syedzayyan/paper_mill_benchmark huggingface dataset:
ppe51Variants Enable Growth of Mycobacterium tuberculosis at Acidic pH by Selectively Promoting Glycerol Uptake.

In defined media supplemented with single carbon sources, mycobacterium tuberculosis (mtb) exhibits carbon source specific growth restriction.When supplied with glycerol as the sole carbon source at p h 5.7, mtb establishes a metabolically active state of nonreplicating persistence known as acid growth arrest.We hypothesized that acid growth arrest on glycerol is not a metabolic restriction, but rather an adaptive response.To test this hypothesis, we selected for and identified several mtb mutants that could grow under these restrictive conditions.All mutations were mapped to theppe51gene and resulted in variants with 3 different amino acid substitutions- s211r, e215k, and a228d.Expression of theppe51variants in mtb promoted growth at acidic p h showing that the mutant alleles are sufficient to cause the dominant gain-of-function, enhanced acid growth (eag) phenotype.Testing growth on other single carbon sources showed the ppe51 variants specifically enhanced growth on glycerol, suggesting ppe51 plays a role in glycerol uptake.Using radiolabeled glycerol, enhanced glycerol uptake was observed in mtb expressing the ppe51 (s211r) variant, with glycerol overaccumulation in triacylglycerol.Notably, the eag phenotype is deleterious for growth in macrophages, where the mutants have selectively faster replication and reduced survival in activated macrophages compared to resting macrophages.Recombinant ppe51 protein exhibited differential thermostability in the wild type (wt) or s211r variants in the presence of glycerol, supporting the model that eag substitutions alter ppe51-glycerol interactions.Together, these findings support that ppe51 variants selectively promote glycerol uptake and that slowed growth at acidic p h is an important adaptive mechanism required for macrophage pathogenesis.importanceit is puzzling why mycobacterium tuberculosis (mtb) cannot grow on glycerol at acidic p h, as it has a carbon source and oxygen, everything it needs to grow.In this study, we found that mtb limits uptake of glycerol at acidic p h to restrict its growth and that mutations inppe51promote uptake of glycerol at acidic p h and enable growth.That is, mtb can grow well at acidic p h on glycerol, but has adapted instead to stop growth.Notably,ppe51variants exhibit enhanced replication and reduced survival in activated macrophages, supporting a role for p h-dependent slowed growth during macrophage pathogenesis.

Journal: Journal of bacteriology (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Crohn's disease-associated Escherichia coli survive in macrophages by suppressing NFκB signaling.

Epidemiological and genetic studies suggest a role for enteric flora in the pathogenesis of crohn's disease (cd).Crohn's disease-associated escherichia coli (cdec) is characterized by their ability to invade epithelial cells and survive and induce high concentration of tnf-α from infected macrophages.However, the molecular mechanisms of cdec survival in infected macrophages are not completely understood.Methods intracellular survival of cdec strain lf82 isolated from inflamed ileum tissue, 13i isolated from inflamed colonic tissue, and control e.Coli strains were tested in the murine macrophage cell line, j774a.1 by gentamicin protection assay.Modulation of intracellular cell signaling pathways by the e.Coli strains were assessed by western blot analysis and confocal microscopy.Results 13i demonstrated increased survival in macrophages with 2.6-fold higher intracellular bacteria compared with lf82, yet both strains induced comparable levels of tnf-α.Lf82 and 13i differentially modulated key mitogen-activated protein kinase pathways during the acute phase of infection; lf82 activated all 3 mitogen-activated protein kinase pathways, whereas 13i activated erk1/2 pathway but not p38 and jnk pathways.Both 13i and lf82 suppressed nuclear translocation of nfκb compared with noninvasive e.Coli strains during the acute phase of infection.However, unlike noninvasive e.Coli strains, 13i and lf82 infection resulted in chronic activation of nfκb during the later phase of infection.Conclusions our results showed that cdec survive in macrophages by initially suppressing nfκb activation.However, persistence of bacterial within macrophages induces chronic activation of nfκb, which correlates with increased tnf-α secretion from infected macrophages.

Journal: Inflammatory bowel diseases (2014)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, U.S. Gov't, Non-P.H.S.
Cervical Mesonephric Adenocarcinoma: A Case Report of a Rare Gynecological Tumor from Embryological Remains of the Female Genital Tract.

Introduction malignant mesonephric tumors are uncommon in the female genital tract, and they are usually located where embryonic remnants of wolffian ducts are detected, such as the uterine cervix.The information about these tumors, their treatment protocol, and prognosis are scarce.Case report a 60-year-old woman with postmenopausal vaginal bleeding was initially diagnosed with endometrial carcinoma.After suspicion co-testing, the patient underwent a loop electrosurgical excision of the cervix and was eventually diagnosed with mesonephric adenocarcinoma.She was subjected to a radical hysterectomy, which revealed international federation of gynecology and obstetrics (figo) ib1 stage, and adjuvant radiotherapy.The follow-up showed no evidence of recurrence after 60 months.Conclusion we present the case of a woman with cervical mesonephric adenocarcinoma.When compared with the literature, this case had the longest clinical follow-up without evidence of recurrence, which reinforces the concept that these tumors are associated with a favorable prognosis if managed according to the guidelines defined for the treatment of patients with cervical adenocarcinomas.Though a rare entity, it should be kept in mind as a differential diagnosis for other cervical cancers.

Journal: Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia (2021)
Publication types: Case Reports;Journal Article
Precocious egg development in wild Calliphora vicina (Diptera: Calliphoridae) - An issue of relevance in forensic entomology?

The list of factors influencing the development of forensically important insects and the related effects on minimum post mortem (pmimin) estimations is long and well established by various authors in forensic entomology over the last decades.Despite the fact that several authors mention precocious egg development, i.e.First instar larva in the genital tract of some species of calliphoridae, as a potential error source for pmiminestimations just two studies were performed to examine the occurrence of precocious eggs both in laboratory and field populations of blow flies.In the present study the occurrence of gravid females with precocious eggs in a wild population of calliphora vicina in frankfurt am main was surveyed over 152 days and their seasonal distribution was analyzed as well as the influence of abiotic variables on their abundance.During the sampling occasions, 5.216 females were sampled of which 44 % were gravid.54 % of all gravid females had a precocious egg/first instar larva in their genital tract.This number varied depending on the season and showed the highest amount in spring with almost 64 % of all gravid females.Hence, precocious eggs in wild populations of blow flies can occur much more frequently than mentioned in forensic literature.Consequences for the evaluation of entomological evidence in forensic casework should not be overrated since focusing alone on the largest larva in a sample is not recommended as the sole reference in an entomological pmiminestimation.The entomological report has to justify its findings, discuss different options and finally state what is considered to be the most likely scenario based on the complete evidence (e.g.Including all species and relevant age cohorts as well as succession data) and the case specific history.

Journal: Forensic science international (2020)
Publication types: Journal Article
Osteosarcopenia Predicts Falls, Fractures, and Mortality in Chilean Community-Dwelling Older Adults.

S the objective of this study was to describe the prevalence of osteosarcopenia and its association with falls, fractures, and mortality in community-dwelling older adults.Design follow-up of alexandros cohorts designed to study disability associated with obesity in older adults.Setting and participants community-dwelling people aged 60 years and older living in chile.Measures at baseline, 1119 of 2372 participants had a dual-energy x-ray absorptiometry scan and the measurements for the diagnosis of sarcopenia.World health organization standards for bone mineral density were used to classify them as normal, osteopenia, and osteoporosis.Sarcopenia was identified using the algorithm from the european working group on sarcopenia in older people 1, validated for the chilean population.Osteosarcopenia was defined as having sarcopenia plus osteoporosis or osteopenia.Results the sample of 1119 participants (68.5% female) had a mean age of 72 years.At baseline, osteoporosis was identified in 23.2%, osteopenia in 49.8%, sarcopenia in 19.5%, and osteosarcopenia in 16.4% of the sample.The prevalence of osteosarcopenia increases with age, reaching 33.7% for those older than 80 years.Sarcopenia was found in 34.4% of osteoporotic people and osteoporosis in 40.8% of those with sarcopenia.After 5640 person-years of follow-up, 86 people died.The mortality was significantly higher for the group with osteosarcopenia (15.9%) compared with those without the condition (6.1%).After an adjusted cox regression analysis, the hazard ratio for death in people with osteosarcopenia was 2.48.Falls, fractures, and functional impairment were significantly more frequent in osteosarcopenic patients.Conclusions and implications osteosarcopenia is a common condition among older adults and is associated with an increased risk of falls, fractures, functional impairment, and mortality.Considering the high proportion of sarcopenia among osteoporotic patients and vice versa, screening for the second condition when the first is suspected should be advised.

Journal: Journal of the American Medical Directors Association (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Lizard tail skeletal regeneration combines aspects of fracture healing and blastema-based regeneration.

Lizards are amniotes with the remarkable ability to regenerate amputated tails.The early regenerated lizard tail forms a blastema, and the regenerated skeleton consists of a cartilage tube (ct) surrounding the regenerated spinal cord.The proximal, but not distal, ct undergoes hypertrophy and ossifies.We hypothesized that differences in cell sources and signaling account for divergent cartilage development between proximal and distal ct regions.Exogenous spinal cord implants induced ectopic ct formation in lizard (anolis carolinensis) blastemas.Regenerated spinal cords expressed shh, and cyclopamine inhibited ct induction.Blastemas containing vertebrae with intact spinal cords formed cts with proximal hypertrophic regions and distal non-hypertrophic regions, whereas removal of spinal cords resulted in formation of proximal ct areas only.In fate-mapping studies, fitc-labeled vertebra periosteal cells were detected in proximal, but not distal, ct areas.Conversely, fitc-labeled blastema cells were restricted to distal ct regions.Proximal cartilage formation was inhibited by removal of periosteum and could be recapitulated in vitro by periosteal cells treated with ihh and bmp-2.These findings suggest that proximal cts are directly derived from vertebra periosteal cells in response to bmp and ihh signaling, whereas distal cts form from blastema cells in response to shh signals from regenerated spinal cords.

Journal: Development (Cambridge, England) (2016)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Case Studies in Physiology: Training adaptation in an elite athlete after breast cancer diagnosis.

The aim of this study was to evaluate the capacity to return to competition of a 28-yr-old female 400-m hurdle elite athlete after a diagnosis of breast cancer.The study lasted 14 mo after diagnosis.She was tested four times (t1-t4) to measure body mass (bm), body mass index (bmi), percentage of total fat mass (tfm%), total fat-free mass (tffm%), bone mineral density (bmd), one-repetition maximum (1rm), and maximal power (mp) in bench press and half squat, maximum oxygen uptake, and 400-m dash and hurdles.T0 (baseline time) was established with values before diagnosis.Bm and bmi increased from t0 to t1 (5.3% and 5.2%) and remained stable.Bmd experienced no change.Tfm% values decreased from t1 to t4 (3.5%).Tffm% values increased from t1 to t3 (0.9%).During t1-t2, the athlete presented a global decline from t0 in 1rmsquat, 1rmbench, mpsquat, and mpbench(32.6%, 27.2%, 37.5%, and 27.6%, respectively).Results during t3-t4 were also lower for these parameters from t0 (23.3%, 20.6%, 23.4%, and 11%).During t1-t2, the v̇o2maxdeclined compared with t0 (1.8% and 6.4%), showing a small increase at t3 (+1%) and reaching the lowest level at t4 (9%).During t1-t2, the time record of 400-m dash (8.3%) and hurdles (7.4%) increased.However, a slight improvement was found at t3 (1.3% and 0.6%, respectively).The results of this case study reflect that exercise training improved body composition, maintained bmd and tffm, but could not completely reverse the worsening of the cardiorespiratory, muscle strength and power, and running performance levels.new & noteworthythis case study follows an elite athlete and measures her performance during cancer treatment.It improves the knowledge on applied physiology showing the details of her training program and demonstrating the strong ability of the athlete to continue training and competing at a high level during antineoplastic treatment.Exercise training improved body composition but failed to restore previous cardiorespiratory, muscle strength and power, and running performance levels.

Journal: Journal of applied physiology (Bethesda, Md. : 1985) (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Skin Eruptions in Acute Hemorrhagic Edema of Young Children: Systematic Review of the Literature.

Acute hemorrhagic edema is a skin-limited small-vessel leukocytoclastic vasculitis, which affects infants 4 weeks to 2 years of age and remits within 3 weeks.The diagnosis is made clinically in not-ill appearing children with acute onset of raised annular or nummular eruptions and edema.In this vasculitis, type, distribution, and evolution of the rash have never been systemically investigated.To address this issue, we employed the data contained in the acute hemorrhagic edema bibliographic database, which incorporates all reports on acute hemorrhagic edema.Summary key features of rash were documented in 383 children.Annular eruptions in a strict sense, usually targetoid, were reported in 375 (98%) cases (many children also presented polycyclic or arciform eruptions).Nummular eruptions were also very common (n = 358; 93%).Purpuric eruptions and ecchymoses were reported in the vast majority of cases.Macules and wheals were described in a minority of cases.Edema, detected in all cases, was mostly painful, indurated and nonpitting.The following regions were affected, in decreasing order, by annular or nummular eruptions: legs, feet, face, arms, ears, trunk, and genitals.With the exception of feet, which were very often affected, the same distribution was reported for edema.The initial eruption was often a wheal or a macule that evolved into a nummular or an annular eruption.Nummular eruptions successively evolved into annular ones.Key message this study carefully characterizes type, distribution, and evolution of skin eruption in acute hemorrhagic edema.The data help physicians to rapidly and noninvasively make the clinical diagnosis of this vasculitis.

Journal: Dermatology (Basel, Switzerland) (2022)
Publication types: Journal Article;Systematic Review
Tebentafusp in advanced uveal melanoma: proof of principle for the efficacy of T-cell receptor therapeutics and bispecifics in solid tumors.

Introduction tebentafusp is a novel bispecific immune mobilizing t cell receptor (tcr)-based agent developed for the treatment of metastatic uveal melanoma, a highly fatal disease with no currently approved treatment options.Recent evidence suggests this drug may become the standard of care for first-line treatment of metastatic uveal melanoma.Areas covered this review focuses on the development and investigation of tebentafusp for metastatic uveal melanoma.First, we discuss preclinical studies followed by clinical evaluation, culminating in a phase iii trial showing improved overall survival with tebentafusp compared to standard of care.Finally, we expand upon key toxicities of tebentafusp and highlight biomarkers that may correlate with drug efficacy.Expert opinion tebentafusp provides a promising advancement to date for the management of metastatic uveal melanoma.Future studies should aim at identifying biomarkers that can predict treatment response or toxicity, combination therapy, application of tebentafusp in the adjuvant setting to reduce the risk of recurrence, and development of bispecifics with activity in other hla subtypes.With its novel mechanism of action, degree of efficacy and safety profile, tebentafusp is expected to change the standard of care for treating metastatic and, potentially localized, uveal melanoma.

Journal: Expert opinion on biological therapy (2022)
Publication types: Journal Article;Review
Synergistic Catalytic Performance of Toluene Degradation Based on Non-Thermal Plasma and Mn/Ce-Based Bimetal-Organic Frameworks.

A series of mn/ce-based bimetal-organic frameworks, recorded as mcdx (x = 1, 2, 4, 6), were prepared by a solvothermal synthesis method to explore their effects and performance in the synergistic catalysis of toluene under the irradiation of non-thermal plasma.The catalytic properties of different manganese loadings in mcdx for degradation of toluene were investigated.The microphysical structures of the material were analyzed by powder x-ray diffraction (pxrd), scanning electron microscopy (sem), fourier transform infrared spectroscopy (ftir) and thermogravimetric analysis (tga).The results showed that a mcdx coupling with non-thermal plasma can greatly improve the degradation efficiency, the energy efficiency and the co2selectivity, and could also significantly reduce the generation of o3in the by-products.Among the test samples, mcd6 with mn:ce = 6:1 (molar ratio) showed the best catalytic performance and stability, exhibited toluene catalytic efficiency 95.2%, co2selectivity 84.2% and energy efficiency 5.99 g/k wh, and reduced o3emission concentration 81.6%.This research provides a reference for the development and application of synergistic catalysis based on bimetal-organic frameworks and non-thermal plasma in the reduction of industrial volatile organic compounds.

Journal: Molecules (Basel, Switzerland) (2022)
Publication types: Journal Article
Indoor and outdoor noise changes due to the COVID-19 lockdown and their effects on individuals' expectations and preferences.

The covid-19 pandemic significantly modified our urban territories.One of the most strongly affected parameters was outdoor noise, caused by traffic and human activity in general, all of which were forced to stop during the spring of 2020.This caused an indubitable noise reduction both inside and outside the home.This study investigates how people reacted to this new unexpected, unwanted and unpredictable situation.Using field measurements, it was possible to demonstrate how the outdoor sound pressure level clearly decreased.Furthermore, by means of an international survey, it was discovered that people had positive reaction to the lower noise level.This preference was generally not related to home typology or location in the city, but rather to a generalized wish to live in a quieter urban environment.

Journal: Scientific reports (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Determination of Three Organochlorine Pesticides in Aqueous Samples by Solid-Phase Extraction Based on Natural Nano Diatomite in Packed Syringe Coupled to Gas Chromatography-Mass Spectrometry.

A rapid, simple, and sensitive technique is proposed based on a miniaturized solid-phase extraction method named mictroextraction in a packed syringe coupled with gas chromatography-mass spectrometry for the preconcentration and determination of three organochlorine pesticides.These include hexachlorobenzene, heptachlor and aldrine in aqueous samples.For the first time, the natural nano diatomite is used a sorbent.Based on this technique, 6.0 mg of the nano sorbent is inserted in a syringe between two polypropylene frits.The analytes would be adsorbed on the solid phase, and would subsequently be eluted using organic solvents.The influence of some important parameters, such as the solution p h, type and volume of the organic desorption solvent, and amount of sorbent on the extraction efficiency of the selected pesticides, is investigated.The proposed method shows good linearity in the range of 0.1 - 40.0 μg l-1, and at low limits of detection in the range of 0.02 - 0.13 μg l-1using the selected ion-monitoring mode.The reproducibility of this method was found to be in the range of 3.5 - 11.1% for the understudied pesticides.In order to evaluate the matrix effect, the developed method is also applied to the preconcentration and determination of the selected pesticides in different water samples.

Journal: Analytical sciences : the international journal of the Japan Society for Analytical Chemistry (2017)
Publication types: Journal Article
Evaluation of a multi-species SARS-CoV-2 surrogate virus neutralization test.

Assays to measure sars-co v-2-specific neutralizing antibodies are important to monitor seroprevalence, to study asymptomatic infections and to reveal (intermediate) hosts.A recently developed assay, the surrogate virus-neutralization test (s vnt) is a quick and commercially available alternative to the "gold standard" virus neutralization assay using authentic virus, and does not require processing at bsl-3 level.The assay relies on the inhibition of binding of the receptor binding domain (rbd) on the spike (s) protein to human angiotensin-converting enzyme 2 (h ace2) by antibodies present in sera.As the s vnt does not require species- or isotype-specific conjugates, it can be similarly used for antibody detection in human and animal sera.In this study, we used 298 sera from pcr-confirmed covid-19 patients and 151 sera from patients confirmed with other coronavirus or other (respiratory) infections, to evaluate the performance of the s vnt.To analyze the use of the assay in a one health setting, we studied the presence of rbd-binding antibodies in 154 sera from nine animal species (cynomolgus and rhesus macaques, ferrets, rabbits, hamsters, cats, cattle, mink and dromedary camels).The s vnt showed a moderate to high sensitivity and a high specificity using sera from confirmed covid-19 patients (91.3% and 100%, respectively) and animal sera (93.9% and 100%), however it lacked sensitivity to detect low titers.Significant correlations were found between the s vnt outcomes and prnt50and the wantai total ig and ig m elisas.While species-specific validation will be essential, our results show that the s vnt holds promise in detecting rbd-binding antibodies in multiple species.

Journal: One health (Amsterdam, Netherlands) (2021)
Publication types: Journal Article