syedzayyan/paper_mill_benchmark huggingface dataset:
Mechanistic insights into inter-chain disulfide bond reduction of IgG1 and IgG4 antibodies.

Therapeutic monoclonal antibodies (m abs), primarily immunoglobin g1 (ig g1) and ig g4 with an engineered cppc motif in its hinge region, are predominant biologics.Inter-chain disulfide bonds of ig g m abs are crucial to maintaining ig g integrity.Inter-chain disulfide bond-reduced low molecular weight (lmw) is considered as one of quality attributes of ig g drug substance and is observed in drug substance manufacturing.In this study, we demonstrate that ig g1 and ig g4 are susceptible to the reducing agent tcep differently and they follow different pathways to form lmws.Our study shows that ig g1 is more sensitive to tcep than ig g4.Both therapeutic ig g1 and human blood plasma ig g1 follow a heavy-heavy-light chain (hhl) pathway, featured with hhl and hh as intermediate species.Human blood plasma ig g4 with a cpsc motif in its hinge region follows heavy-light chain (hl) pathway, featured with hl as the intermediate species.However, therapeutic ig g4 follows a hybrid pathway with the hl pathway as the primary and the hhl pathway as the secondary.These experimental observations are further explained using solvent accessibility of inter-chain disulfide bonds obtained from computational modeling and molecular dynamics simulations.Findings from this study provide mechanistic insights of lmw formation of ig g1 and ig g4, which suggest selection of ig g1 or ig g4 for bispecific antibodies and cysteine-based antibody-drug conjugates.Key points: • experimentally discovered preferable disulfide bond reduction pathways between ig g1 and ig g4 antibodies, driven by the different solvent accessibilities of these disulfide bonds.• computationally explained the solvent accessibility aided by molecular dynamics simulations.• provided insights in developing robust biologics process and designing bispecific antibodies and cysteine-based antibody-drug conjugates.

Journal: Applied microbiology and biotechnology (2022)
Publication types: Journal Article
The EMT-activator ZEB1 is unrelated to platinum drug resistance in ovarian cancer but is predictive of survival.

The igrovcddp cisplatin-resistant ovarian cancer cell line is an unusual model, as it is also cross-resistant to paclitaxel.Igrovcddp, therefore, models the resistance phenotype of serous ovarian cancer patients who have failed frontline platinum/taxane chemotherapy.Igrovcddp has also undergone epithelial-mesenchymal transition (emt).We aim to determine if alterations in emt-related genes are related to or independent from the drug-resistance phenotypes.Emt gene and protein markers, invasion, motility and morphology were investigated in igrovcddp and its parent drug-sensitive cell line igrov-1.Zeb1 was investigated by q pcr, western blotting and si rna knockdown.Zeb1 was also investigated in publicly available ovarian cancer gene-expression datasets.Igrovcddp cells have decreased protein levels of epithelial marker e-cadherin (6.18-fold, p = 1.58e-04) and higher levels of mesenchymal markers vimentin (2.47-fold, p = 4.43e-03), n-cadherin (4.35-fold, p = 4.76e-03) and zeb1 (3.43-fold, p = 0.04).Igrovcddp have a spindle-like morphology consistent with emt.Knockdown of zeb1 in igrovcddp does not lead to cisplatin sensitivity but shows a reversal of emt-gene signalling and an increase in cell circularity.High zeb1 gene expression (hr = 1.31, n = 2051, p = 1.31e-05) is a marker of poor overall survival in high-grade serous ovarian-cancer patients.In contrast, zeb1 is not predictive of overall survival in high-grade serous ovarian-cancer patients known to be treated with platinum chemotherapy.The increased expression of zeb1 in igrovcddp appears to be independent of the drug-resistance phenotypes.Zeb1 has the potential to be used as biomarker of overall prognosis in ovarian-cancer patients but not of platinum/taxane chemoresistance.

Journal: Human cell (2022)
Publication types: Journal Article
Optimizing Meropenem in Highly Resistant Klebsiella pneumoniae Environments: Population Pharmacokinetics and Dosing Simulations in Critically Ill Patients.

Critically ill patients are characterized by substantial pathophysiological changes that alter the pharmacokinetics (pk) of hydrophilic antibiotics, including carbapenems.Meropenem is a key antibiotic for multidrug-resistant gram-negative bacilli, and such pathophysiological alterations can worsen treatment outcomes.This study aimed to determine the population pk of meropenem and to propose optimized dosing regimens for the treatment of multidrug-resistant klebsiella pneumoniae in critically ill patients.Two plasma samples were collected from eligible patients over a dosing interval.Nonparametric population pk modeling was performed using pmetrics.Monte carlo simulations were applied to different dosing regimens to determine the probability of target attainment and the cumulative fraction of response, taking into account the local mic distribution for k.Pneumoniae.The targets of 40% and 100% for the fraction of time that free drug concentrations remained above the mic (ƒt>mic) were tested, as suggested for critically ill patients.A one-compartment pk model using data from 27 patients showed high interindividual variability.Significant pk covariates were the 8-h creatinine clearance for meropenem and the presence of an indwelling catheter for pleural, abdominal, or cerebrospinal fluid drainage for the meropenem volume of distribution.The target 100% ƒt>mic for k.Pneumoniae, with a mic of ≤2 mg/liter, could be attained by the use of a continuous infusion of 2.0 g/day.Meropenem therapy in critically ill patients could be optimized for k.Pneumoniae isolates with an mic of ≤2 mg/liter by using a continuous infusion in settings with more than 50% isolates have a mic of ≥32mg/l.

Journal: Antimicrobial agents and chemotherapy (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Cardiovascular Surgery Procedural Training and Evaluation: Current Status and Future Directions.

The increasing complexity of heart disease manifestations and treatments as well as technological advancements make cardiovascular surgery an evolving specialty.In this review, we provide an overview of the factors leading to new developments in this field and discuss the adopted pathways to train cardiovascular surgeons in the united states.We also review the current challenges to the existing training culture and discuss the need to adopt adjuvant strategies to fulfill the societal expectations of what it means to be a competent cardiovascular surgeon.

Journal: Methodist DeBakey cardiovascular journal (2022)
Publication types: Journal Article;Review
Circ_0000215 Exerts Oncogenic Function in Nasopharyngeal Carcinoma by Targeting miR-512-5p.

Increasing circular rnas (circ rnas) are reported to participate in cancer progression.Nonetheless, the role of circ rnas in nasopharyngeal carcinoma (npc) has not been fully clarified.This work is aimed to probe the role of circ_0000215 in npc.methods:circ_0000215 expression in npc tissues and cell lines was examined by quantitative real-time polymerase chain reaction (q rt-pcr).Cell counting kit-8 (cck-8) assay, 5-bromo-2'-deoxyuridine (brd u) assay, scratch healing assay and transwell experiment were executed to investigate the regulatory function of circ_0000215 on the proliferation, migration and invasion of npc cells.Rna immunoprecipitation (rip), pull-down and dual-luciferase reporter experiments were utilized to determine the binding relationship between circ_0000215 and mi r-512-5p, and between mi r-512-5p and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1) 3'utr.The effects of circ_0000215 on npc growth and metastasisin vivowere examined with nude mice model.Western blot was applied to detect the regulatory effects of circ_0000215 and mi r-512-5p on pik3r1 expression.results:circ_0000215 was overexpressed in npc tissues and cell lines.The functional experiments confirmed that knockdown of circ_0000215 impeded the growth and metastasis of npc cellsin vitroandin vivo.Additionally, circ_0000215 could also work as a molecular sponge to repress mi r-512-5p expression.Pik3r1 was validated as a target gene of mi r-512-5p, and circ_0000215 could increase the expression level of pik3r1 in npc cells via suppressing mi r-512-5p.conclusion:circ_0000215 is overexpressed in npc and exerts oncogenic effects in npc through regulating mi r-512-5p/pik3r1 axis.

Journal: Frontiers in cell and developmental biology (2021)
Publication types: Journal Article
Saccharomyces boulardii CNCM I-745changes lipidemic profile and gut microbiota in a hamster hypercholesterolemic model.

Hypercholesterolemia is a main risk factor of cardiovascular disease.Probiotics are a safe approach to reduce elevated cholesterol without any deleterious effect to human health.saccharomyces boulardii cncm i-745 probiotic properties are well documented in a context of intestinal dysbiosis.Recentin vitroand preclinical studies have suggested its potential effects on dyslipidemia.This is the first controlled study investigating the effects of s.Boulardii cncm i-745 on lipidemic profile and gut microbiota in a hamster hypercholesterolemic model.Daily administration (3 g/kg) of s.Boulardiifor 21 or 39 days in hamsters fed a 0.3% cholesterol-diet significantly reduced total plasma cholesterol (p<0.001) and increased faecal total cholesterol (p<0.05) compared to vehicle-treated animals.s.Boulardiisignificantly modified the gut microbiota composition of the hamster fed a 0.3% cholesterol-diet.These microbial abundancy modifications of the microbiota were correlated to variations of lipidemic values or liver genes expressions.In particularly we found that abundance of g_allobaculum, the most modified taxon after s.Boulardiitreatment (+236%;p<0.05), was correlated to variations in plasmatic lipoproteins level and abcg5hepatic gene expression.We also observed a not previously described correlation between the levels of g_oxalobacterin the gut microbiota and total cholesterol plasma concentration.In conclusion, we confirmed the cholesterol-lowering effects of s.Boulardiiintake and we demonstrated for the first time the s.Boulardiieffect on gut microbiota in the context of hypercholesterolemia in hamsters.Our results provide new insights for a beneficial and safe approach of hypercholesterolemia treatment and could be considered for clinical development, alone or in addition to conventional treatment.

Journal: Beneficial microbes (2019)
Publication types: Journal Article
Broadband and low-loss TM-pass polarizer using tilted subwavelength structures.

Photonic systems built on the silicon-on-insulator platform exhibit a strong birefringence, and must thus be operated with a single polarization for most applications.Hence, on-chip polarizers that can effectively suppress an undesired polarization state are key components for these systems.Polarizers that extinguish te polarized light while letting tm polarized light pass with low losses are particularly challenging to design for the standard 220 nm silicon-on-insulator platform, because the modal confinement is stronger for te polarization than for tm polarzation.Here, we propose and design a broadband, low loss and high extinction ratio tm-pass polarizer by engineering a bragg grating that reflects the fundamental te mode into the first order te mode using a subwavelength metamaterial which at the same time allows the tm mode to pass.Our device achieves an extinction ratio in excess of 20 d b, insertion losses below 0.5 d b and back-reflections of the fundamental te mode of the order of -20 d b in a bandwidth of 150 nm as demonstrated with full 3d-fdtd simulations.

Journal: Optics express (2022)
Publication types: Journal Article
Health care utilization as a predictor of death anxiety in older adults.

The relationship between health care utilization and death anxiety in older adults is underexplored.This secondary analysis of the 2012 health and retirement study examined health care utilization as a predictor of death anxiety in a nationally representative sample of american older adults (n= 3,960).Hierarchical binary logistic regression results revealed that overnight hospitalization, overnight nursing home placement, and outpatient visit were all statistically significant predictors of death anxiety.Outpatient visit was the strongest health care utilization predictor in the model.Increased end-of-life training for providers may improve patient-provider communication and alleviate patients' death anxiety.Future research should explore the directionality between study variables.

Journal: Death studies (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural
Trends in interest of COVID-19 on Polish Internet.

Introduction this study aims to investigate the social interest in sars-co v-2 and covid-19 in the internet media during the epidemic in poland and serves as a complement to longitudinal surveys monitoring public perception in real time.Methods we quantitatively analyzed "coronavirus" digital footprints on the internet, in particular, on google, twitter, you tube, wikipedia and electronic media represented by event registry, from 15.01 to 07.04.2020 (before and after official introduction of covid-19 to poland on 04.03.2020).We present results on trend analysis supported by statistical techniques.Results we identified six major temporal clusters of the interest on the topic covid-19: 1) chinese, 2) italian, 3) waiting, 4) mitigations, 5) physical distancing and lockdown, 6) anti-crisis shield.There was an exponential increase of the interest when the polish government "declared a war against disease" around 11/12.03.2020 with a massive response activity.Later on, there was a decay in the interest with additional phases related to physical distancing and an anti-crisis legislation act associated with pronounced local peaks.We have found that declarations of response strategies by the polish prime minister or the minister of health gathered the highest attention of internet users.So already enacted or in force events do not affect the interest to such an extent.We have observed very weak or even negative correlations between a colloquial search term "antiviral mask" in google, encyclopaedic definition in wikipedia "sars-co v-2" as well as official covid-19 incidence series, implying different mechanisms governing the search for knowledge, panic related behaviour and actual burden of covid-19.Conclusions traditional and social media do not only reflect reality, but also create it.Interest in covid-19 (measured by topic intensity on the internet) is unrelated to the officially notified viral pressure (measured by incidence) and probably physical risk of acquiring infection in poland.As traditional media are ahead of social media in time, we advise to choose traditional news media for a quick dissemination of information, however for a greater impact, social media should be used.Otherwise public information campaigns might have less impact on society than expected.

Journal: Przeglad epidemiologiczny (2020)
Publication types: Journal Article
Ultrasound and Other Advanced Hemodynamic Monitoring Techniques in the Intensive Care Unit.

The ideal device for hemodynamic monitoring of critically ill patients in the intensive care unit (icu) or the operating room has not yet been developed.This would need to be affordable, consistent, have a very low margin of error (<30%), be minimally or noninvasive, and allow the clinician to make a reasonable therapeutic decision that consistently led to better outcomes.Such a device does not yet exist.This article will describe the distinct options we, as critical care physicians, currently possess for this herculean endeavor.

Journal: The Surgical clinics of North America (2022)
Publication types: Journal Article;Review
Heart and Breathing Rate Variations as Biomarkers for Anxiety Detection.

With advances in portable and wearable devices, it should be possible to analyze and interpret the collected biosignals from those devices to tailor a psychological intervention to help patients.This study focuses on detecting anxiety by using a portable device that collects electrocardiogram (ecg) and respiration (rsp) signals.The feature extraction focused on heart-rate variability (hrv) and breathing-rate variability (brv).We show that a significant change in these signals occurred between the non-anxiety-induced and anxiety-induced states.The hrv biomarkers were the mean heart rate (mhr; p ̄ = 0.04), the standard deviation of the heart rate (sd; p ̄ = 0.01), and the standard deviation of nn intervals (sdnn; p ̄ = 0.03) for ecg signals, and the mean breath rate (mbr; p ̄ = 0.002), the standard deviation of the breath rate (sd; p ̄ < 0.0001), the root mean square of successive differences (rmssd; p ̄ < 0.0001) and sdnn (p ̄ < 0.0001) for rsp signals.This work extends the existing literature on the relationship between stress and hrv/brv by being the first to introduce a transitional phase.It contributes to systematically processing mental and emotional impulse data in humans measured via ecg and rsp signals.On the basis of these identified biomarkers, artificial-intelligence or machine-learning algorithms, and rule-based classification, the automated biosignal-based psychological assessment of patients could be within reach.This creates a broad basis for detecting and evaluating psychological abnormalities in individuals upon which future psychological treatment methods could be built using portable and wearable devices.

Journal: Bioengineering (Basel, Switzerland) (2022)
Publication types: Journal Article
Forecasting the spread of SARS-CoV-2 in the campania region using genetic programming.

Coronavirus disease 19 (covid-19) is an infectious disease caused by the sars-co v-2 virus, which is responsible for the ongoing global pandemic.Stringent measures have been adopted to face the pandemic, such as complete lockdown, shutting down businesses and trade, as well as travel restrictions.Nevertheless, such solutions have had a tremendous economic impact.Although the use of recent vaccines seems to reduce the scale of the problem, the pandemic does not appear to finish soon.Therefore, having a forecasting model about the covid-19 spread is of paramount importance to plan interventions and, then, to limit the economic and social damage.In this paper, we use genetic programming to evidence dependences of the sars-co v-2 spread from past data in a given country.Namely, we analyze real data of the campania region, in italy.The resulting models prove their effectiveness in forecasting the number of new positives 10/15 days before, with quite a high accuracy.The developed models have been integrated into the context of svimac-19, an analytical-forecasting system for the containment, contrast, and monitoring of covid-19 within the campania region.

Journal: Soft computing (2022)
Publication types: Journal Article
Tanshinone I inhibits metastasis of cervical cancer cells by inducing BNIP3/NIX-mediated mitophagy and reprogramming mitochondrial metabolism.

Cervical cancer is the most common malignancy of the female lower genital tract.Tanshinone i (tan i) is one of the crucial lipid-soluble components of red sage (salvia miltiorrhiza).While its mode of action against cervical cancer is unclear.Purpose our study aimed to explore the role of tan i on cervical cancer in vitro.Study design and methods effects of tan i on cervical cancer cells viability, migration and mitochondrial function were investigated by cell counting kit-8, transwell and fluorescence laser confocal microscope assays respectively.The potential mechanism of tan i was uncovered by an integrative approach combining rna profiling and hydrogen nuclear magnetic resonance-based metabolic analysis, molecular docking and western blot.Results tan i significantly inhibited the growth and colony formation of he la and si ha cells.It induced apoptosis and cell cycle s phase arrest at low (12.5-25 μm) but not high (50 μm) concentrations.It also altered the he la cell ultrastructure, decreased the membrane potential and increased the total mitochondrial content.Further, tan i induced autophagic flux and the colocalization of mitochondria with lysosomes, led to decreased adhesion, invasion, and migration of cervical cancer cells.Transcriptomic analysis revealed that tan i altered the rna profile and signal processing in he la cells.Tan i significantly impacted "central carbon metabolism in cancer" and "mitophagy-animal" processes.A global metabolic analysis identified 25 metabolites affected by tan i treatment in he la cells.Changes in the metabolic profile indicated that tan i affected such processes as protein digestion and absorption, central carbon metabolism in cancer, and aminoacyl-t rna biosynthesis in cervical cancer cells.Furthermore, tan i significantly induced the expression of mitophagy-related proteins bnip3, nix and optineurin and the conversion from lc3-i to lc3-ii, inhibited the ndp52 and p62 level in a concentration-dependent manner.While cq further increased the conversion of lc3-i to lc3-ii and the expression of p62.Moreover, tan i interacted with bnip3 and nix through hydrogen bond.Tan i induce mitophagy could be prevented by bnip3 and nix si rna transfection.Conclusion tan i induced the bnip3/nix-mediated mitophagy, and reprogrammed the mitochondrial metabolism in cervical cancer cells, thus inhibiting metastasis.

Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (2022)
Publication types: Journal Article
Pregnancy outcomes of rare autosomal trisomies results in non-invasive prenatal screening: clinical follow-up data from a single tertiary centre.

This study was performed to assess the association between detection of rare autosomal trisomies (rats) by non-invasive prenatal screening (nips) and adverse pregnancy outcomes.We retrospectively analyzed women with high-risk rats results from january 2014 to december 2020.The women's clinical information was collected, and their pregnancy outcomes were compared with those of women with low-risk results.In total, 151 (0.24%) rats results were reported among 62,752 nips examinations.Sixty-five women chose to undergo amniocentesis for confirmation, which revealed 3 cases of true fetal mosaicism for rats and a positive predictive value of 4.6% (3/65).Among the 139 women with available outcomes, 26 (18.7%) had a preterm birth, 10 (7.2%) underwent pregnancy termination because of fetal defects and 5 (3.6%) had miscarriages.Interestingly, compared with the control group, pregnancies in which nips revealed trisomy 16 (t16), t22, t9 and t2 were at higher risk of adverse outcomes, including preterm birth, miscarriage and ultrasound abnormalities.However, the risk of adverse outcomes was comparable between the control group and pregnancies with positive results of t7, t3, t8 and t20.In summary, the risk of adverse pregnancy outcomes was higher in women with specific rats-positive nips results.Pregnancies with t16, t22, t9 and t2 results, even if false-positive, should be considered high-risk pregnancies.

Journal: Journal of cellular and molecular medicine (2022)
Publication types: Journal Article