syedzayyan/paper_mill_benchmark huggingface dataset:
Genome-wide linkage search for cancer susceptibility loci in a cohort of non BRCA1/2 families in Sri Lanka.

Although linkage studies have been utilized for the identification of variants associated with cancer in the world, little is known about their role in non brca1/2 individuals in the sri lankans.Hence we performed linkage analysis to identify susceptibility loci related to the inherited risk of cancer in a cohort of sri lankans affected with hereditary breast cancer.The illumina global screening array having 654,027 single nucleotide polymorphism markers was performed in four families, in which at least three individuals within third degree relatives were affected by breast cancer.Two-point parametric linkage analysis was conducted assuming disease allele frequency of 1%.Penetrance was set at 90% for carriers with a 10% phenocopy rate.Results thirty-one variants exhibited genome-wide suggestive hlods.The top overall hlod score was at rs1856277, an intronic variant in myo16 on chromosome 13.The two most informative families also suggested several candidate linked loci in genes, including erap1, rprm, wwox, cdh1, exoc1, hus1b, stim1 and tusc1.This study provides the first step in identifying germline variants that may be involved in risk of cancer in cancer-aggregated non-brca1/2 families from the understudied sri lankan population.Several candidate linked regions showed suggestive evidence of linkage to cancer risk.

Journal: BMC research notes (2022)
Publication types: Journal Article
Multispecies comparative analysis reveals transcriptional specificity during Mongolian horse testicular development.

Mongolian horses have been bred and used for labor and transport for centuries.Nevertheless, traits of testicular development in mongolian horses have rarely been studied; particularly, studies regarding the transcriptional regulation characteristics of testicular development are lacking.In this paper, transcription specificity during testicular development in mongolian horses is highlighted via a multispecies comparative analysis and weighted gene co-expression network analysis (wgcna).Interestingly, the results showed that most genes were up-regulated in the testes after sexual maturity, which is a phenomenon conserved across species.Moreover, we observed nine key genes involved in regulating mongolian horse testicular development.Notably, unique transcription signatures of testicular development in mongolian horses are emphasized, which provides a novel insight into the mechanistic study of their testicular development.

Journal: Reproduction in domestic animals = Zuchthygiene (2022)
Publication types: Journal Article
Sphingomyelinase activity promotes atrophy and attenuates force in human muscle fibres and is elevated in heart failure patients.

Activation of sphingomyelinase (smase) as a result of a general inflammatory response has been implicated as a mechanism underlying disease-related loss of skeletal muscle mass and function in several clinical conditions including heart failure.Here, for the first time, we characterize the effects of smase activity on human muscle fibre contractile function and assess skeletal muscle smase activity in heart failure patients.Methods the effects of smase on force production and intracellular ca2+handling were investigated in single intact human muscle fibres.Additional mechanistic studies were performed in single mouse toe muscle fibres.Rna sequencing was performed in human muscle bundles exposed to smase.Intramuscular smase activity was measured from heart failure patients (n = 61, age 69 ± 0.8 years, nyha iii-iv, ejection fraction 25 ± 1.0%, peak vo214.4 ± 0.6 m l × kg × min) and healthy age-matched control subjects (n = 10, age 71 ± 2.2 years, ejection fraction 60 ± 1.2%, peak vo225.8 ± 1.1 m l × kg × min).Smase activity was related to circulatory factors known to be associated with progression and disease severity in heart failure.Results sphingomyelinase reduced muscle fibre force production (-30%, p < 0.05) by impairing sarcoplasmic reticulum (sr) ca2+release (p < 0.05) and reducing myofibrillar ca2+sensitivity.In human muscle bundles exposed to smase, rna sequencing analysis revealed 180 and 291 genes as up-regulated and down-regulated, respectively, at a fdr of 1%.Gene-set enrichment analysis identified 'proteasome degradation' as an up-regulated pathway (average fold-change 1.1, p = 0.008), while the pathway 'cytoplasmic ribosomal proteins' (average fold-change 0.8, p < 0.0001) and factors involving proliferation of muscle cells (average fold-change 0.8, p = 0.0002) where identified as down-regulated.Intramuscular smase activity was ~20% higher (p < 0.05) in human heart failure patients than in age-matched healthy controls and was positively correlated with markers of disease severity and progression, and with several circulating inflammatory proteins, including tnf-receptor 1 and 2.In a longitudinal cohort of heart failure patients (n = 6, mean follow-up time 2.5 ± 0.2 years), smase activity was demonstrated to increase by 30% (p < 0.05) with duration of disease.Conclusions the present findings implicate activation of skeletal muscle smase as a mechanism underlying human heart failure-related loss of muscle mass and function.Moreover, our findings strengthen the idea that smase activation may underpin disease-related loss of muscle mass and function in other clinical conditions, acting as a common patophysiological mechanism for the myopathy often reported in diseases associated with a systemic inflammatory response.

Journal: Journal of cachexia, sarcopenia and muscle (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
ASO Author Reflections: Endoscopic Management is Reasonable for <2 cm Duodenal Neuroendocrine Tumors.

Optimal management of duodenal neuroendocrine tumors (dnets) has not been well-defined, especially for dnets 1-2 cm in size.Recent studies comparing endoscopic mucosal resection (emr) and surgical resection demonstrate emr is safe and effective for these intermediate-sized dnets.Expert and consensus guidelines could consider updating recommendations to reflect the outcomes of emr in dnets and the importance of endoscopic surveillance in these patients to evaluate for local recurrence.

Journal: Annals of surgical oncology (2022)
Publication types: Journal Article
Prophylactic Heme Arginate Infusion for Acute Intermittent Porphyria.

S:this study aimed to evaluate the efficacy of long-term weekly prophylactic heme arginate (ha) infusions in reducing attack frequency and severity in female aip patients.methods:we report the results of five female aip patients with frequent recurrent attacks (>9/year) before and after institution of weekly prophylaxis with heme arginate (3 mg/kg body weight).All five cases had confirmed disease-associated mutations in the porphobilinogen deaminase gene, and all had received genetic and clinical counseling about aip.results:in the five included patients, average annual attack rate (aar) in the year prior to ha prophylaxis was 11.82 (range 9.03-17.06), and average total ha usage was 32.60 doses (range: 13.71-53.13).After 2.58-14.64 years of ha prophylaxis, average aar was reduced to 2.23 (range 0.00-5.58), and attack severity (i.e., doses required per attack) was reduced from 2.81 to 1.39 doses/attack.Liver and renal function remained stable during weekly administration of ha prophylaxis.The most common complications were port-a catheter-related events.No other complications or safety concerns occurred with long-term use of ha prophylaxis.conclusion:our study demonstrated women with aip receiving weekly prophylactic ha infusions resulted in fewer episodes that required acute ha treatment while maintaining stable renal and liver function.Weekly prophylactic ha infusions effectively prevent frequent porphyric attacks and reduce attack severity.

Journal: Frontiers in pharmacology (2021)
Publication types: Journal Article
Macrophage Mitochondrial Biogenesis and Metabolic Reprogramming Induced by Leishmania donovani Require Lipophosphoglycan and Type I Interferon Signaling.

Pathogen-specific rewiring of host cell metabolism creates the metabolically adapted microenvironment required for pathogen replication.Here, we investigated the mechanisms governing the modulation of macrophage mitochondrial properties by the vacuolar pathogen leishmania.We report that induction of oxidative phosphorylation and mitochondrial biogenesis by leishmania donovani requires the virulence glycolipid lipophosphoglycan, which stimulates the expression of key transcriptional regulators and structural genes associated with the electron transport chain.leishmania-induced mitochondriogenesis also requires a lipophosphoglycan-independent pathway involving type i interferon (ifn) receptor signaling.The observation that pharmacological induction of mitochondrial biogenesis enables an avirulent lipophosphoglycan-defective l.Donovani mutant to survive in macrophages supports the notion that mitochondrial biogenesis contributes to the creation of a metabolically adapted environment propitious to the colonization of host cells by the parasite.This study provides novel insight into the complex mechanism by which leishmaniametacyclic promastigotes alter host cell mitochondrial biogenesis and metabolism during the colonization process.importanceto colonize host phagocytes,leishmaniametacyclic promastigotes subvert host defense mechanisms and create a specialized intracellular niche adapted to their replication.This is accomplished through the action of virulence factors, including the surface coat glycoconjugate lipophosphoglycan.In addition,leishmaniainduces proliferation of host cell mitochondria as well as metabolic reprogramming of macrophages.These metabolic alterations are crucial to the colonization process of macrophages, as they may provide metabolites required for parasite growth.In this study, we describe a new key role for lipophosphoglycan in the stimulation of oxidative phosphorylation and mitochondrial biogenesis.We also demonstrate that host cell pattern recognition receptors toll-like receptor 4 (tlr4) and endosomal tlrs mediate these leishmania-induced alterations of host cell mitochondrial biology, which also require type i ifn signaling.These findings provide new insight into how leishmaniacreates a metabolically adapted environment favorable to their replication.

Journal: mBio (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Electrochemically Mediated Carboxylative Cyclization of Allylic/Homoallylic Amines with CO2at Ambient Pressure.

Co2is an important c1 resource.We report a method for the synthesis of pharmacologically active 2-oxazolidinones by reacting co2with allylic amines.As opposed to previous addition reactions, the unsaturated double bonds are preserved.Thus, the product is more plastic and easier to use for subsequent structural modification.Furthermore, this method can also be applied to the synthesis of six-membered heterocycles (1,3-oxazinan-2-ones) and the participation of a low concentration of co2, indicating it has certain practicability.

Journal: Organic letters (2022)
Publication types: Journal Article
Assessment of the Impact of Selected Industrial Wastewater on the Nitrification Process in Short-Term Tests.

Many chemical compounds can inhibit the nitrification process, especially organic compounds used in the chemical industry.This results in a decrease in the nitrification intensity or even a complete termination of this process.As the technological design of the selected municipal and industrial wastewater treatment plant (wwtp) assumed the dephosphation process, without taking into account nitrification, it was necessary to reduce the concentration of ammonium nitrogen in the treated sewage supplied to the vistula river.Therefore, the aim of the research was to determine the inhibition of nitrification in the activated sludge method under the influence of industrial wastewater from the production of various organic compounds and to select the most toxic wastewater in relation to nitrifiers.The assessment of nitrification inhibition was carried out on the basis of the method of short-term (4-h) impact of the tested sewage on nitrifying bacteria in the activated sludge.The research covered nine different types of chemical sewage, including wastewater from the production of synthetic rubbers, styrene plastics, adhesives, solvents and emulsifiers.The nitrification process was inhibited to the highest degree by wastewater from the production of styrene-butadiene rubbers (72%).Only wastewater from the production of methacrylate (polymethyl methacrylate) had the lowest degree of inhibition: 16%.These wastewaters also have a toxic effect on the entire biocenosis and adversely affect the structure of activated sludge flocs.The attempts to filter toxic wastewater through the ash basins significantly relieved the inhibition of nitrification.

Journal: International journal of environmental research and public health (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Dietary intake in lactating mothers in China 2018: report of a survey.

The nutritional status of lactating mothers (lms) is related to their own health and significantly impacts the secretion of breast-milk, and subsequently the growth and development of infants.Due to the influence of regional economy, traditional habits, and lack of nutrition knowledge, the problem of poor dietary nutrition among chinese lms is prominent.We aimed to evaluate and compare the dietary and nutrient intakes in lms from urban and rural areas in china to provide baseline data for the implementation of relevant health guidance and strategies.Methods a multi-stage sampling method was used to recruit urban and rural lms from 13 provinces and municipalities in china.An online dietary record using food photographs was employed to keep track of what the lms had eaten in 2 days in the form of face-to-face interview.A total of 954 participants were included in the final analysis.Data expressed as quartiles p50 (p25; p75) were compared using the mann-whitney u-test (level of significance: p < 0.05).Results the consumption of staple food was higher in the rural (283.37 g/d) than in the urban areas (263.21 g/d).The consumption of vegetables, fruits, fish, shrimp, and shellfish, milk and dairy products was lower than the recommended amounts in both areas, and the insufficient intake of these food types was more serious in rural areas.While the energy intake of 83.8% of all lms was lower than the estimated energy reference, it was comparable in the urban and rural areas.The intake of macronutrients (carbohydrates, protein, and fats) in rural areas was lower than in urban areas.The intake of some vitamins (va, vb1, vb2, vb9and vc) and minerals (calcium, magnesium, iodine and copper) was not ideal for lms in both rural and urban areas.Conclusions overall, the dietary intake in lms was lower than the recommended levels.Many essential nutrients failed to meet the recommended doses, both in the urban and rural areas.The deficiencies in micronutrients were more prevalent in rural compared to urban areas.Educating lms about women's health and appropriate dietary intake is, therefore, essential.

Journal: Nutrition journal (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Evaluation of admission levels of P, E and L selectins as predictors for thrombosis in hospitalized COVID-19 patients.

Thromboembolic complications are the most reported cause of death in coronavirus disease-2019 (covid-19).Hypercoagulability, platelets activation and endotheliopathy are well-recognized features in covid-19 patients.The aim of this work was to evaluate circulating soluble selectins p, e and l at the time of hospital admission as predictors for upcoming thrombosis.This retrospective study included 103 hospitalized covid-19 patients and 50 healthy volunteer controls.Covid-19 patients were categorized into two groups; group 1 who developed thrombosis during hospitalization and group 2 who did not.Soluble selectins were quantitated using elisa technique.Higher levels of s p-selectin, s e-selectin and s l-selectin were detected in covid-19 patients compared to controls.Furthermore, significantly higher levels were found in group 1 compared to group 2.Their means were [5.86 ± 1.72 ng/m l vs.2.51 ± 0.81 ng/m l]; [50 ± 8.57 ng/m l vs.23.96 ± 6.31 ng/m l] and [4.66 ± 0.83 ng/m l vs.2.95 ± 0.66 ng/m l] for s p-selectin, s e-selectin and s l-selectin respectively.The elevated selectins correlated with the currently used laboratory biomarkers of disease severity.After adjustment of other factors, s p-selectin, s e-selectin and s l-selectin were independent predictors for thrombosis.At s p-selectin ≥ 3.2 ng/m l, s e-selectin ≥ 32.5 ng/m l and s l-selectin ≥ 3.6 ng/m l thrombosis could be predicted with 97.1%, 97.6% and 96.5% sensitivity.A panel of the three selectins provided 100% clinical sensitivity.Admission levels of circulating soluble selectins p, e and l can predict thrombosis in covid-19 patients and could be used to identify patients who need prophylactic anticoagulants.E-selectin showed a superior clinical performance, as thrombo-inflammation biomarker, to the most commonly studied p-selectin.

Journal: Clinical and experimental medicine (2022)
Publication types: Journal Article
Exploiting Urazole's Acidity for Fabrication of Hydrogels and Ion-Exchange Materials.

In this study, the acidity of urazole (p ka 5-6) was exploited to fabricate a hydrogel in two simple and scalable steps.Commercially available poly(hexamethylene)diisocyanate was used as a precursor to synthesize an urazole containing gel.The formation of urazole was confirmed by ft-ir and1h-nmr spectroscopy.The hydrogel was characterized by microscopy imaging as well as spectroscopic and thermo-gravimetric analyses.Mechanical analysis and cell viability tests were performed for its initial biocompatibility evaluation.The prepared hydrogel is a highly porous hydrogel with a young's modulus of 0.91 mpa, has a swelling ratio of 87%, and is capable of exchanging ions in a medium.Finally, a general strategy was demonstrated to embed urazole groups directly into a crosslinked material.

Journal: Gels (Basel, Switzerland) (2021)
Publication types: Journal Article
Compound Heterozygosity for Silent Cap +1570 (T>C) (HBB: c*96T>C), Codon 39 (C>T) (HBB: c.118C>T) and the Presence of αααanti-3.7/αα in Greece. A Case Presentation.

The rare point mutation cap +1570 (t>c) (hbb: c*96t>c) has been reported in families of czech, greek, turkish and italian origin.The mutation contributes to a reduction of the β-globin chain synthesis, and in heterozygous carriers, it causes a silent phenotype, while in compound heterozygosity with severe β-thalassemia (β-thal) mutations, it leads to a non transfusion dependent β-thal intermedia (β-ti) state.We report a case of compound heterozygosity for codon 39 (c>t) (hbb: c.118c>t) and cap +1570, in addition to the presence of αααanti-3.7/αα.

Journal: Hemoglobin (2018)
Publication types: Case Reports;Journal Article
Role of Immunity and Vaginal Microbiome in Clearance and Persistence of Human Papillomavirus Infection.

Cervical cancer disproportionately affects women of reproductive age, with 80% of cases occurring in low- and middle-income countries.Persistent infection with high-risk human papillomavirus (hpv) genotypes has been described as the most common non-systemic biological risk factor for the development of cervical cancer.The mucosal immune system plays a significant role in controlling hpv infection by acting as the first line of host defense at the mucosal surface.However, the virus can evade host immunity using various mechanisms, including inhibition of the antiviral immune response necessary for hpv clearance.Pro-inflammatory cytokines and the vaginal microbiome coordinate cell-mediated immune responses and play a pivotal role in modulating immunity.Recently, diverse vaginal microbiome (associated with bacterial vaginosis) and genital inflammation have emerged as potential drivers of high-risk hpv positivity and disease severity in women.The potential role of these risk factors on hpv recurrence and persistence remains unclear.This article reviews the role of cellular or cytokine response and vaginal microbiome dysbiosis in the clearance, persistence, and recurrence of hpv infection.

Journal: Frontiers in cellular and infection microbiology (2022)
Publication types: Journal Article;Review;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Extramural
Oligometastatic Disease in the Liver: The Role of Interventional Oncology.

Oligometastatic disease represents a clinically discrete intermediate stage of cancer progression and is an expanding area of research.While surgical metastatectomy has been recognized for decades as an effective treatment option in select patients, options for metastasis-directed therapy have broadened in scope with advancements in the armamentarium of non- and minimally invasive modalities.Recent preclinical studies investigating the immunology surrounding liver metastases demonstrate treatment resistance to immunotherapy in affected patients and show how locoregional therapy has the ability to overcome this resistance.In this paper, we review advancements in our understanding of oligometastatic disease, metastasis-directed therapy, effect of liver metastasis on response to immunotherapy, and the burgeoning role of image-guided interventions in complementing cancer immunotherapy at the exciting crossroads of interventional oncology and immuno-oncology.

Journal: The British journal of radiology (2022)
Publication types: Journal Article;Review