syedzayyan/paper_mill_benchmark huggingface dataset:
The relationship between glucose variability and insulin sensitivity and oxidative stress in subjects with prediabetes.

The present study assessed the relationship between glucose variability (gv) and insulin levels, insulin resistance and oxidative stress at early stages of glucose intolerance.Material and methods a total of 50 subjects - 12 males and 38 females, mean age 55.6 ± 9.7 years, mean bmi 28.4 ± 6.4 kg/m2, divided into 2 groups according to glucose tolerance: 32 with prediabetes and 18 with normal glucose tolerance were included.Glucose tolerance was assessed by ogtt according to who 2006 criteria.Plasma glucose and serum insulin were measured at fasting, 120-minute and 180-minute during the test; and ox ldl and 3-nitrotyrosine - at fasting and 120-minute.Homa-ir and ogis indexes were calculated.Hb a1c and lipid levels was assessed.Continuous glucose monitoring was performed with a blind sensor (free style libre pro) for a mean period of 13.6 ± 2.3 days.Results our results demonstrate significantly increased insulin resistance in subjects with prediabetes, whereas there is no difference in oxidative stress markers between the two groups.Ox ldl and 3-nt correlate positively with insulin levels and homa-ir and negatively with ogis in both groups.There is a positive association between oxidative stress markers and 120-minute glucose in the prediabetes group.Insulin levels and homa-ir are positively related to plasma glucose and reciprocally to cv and m-value in prediabetes, since the latter association is with borderline significance after adjustment for hypertension and smoking.Conclusions our results demonstrate a significant correlation between oxidative stress and insulin resistance at early stages of glucose intolerance.Both chronic hyperglycemia and gv seem to be related to insulin levels and insulin resistance, and just postload glycaemia to oxidative stress in prediabetes.

Journal: Diabetes research and clinical practice (2019)
Publication types: Journal Article
Frontal fibrosing alopecia: survey of severity assessment methods in routine clinical practice and validation of the International Frontal Fibrosing Alopecia Cooperative Group measurement guidance.

The lack of validated and responsive outcome measures in the management of frontal fibrosing alopecia (ffa) significantly limits assessment of disease progression and treatment response over time.Aim to understand how ffa extent and progression is currently assessed in uk specialist centres, to validate components of the international ffa cooperative group (iffacg) statement on ffa assessment, and to identify pragmatic advice to improve ffa management in clinic.Methods consultant dermatologists with a specialist interest in hair loss (n = 17) were invited to take part.Preferred ffa assessment methods were explored using questionnaires and clinical scenarios.Participants were asked to identify and mark the current hairline in 10 frontal and 10 temporal hairline images (questionnaire 1), with assessment repeated 3 months later to assess intraindividual variability (questionnaire 2) and 12 months later to test whether interindividual accuracy could be improved with simple instruction (questionnaire 3).Results all 17 clinicians (100%) completed the questionnaire at each time interval.We identified a wide variation in assessment techniques used by our experts.Measurements were perceived as the most accurate method of assessing frontal recession whereas photography was preferred for temporal recession.Inter-rater reliability between clinicians measuring the frontal hairline scenarios indicated a moderate strength of agreement [intraclass coefficient (icc) = 0.61; 95% ci 0.40-0.85], yet intrarater reliability was found to be poor with wide limits of agreement (-8.71 mm to 9.92 mm) on follow-up.Importantly, when clear guidance was provided on how the hairline should be identified (questionnaire 3), inter-rater reliability improved significantly, with icc = 0.70, suggesting moderate agreement (95% ci 0.51-0.89; p < 0.001).A similar pattern was seen with temporal hairline measurements, which again improved in accuracy with instruction.Conclusion we found that accuracy of measurements in ffa can be improved with simple instruction and we have validated components of the iffacg measurement recommendations.

Journal: Clinical and experimental dermatology (2022)
Publication types: Journal Article
Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?

Patients with covid-19 present a wide spectrum of disease severity, from asymptomatic cases in the majority to serious disease leading to critical care and even death.Clinically, four different scenarios occur within the typical disease timeline: first, an incubation and asymptomatic period; second, a stage with mild symptoms due mainly to the virus itself; third, in up to 20% of the patients, a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome; and finally, a post-acute sequelae (pasc) phase, which present symptoms that can range from mild or annoying to actually quite incapacitating.Although the most common manifestation is acute respiratory failure of the lungs, other organs are also frequently involved.The clinical manifestations of the covid-19 infection support a key role for endothelial dysfunction in the pathobiology of this condition.The virus enters into the organism via its interaction with angiotensin-converting enzyme 2-receptor that is present prominently in the alveoli, but also in endothelial cells, which can be directly infected by the virus.Cytokine release syndrome can also drive endothelial damage independently.Consequently, a distinctive feature of sars-co v-2 infection is vascular harm, with severe endothelial injury, widespread thrombosis, microangiopathy, and neo-angiogenesis in response to endothelial damage.Therefore, endothelial dysfunction seems to be the pathophysiological substrate for severe covid-19 complications.Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity.In addition, the endothelium could represent a very attractive target to both prevent and treat these complications.To establish an adequate therapy, the underlying pathophysiology and corresponding clinical stage should be clearly identified.In this review, the clinical features of covid-19, the central role of the endothelium in covid-19 and in other pathologies, and the potential of specific therapies aimed at protecting the endothelium in covid-19 patients are addressed.

Journal: Cardiovascular drugs and therapy (2022)
Publication types: Journal Article;Review
The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial.

There is increasing evidence that dysregulation of polyunsaturated fatty acids (fas) mediated membrane function plays a role in the pathophysiology of schizophrenia.Even though preclinical findings have supported the anti-inflammatory properties of omega-3 fas on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood.In the current study, we investigated the relationship of erythrocyte omega-3 fas with plasma immune markers in a clinical high risk for psychosis (chr) sample.In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 fas and clinical outcomes were mediated via plasma immune markers.Clinical outcomes for chr participants in the neurapro clinical trial were measured using the brief psychiatric rating scale (bprs), schedule for the scale of assessment of negative symptoms (sans) and social and occupational functioning assessment scale (sofas) scales.The erythrocyte omega-3 index [eicosapentaenoic acid (epa) + docosahexaenoic acid (dha)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively.In linear regression models, the baseline plasma concentrations of interleukin (il)-15, intercellular adhesion molecule (icam)-1 and vascular cell adhesion molecule (vcam)-1 were negatively associated with baseline omega-3 index.In addition, 6-month change in il-12p40 and tnf-α showed a negative association with change in omega-3 index.In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with vcam-1 and tnf-α respectively at follow-up.Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 fas and clinical outcomes (psychotic symptoms and functioning) in chr participants.Our results indicate a predominantly anti-inflammatory relationship of omega-3 fas on plasma inflammatory status in chr individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up.Both immune and non-immune biological effects of omega-3 fas would be resourceful in understanding the clinical benefits of omega-3 fas in chr papulation.

Journal: Brain, behavior, and immunity (2022)
Publication types: Clinical Trial;Journal Article;Research Support, Non-U.S. Gov't
Fluorescence Resonance Energy Transfer-Based DNA Nanoprism with a Split Aptamer for Adenosine Triphosphate Sensing in Living Cells.

We have developed a dna nanoprobe for adenosine triphosphate (atp) sensing in living cells, based on the split aptamer and the dna triangular prism (tp).In which nucleic acid aptamer was split into two fragments, the stem of the split aptamer was respectively labeled donor and acceptor fluorophores that underwent a fluorescence resonance energy transfer if two atp molecules were bound as target molecule to the recognition module.Hence, atp as a target induced the self-assembly of split aptamer fragments and thereby brought the dual fluorophores into close proximity for high fluorescence resonance energy transfer (fret) efficiency.In the in vitro assay, an almost 5-fold increase in fa/fdsignal was observed, the fluorescence emission ratio was found to be linear with the concentration of atp in the range of 0.03-2 m m, and the nanoprobe was highly selective toward atp.For the strong protecting capability to nucleic acids from enzymatic cleavage and the excellent biocompatibility of the tp, the dna tp nanoprobe exhibited high cellular permeability, fast response, and successfully realized "fret-off" to "fret-on" sensing of atp in living cells.Moreover, the intracellular imaging experiments indicated that the dna tp nanoprobe could effectively detect atp and distinguish among changes of atp levels in living cells.More importantly, using of the split aptamer and the fret-off to fret-on sensing mechanism could efficiently avoid false-positive signals.This design provided a strategy to develop biosensors based on the dna nanostructures for intracellular molecules analysis.

Journal: Analytical chemistry (2017)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Novel Hybrids of 3-Substituted Coumarin and Phenylsulfonylfuroxan as Potent Antitumor Agents with Collateral Sensitivity against MCF-7/ADR.

Twenty-three new coumarin-furoxan hybrids were synthesized, which exhibited nanomole antiproliferation activities in a2780, a2780/cddp, mcf-7/adr, and mda-mb-231.Among them, compound9showed the strongest collateral sensitivity to mcf-7/adr with 499-fold potency compared with mcf-7.Notably, the solubility of compound9increased 70-fold compared with the lead2.And preliminary pharmacological studies displayed that compound9obviously increased rh123 accumulation in mcf-7/adr and released no to produce ros in lysosomes, which were able to damage lysosomal membrane and induce apoptosis.These results reasonably explained that the collateral sensitivity of compound9to mcf-7/adr was closely related to p-gp-mediated lysosome damage and apoptosis.Additionally, compound9showed a very weak cytotoxicity both in mcf-10a and h erg potassium channels and had a desirable safety in ion cyclotron resonance (icr) mice.Hence, compound9was merited to further study for developing a desirable candidate against mdr mcf-7/adr via a potential mechanism of collateral sensitivity in mdr cancer cell lines.

Journal: Journal of medicinal chemistry (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Effect of Six-Month Postoperative Endothelial Cell Density on Graft Survival after Descemet Membrane Endothelial Keratoplasty.

To analyze if 6-month endothelial cell density (ecd) affects long-term ecd outcome and graft survival 5 years after descemet membrane endothelial keratoplasty (dmek) in eyes with fuchs endothelial corneal dystrophy (fecd).Design retrospective cohort study.Participants a total of 585 dmek eyes were included.The study group was divided into 4 groups based on 6-month ecd quartiles: group 1 (n = 146) with 313 to 1245 cells/mm2, group 2 (n = 148) with 1246 to 1610 cells/mm2, group 3 (n = 145) with 1611 to 1938 cells/mm2, and group 4 (n = 146) with 1939 to 2760 cells/mm2.Group 1 was further split into subgroups 1a (n = 36) with 6-month ecd of ≤828 cells/mm2, 1b (n = 37) with 829 to 1023 cells/mm2, 1c (n = 37) with 1024 to 1140 cells/mm2, and 1d (n = 36) 1141 to 1245 cells/mm2.Methods descemet membrane endothelial keratoplasty.Main outcome measures long-term ecd, graft survival, and postoperative complication rates.Results for group 1, 6-month ecd decreased from 951 (±233) cells/mm2(n = 146) to 735 (±216) cells/mm2(n = 99) at 5 years postoperatively.Group 1 graft survival probability was 0.95 (95% confidence interval [ci], 0.91-0.99] at 5 years postoperatively, which was lower than for groups 2 to 4 (p = 0.001).Five-year graft survival in subgroup 1a was 0.79 (95% ci, 0.67-0.94), which was lower than in subgroups 1b to 1d (p = 0.001).Preoperative ecd did not influence graft survival (p = 0.400), and higher 6-month ecd values were associated with lower graft failure rates (hazard ratio, 0.994; 95% ci, 0.99-1.00; p = 0.001).Conclusions six-month ecd is associated with dmek graft survival.High early cell loss after dmek negatively affects long-term ecd outcome and graft survival.Grafts in the lowest 6-month ecd subgroup (≤828 cells/mm2) are at higher risk of failure within 5 years after dmek.To ensure sufficiently high 6-month ecd, preoperative graft quality assessment should be optimized, and cellular stress induced to the graft should be minimized.Additionally, developing therapeutic options for the treatment of low postoperative ecd could further improve dmek graft longevity.

Journal: Ophthalmology (2021)
Publication types: Journal Article
Global Development of Research on Anorectal Malformations over the Last Five Decades: A Bibliometric Analysis.

Anorectal malformations (arm) are one of the most challenging congenital malformations in pediatric surgery.We aimed to assess the research activity on arm over the last five decades.Methods data on original research publications were retrieved from the web of science core collection (1970-2020), and analyzed for countries, authors, scientific journals, and top-ten papers.Scientific quantity was assessed by the number of publications.Research quality was estimated from the number of citations, average citation rate per item (aci), and h-index.Results a total number of 1595 articles with 19,419 citations (aci = 12.2; h-index = 54) were identified.The annual number of publications and citations significantly increased over time (p< 0.0001).The usa (n= 386; 24.2%), japan (n= 153; 9.6%), and china (n= 137; 8.6%) were the most productive countries; and the usa (n= 7850; aci = 20.3; h-index = 44), japan (n= 1937; aci = 12.6; h-index = 21), and the netherlands (n= 1318; aci = 17.3; h-index = 22) were the top cited countries.Articles were preferentially published in jps (n= 391; 24.5%), psi (n= 181; 11.3%), and ejps (n= 56; 3.5%).Top-ten cited papers focused on classification (n= 1), surgical technique (n= 3), associated syndromes (n= 2), postoperative outcome (n= 3), and basic research (n= 1).Conclusion this bibliometric study provides valuable insights into the global development of arm research, and shows that clinical studies and international collaborations dominate in this field.

Journal: Children (Basel, Switzerland) (2022)
Publication types: Journal Article
Altering the binding affinities of tetraruthenocycles for polycyclic aromatic hydrocarbons by post-assembly modification.

We developed a strategy for manipulating the binding strength of polycyclic aromatic hydrocarbons (pahs)viacovalent post-assembly modification (pam) of tetranuclear ruthenium macrocycles containings-tetrazine ligands.The macrocycles act as efficient receptors for various pahs.Inverse electron demand diels-alder (iedda) reaction of the macrocycles was applied to reduce the binding ability significantly.

Journal: Chemical communications (Cambridge, England) (2022)
Publication types: Journal Article
Comparative efficacy and safety of neoadjuvant radiotherapy for patients with borderline resectable, and locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis protocol.

Introduction the optimal dose and treatment modality of neoadjuvant radiotherapy applied for treating borderline resectable and locally advanced pancreatic ductal adenocarcinoma (pdac) have been debated topics in oncology.The objective of the present network meta-analysis (nma) is to study and compare the efficacy and safety of neoadjuvant radiotherapy comprehensively using different doses in patients with borderline resectable pancreatic cancer (brpc) and locally advanced pancreatic cancer (lapc).Methods and analysis four electronic databases, including pub med, embase, cochrane library and web of science, will be searched thoroughly to identify relevant studies published from 2006 to october 2020.Electronic searching by titles using neoadjuvant treatments for pdac will be performed in the annual meetings of european society of medical oncology and american society of clinical oncology (2018-2020).Clinicaltrials gov will also be searched for grey literature.Two reviewers will perform search strategies and extract data independently.R0 resection rate and local control rate are defined as primary outcomes.Secondary outcomes include overall survival, disease-free survival and acute and late grade 3 and grade 4 toxicities.For randomised control trials, the risk of bias will be assessed using the cochrane risk of bias tool, while the risk of bias for non-randomised, observational studies will be evaluated using the risk of bias in non-randomised studies-of interventions.The quality of evidence will be evaluated using the version of cochrane tool and grades of recommendation, assessment, development and evaluation.Subgroup analysis and sensitivity analysis will be conducted in the present nma.Ethics and dissemination this study will synthesise the evidence regarding dose schedule of neoadjuvant radiotherapy in patients with brpc and lapc.We hope the findings from this nma will help clinicians and patients select the optimal modality and dose schedule of neoadjuvant radiotherapy with respect to patient-reported outcomes.As no primary data collection will be undertaken, no ethics approval is required.The results will be disseminated through peer-reviewed journal.Prospero registration number crd42020222408.

Journal: BMJ open (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Cushing syndrome as a failed cardiac screen in a patient with McCune-Albright syndrome: a case report.

Mc cune-albright syndrome is a complex disorder encompassing multiple endocrinopathies.These manifestations are secondary to a mutation in the stimulatory g-protein alpha subunit.Cushing syndrome is due to autonomous secretory function of the adrenal gland and is present in 7.1% of patients with mc cune-albright syndrome.Cardiac newborn screenings assist in the identification of critical congenital heart disease.These screenings have become part of routine postnatal care nationwide.Case report a 6-week-old caucasian male presented to a cardiologist at the university of tennessee health science center with left ventricular hypertrophy and poor feeding after a failed cardiac newborn screen.He had been previously seen at 2 weeks by a cardiologist on follow-up for abnormal critical congenital heart disease screening.Electrocardiogram and echocardiographic studies identified hypertrophic cardiomyopathy.Other examination findings revealed multiple characteristic café-au-lait lesions along with hypotonia and rounded facies.Given his cardiac disease, he was admitted to the hospital, where an evaluation was done for cushing syndrome, showing elevated cortisol by immunoassay of 38 μg/d l (1.7-14.0 μg/d l, vitros 5600) after a dexamethasone suppression test and urinary cortisol elevated to 35 μg/d l/24 hours (reference range 3-9 μg/d l/24 hours) (esoterix; calabasas, ca).He was started on metyrapone therapy to block synthesis of cortisol.His cortisol improved and was suppressed less than 2 μg/d l.His hypertension and clinical features of cushing syndrome improved.Conclusions this case demonstrates a unique presentation of cushing syndrome in a young infant.This is the first case to our knowledge showing significant left ventricular hypertrophy resulting from cushing syndrome identified following a failure on a critical congenital heart disease screen.It highlights the importance of considering of mc cune-albright syndrome in patients with cushing syndrome, especially if other clinical features are present.Medical therapy can be used to treat cushing syndrome and can result in improvement in the cardiovascular pathology.

Journal: Journal of medical case reports (2022)
Publication types: Case Reports;Journal Article
Genetic predisposition to neurodegenerative diseases and risk of stroke: A Mendelian randomization study.

Traditional epidemiological studies suggested that neurodegenerative diseases (nd) might correlate with stroke.We intend to explore whether the two most common neurodegenerative diseases [alzheimer's disease (ad) and parkinson's disease (pd)] are causally associated with stroke and its subtypes.Methods two-sample mendelian randomization (mr) method was used to explore the causal relationships.Candidate genetic instrumental variables (ivs) for ad and pd were collected from the genome-wide association studies (gwas) in european populations.The inverse-variance weighted (ivw) method was the primary method of mr analysis, and the weighted median method was supplementary.In addition, the mr-egger method and the mr-presso test were used as well.Results we found no causal effects of ad on stroke, ischemic stroke (is), or intracerebral hemorrhage (ich).As for pd and stroke, our preliminary results showed pd could causally influence the risk of stroke [odds ratio (or): 1.04; 95% confidence interval (ci): 1.02-1.07;p= 0.001 by the ivw method], although the alternative method did not support this result.We identified the positive causal relationship between pd and the risk of is (or = 1.04; 95% ci: 1.02-1.07;p= 0.001 by the ivw method), and the alternative mr methods produced similar results.The present study found there was no causal relationship between pd and ich.Conclusion this study found a causal relationship between genetic susceptibility to pd and the incidence of stroke (especially is) in the european population; however, there was no causal relation between ad and stroke risk.

Journal: Frontiers in neuroscience (2022)
Publication types: Journal Article