syedzayyan/paper_mill_benchmark huggingface dataset:
Association betweenEGFRgene mutant protein expression and T790M mutation after first-generation EGFR-TKI treatment resistance: a retrospective, single-arm clinical study.

Epidermal growth factor receptor-tyrosine kinase inhibitor (egfr-tki) is an important treatment for lung adenocarcinoma patients with egfrgene mutations.The purpose of this study was to review the efficacy of first-generation egfr-tkis and the incidence of t790m after first-generation tki resistance in stage iv lung adenocarcinoma patients with positive egfrgene mutation expression associated with egfr mutant protein.Methods tumor tissues were collected from stage iv lung adenocarcinoma patients with egfrgene mutation who received first-generation egfr-tki targeted therapy.Patients were followed up through outpatient and inpatient systems.Immunohistochemistry was used to detect the expression of corresponding egfr mutant protein in tumor tissues.The incidence of t790m mutation after first-generation tki resistance and the correlation between the mutant protein and progression-free survival (pfs) after first-generation tki treatment were investigated.Results t790m mutation rates were 37.93% (11/29) and 42.50% (17/40) in the egfrmutation groups, respectively, after first-generation tki treatment for drug resistance.In patients with exon 19 deletion, t790m mutations were found in 63.64% (7/11) of patients with positive protein expression and 22.22% (4/18) of patients with negative protein expression (p=0.026; χ2=4.974).The mutation rate of t790m after drug resistance in patients with l858r mutation was 53.57% (15/28) and 16.67% (2/12) in the protein expression-positive and negative groups, respectively (χ2=4.682, p=0.030).The variations were statistically significant.Conclusions after resistance to the first-generation egfr-tki treatment, the occurrence of t790m mutation may be related to the expression of egfr mutant protein in patients with egfrgene mutation.

Journal: Annals of translational medicine (2022)
Publication types: Journal Article
Identification of Glycolaldehyde Enol (HOHC═CHOH) in Interstellar Analogue Ices.

Glycolaldehyde is considered the entry point in the aqueous prebiotic formose (butlerow) reaction although it mainly exists in its unreactive hydrated form in aqueous solution.The characterization of the more reactive nucleophilic enol form under interstellar conditions has remained elusive to date.Here we report on the identification of glycolaldehyde enol (1,2-ethenediol, hohc═choh) in low temperature methanol-bearing ices at temperatures as low as 5 k.Exploiting isotope labeling and isomer-selective photoionization coupled with reflectron time-of-flight mass spectrometry, our results unravel distinct reaction pathways to 1,2-ethenediol, thus demonstrating the kinetic stability, availability for prebiotic sugar formation, and potential detectability in deep space.

Journal: Journal of the American Chemical Society (2021)
Publication types: Journal Article;Research Support, U.S. Gov't, Non-P.H.S.;Research Support, Non-U.S. Gov't
Effect of enzymatic hydrolysis on digestibility and morpho-structural properties of hydrothermally pre-treated red rice starch.

The objective of this work was to evaluate the effects of enzymatic hydrolysis on digestibility and morphological and structural properties of hydrothermally pre-treated (hpt) red rice starch.The pre-treatments were performed in autoclave and cooking for the modification of rice grains and native starch.In vitro starch digestibility was performed consecutively and semi-simultaneously using α-amylase and amyloglucosidase.A first-order mathematical model was used to adjust the hydrolysis kinetic data, which made it possible to calculate the surface area, hydrolysis index, and glycemic index of the starch.Scanning electron microscopy images (sem), fourier transform infrared (ftir) spectra and x-ray diffraction (xrd) were also performed to investigate the characteristics of the post-hydrolysis starch samples.The autoclaved starch hss-a3, which was subjected to 121 °c/1.08 bar for 10 min, showed the highest in vitro digestibility values (80.08 %).Both starch samples showed increase of particle size and enzymatic digestibility after hpt.Ftir spectra of the starch samples showed that there was no appearance of new functional groups.However, xrd evidenced that hpt changed the intensity of the peaks and the type of crystallinity was changed for autoclaved starch (a3) from type a to vh, with crystallinity ranging from 21.71 % to 26.42 %.The semi-simultaneous approach showed more advantages due to the highest in vitro digestibility as well as reducing the processing time and use of reagents.

Journal: International journal of biological macromolecules (2022)
Publication types: Journal Article
Validation of patient-specific 3D impression models for pelvic oncological orthopedic surgery.

Introduction pelvic ring tumors pose a challenge due to the difficulty in obtaining adequate surgical margins.Tools such as surgical navigation or 3d printing for the fabrication of patient-specific surgical positioning templates help in preoperative planning and intraoperative execution.Their correct positioning is essential in complex locations such as the pelvis, so it is necessary to identify positioning errors.The aim of this study is to demonstrate the reliability of 3d template placement for pelvic ring osteotomies.Material and methods experimental study in cadaver with 10 hemipelvis.Ct was performed to obtain the three-dimensional model, planning of osteotomies, design of positioning templates in ischiopubic (i), iliopubic (p), supracetabular (s) and iliac crest (c) branches; and a positioning marker (rigid-body) on the c and s templates for navigation.The templates and rigid-body are 3d printed and positioned according to pre-planning.Navigation allows the final position of the inserts and osteotomies to be checked.Results the positioning of the templates with respect to the preoperative planning varied depending on the location, being greater the error in those of the iliac crest.Using navigation the mean error of distance to the cutting plane is 3.5mm, except in pubis (5-8mm), being conditioned by the position of the rigid body.Conclusion the use of patient-specific templates printed in 3d is a reliable tool for performing osteotomies in pelvic cancer surgery.

Journal: Revista espanola de cirugia ortopedica y traumatologia (2022)
Publication types: Journal Article
I-Impute: a self-consistent method to impute single cell RNA sequencing data.

Single-cell rna-sequencing (sc rna-seq) is becoming indispensable in the study of cell-specific transcriptomes.However, in sc rna-seq techniques, only a small fraction of the genes are captured due to "dropout" events.These dropout events require intensive treatment when analyzing sc rna-seq data.For example, imputation tools have been proposed to estimate dropout events and de-noise data.The performance of these imputation tools are often evaluated, or fine-tuned, using various clustering criteria based on ground-truth cell subgroup labels.This limits their effectiveness in the cases where we lack cell subgroup knowledge.We consider an alternative strategy which requires the imputation to follow a "self-consistency" principle; that is, the imputation process is to refine its results until there is no internal inconsistency or dropouts from the data.Results we propose the use of "self-consistency" as a main criteria in performing imputation.To demonstrate this principle we devised i-impute, a "self-consistent" method, to impute sc rna-seq data.I-impute optimizes continuous similarities and dropout probabilities, in iterative refinements until a self-consistent imputation is reached.On the in silico data sets, i-impute exhibited the highest pearson correlations for different dropout rates consistently compared with the state-of-art methods saver and sc impute.Furthermore, we collected three wetlab datasets, mouse bladder cells dataset, embryonic stem cells dataset, and aortic leukocyte cells dataset, to evaluate the tools.I-impute exhibited feasible cell subpopulation discovery efficacy on all the three datasets.It achieves the highest clustering accuracy compared with saver and sc impute.Conclusions a strategy based on "self-consistency", captured through our method, i-impute, gave imputation results better than the state-of-the-art tools.Source code of i-impute can be accessed at .

Journal: BMC genomics (2020)
Publication types: Journal Article
An Association Study of DNA Methylation and Gene Expression in Angelman Syndrome: A Bioinformatics Approach.

Angelman syndrome (as) is a neurodevelopmental disorder caused by the loss of function of the e3-ligase ube3a.Despite multiple studies, as pathophysiology is still obscure and has mostly been explored in rodent models of the disease.In recent years, a growing body of studies has utilized omics datasets in the attempt to focus research regarding the pathophysiology of as.Here, for the first time, we utilized a multi-omics approach at the epigenomic level and the transcriptome level, for human-derived neurons.Using publicly available datasets for dna methylation and gene expression, we found genome regions in proximity to gene promoters and intersecting with gene-body regions that were differentially methylated and differentially expressed in as.We found that overall, the genome in as postmortem brain tissue was hypo-methylated compared to healthy controls.We also found more upregulated genes than downregulated genes in as.Many of these dysregulated genes in neurons obtained from as patients are known to be critical for neuronal development and synaptic functioning.Taken together, our results suggest a list of dysregulated genes that may be involved in as development and its pathological features.Moreover, these genes might also have a role in neurodevelopmental disorders similar to as.

Journal: International journal of molecular sciences (2022)
Publication types: Journal Article
Trinuclear Cyanido-Bridged [Cr2Fe] Complexes: To Be or not to Be a Single-Molecule Magnet, a Matter of Straightness.

Trinuclear systems of formula [{cr(ln3o2ph)(cn)2}2m(h2ln3o2r)] (m=mn iiand fe ii, ln3o2rstands for pentadentate ligands) were prepared in order to assess the influence of the bending of the apical m-n≡c linkages on the magnetic anisotropy of the fe iiderivatives and in turn on their single-molecule magnet (smm) behaviors.The cyanido-bridged [cr2m] derivatives were obtained by assembling trans-dicyanido cr iiicomplex [cr(ln3o2ph)(cn)2]-and divalent pentagonal bipyramid complexes [mii(h2ln3o2r)]2+with various r substituents (r=nh2, cyclohexyl, s,s-mandelic) imparting different steric demand to the central moiety of the complexes.A comparative examination of the structural and magnetic properties showed an obvious effect of the deviation from straightness of the m-n≡c alignment on the slow relaxation of the magnetization exhibited by the [cr2fe] complexes.Theoretical calculations have highlighted important effects of the bending of the apical c-n-fe linkages on both the magnetic anisotropy of the fe iicenter and the exchange interactions with the cr iiiunits.

Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (2021)
Publication types: Journal Article
Measurement Properties of the Brief Pain Inventory-Short Form (BPI-SF) and Revised Short McGill Pain Questionnaire Version-2 (SF-MPQ-2) in Pain-related Musculoskeletal Conditions: A Systematic Review.

The objective of this study was to systematically locate, critically appraise, and summarize clinical measurement research addressing the use of brief pain inventory-short form (bpi-sf) and revised short mc gill pain questionnaire version-2 (sf-mpq-2) in pain-related musculoskeletal (msk) conditions.Materials and methods we systematically searched 4 databases (medline, cinahl, embase, and scopus) and screened articles to identify those reporting the psychometric properties (eg, validity, reliability) and interpretability (eg, minimal clinically important difference) of bpi-sf and sf-mpq-2 as evaluated in pain-related msk conditions.Independently, 2 reviewers extracted data and assessed the quality of evidence with a structured quality appraisal tool and the updated cosmin guidelines.Results in all, 26 articles were included (bpi-sf, n=17; sf-mpq-2, n=9).Both tools lack reporting on their cross-cultural validities and measurement error indices (eg, standard error of measurement).High-quality studies suggest the tools are internally consistent (α=0.83 to 0.96), and they associate modestly with similar outcomes (r=0.3 to 0.69).Strong evidence suggests the bpi-sf conforms to its 2-dimensional structure in msk studies; the sf-mpq-2 4-factor structure was not clearly established.Seven reports of high-to-moderate quality evidence were supportive of the bpi-sf known-group validity (n=2) and responsiveness (n=5).One report of high quality established the sf-mpq-2 responsiveness.Discussion evidence of high-to-moderate quality supports the internal consistency, criterion-convergent validity, structural validity, and responsiveness of the bpi-sf and sf-mpq-2 and establishes their use as generic multidimensional pain outcomes in msk populations.However, more studies of high quality are still needed on their retest reliability, known-group validity, cross-cultural validity, interpretability properties, and measurement error indices in different msk populations.

Journal: The Clinical journal of pain (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Systematic Review
Rhythmic adenosine triphosphate release from the cyanobacterial circadian clock protein KaiC revealed by real-time monitoring of bioluminescence using firefly luciferase.

The cyanobacterial circadian clock is composed of three clock proteins, kai a, kai b and kai c.This kai abc clock system can be reconstituted in vitro in the presence of adenosine triphosphate (atp) and mg2+, and shows circadian rhythms in the phosphorylation level and atpase activity of kai c.Previously, we found that atp regulates a complex formation between kai b and kai c, and kai c releases atp from kai c itself (plo s one, 8, 2013, e80200).In this study, we examined whether the atp release from kai c shows any rhythms in vitro.We monitored the release of atp from wild-type and atpase motif mutants of kai c as a bioluminescence in real time using a firefly luciferase assay in vitro and obtained the following results: (a) atp release from kai c oscillated even without kai a and kai b although period of the oscillation was not 24 hr; (b) atp was mainly released from the n-terminal domain of kai c; and (c) the atp release was enhanced and suppressed by kai b and kai a, respectively.These results suggest that kai c can generate basal oscillation as a core clock without kai a and kai b, whereas these two proteins contribute to adjusting and stabilizing the oscillation.

Journal: Genes to cells : devoted to molecular & cellular mechanisms (2021)
Publication types: Journal Article
Bioproduction of Natural Phenethyl Acetate, Phenylacetic Acid, Ethyl Phenylacetate, and Phenethyl Phenylacetate from Renewable Feedstock.

Natural phenethyl acetate (pea), phenylacetic acid (paa), ethyl phenylacetate (et-pa), and phenethyl phenylacetate (pe-pa) are highly desirable aroma chemicals, but with limited availability and high price.Here, green, sustainable, and efficient bioproduction of these chemicals as natural products from renewable feedstocks was developed.Pea and paa were synthesized from l-phenylalanine (l-phe) via novel six- and five-enzyme cascades, respectively.Whole-cell-based cascade biotransformation of 100 mm l-phe in a two-phase system (aqueous/organic: 1 : 0.5 v/v) containing ethyl oleate or biodiesel as green solvent gave 13.6 g l-1pea (83.1 % conv.) and 11.6 g l-1paa (87.1 % conv.), respectively.Coupled fermentation and biotransformation approach produced 10.4 g l-1pea and 9.2 g l-1paa from glucose or glycerol, respectively.The biosynthesized paa was converted to natural et-pa and pe-pa by esterification using lipases with ethanol or 2-phenylethanol derived from sugar, affording 2.7 g l-1et-pa (83.1 % conv.) and 4.6 g l-1pe-pa (96.3 % conv.), respectively.

Journal: ChemSusChem (2022)
Publication types: Journal Article
Estimating the Optimal Dexketoprofen Pharmaceutical Formulation with Machine Learning Methods and Statistical Approaches.

S orally disintegrating tablets (odts) can be utilized without any drinking water; this feature makes odts easy to use and suitable for specific groups of patients.Oral administration of drugs is the most commonly used route, and tablets constitute the most preferable pharmaceutical dosage form.However, the preparation of odts is costly and requires long trials, which creates obstacles for dosage trials.The aim of this study was to identify the most appropriate formulation using machine learning (ml) models of odt dexketoprofen formulations, with the goal of providing a cost-effective and timereducing solution.Methods this research utilized nonlinear regression models, including the k-nearest neighborhood (k-nn), support vector regression (svr), classification and regression tree (cart), bootstrap aggregating (bagging), random forest (rf), gradient boosting machine (gbm), and extreme gradient boosting (xgboost) methods, as well as the t-test, to predict the quantity of various components in the dexketoprofen formulation within fixed criteria.Results all the models were developed with python libraries.The performance of the ml models was evaluated with r2 values and the root mean square error.Hardness values of 0.99 and 2.88, friability values of 0.92 and 0.02, and disintegration time values of 0.97 and 10.09 using the gbm algorithm gave the best results.Conclusions in this study, we developed a computational approach to estimate the optimal pharmaceutical formulation of dexketoprofen.The results were evaluated by an expert, and it was found that they complied with food and drug administration criteria.

Journal: Healthcare informatics research (2021)
Publication types: Journal Article
Increased ecological resource variability during a critical transition in hominin evolution.

Although climate change is considered to have been a large-scale driver of african human evolution, landscape-scale shifts in ecological resources that may have shaped novel hominin adaptations are rarely investigated.We use well-dated, high-resolution, drill-core datasets to understand ecological dynamics associated with a major adaptive transition in the archeological record ~24 km from the coring site.Outcrops preserve evidence of the replacement of acheulean by middle stone age (msa) technological, cognitive, and social innovations between 500 and 300 thousand years (ka) ago, contemporaneous with large-scale taxonomic and adaptive turnover in mammal herbivores.Beginning ~400 ka ago, tectonic, hydrological, and ecological changes combined to disrupt a relatively stable resource base, prompting fluctuations of increasing magnitude in freshwater availability, grassland communities, and woody plant cover.Interaction of these factors offers a resource-oriented hypothesis for the evolutionary success of msa adaptations, which likely contributed to the ecological flexibility typical of homo sapiensforagers.

Journal: Science advances (2020)
Publication types: Journal Article;Research Support, U.S. Gov't, Non-P.H.S.;Research Support, Non-U.S. Gov't
BRD4 in physiology and pathology: ''BET'' on its partners.

Bromodomain-containing 4 (brd4), a member of bromo and extra-terminal (bet) family, recognizes acetylated histones and is of importance in transcription, replication, and dna repair.It also binds non-histone proteins, dna and rna, contributing to development, tissue growth, and various physiological processes.Additionally, brd4 has been implicated in driving diverse diseases, ranging from cancer, viral infection, inflammation to neurological disorders.Inhibiting its functions with bet inhibitors (betis) suppresses the progression of several types of cancer, creating an impetus for translating these chemicals to the clinic.The diverse roles of brd4 are largely dependent on its interaction partners in different contexts.In this review we discuss the molecular mechanisms of brd4 with its interacting partners in physiology and pathology.Current development of betis is also summarized.Further understanding the functions of brd4 and its partners will facilitate resolving the liabilities of present betis and accelerate their clinical translation.

Journal: BioEssays : news and reviews in molecular, cellular and developmental biology (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Review
Effective Approaches to Study the Genetic Variability of SARS-CoV-2.

Significant efforts are being made in many countries around the world to respond to the covid-19 pandemic by developing diagnostic reagent kits, identifying infected people, determining treatment methods, and finally producing effective vaccines.However, novel coronavirus variants may potentially reduce the effectiveness of all these efforts, demonstrating increased transmissibility and abated response to therapy or vaccines, as well as the possibility of false negative results in diagnostic procedures based on nucleic acid amplification methods.Since the end of 2020, several variants of concern have been discovered around the world.When information about a new, potentially more dangerous strain of pathogen appears, it is crucial to determine the moment of its emergence in a region.Eventually, that permits taking timely measures and minimizing new risks associated with the spreading of the virus.Therefore, numerous nations have made tremendous efforts to identify and trace these virus variants, which necessitates serious technological processes to sequence a large number of viral genomes.Here, we report on our experience as one of the primary laboratories involved in monitoring sars-co v-2 variants in russia.We discuss the various approaches used, describe effective protocols, and outline a potential technique combining several methods to increase the ability to trace genetic variants while minimizing financial and labor costs.

Journal: Viruses (2022)
Publication types: Journal Article