syedzayyan/paper_mill_benchmark huggingface dataset:
Prenatal exposure to the Chinese famine of 1959-62 and risk of cardiovascular diseases in adulthood: findings from the China PEACE million persons project.

S much remains unknown about the role of prenatal exposure to environmental stressors in the development of cardiovascular diseases (cvd).The current study aimed to investigate whether exposure to famine early in life was associated with a higher risk of cvd in adulthood.Methods and results among 71 667 men and women participated in the patient-centred evaluative assessment of cardiac events (peace) million persons project in southern china, specific years of birth were used to define two cohorts: the exposed group (born during the famine of 1959-62) and the non-exposed group [born before the famine (1949-58) or after the famine (1963-72)].Multivariable-adjusted generalized linear models were used to examine the associations of famine exposure with the risk of developing cvd, as well as with the 10-year cvd risk defined by well-established risk scores.Compared with the non-famine group, early-life exposure to the chinese famine was significantly associated with increased risks of total cvd (odds ratio, or = 1.28, 95% confidence interval: 1.16-1.41), coronary heart disease [or: 1.23 (1.07-1.41)], acute myocardial infarction [or: 1.32 (1.01-1.70)], heart failure [or: 2.01 (1.53-2.60)], and stroke [or: 1.28 (1.12-1.45)] in adulthood.In those without established cvd, early-life exposure to the famine was associated with higher levels of total cholesterol, systolic blood pressure, waist circumference, risk of diabetes, and therefore 10-year cvd risk.Conclusion early-life exposure to the chinese famine is associated with an elevated cvd risk later in life, independent of known risk factors.

Journal: European journal of preventive cardiology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Comparison of Er,Cr:YSGG laser to minimally invasive surgical technique in the treatment of intrabony defects: Six-month results of a multicenter, randomized, controlled study.

The purpose of this publication is to report on the six-month clinical results and patient-reported outcomes (pros) comparing the surgical use of the erbium, chromium-doped: yttrium, scandium, gallium, and garnet (er,cr:ysgg) laser (erl) and minimally invasive surgical technique (mist) for the treatment of intrabony defects in subjects with generalized periodontitis stage iii, grade b.Methods fifty-three adults (29 females and 24 males; aged 19 to 73 years) with 79 intrabony defects were randomized following scaling and root planing (srp) to receive erl monotherapy (n = 27) or mist (n = 26).Recession, probing depth (pd), clinical attachment level (cal), treatment time, and pros were assessed and compared for each treatment group.Clinical measurements were recorded at baseline, 4 to 6 weeks following srp, and 6 months following surgical therapy.Results the following primary and secondary outcome variables were non-inferior with the following margins: cal with a non-inferiority margin of 0.6 mm (p = 0.05), pd with a non-inferiority margin of 0.5 mm (p = 0.05).Recession with a non-inferiority margin of 0.4 mm (p = 0.05).Faster procedure times were found for erl (16.39 ± 6.21 minutes) versus mist (20.17 ± 5.62 minutes), p = 0.0002.In the first 2 to 3 days of post-therapeutic diary outcomes, subjects reported less bruising, facial swelling, and use of ice pack for the erl group.Conclusions this is the first multicenter, randomized, masked, and controlled study demonstrating the erl is not inferior to mist in terms of clinical outcomes but is superior in pros for the surgical treatment of intrabony defects.

Journal: Journal of periodontology (2021)
Publication types: Journal Article;Multicenter Study;Randomized Controlled Trial;Research Support, Non-U.S. Gov't
Live human-robot interactive public demonstrations with automatic emotion and personality prediction.

Communication with humans is a multi-faceted phenomenon where the emotions, personality and non-verbal behaviours, as well as the verbal behaviours, play a significant role, and human-robot interaction (hri) technologies should respect this complexity to achieve efficient and seamless communication.In this paper, we describe the design and execution of five public demonstrations made with two hri systems that aimed at automatically sensing and analysing human participants' non-verbal behaviour and predicting their facial action units, facial expressions and personality in real time while they interacted with a small humanoid robot.We describe an overview of the challenges faced together with the lessons learned from those demonstrations in order to better inform the science and engineering fields to design and build better robots with more purposeful interaction capabilities.This article is part of the theme issue 'from social brains to social robots: applying neurocognitive insights to human-robot interaction'.

Journal: Philosophical transactions of the Royal Society of London. Series B, Biological sciences (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Effect of routine preoperative screening for aortic calcifications using noncontrast computed tomography on stroke rate in cardiac surgery: the randomized controlled CRICKET study.

S to evaluate if routine screening for aortic calcification using unenhanced ct lowers the risk of stroke and alters the surgical approach in patients undergoing general cardiac surgery compared with standard of care (so c).Methods in this prospective, multicenter, randomized controlled trial, adult patients scheduled for cardiac surgery from september 2014 to october 2019 were randomized 1:1 into two groups: so c alone, including chest radiography, vs.So c plus preoperative noncontrast ct.The primary endpoint was in-hospital perioperative stroke.Secondary endpoints were preoperative change of the surgical approach, in-hospital mortality, and postoperative delirium.The trial was halted halfway for expected futility, as the conditional power analysis showed a chance < 1% of finding the hypothesized effect.Results a total of 862 patients were evaluated (so c-group: 433 patients (66 ± 11 years; 74.1% male) vs.So c + ct-group: 429 patients (66 ± 10 years; 69.9% male)).The perioperative stroke rate (so c + ct: 2.1%, 9/429 vs.So c: 1.2%, 5/433, p = 0.27) and rate of changed surgical approach (so c + ct: 4.0% (17/429) vs.So c: 2.8% (12/433, p = 0.35) did not differ between groups.In-hospital mortality and postoperative delirium were comparable between groups.In the so c + ct group, aortic calcification was observed on ct in the ascending aorta in 28% (108/380) and in the aortic arch in 70% (265/379).Conclusions preoperative noncontrast ct in cardiac surgery candidates did not influence the surgical approach nor the incidence of perioperative stroke compared with standard of care.Aortic calcification is a frequent finding on the ct scan in these patients but results in major surgical alterations to prevent stroke in only few patients.Key points • aortic calcification is a frequent finding on noncontrast computed tomography prior to cardiac surgery.• routine use of noncontrast computed tomography does not often lead to a change of the surgical approach, when compared to standard of care.• no effect was observed on perioperative stroke after cardiac surgery when using routine noncontrast computed tomography screening on top of standard of care.

Journal: European radiology (2022)
Publication types: Journal Article;Multicenter Study;Randomized Controlled Trial
Interferon resistance of emerging SARS-CoV-2 variants.

The emergence of sars-co v-2 variants with enhanced transmissibility, pathogenesis, and resistance to vaccines presents urgent challenges for curbing the covid-19 pandemic.While spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of sars-co v-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence sars-co v-2 evolution.Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and five major variants of concern that include the b.1.1.7 (alpha), b.1.351 (beta), p.1 (gamma), b.1.617.2 (delta), and b.1.1.529 (omicron) lineages.Our data reveal that relative to ancestral isolates, sars-co v-2 variants of concern exhibited increased interferon resistance, suggesting that evasion of innate immunity may be a significant, ongoing driving force for sars-co v-2 evolution.These findings have implications for the increased transmissibility and/or lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

Journal: Proceedings of the National Academy of Sciences of the United States of America (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Intramural;Research Support, N.I.H., Extramural
Home-based, tunnelled peritoneal drainage system as an alternative treatment option for patients with refractory ascites.

Onset of refractory ascites is the hallmark of end-stage liver disease.If liver transplantation (ltx) is not available and contraindications for a transjugular portosystemic shunt (tips) are present, repeated paracentesis remains the standard of care (soc).Home-based, tunnelled peritoneal catheters (pe ca) have been suggested as an alternative treatment option.However, data on patients with cirrhosis are scarce.Aim to evaluate the safety of pe ca in these patients compared to soc.Methods overall, 223 patients with cirrhosis, a contraindication for tips and refractory ascites were included in this retrospective study.Pe ca implant was performed in 152 patients, whereas 71 were treated with soc.Analysed end points included device explant-free survival, mortality, acute kidney injury (aki) and hyponatraemia.In the second approach, propensity score matching (ppsm) was performed to adjust for confounding factors.Results in patients with pe ca, median device explant-free survival was 74 days and 52 explants were recorded within the first 90 days.Within 90 days, patients with pe ca had lower mortality than soc (p = 0.11), and spontaneous bacterial peritonitis (sbp) incidence did not differ (p = 0.82).Regarding aki and hyponatraemia, there was a trend towards a higher incidence in the pe ca group (p = 0.13 and p = 0.08), and the risk for rehospitalisation was higher in those with a pe ca (hr: 2.11, p = 0.04).After ppsm, mortality was lower in the pe ca group (hr:0.40; p = 0.03), whereas the incidence of sbp and hyponatraemia was comparable (p = 0.80 and p = 0.28) and aki was more frequent in those with a pe ca (p = 0.08).Conclusion the implant of pe ca allows home-based therapy of patients with cirrhosis and refractory ascites and a contraindication for tips.However, the risk for complications has to be considered and prospective studies are needed.

Journal: Alimentary pharmacology & therapeutics (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Cyclocreatine Suppresses Creatine Metabolism and Impairs Prostate Cancer Progression.

Prostate cancer is the second most common cause of cancer mortality in men worldwide.Applying a novel genetically engineered mouse model (gemm) of aggressive prostate cancer driven by deficiency of the tumor suppressors pten and sprouty2 (spry2), we identified enhanced creatine metabolism as a central component of progressive disease.Creatine treatment was associated with enhanced cellular basal respiration in vitro and increased tumor cell proliferation in vivo.Stable isotope tracing revealed that intracellular levels of creatine in prostate cancer cells are predominantly dictated by exogenous availability rather than by de novo synthesis from arginine.Genetic silencing of creatine transporter slc6a8 depleted intracellular creatine levels and reduced the colony-forming capacity of human prostate cancer cells.Accordingly, in vitro treatment of prostate cancer cells with cyclocreatine, a creatine analog, dramatically reduced intracellular levels of creatine and its derivatives phosphocreatine and creatinine and suppressed proliferation.Supplementation with cyclocreatine impaired cancer progression in the pten- and spry2-deficient prostate cancer gemms and in a xenograft liver metastasis model.Collectively, these results identify a metabolic vulnerability in prostate cancer and demonstrate a rational therapeutic strategy to exploit this vulnerability to impede tumor progression.Significance enhanced creatine uptake drives prostate cancer progression and confers a metabolic vulnerability to treatment with the creatine analog cyclocreatine.

Journal: Cancer research (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Second Booster BNT162b2 Restores SARS-CoV-2 Humoral Response in Patients With Multiple Myeloma, Excluding Those Under Anti-BCMA Therapy.

Covid-19 vaccination leads to a less intense humoral response in patients with multiple myeloma (mm) compared with healthy individuals, whereas the sars-co v-2-specific immunity fades over time.The purpose of this study was to explore the kinetics of sars-co v-2 neutralizing antibodies (nabs) in patients with mm after vaccination with the bnt162b2 m rna vaccine, focusing on their response before (b4d) and at 1 month after the fourth vaccination (m1p4d).Overall, 201 patients with a median age of 67 years were included, whereas 114 (56.7%) were men.The median nabs levels b4d were 80.0% (±3.5%) and at m1p4d they increased to a median value of 96.1% (±3.7%).The nab values at m1p4d were similar to those at 1 month post the third dose and superior to all previous timepoints.At m1p4d, the nabs levels of all the treatment groups increased, apart from the anti-bcma group.A significant increase in median nabs values was observed for those receiving cd38-based treatment (n = 43, from 71.0% b4d to 96.0% at m1p4d) and those who did not receive cd38- or bcma-targeted therapy (n = 137, from 89.6% b4d to 96.3% at m1p4d).Regarding the patients under bcma-based therapy (n = 21), there was no remarkable increase in nabs values following the second booster shot (from 3.0% b4d to 4.0% at m1p4d).In conclusion, booster vaccination with the bnt162b2 results in a substantially improved humoral response against sars-co v-2 in patients with mm.Anti-bcma treatment remains an adverse predictive factor for nabs response; thus, tailored prevention measures should be considered for this patient subgroup.

Journal: HemaSphere (2022)
Publication types: Journal Article
Novel PSEN1 and PSEN2 Mutations Identified in Sporadic Early-onset Alzheimer Disease and Posterior Cortical Atrophy.

/purpose sporadic early-onset alzheimer disease (s eoad) and its visual variant, posterior cortical atrophy (pca), have a disease onset at less than 65 years of age with no familial aggregation.The etiology and genetic basis of these diseases remain poorly understood.Our study aimed to identify additional mutations or variants associated with s eoad and pca and to further examine their genetic and phenotypic spectrums.Methods we performed whole-exome sequencing and analyzed the clinical and neuroimaging features of mutation carriers with 29 patients having s eoad and 25 having pca.Results nine rare damaging variants were identified in 4 patients with s eoad and 3 with pca.A novel mutation (p.a136v) in psen1 was identified in a patient with s eoad and a likely pathogenic variant (p.m239t) was identified for psen2 in a patient with pca.In addition, 7 rare damaging variants were detected in other genes related to neurodegenerative diseases.The patient carrying the psen1 p.a136v mutation presented with typical clinical and imaging features of s eoad, and the pca patient with the psen2 p.m239t mutation presented with visuospatial impairment as the initial symptom.Conclusion our study expands the psen1 mutation spectrum of s eoad and highlights the importance of screening psen1 and/or psen2 mutations in pca patients.

Journal: Alzheimer disease and associated disorders (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Gold Nanoconjugates for miRNA Modulation in Cancer Therapy: From miRNA Silencing to miRNA Mimics.

Cancer is a major healthcare burden and cause of death worldwide, with an estimated 19.3 million new cancer cases and 10 million cancer deaths globally only in 2020.While several anticancer therapeutics are available to date, many of these still show low treatment efficacy and high off-target effects and adverse reactions.This prompts a serious need to develop novel therapies that can decrease the side effects and increase treatment efficacy.Micro rnas (mi rnas) can have a role in tumor development and progression, making them important targets for the improvement of anticancer therapies.In this context, gold nanoparticles have been widely studied for different clinical applications due to their biocompatibility and possibility of customization, and gold nanoconjugates targeting mi rnas are being developed for cancer diagnosis and treatment.Here we summarize the research developed so far and how it can contribute to cancer treatment, discuss how it can be improved, and present the current challenges and future perspectives on their design and application.

Journal: ACS materials Au (2022)
Publication types: Journal Article;Review
Poor Separation of Clinical Symptom Profiles by DSM-5 Disorder Criteria.

Assessment of mental illness typically relies on a disorder classification system that is considered to be at odds with the vast disorder comorbidity and symptom heterogeneity that exists within and across patients.Patients with the same disorder diagnosis exhibit diverse symptom profiles and comorbidities creating numerous clinical and research challenges.Here we provide a quantitative analysis of the symptom heterogeneity and disorder comorbidity across a sample of 107,349 adult individuals (aged 18-85 years) from 8 english-speaking countries.Data were acquired using the mental health quotient, an anonymous, online, self-report tool that comprehensively evaluates symptom profiles across 10 common mental health disorders.Dissimilarity of symptom profiles within and between disorders was then computed.We found a continuum of symptom prevalence rather than a clear separation of normal and disordered.While 58.7% of those with 5 or more clinically significant symptoms did not map to the diagnostic criteria of any of the 10 dsm-5 disorders studied, those with symptom profiles that mapped to at least one disorder had, on average, 20 clinically significant symptoms.Within this group, the heterogeneity of symptom profiles was almost as high within a disorder label as between 2 disorder labels and not separable from randomly selected groups of individuals with at least one of any of the 10 disorders.Overall, these results quantify the scale of misalignment between clinical symptom profiles and dsm-5 disorder labels and demonstrate that dsm-5 disorder criteria do not separate individuals from random when the complete mental health symptom profile of an individual is considered.Greater emphasis on empirical, disorder agnostic approaches to symptom profiling would help overcome existing challenges with heterogeneity and comorbidity, aiding clinical and research outcomes.

Journal: Frontiers in psychiatry (2021)
Publication types: Journal Article
Thin platelet-like COF nanocomposites for blood brain barrier transport and inhibition of brain metastasis from renal cancer.

Effective treatment of brain metastases is hindered by the blood-brain barrier (bbb) and the rapid development of resistance to drug therapy.Moreover, the clinical application of general formulations is hampered by biological barriers and biological elimination.To tackle this challenge, we report a feasible approach for the assembly of polymer-covalent organic framework (cof) nanocomposites into 150 nm thin platelets as a drug delivery vehicle for enhanced retention in brain tumours.Using intravital imaging, we demonstrate that these polymer-cof nanocomposites are able to traverse the bbb in mice and achieve direct tumour accumulation in intracranial orthotopic models of brain metastasis from renal cancer (bmrc).These nanocomposites can target brain tumour cells and respond to tumour microenvironmental characteristics, including acidic and redox conditions.Intracranial tumour acidity triggers the breakdown of the nanoassemblies to polymer-cof nanocomposites due to the presence of borate bonds.Furthermore, in vivo studies on the nanocomposites showed enhanced brain tumour-targeting efficiency and therapeutic effects compared to those of free-drug dosing.Mice treated with drug-loaded polymer-cof nanocomposites also show protection from systemic drug toxicity and improved survival, demonstrating the preclinical potential of this nanoscale platform to deliver novel combination therapies to bmrc and other central nervous system (cns) tumours.

Journal: Journal of materials chemistry. B (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Small cell carcinoma of the ovary, pulmonary type: A role for adjuvant radiotherapy after carboplatin and etoposide?

Primary small cell ovarian cancer of pulmonary type (sccopt) remains a rare ovarian tumor.Its aggressive nature is associated with poor survival outcomes.Current treatment algorithms rely on systemic chemotherapy, primarily involving platinum agents.However, given its low incidence, less is known about the potential benefits of other treatments.Case presentation we report a case of an 80-year-old woman who was found to have a complex pelvic mass with a mildly elevated ca-125.She underwent a laparotomy for staging with tumor debulking; she had bulky unresectable adenopathy and pathology was consistent with stage iiic sccopt.Postoperative imaging revealed progression of disease.She received six cycles of carboplatin and etoposide followed by consolidative radiation therapy to herpara-aortic lymph nodes.She remains disease-free for over four years after completion of adjuvant therapy.Discussion histologically, sccopt resembles small cell carcinomas of the lung, which are treated with a combination of chemotherapy and radiation therapy.New approaches that build upon the current treatment approaches and incorporate strategies from non-gynecologic tumor types could be beneficial.

Journal: Gynecologic oncology reports (2022)
Publication types: Case Reports;Journal Article
Local Treatment of Non-small Cell Lung Cancer with a Spray-Dried Bevacizumab Formulation.

Local delivery of biotherapeutics to the lung holds great promise for treatment of lung diseases, but development of physically stable, biologically active dry powder formulations of large molecules for inhalation has remained a challenge.Here, spray drying was used to manufacture a dry powder pulmonary formulation of bevacizumab, a monoclonal antibody approved to treat non-small cell lung cancer (nsclc) by intravenous infusion.By reformulating bevacizumab for local delivery, reduced side effects, lower doses, and improved patient compliance are possible.The formulation had aerosol properties suitable for delivery to the deep lung, as well as good physical stability at ambient temperature for at least 6 months.Bevacizumab's anti-vegf bioactivity was not impacted by the manufacturing process.The formulation was efficacious in an in vivo rat model for nsclc at a 10-fold decrease in dose relative to the intravenous control.

Journal: AAPS PharmSciTech (2021)
Publication types: Journal Article