syedzayyan/paper_mill_benchmark huggingface dataset:
Reduced PGC-1β protein expression may underlie corticosterone inhibition of mitochondrial biogenesis and oxidative phosphorylation in chicken muscles.

To uncover the molecular mechanism underlying glucocorticoid-induced loss of mitochondrial integrity in skeletal muscles, studies were performed to investigate whether the peroxisome proliferator-activated receptor γ coactivator 1 (pgc-1)-mediated pathway was involved in this process.In anin vivotrial, 3 groups of 30-d-old arbor acres male broilers were randomly subjected to one of the following treatments for 7 days: corticosterone (cort, 30 mg/kg diet), control (blank), and pair-feeding (restricted to the same feed intake as for the cort treatment), each with 6 replicates of 15 birds.Mitochondrial abundance, morphology, and function were determined in thepectoralis majorandbiceps femorismuscles.In anin vitrotrial, a primary culture of embryonic chick myotubes was incubated with a serum-free medium for 24 h in the presence or absence of cort (0, 200, and 1,000 n m).Results showed that cort destroyed mitochondrial ultrastructure (p< 0.01), and decreased the enzymatic activity and protein expression of respiratory chain complexes (p< 0.05), leading to an inferior coupling efficiency (p< 0.05).As reflected by a decline in mitochondrial density (p< 0.01) and mitochondrial dna copy number (p< 0.05), cort reduced mitochondrial contents.Among all three pgc-1 family members, only pgc-1β was down-regulated by cort at the protein level (p< 0.05).Some aspects of these responses were tissue-specific and seemed to result from the depressed feed intake.Overall, cort may impair mitochondrial biogenesis and oxidative phosphorylation in a pgc-1β-dependent manner in chicken muscles.

Journal: Frontiers in physiology (2022)
Publication types: Journal Article
Expression of immune markers of white sturgeon (Acipenser transmontanus) during Veronaea botryosa infection at different temperatures.

Systemic phaeohyphomycosis caused by veronaea botryosa is one of the most important emergent diseases to affect sturgeon aquaculture in north america.White sturgeon (acipenser transmontanus) cultured at temperatures above 15 °c are at higher risk of severe disseminated disease and higher mortalities.Despite this, little is known regarding disease pathogenesis and the immune response to infection.The objective of this study was to investigate the acute (2 days post-challenge [dpc]) and chronic (32 dpc) response of white sturgeon at 13 °c and 18 °c challenged with v.Botryosa via intramuscular injection, using gene expression analysis of a diverse array of soluble immune and inflammatory mediators.Significantly greater amounts of irf8 (p < 0.05) and tfg-β (p < 0.05) genes were detected in gills of exposed fish at 18 °c when compared to those at 13 °c 32 dpc.Transcript levels of haptoglobin, serotransferrin, serum amyloid, cathelicidin, tnf-α, and il-17 were significantly increased in splenic tissues of challenged fish maintained at 18 °c late in infection (p < 0.05).However, only haptoglobin and serotransferrin transcript abundance were significantly greater in exposed fish when compared to controls 32dpc.Moreover, haptoglobin transcripts at this time point were significantly greater in exposed fish at 18 °c when compared to those challenged at 13 °c.Fewer differences were detected in fish kept at 13 °c.In agreement with transcript quantification, western blot assessment of haptoglobin showed increased levels in the challenged fish maintained at 18 °c.

Journal: Comparative biochemistry and physiology. Part D, Genomics & proteomics (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
What's new in atopic eczema? An analysis of systematic reviews published in 2019. Part 2: treatment.

This review forms part of a series of annual evidence updates on atopic eczema (ae), and provides a summary of key findings from systematic reviews (srs) published or indexed in 2019 related to ae treatment.Several srs assessed the efficacy of topical corticosteroids (tcs), topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors and topical janus kinase/signal transducer and activator of transcription (jak/stat) pathway inhibitors.However, there is a lack of good-quality trials comparing topical treatment agents with tcs, which remain the standard of care for patients with ae.Most of the included trials lack meaningful comparisons as they used vehicle as a comparator.There is also lack of harmonization of outcome measures for ae across studies.Large, well-designed rcts are needed to further determine whether any specific emollients offer superior benefit.There is evidence highlighting limited benefit of oral h1 antihistamines as 'add-on' therapy to topical treatment of eczema.Mycophenolate mofetil may have a role in patients with refractory ae.Among biologic therapies, most of the efficacy data relate to dupilumab.Furthermore, there is growing evidence for the efficacy and safety of systemic jak/stat pathway inhibitors, but the existing data are of low quality.

Journal: Clinical and experimental dermatology (2021)
Publication types: Journal Article;Review
Prevalence and Therapeutic Challenges of Fungal Drug Resistance: Role for Plants in Drug Discovery.

Antimicrobial resistance is a global issue that threatens the effective practice of modern medicine and global health.The emergence of multidrug-resistant (mdr) fungal strains of candida aurisand azole-resistant aspergillus fumigatuswere highlighted in the centers for disease control and prevention's (cdc) 2019 report,antibiotic resistance threats in the united states.Conventional antifungals used to treat fungal infections are no longer as effective, leading to increased mortality.Compounding this issue, there are very few new antifungals currently in development.Plants from traditional medicine represent one possible research path to addressing the issue of mdr fungal pathogens.In this commentary piece, we discuss how medical ethnobotany-the study of how people use plants in medicine-can be used as a guide to identify plant species for the discovery and development of novel antifungal therapies.

Journal: Antibiotics (Basel, Switzerland) (2020)
Publication types: Journal Article
Trimethylation and Acetylation of β-Catenin at Lysine 49 Represent Key Elements in ESC Pluripotency.

Wnt/β-catenin signaling is required for embryonic stem cell (esc) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unknown.Here, we show that lysine 49 (k49) of β-catenin is trimethylated (β-cat me3) by ezh2 or acetylated (β-cat ac) by cbp.Significantly, β-cat me3 acts as a transcriptional co-repressor of the neuronal differentiation genes sox1 and sox3, whereas β-cat ac acts as a transcriptional co-activator of the key mesodermal differentiation gene t-brachyury (t-bra).Furthermore, β-cat me3 and β-cat ac are alternatively enriched on repressed or activated genes, respectively, during esc and adult stem cell differentiation into neuronal or mesodermal progenitor cell lineages.Importantly, expression of a β-catenin k49a mutant results in major defects in esc differentiation.We conclude that β-catenin k49 trimethylation and acetylation are key elements in regulating esc pluripotency and differentiation potential.

Journal: Cell reports (2017)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome-Intestine-Pancreas Axis.

The prevalence of type 2 diabetes mellitus (t2d) is increasing worldwide, and there are no long-term preventive strategies to stop this growth.Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of t2d, while microbiome modulators may be beneficial for t2d prevention.However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available.Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced t2d in mice.We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt).Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls.Surprisingly, the control yogurt exacerbated diabetes progression.Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as proteobacteria and enterobacteriaceae.In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets.These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.

Journal: International journal of molecular sciences (2021)
Publication types: Journal Article
Cost-effectiveness threshold of first-trimester Down syndrome maternal serum screening for the use of cell-free DNA as a second-tier screening test.

Introduction we aimed to identify the most relevant cost-effectiveness threshold of first-trimester down syndrome (ds) maternal serum screening (t21t1) for the use of cell-free dna (cf dna) as a second-tier test in the french context.Method a cost-effectiveness analysis was performed on 108,121 singleton pregnancies using a simulation model.The threshold of t21t1 screening was ranged from 1/51 to 1/1,000 in steps of 1/50.The most relevant threshold was based on cost-effectiveness ratio (cer; costs = direct medical costs after t21t1 screening/ effectiveness = number of ds cases identified).Results in the sample, 161 cases of ds were identified.At the threshold of ≥ 1/50, 47.2% of total ds cases were diagnosed.In the simulation model, for a threshold ≥ 1/250, 73.9% of total ds cases were diagnosed, for ≥ 1/500, 78.8% and for ≥ 1/1,000, only two additional cases were diagnosed.The slope of the cost increase was slight from threshold ≥ 1/250 (978,634 €), then steep up to 1/500 (1,966,576 €) and increased exponentially to 1/1,000 (3,980,216 €).The cer was 38,560 for a threshold ≥ 1/500.Conclusion the most cost-effective threshold for cf dna as a second-tier test seems to be ≥ 1/500.For higher thresholds, costs increase dramatically for only a few additional cases of ds identified.

Journal: Annales de biologie clinique (2021)
Publication types: Journal Article
MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p.

The aim of this study was to clarify the role of lnc rna metastasis-associated lung adenocarcinoma transcript 1 (malat1) in proliferation, migration, and invasion of malignant pleural mesothelioma (mpm) cells.The quantitative reverse transcription polymerase chain reaction (rt-q pcr) was used to detect the expression of malat1 in mpm cell lines.The effects of malat1 and mi r-141-3p on the proliferation, migration, and invasion of mpm cells were studied through a series ofin vitrocellular experiments.The flow cytometry was utilized to detect the cell apoptosis.The dual-luciferase reporter assay was employed to explore the binding relationship among malat1, mi r-141-3p, and yes-associated protein 1 (yap1).Malat1 was overexpressed in mpm cell lines, while its knockdown significantly inhibited the cell proliferation, migration, and invasion, and increased the number of mpm cells in the g0/g1 phase.In addition, malat1 could directly bind to mi r-141-3p and inhibit its expression.Yap1 has been identified as a downstream target of mi r-141-3p, and its expression level was inhibited by mi r-141-3p.Malat1 can be used as a competitive endogenous rna (ce rna) to regulate the yap1-hippo signaling pathway through mi r-141-3p, promote the proliferation, migration, and invasion of mpm cells, and provide a new target for the therapy of mpm.

Journal: Open medicine (Warsaw, Poland) (2021)
Publication types: Journal Article
Parental Attachment and Peer Relationships in Adolescence: A Systematic Review.

According to attachment theory, children's early experiences with their primary caregivers, in terms of protection and security, are the basis for socioemotional development and for the establishment of close relationships throughout their lives.During adolescence, friends and peers become a primary developmental environment, and thereby establishing quality bonds with peers will foster good psychological adjustment.The aim of the present study was to review the evidence on the relation of parental attachment to the quality of peer relationships during adolescence.A systematic review was conducted according to the recommendations of the preferred reporting items for systematic reviews and meta-analyses guidelines.The search was performed in the psyc info, scopus, and web of science (wos) databases.Inclusion criteria were studies published since 2001, in english, that are academic publications in scientific journals, that explore adolescence, and that analyze the relationship between attachment styles and adolescent peer interactions.The search resulted in 1438 studies, of which 19 studies met the criteria and were included in the review.The results highlighted that secure attachment predicts and promotes the creation of affective relationships with peers and friends based on communication, support, intimacy, trust, and quality.In addition, some variables, such as gender differences or family characteristics, were found to be involved in attachment and provide a better understanding.

Journal: International journal of environmental research and public health (2022)
Publication types: Journal Article;Review;Systematic Review
Radiographic Study Evaluating Perforator Vessels in the Ischiorectal Fossa for Safe Elevation of Island Flaps.

Perforator flaps based on the ischiorectal fossa (irf) (ie, internal pudendal artery perforator flaps) are useful for perineal reconstruction.The three-dimensional characterization of perforator arteries in the irf remains unclear, as the irf contains thick adipose tissue as well as organs, such as the rectum, vagina, and urethra.This study aimed to evaluate perforators in the irf to guide the safe elevation of skin flaps designed based on the irf.Methods irf vessels were examined in 200 bilateral computed tomography angiography scans performed in 100 patients.We examined branching patterns arising from the internal iliac artery and the origins of the skin perforators in the irf.Results the branching patterns of the internal iliac artery were divided into three groups: perforators derived exclusively from the internal pudendal artery (78%), perforators derived from the internal pudendal artery and the inferior gluteal artery (18%), and perforators derived exclusively from the inferior gluteal artery (4%).The average number of perforators in the irf was 1.5 ± 0.7.The number of perforators was significantly higher in women than in men.The perforator arteries were found exclusively around the medial and dorsal sides of the ischial tuberosity.Conclusions we found that perforators in the irf were stable.All cases had more than one skin perforator, which was mainly derived from the internal pudendal artery.Although perforators cannot be identified during flap elevation because the fatty tissue in the irf is very thick, physicians must focus on preserving the perforator-containing fatty tissue around the ischial tuberosity.

Journal: Plastic and reconstructive surgery. Global open (2022)
Publication types: Journal Article
Immunoreactive distribution of gonadotropin-inhibitory hormone precursor, RFRP, in a temperate bat species (Eptesicus fuscus).

Gonadotropin-inhibitory hormone (gn ih, also known rfrp-3 in mammals) is an important regulator of the hypothalamic-pituitary-gonadal axis and downstream reproductive physiology.Substantial species differences exist in the localization of cell bodies producing rfrp-3 and patterns of fiber immunoreactivity in the brain, raising the question of functional differences.Many temperate bat species exhibit unusual annual reproductive patterns.Male bats upregulate spermatogenesis in late spring which is asynchronous with periods of mating in the fall, while females have the physiological capacity to delay their reproductive investment over winter via sperm storage or delayed ovulation/fertilization.Neuroendocrine mechanisms regulating reproductive timing in male and female bats are not well-studied.We provide the first description of rfrp-precursor peptide of gn ih -expression and localization in the brain of any bat using a widespread temperate species (eptesicus fuscus, big brown bat) as a model.Rfrp m rna expression was detected in the hypothalamus, testes, and ovaries of big brown bats.Cellular rfrp-immunoreactivity was observed within the periventricular nuclei, dorsomedial nucleus of the hypothalamus, arcuate nucleus (arc), and median eminence (me).As in other vertebrates, rfrp fiber immunoreactivity was widespread, with the greatest density observed in the hypothalamus, preoptic area, arc, me, midbrain, and thalamic nuclei.Putative interactions between rfrp-ir fibers and gonadotropin-releasing hormone (gn rh) cell bodies were observed in 16% of gn rh-immunoreactive cells, suggesting direct regulation of gn rh via rfrp signaling.This characterization of rfrp distribution contributes to a deeper understanding of bat neuroendocrinology, which serves as foundation for manipulative approaches examining changes in reproductive neuropeptide signaling in response to environmental and physiological challenges within, and among, bat species.

Journal: The Journal of comparative neurology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Double freeform surfaces design for beam shaping with non-planar wavefront using an integrable ray mapping method.

We propose a method to design double smooth freeform surfaces applied in beam shaping with a ray mapping method in the paper.We couple the calculation of ray mapping and the construction of freeform surfaces to approach the surface normal field integrability condition based on the symplectic flow mapping scheme.In this paper, the incident beam wavefront is not limited to be planar or spherical.Several challenging design examples are presented that include transforming a circular gaussian beam to an unconventional beam with variously shaped contour, and transforming an elliptic beam to a convergent beam with complex irradiance distribution in non-paraxial regime.The results show the high efficiency and feasibility of the proposed method in designing freeform optics for beam shaping applications.

Journal: Optics express (2019)
Publication types: Journal Article
Sequence and Nuclease Requirements for Breakage and Healing of a Structure-Forming (AT)n Sequence within Fragile Site FRA16D.

Common fragile sites (cfss) are genomic regions that display gaps and breaks in human metaphase chromosomes under replication stress and are often deleted in cancer cells.We studied an ∼300-bp subregion (flex1) of human cfs fra16d in yeast and found that it recapitulates characteristics of cfs fragility in human cells.Flex1 fragility is dependent on the ability of a variable-length at repeat to form a cruciform structure that stalls replication.Fragility at flex1 is initiated by structure-specific endonuclease mus81-mms4 acting together with the slx1-4/rad1-10 complex, whereas yen1 protects flex1 against breakage.Sae2 is required for healing of flex1 after breakage.Our study shows that breakage within a cfs can be initiated by nuclease cleavage at forks stalled at dna structures.Furthermore, our results suggest that cfss are not just prone to breakage but also are impaired in their ability to heal, and this deleterious combination accounts for their fragility.

Journal: Cell reports (2019)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
Pembrolizumab plus dinaciclib in patients with hematologic malignancies: the phase 1b KEYNOTE-155 study.

Preclinical data demonstrated that combining an anti-programmed cell death 1 (pd-1) inhibitor with a cyclin-dependent kinase 9 (cdk9) inhibitor provided enhanced antitumor activity with no significant toxicities, suggesting this combination may be a potential therapeutic option.The multicohort, phase 1 keynote-155 study evaluated the safety and antitumor activity of the pd-1 inhibitor pembrolizumab plus the cdk9 inhibitor dinaciclib in patients with relapsed or refractory (rr) chronic lymphocytic leukemia (cll), diffuse large b-cell lymphoma (dlbcl) and multiple myeloma (mm).Patients enrolled were ≥18 years of age with a confirmed diagnosis of cll, dlbcl, or mm.The study included 2 phases: a dose-evaluation phase to determine dose-limiting toxicities and a signal-detection phase.Patients received pembrolizumab 200 mg every 3 weeks plus dinaciclib 7 mg/m2 on day 1 and 10 mg/m2 on day 8 of cycle 1 and 14 mg/m2 on days 1 and 8 of cycles 2 and later.Primary endpoint was safety, and a key secondary endpoint was objective response rate (orr).Seventy-two patients were enrolled and received ≥1 dose of study treatment (cll, n = 17; dlbcl, n = 38; mm, n = 17).Pembrolizumab plus dinaciclib was generally well tolerated and produced no unexpected toxicities.The orrs were 29.4% (5/17, rr cll), 21.1% (8/38, rr dlbcl), and 0% (0/17, rr mm), respectively.At data cutoff, all 72 patients had discontinued treatment, 38 (52.8%) because of progressive disease.These findings demonstrate activity with combination pembrolizumab plus dinaciclib and suggest that a careful and comprehensive approach to explore anti-pd-1 and cdk9 inhibitor combinations is warranted.This trial was registered at www.clinicaltrials.gov as nct02684617.

Journal: Blood advances (2022)
Publication types: Clinical Trial, Phase I;Journal Article;Research Support, Non-U.S. Gov't