syedzayyan/paper_mill_benchmark huggingface dataset:
Structurally Informed Mutagenesis of a Stereochemically Promiscuous Aldolase Produces Mutants That Catalyze the Diastereoselective Syntheses of All Four Stereoisomers of 3-Deoxy-hexulosonic Acid.

A 2-keto-3-deoxygluconate aldolase from the hyperthermophile sulfolobus solfataricuscatalyzes the nonstereoselective aldol reaction of pyruvate and d-glyceraldehyde to produce 2-keto-3-deoxygluconate (d-kdglc) and 2-keto-3-deoxy-d-galactonate (d-kdgal).Previous investigations into curing the stereochemical promiscuity of this hyperstable aldolase used high-resolution structures of the aldolase bound to d-kdglc or d-kdgal to identify critical amino acids involved in substrate binding for mutation.This structure-guided approach enabled mutant variants to be created that could stereoselectively catalyze the aldol reaction of pyruvate and natural d-glyceraldehyde to selectively afford d-kdglc or d-kdgal.Here we describe the creation of two further mutants of this sulfolobusaldolase that can be used to catalyze aldol reactions between pyruvate and non-natural l-glyceraldehyde to enable the diastereoselective synthesis of l-kdglc and l-kdgal.High-resolution crystal structures of all four variant aldolases have been determined (both unliganded and liganded), including variant 1 with d-kdglc, variant 2 with pyruvate, variant 3 with l-kdglc, and variant 4 with l-kdgal.These structures have enabled us to rationalize the observed changes in diastereoselectivities in these variant-catalyzed aldol reactions at a molecular level.Interestingly, the active site of variant 4 was found to be sufficiently flexible to enable catalytically important amino acids to be replaced while still retaining sufficient enzymic activity to enable production of l-kdgal.

Journal: ACS catalysis (2022)
Publication types: Journal Article
Not all stage I and II endometrial cancers are created equal: Recurrence-free survival and cause-specific survival after observation or vaginal brachytherapy alone in all subgroups of early-stage high-intermediate and high-risk endometrial cancer.

To evaluate recurrence-free survival (rfs) and cause-specific survival (css) after observation or vaginal brachytherapy (vb) alone in all subgroups of early-stage high-intermediate (hir) and high-risk endometrial cancer (ec).Methods we identified patients with stage i hir (gog-249 criteria) and stage ii endometrioid ec, and stage i and ii non-endometrioid ec who underwent surgery at mayo clinic and cleveland clinic between 1999 and 2016.Three-year rfs and css after observation or vb only were estimated in 16 subgroups defined by risk factors.Results among 4156 ecs, we identified 447 (10.8%) stage i endometrioid hir, 52 (1.3%) stage ii endometrioid, 350 (8.4%) stage i non-endometrioid, and 17 (0.4%) stage ii non-endometrioid ecs; observation or vb alone was applied in 349 (78.1%), 24 (46.2%), 187 (53.4%), and 2 (11.8%) patients, respectively.After observation or vb, stage i hir endometrioid ec subgroups with 95% (lower 95% confidence intervals limit: 89.8%), whereas subgroups with ≥2 factors had poorer outcomes.No ec-related deaths after 3 years were reported in 97 stage ia non-endometrioid ecs without myometrial invasion.Stage ii ecs had poor outcomes regardless of histology.Conclusions observation or vb only may be sufficient in stage i endometrioid hir ecs with <2 factors among grade 3, lvsi, or ib and in stage ia non-endometrioid ecs without myometrial invasion.Stratification of early-stage hir and high-risk ecs into risk subgroups potentially alleviates the overtreatment and undertreatment risk and should be considered in future research.

Journal: Gynecologic oncology (2022)
Publication types: Journal Article
Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis.

S in early rheumatoid arthritis (e ra) plasma levels of specific chemokines have been shown to correlate with disease activity.However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated e ra.Methods this study included 347 swedish patients with untreated e ra from the larger nord-star randomised treatment trial.Here, e ra patients were treated with methotrexate combined with either prednisolone, anti-tnf (certolizumab-pegol), ctla-4ig (abatacept) or anti-il6 receptor (tocilizumab).The primary clinical outcome was remission by clinical disease activity index (cdai) defined as cdai ≤ 2.8.Disease activity was assessed by cdai, das28-esr, das28-crp, swollen joint counts, tender joint counts, esr and crp.The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or elisa.Results baseline plasma concentrations of cxcl10, cxcl8, cxcl9, cxcl11, cxcl5 and ccl2 correlated with baseline disease activity measures.After 24 weeks of treatment, plasma levels of cxcl10, cxcl8, cxcl9, cxcl11 and cxcl13 decreased in all treatment groups except in patients treated with anti-il6 receptor.In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups.Conclusions in patients with untreated e ra, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti‐tnf, ctla‐4ig or anti‐il6r.

Journal: Clinical and experimental rheumatology (2022)
Publication types: Journal Article
Social position and economic system justification in Canada: Implications for advancing health equity and social justice from an exploratory study of factors shaping economic system justification.

Many socio-economic reforms that could reduce health disparities are not implemented because people justify existing systems and fear changes thereto.This study aimed to identify socio-demographic factors associated with system justifying beliefs to better understand how they are maintained in canada.In doing so, we hypothesized that (1) systems justification is a default cognitive position, buttressed by the palliative benefits of system-justification, (2) lack of success in a given system generally motivates people to doubt the legitimacy of that system, and (3) system-justifying beliefs are rejected only when the costs of doing so are low enough and/or the benefits are high enough to outweigh the innate needs-fulfillment benefits of system-justification.Methods testing these hypotheses, we recruited participants living in canada, aged 16+, to complete an online survey after being recruitedviapaid social media advertisements.Multivariable regression models identified factors associated with economic system justification scale (esjs) scores.Explanatory variables included demographic measures of social position, self-rated health, and patterns of social inclusion.Results among 2,619 participants, system-justifying beliefs were wide-spread, with the average level of support across esjs scale items exceeding 50%.Lower esjs scores were associated with worse health, more loneliness, and lower socioeconomic status.Despite the pattern that marginalization erodes system-justification, several historically marginalized characteristics (e.g., non-white ethnicity and non-binary gender) were associated with relatively high system-justification, compared to matching privileged characteristics (e.g., white ethnicity; masculine gender).Conclusion supporting our hypotheses, we identify a general trend that social marginalization is associated with less system-justification.Those benefitting from the status quo (e.g., healthier, wealthier, less lonely) were more likely to hold system-justifying beliefs.However, some groups who are disadvantaged within the existing system reported higher system-justification-suggesting that system oppression may be a key moderator of the effect of social position on system justification.

Journal: Frontiers in public health (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Contemporary biomedical engineering perspective on volitional evolution for human radiotolerance enhancement beyond low-earth orbit.

A primary objective of the national aeronautics and space administration (nasa) is expansion of humankind's presence outside low-earth orbit, culminating in permanent interplanetary travel and habitation.Having no inherent means of physiological detection or protection against ionizing radiation, humans incur capricious risk when journeying beyond low-earth orbit for long periods.Nasa has made large investments to analyze pathologies from space radiation exposure, emphasizing the importance of characterizing radiation's physiological effects.Because natural evolution would require many generations to confer resistance against space radiation, immediately pragmatic approaches should be considered.Volitional evolution, defined as humans steering their own heredity, may inevitably retrofit the genome to mitigate resultant pathologies from space radiation exposure.Recently, uniquely radioprotective genes have been identified, conferring local or systemic radiotolerance when overexpressedin vitroandin vivo.Aiding in this process, the crispr/cas9 technique is an inexpensive and reproducible instrument capable of making limited additions and deletions to the genome.Although cohorts can be identified and engineered to protect against radiation, alternative and supplemental strategies should be seriously considered.Advanced propulsion and mild synthetic torpor are perhaps the most likely to be integrated.Interfacing artificial intelligence with genetic engineering using predefined boundary conditions may enable the computational modeling of otherwise overly complex biological networks.The ethical context and boundaries of introducing genetically pioneered humans are considered.

Journal: Synthetic biology (Oxford, England) (2021)
Publication types: Journal Article;Review
Alcohol consumption patterns and growth differentiation factor 15 among life-time drinkers aged 65+ years in Spain: a cross-sectional study.

S to examine the association of alcohol consumption patterns with growth differentiation factor 15 (gdf-15) in older drinkers, separately among individuals with cardiovascular disease (cvd)/diabetes and those without them, as gdf-15 is a strong biomarker of chronic disease burden.Design cross-sectional study.Setting population-based study in madrid (spain).Participants a total of 2051 life-time drinkers aged 65+ years included in the seniors-enrica-2 study in 2015-17.Participants' mean age was 71.4 years and 55.4% were men.Measurements according to their average life-time alcohol intake, participants were classified as occasional (≤ 1.43 g/day), low-risk (men: > 1.43-20 g/day; women: > 1.43-10 g/day), moderate-risk (men: > 20-40 g/day; women: > 10-20 g/day) and high-risk drinkers (men: > 40 g/day; women: > 20 g/day; or binge drinkers).We also ascertained wine preference (> 80% of alcohol derived from wine), drinking with meals and adherence to a mediterranean drinking pattern (mdp) defined as low-risk drinking, wine preference and one of the following: drinking only with meals; higher adherence to the mediterranean diet; or any of these.Findings in participants without cvd/diabetes, gdf-15 increased by 0.27% [95% confidence interval (ci) = 0.06%, 0.48%] per 1 g/day increment in alcohol among high-risk drinkers, but there was no clear evidence of association in those with lower intakes or in the overall group, or across categories of alcohol consumption status.Conversely, among those with cvd/diabetes, gdf-15 rose by 0.19% (95% ci = 0.05%, 0.33%) per 1 g/day increment in the overall group and gdf-15 was 26.89% (95% ci = 12.93%, 42.58%) higher in high-risk versus low-risk drinkers.Drinking with meals did not appear to be related to gdf-15, but among those without cvd/diabetes, wine preference and adherence to the mdp were associated with lower gdf-15, especially when combined with high adherence to the mediterranean diet.Conclusions among older life-time drinkers in madrid, spain, high-risk drinking was positively associated with growth differentiation factor 15 (a biomarker of chronic disease burden).There was inconclusive evidence of a beneficial association for low-risk consumption.

Journal: Addiction (Abingdon, England) (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Advocating Electrically Conductive Scaffolds with Low Immunogenicity for Biomedical Applications: A Review.

Scaffolds support and promote the formation of new functional tissues through cellular interactions with living cells.Various types of scaffolds have found their way into biomedical science, particularly in tissue engineering.Scaffolds with a superior tissue regenerative capacity must be biocompatible and biodegradable, and must possess excellent functionality and bioactivity.The different polymers that are used in fabricating scaffolds can influence these parameters.Polysaccharide-based polymers, such as collagen and chitosan, exhibit exceptional biocompatibility and biodegradability, while the degradability of synthetic polymers can be improved using chemical modifications.However, these modifications require multiple steps of chemical reactions to be carried out, which could potentially compromise the end product's biosafety.At present, conducting polymers, such as poly(3,4-ethylenedioxythiophene) poly(4-styrenesulfonate) (pedot: pss), polyaniline, and polypyrrole, are often incorporated into matrix scaffolds to produce electrically conductive scaffold composites.However, this will reduce the biodegradability rate of scaffolds and, therefore, agitate their biocompatibility.This article discusses the current trends in fabricating electrically conductive scaffolds, and provides some insight regarding how their immunogenicity performance can be interlinked with their physical and biodegradability properties.

Journal: Polymers (2021)
Publication types: Journal Article;Review
Dynamic evaluation on the energy and environmental performance of China's transportation sector: a ZSG-MEA window analysis.

The transportation sector is one of the important energy consumption and carbon emission sources.This paper extends the multi-directional efficiency analysis (mea) to zero-sum game mea (zsg-mea) with considering the co2emission as a fixed-sum undesirable output to measure the energy and environmental performance (eep) of the transportation sector.The zsg-mea window analysis is applied to dynamically evaluate the eep of china's transportation sector in 30 provincial-level regions during 2008-2017.Some interesting findings are obtained: (i) the eep of the transportation sector in most regions has not been performed well but the average eep of the transportation sector in most regions has been gradually improved since 2011.A general trend is that the transportation sector in the east area wins the best average eep, and the average eep of the central area is better than that of the west area, but their gap is narrowing from 2012.(ii) the eep fluctuation verifies the greatest imbalance of eep among the east area's regions.Both the east area and the central area are narrowing the imbalance in recent years, but the west area has an inverse trend.(iii) the performance of co2emissions is better than that of energy consumption in all three areas, which implies that china's transportation sector seems to have paid more attention on emission reduction than energy conservation.Besides, the east area has the best performance of energy consumption and co2emissions from an overall perspective.And the energy consumption and co2emissions in the central area perform better than the west area before 2013, but then shows an entangled state from 2013.(iv) from the average variable specific zsg-mea efficiency, the industrial added value of transportation sector performs better than other variables in the east area and central area, but the situation in the west area is inverse.Some useful insights are provided according to these findings.

Journal: Environmental science and pollution research international (2021)
Publication types: Journal Article
Study of the protective effects of cyanocobalamin on methotrexate induced nephrotoxicity in rats.

Methotrexate (mtx) is a chemotherapeutic drug, used mainly in many cancerous stages, inflammatory and auto-immune diseases, but its use has been limited by its nephrotoxicity.Cyanocobalamin is a water-soluble vitamin possessing nephro-protective properties.The aim of this study was to investigate the effect of cyanocobalamin on the nephrotoxicity of methotrexate.methods:in the study 42 albino adult female rats were used, divided into six groups each containing seven rats (n=7).1stgroup: control group (negative control), 7 rats were injected intraperitoneally with 0.5ml/kg/day ns.Second group: 7 rats were injected intraperitoneally with a single dose of methotrexate (20 mg/kg) for 4 days.Third group: 7 rats were given intraperitoneally cyanocobalamin at a dose (1.5 mg/kg/day) for two weeks, fourth, fifth, sixth group: 7 rats from each group were injected intraperitoneally with different concentrations of cyanocobalamin (0.5, 1, 1.5 mg/kg /day), respectively, for two weeks and mtx (20 mg/kg), which was injected only on day 11.On day 15, rats from all groups were euthanized, and blood samples were taken for biochemical tests, including evaluating serum urea and creatinine.The kidneys were extracted for histological investigation and evaluation of antioxidant (gsh) and oxidative stress (mda) by using kidney tissue homogenates.results:this study revealed that kidney damage, produced by the mtx (group ii), is manifested by significantly elevated (p<0.05) urea and creatinine.On the contrary, the cyanocobalamin groups (iv, v, vi) significantly (p<0.05) reduced urea and creatinine.Renal antioxidant defense systems, such as reduced glutathione depleted by mtx therapy, were restored to normal levels by cyanocobalamin.Furthermore, cyanocobalamin reduced oxidative stress (mda) and histologically reduced renal tissue injury induced by mtx.conclusions:in conclusion, the study revealed that cyanocobalamin has a nephroprotective action upon mtx-induced renal damage in rats; cyanocobalamin may offer a protective effect, such as antioxidant action.

Journal: F1000Research (2022)
Publication types: Journal Article
Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson's disease.

Maintaining consistent levodopa benefits while simultaneously controlling dyskinesia can be difficult.Recently, an amantadine delayed release/extended release (dr/er) formulation (gocovri®) indicated for dyskinesia received additional fda approval as an adjunct to levodopa for the treatment of off episodes.We evaluated off time reductions with amantadine-dr/er in a pooled analysis of two phase iii amantadine-dr/er trials (nct02136914, nct02274766) followed by a 2-year open-label extension trial (nct02202551).Off outcomes were analyzed for the m itt population, as well as stratified by baseline off time of ≥2.5 h/day or <2.5 h/day.At week 12, mean placebo-subtracted treatment difference in off time was -1.00 [-1.57, -0.44] h in the m itt population (n = 196), -1.2 [-2.08, -0.32] h in the ≥2.5 h subgroup (n = 102) and -0.77 [-1.49, -0.06] in the <2.5 h subgroup (n = 94).Amantadine-dr/er-treated participants showed reduced mds-updrs part iv motor fluctuation subscores by week 2 that were maintained below baseline to week 100.

Journal: NPJ Parkinson's disease (2022)
Publication types: Journal Article
Interfacial π-π Interactions Induced Ultralight, 300 °C-Stable, Wideband Graphene/Polyaramid Foam for Electromagnetic Wave Absorption in Both Gigahertz and Terahertz Bands.

High-performance electromagnetic wave-absorbing (ema) materials used in high-temperature environments are of great importance in both civil and military fields.Herein, we have developed the ultralight graphene/polyaramid composite foam for wideband electromagnetic wave absorption in both gigahertz and terahertz bands, with a higher service temperature of 300 °c.It is found that strong interfacial π-π interactions are spontaneously constructed between graphene and polyaramids (pa), during the foam preparation process.This endows the foam with two advantages for its ema performance.First, the π-π interactions trigger the interfacial polarization for enhanced microwave dissipation, as confirmed by the experimental and simulation results.The composite foam with an ultralow density (0.0038 g/cm3) shows a minimum reflection loss (rl) of -36.5 d b and an effective absorption bandwidth (eab) of 8.4 ghz between 2 and 18 ghz band.Meanwhile, excellent terahertz (thz) absorption is also achieved, with eab covering the entire 0.2-1.6 thz range.Second, the interfacial π-π interactions promote pa to present a unique in-plane orientation configuration along the graphene surface, thus making pa the effective antioxidation barrier layer for graphene at high temperatures.The ema performance of the foam could be completely preserved after 300 °c treatment in air atmosphere.Furthermore, the composite foam exhibits multifunctions, including good compressive, thermal insulating, and flame-retardant properties.We believe that this study could provide useful guidance for the design of next-generation ema materials used in harsh environments.

Journal: ACS applied materials & interfaces (2022)
Publication types: Journal Article
Detailed Visualization of Phase Evolution during Rapid Formation of Cu(InGa)Se2Photovoltaic Absorber from Mo/CuGa/In/Se Precursors.

Amongst several processes which have been developed for the production of reliable chalcopyrite cu(in ga)se2photovoltaic absorbers, the 2-step metallization-selenization process is widely accepted as being suitable for industrial-scale application.Here we visualize the detailed thermal behavior and reaction pathways of constituent elements during commercially attractive rapid thermal processing of glass/mo/cu ga/in/se precursors on the basis of the results of systematic characterization of samples obtained from a series of quenching experiments with set-temperatures between 25 and 550 °c.It was confirmed that the se layer crystallized and then melted between 250 and 350 °c, completely disappearing at 500 °c.The formation of cu in se2and cu(in ga)se2was initiated at around 450 °c and 550 °c, respectively.It is suggested that pre-heat treatment to control crystallization of se layer should be designed at 250-350 °c and cu(in ga)se2formation from cu ga/in/se precursors can be completed within a timeframe of 6 min.

Journal: Scientific reports (2018)
Publication types: Journal Article
Benefits, mechanisms, and risks of intermittent fasting in metabolic syndrome and type 2 diabetes.

One of the emergent nutritional strategies for improving multiple features of cardiometabolic diseases is the practice of intermittent fasting (if), which consists of alternating periods of eating and fasting.If can reduce circulating glucose and insulin levels, fat mass, and the risk of developing age-related pathologies.If appears to upregulate evolution-conserved adaptive cellular responses, such as stress-response pathways, autophagy, and mitochondrial function.If was also observed to modulate the circadian rhythms of hormones like insulin or leptin, among others, which levels change in conditions of food abundance and deficit.However, some contradictory results regarding the duration of the interventions and the anterior metabolic status of the participants suggest that more and longer studies are needed in order to draw conclusions.This review summarizes the current knowledge regarding the role of if in the modulation of mechanisms involved in type 2 diabetes, as well as the risks.

Journal: Journal of physiology and biochemistry (2022)
Publication types: Journal Article;Review