxel had a synergistic effect on cell proliferation in vitro and reduced tumor growth in vivo.Conclusions our study shows high phosphorylation of several oncogenic receptor tyrosine kinases in pdac cells and validated fak inhibition as potential synergistic target with nab-paclitaxel against this devastating disease.

Journal: Journal of experimental & clinical cancer research : CR (2021)
Publication types: Journal Article
Electrolyte and Acid-Base Disorders Associated with Cancer Immunotherapy.

Novel immunotherapy drugs have changed the landscape of cancer medicine.Immune checkpoint inhibitors and chimeric antigen receptor t cells are being used and investigated in almost all types of cancers.Immune-related adverse events have been associated with immunotherapies.Aki has been the most commonly associated kidney adverse event.In this review, we showcase the several associated electrolyte disorders seen with immunotherapy.Immune checkpoint inhibitors can lead to hyponatremia by several mechanisms, with the syndrome of inappropriate antidiuresis being the most common.Endocrine causes of hyponatremia are rare.Hypokalemia is not uncommon and is associated with both proximal and distal renal tubular acidosis.Hypercalcemia associated with immune checkpoint inhibitors has led to some interesting observations, including immune checkpoint inhibitor-induced parathyroid hormone-related peptide production, sarcoid-like granulomas, and hyperprogression of the disease.Hypocalcemia and hyperphosphatemia may be seen with immune checkpoint inhibitor-induced tumor lysis syndrome.Chimeric antigen receptor t cell therapy-associated electrolyte disorders are also common.This is associated chiefly with hyponatremia, although other electrolyte abnormalities can occur.Early recognition and prompt diagnosis may help providers manage the mechanistically varied and novel electrolyte disorders associated with immunotherapy.

Journal: Clinical journal of the American Society of Nephrology : CJASN (2022)
Publication types: Journal Article;Review;Research Support, N.I.H., Extramural
mD-UPLC-MS/MS: Next Generation of mAb Characterization by Multidimensional Ultraperformance Liquid Chromatography-Mass Spectrometry and Parallel On-Column LysC and Trypsin Digestion.

For the past few years, multidimensional liquid chromatography-mass spectrometry (lc-ms) systems have been commonly used to characterize post-translational modifications (ptms) of therapeutic antibodies (m abs).In most cases, this is performed by fractionation of charge variants by ion-exchange chromatography and subsequent online lc-ms peptide mapping analysis.In this study, we developed a multidimensional ultra-performance-liquid-chromatography-mass spectrometry system (m d-uplc-ms/ms) for ptm characterization and quantification, allowing both rapid analysis and decreased risk of artificial modifications during sample preparation.We implemented uplc columns for peptide mapping analysis, facilitating the linkage between m d-lc and routine lc-ms workflows.Furthermore, the introduced system incorporates a novel in-parallel trypsin and lys c on-column digestion setup, followed by a combined peptide mapping analysis.This parallel digestion with different enzymes enhances characterization by generating two distinct peptides.Using this approach, a low retentive ethylene oxide adduct of a bispecific antibody was successfully characterized within this study.In summary, our approach allows versatile and rapid analysis of ptms, enabling efficient characterization of therapeutic molecules.

Journal: Analytical chemistry (2022)
Publication types: Journal Article
Effects of cadmium and cobalt mixtures on growth and photosynthesis of Raphidocelis subcapitata (Chlorophyceae).

Metals occur simultaneously in the environment, and therefore it is important to know their toxicity and mechanism of action when associated with another metal.Furthermore, anthropogenic actions increase their concentrations in the environment where they can interact and undergo transformations that can even increase their toxicity.This study aimed to evaluate the effects of cadmium (cd) and cobalt (co), isolated and combined, on the microalgae raphidocelis subcapitata.Regarding the toxicity of isolated metals, the ic5096 h was 0.08 mg l-1of cd and 0.16 mg l-1of co.Cell density decreased at all concentrations of the cd tested.The parameters related to cell size, cell complexity and mean cell chlorophyll a (chl a) fluorescence were significantly affected by both metals.According to species sensitivity curves (ssd), the microalgae r.Subcapitata was the second most sensitive organism to co exposure and the tenth concerning cd.Metal mixture data were best fitted to the concentration addition (ca) model and dose-ratio dependence (dr) deviation, showing synergism at high concentrations of co and low concentrations of cd.Besides that, antagonism was observed at low concentrations of co and high concentrations of cd.Photosynthetic performance, assessed by maximum quantum yield (φm) and oxygen evolving complex (oec), presented antagonism effects for both analyzed parameters.Thus, the mixture of cd and co showed synergistic and antagonistic interactions for the parameters analyzed in r.Subcapitata, indicating the importance of understanding the mechanisms of toxicity of metal mixtures in phytoplankton.

Journal: Aquatic toxicology (Amsterdam, Netherlands) (2022)
Publication types: Journal Article