syedzayyan/paper_mill_benchmark huggingface dataset:
Effect of Health Disparities on Refusal of Trimodality Therapy in Localized Esophageal Adenocarcinoma: A Propensity Score Matched Analysis of the National Cancer Database.

Factors associated with refusal of multimodality therapy in patients with localized esophageal adenocarcinoma (ea) remain unknown.We hypothesized that sociodemographic disparities affect decision to pursue optimal trimodally therapy for patients with ea.Methods ncdb for esophageal cancer (2004-2017) was utilized.Included were patients diagnosed with c t3-t4 c n0 or c tany n1-3 ea of the mid-lower esophagus.Annual institutional esophagectomy volumes were categorized as low (<20/year) and high (≥20/year).Conditional logistic regression was used to identify predictors of refusal of offered treatment.Kaplan meier method was used to compare survival.Results 13 091 patients met selection criteria, mean age was 62.4 ± 9.6 years and 11 581 (88.5%) were males.633 (4.8%) patients refused at least one component of recommended treatment (chemotherapy, radiation, and esophagectomy), most commonly refusal of surgery (n = 554, 4.2%).On multivariable analysis, factors predictive of treatment refusal included older age, female gender, black race, no insurance, low income (below poverty), mid-esophageal tumors, and treatment at low-volume centers.Patients who were recommended treatment but refused had significantly worse survival than those who adhered to treatment (median 23.1 ± 1.1 vs.32.1 ± 1.2 months;p< .001).Conclusions in this study, sociodemographic disparities and center volume were among factors predictive of therapy refusal in patients with localized esophageal adenocarcinoma.While understanding potential reasons for treatment refusal is critical, this data suggests that socioeconomic variables may drive patient decisions.

Journal: The American surgeon (2023)
Publication types: Journal Article
The strategy for vaginal rejuvenation: CO2laser or vaginoplasty?

Vaginal laxity may result from trauma to the pelvic floor muscle, which may affect patients' sensation and quality of life.Vaginal rejuvenation, including surgical or nonsurgical interventions, aims to improve laxity.In this study, we aimed to establish a strategy for vaginal rejuvenation by comparing surgical and nonsurgical methods.Methods a retrospective clinical study was performed on patients who complained about vaginal laxity from 2017 to 2019.The degree of vaginal laxity severity was evaluated by vaginal examination in each patient.The patients were categorized as having a light, moderate or severe degree of vaginal laxity, and different correction methods were chosen accordingly.The female sexual function index (fsfi) questionnaire was administered to the patients preoperatively and at three months and one year after treatment.Results seventeen patients with severe-degree vaginal laxity were treated with vaginoplasty.The total fsfi score was 23.21±2.57 before the operation and significantly increased to 29.36±1.84 (p<0.01) at one year after surgery.Eleven patients with moderate-degree vaginal laxity were treated with vaginoplasty and had a significant improvement in the total fsfi score at one year after surgery (29.86±1.74, p<0.01) compared with the fsfi score before surgery (23.41±2.84).Three patients with moderate-degree vaginal laxity were treated with a co2laser and tended to have increased fsfi scores but did not show significant improvement after the operation.Co2laser treatment was performed on 16 patients with light-degree vaginal laxity.The total fsfi score improved from 23.76±2.35 to 26.16±2.58 at one year (p<0.05).Conclusions the strategy for vaginal rejuvenation should be selected based on the degree of vaginal laxity severity.Surgical treatment is suitable for severe- and moderate-degree vaginal laxity while nonsurgical treatment is suitable for light-degree vaginal laxity.

Journal: Annals of translational medicine (2021)
Publication types: Journal Article
Association of Glycemic Control Trajectory with Short-Term Mortality in Diabetes Patients with High Cardiovascular Risk: a Joint Latent Class Modeling Study.

The relationship between risk factor or biomarker trajectories and contemporaneous short-term clinical outcomes is poorly understood.In diabetes patients, it is unknown whether hemoglobin a1c (hb a1c) trajectories are associated with clinical outcomes and can inform care in scenarios in which a single hb a1c is uninformative, for example, after a diagnosis of coronary artery disease (cad).Objective to compare associations of hb a1c trajectories and single hb a1c values with short-term mortality in diabetes patients evaluated for cad design: retrospective observational cohort study participants: diabetes patients (n = 7780) with and without angiographically defined cad main measures: we used joint latent class mixed models to simultaneously fit hb a1c trajectories and estimate association with 2-year mortality after cardiac catheterization, adjusting for clinical and demographic covariates.Key results three hba1c trajectory classes were identified: individuals with stable glycemia (class a; n = 6934 [89%]; mean baseline hb a1c 6.9%), with declining hb a1c (class b; n = 364 [4.7%]; mean baseline hb a1c 11.6%), and with increasing hb a1c (class c; n = 482 [6.2%]; mean baseline hb a1c 8.5%).Hb a1c trajectory class was associated with adjusted 2-year mortality (3.0% [95% ci 2.8, 3.2] for class a, 3.1% [2.1, 4.2] for class b, and 4.2% [3.4, 4.9] for class c; global p = 0.047, p = 0.03 comparing classes a and c, p > 0.05 for other pairwise comparisons).Baseline hb a1c was not associated with 2-year mortality (p = 0.85; hazard ratios 1.01 [0.96, 1.06] and 1.02 [0.95, 1.10] for hb a1c 7-9% and ≥ 9%, respectively, relative to hb a1c < 7%).The association between hb a1c trajectories and mortality did not differ between those with and without cad (interaction p = 0.1).Conclusions in clinical settings where single hb a1c measurements provide limited information, hb a1c trajectories may help stratify risk of complications in diabetes patients.Joint latent class modeling provides a generalizable approach to examining relationships between biomarker trajectories and clinical outcomes in the era of near-universal adoption of electronic health records.

Journal: Journal of general internal medicine (2020)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
Lipid-Laden Macrophages and Inflammation in Atherosclerosisand Cancer: An Integrative View.

Atherosclerotic arterial plaques and malignant solid tumors contain macrophages, which participate in anaerobic metabolism, acidosis, and inflammatory processes inherent in the development of either disease.The tissue-resident macrophage populations originate from precursor cells derived from the yolk sac and from circulating bone marrow-derived monocytes.In the tissues, they differentiate into varying functional phenotypes in response to local microenvironmental stimulation.Broadly categorized, the macrophages are activated to polarize into proinflammatory m1 and anti-inflammatory m2 phenotypes; yet, noticeable plasticity allows them to dynamically shift between several distinct functional subtypes.In atherosclerosis, low-density lipoprotein (ldl)-derived cholesterol accumulates within macrophages as cytoplasmic lipid droplets thereby generating macrophage foam cells, which are involved in all steps of atherosclerosis.The conversion of macrophages into foam cells may suppress the expression of given proinflammatory genes and thereby initiate their transcriptional reprogramming toward an anti-inflammatory phenotype.In this particular sense, foam cell formation can be considered anti-atherogenic.The tumor-associated macrophages (tams) may become polarized into anti-tumoral m1 and pro-tumoral m2 phenotypes.Mechanistically, the tams can regulate the survival and proliferation of the surrounding cancer cells and participate in various aspects of tumor formation, progression, and metastasis.The tams may accumulate lipids, but their type and their specific roles in tumorigenesis are still poorly understood.Here, we discuss how the phenotypic and functional plasticity of macrophages allows their multifunctional response to the distinct microenvironments in developing atherosclerotic lesions and in developing malignant tumors.We also discuss how the inflammatory reactions of the macrophages may influence the development of atherosclerotic plaques and malignant tumors, and highlight the potential therapeutic effects of targeting lipid-laden macrophages in either disease.

Journal: Frontiers in cardiovascular medicine (2022)
Publication types: Journal Article;Review
Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion.

Anaphylatoxin c3a is a small signaling polypeptide that is generated during complement activation.C3a is involved in the regulation of various innate and adaptive immune system processes; however, the role of c3a in macrophage differentiation and polarization is poorly elucidated.Here we showed that c3a impairs alternative m2 polarization of human macrophages and suppressed cd206, il1ra and ccl22 expression.C3a leads to a decrease of nuclear receptor pparγ expression via the erk1/2 signaling pathway, resulting in repressed pparγ-dependent activation of cd36, fabp4 and lxrα genes and blunted response to an lxr ligand to901317.Using small interfering rna and agonist/antagonist approaches we showed that c3a decreases cd206, il1ra and ccl22 transcription at least partly in a pparγ-dependent manner in m2 macrophages.Moreover, c3a impairs efferocytosis by m2 macrophages and inhibits their migratory activity.By contrast, macrophages treated with c3a during differentiation show blunted response to lipopolysaccharide stimulation owing to downregulation of tlr4 and lipid raft content.At the same time, differentiation of macrophages with c3a does not change m1 polarization in interferon gamma (ifnγ) and ifnγ + lipopolysaccharide-treated macrophages.These data provide a novel role of complement system and c3a in the regulation of m2 macrophage polarizations and suggest crosstalk between c3a, tlr4, pparγ and lxr signaling pathways.

Journal: Immunology and cell biology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
PD-1-cis IL-2R agonism yields better effectors from stem-like CD8+T cells.

Expansion and differentiation of antigen-experienced pd-1+tcf-1+stem-like cd8+t cells into effector cells is critical for the success of immunotherapies based on pd-1 blockade1-4.Hashimoto et al.Have shown that, in chronic infections, administration of the cytokine interleukin (il)-2 triggers an alternative differentiation path of stem-like t cells towards a distinct population of 'better effector' cd8+t cells similar to those generated in an acute infection5.Il-2 binding to the il-2 receptor α-chain (cd25) was essential in triggering this alternative differentiation path and expanding better effectors with distinct transcriptional and epigenetic profiles.However, constitutive expression of cd25 on regulatory t cells and some endothelial cells also contributes to unwanted systemic effects from il-2 therapy.Therefore, engineered il-2 receptor β- and γ-chain (il-2rβγ)-biased agonists are currently being developed6-10.Here we show that il-2rβγ-biased agonists are unable to preferentially expand better effector t cells in cancer models and describe pd1-il2v, a new immunocytokine that overcomes the need for cd25 binding by docking in cis to pd-1.Cis binding of pd1-il2v to pd-1 and il-2rβγ on the same cell recovers the ability to differentiate stem-like cd8+t cells into better effectors in the absence of cd25 binding in both chronic infection and cancer models and provides superior efficacy.By contrast, pd-1- or pd-l1-blocking antibodies alone, or their combination with clinically relevant doses of non-pd-1-targeted il2v, cannot expand this unique subset of better effector t cells and instead lead to the accumulation of terminally differentiated, exhausted t cells.These findings provide the basis for the development of a new generation of pd-1 cis-targeted il-2r agonists with enhanced therapeutic potential for the treatment of cancer and chronic infections.

Journal: Nature (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Gradient differences of immunotherapy efficacy in metastatic melanoma related to sunlight exposure pattern: A population-based study.

Immune checkpoint inhibitors (icis) have revolutionized metastatic melanoma (mm) treatment in just a few years.Ultraviolet (uv) in sunlight is the most significant environmental cause of melanoma, which is considered to be the main reason for tumor mutation burden (tmb) increase in melanoma.High tmb usually predicts that pd-1 inhibitors are effective.The sunlight exposure pattern of mm might be a clinical feature that matches tmb.The relationship between sunlight exposure patterns and immunotherapy response in mm is unclear.This study aims to investigate the correlation between sunlight exposure patterns and immunotherapy response in mm and establish nomograms that predict 3- and 5-year overall survival (os) rate.Methods we searched the surveillance, epidemiology, and end results (seer) database and enrolled mm cases from 2005-2016.According to the advent of icis in 2011, the era was divided into the non-icis era (2005-2010) and the icis era (2011-2016).Patients were divided into three cohorts according to the primary site sunlight exposure patterns: head and neck in the first cohort, trunk arms and legs in the second cohort, and acral sites in the third cohort.We compared survival differences for each cohort between the two eras, performed stratified analysis, established nomograms for predicting 3- and 5-year os rate, and performed internal validation.Results comparing the survival difference between the icis and non-icis era, head and neck melanoma showed the greatest improvement in survival, with 3- and 5-year os rate increasing by 10.2% and 9.1%, respectively (p=0.00011).In trunk arms and legs melanoma, the 3- and 5-year os rate increased by 4.6% and 3.9%, respectively (p<0.0001).There is no improvement in survival in acral melanoma (am) between the two eras (p=0.78).The receiver operating characteristic (roc) curve, area under the roc curve (auc) and calibration graphs show good discrimination and accuracy of nomograms.Decision curve analysis (dca) suggests good clinical utility of nomograms.Conclusions based on the classification of sunlight exposure patterns, there is a gradient difference in immunotherapy efficacy for mm.The degree of sunlight exposure is positively correlated with immunotherapy response.The nomograms are sufficiently accurate to predict 3- and 5-year os rate for mm, allowing for individualized clinical decisions for future clinical work.

Journal: Frontiers in oncology (2022)
Publication types: Journal Article
Country of birth as a potential determinant of inadequate antenatal care use among women giving birth in Brussels. A cross-sectional study.

One of the mechanisms explaining perinatal health inequalities could be inadequate antenatal care among some immigrant groups.Few european studies compared antenatal care use between different groups of immigrants taking into account individual characteristics.This research investigates the associations of three birth regions with the use of antenatal care, by also considering socioeconomic and migration-related determinants.Methods we included 879 mothers born in belgium, north africa, and sub-saharan africa, and interviewed them in four brussels hospitals after they gave birth, using an adapted version of the migrant-friendly maternity care questionnaire.We additionally collected clinical data from hospital records.We carried out descriptive analyses and ran univariate and multivariable logistic regression models to estimate the associations of socioeconomic and migration characteristics with a) late start of antenatal care and b) less than minimum recommended number of consultations.Results the vast majority of women in this study had adequate care in terms of timing (93.9%), frequency of consultations (82.2%), and self-reported access (95.9%).Region of birth was an independent risk factor for late initiation of care, but not for infrequent consultations.Women born in sub-saharan africa were more prone to accessing care late (or 3.3, 95%ci 1.5-7.7), but were not more at risk of infrequent consultations.Women born in north africa, had similar adequacy of care compared to the belgium-born population.The three groups also differed in terms of socioeconomic profiles and socioeconomic predictors of antenatal care use.Housing type, professional activity, and health insurance status were important predictors of both outcomes.Conclusions this study showed that the region of birth was partly associated with adequacy of care, in terms of initiation, but not number of consultations.Further dimensions of adequacy of care (content, quality) should be studied in the future.Socioeconomic factors are also key determinants of antenatal care use.

Journal: PloS one (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
First Provider Seen for an Acute Episode of Low Back Pain Influences Subsequent Health Care Utilization.

Costs associated with low back pain (lbp) continue to rise.Despite numerous clinical practice guidelines, the evaluation and treatments for lbp are variable and largely depend on the individual provider.As yet, little attention has been given to the first choice of provider.Early research indicates that the choice of first provider and the timing of interventions for lbp appear to influence utilization.We sought to examine the association between the first provider seen and health care utilization.Methods using 2015-2018 data from a large insurer, this retrospective analysis focused on patients (29,806) seeking care for a new episode of lbp.The study identified the first provider chosen and examined the following year of medical utilization.Cox proportional hazards models were calculated using inverse probability weighting on propensity scores to evaluate the time to event and the relationship to the first choice of provider.Results the primary outcome was the timing and use of health care resources.Total health care use was lowest in those who first sought care with chiropractic care or physical therapy.Highest health care use was seen in those patients who chose the emergency department.Conclusion overall, there appears to be an association between the first choice of provider and future health care use.Chiropractic care and physical therapy provide nonpharmacologic and nonsurgical, guideline-based interventions.The use of physical therapists and chiropractors as entry points into the health system appears related to a decrease in immediate and long-term use of health resources.This study expands the existing body of literature and provides a compelling case for the influence of the first provider on an acute episode of lbp.Impact the first provider seen for an acute episode of lbp influences immediate treatment decisions, the trajectory of a specific patient episode, and future health care choices in the management of lbp.

Journal: Physical therapy (2023)
Publication types: Journal Article
Evaluation ofKRAS,NRASandBRAFmutational status and microsatellite instability in early colorectal carcinomas invading thesubmucosa(pT1): towards an in-house molecular prognostication for pathologists?

We aimed to study the prognostic value of kras,nras,brafmutations and microsatellite stable (mss)/instable (msi) in the field of colorectal cancer invading thesubmucosa(ie, p t1 colorectal cancer (crc)).Methods we led a case-control study in tumour samples from 60 patients with p t1 crc with (20 cases) and without (40 cases) metastatic evolution (5 years of follow-up) which were analysed for kras,nras,brafmutations (idylla testing and next generation sequencing, ngs) and mss/msi status (idylla testing and expression of mismatch repair (mmr) proteins using immunohistochemistry).Results krasmutations were encountered in 11/20 (55%) cases and 21/40 (52.5%) controls (or=1.11 (0.38 to 3.25), p=0.8548),nrasmutations in 1/20 (5%) cases and 3/40 (7.5%) controls (or=3.08 (0.62 to 15.39), p=0.1698) and brafmutations in 3/20 (15%) cases and 6/40 (15%) controls (or=1.00 (0.22 to 4.5), p=1.00).A msi status was diagnosed in 3/20 (15%) cases and 5/40 (12.5%) controls (or=1.2353 (0.26 to 5.79), p=0.7885).Beyond the absence of significant association between the metastatic evolution and any of the studied molecular parameters, we observed a very good agreement between methods analysing kras, nrasand brafmutations (kappa value of 0.849 (0.748 to 0.95) between idylla and ngs) and mss/msi (idylla)-proficient mmr/deficient mmr (immunohistochemistry) status (kappa value of 1.00).Conclusion although being feasible using the fully automated idylla method as well as ngs, the molecular testing of kras, nras, brafand mss/msi status does not seem useful for prognostic purpose in the field of p t1 crc.

Journal: Journal of clinical pathology (2020)
Publication types: Journal Article
Vasodilatation stress cardiovascular magnetic resonance imaging: Feasibility, workflow and safety in a large prospective registry of more than 35,000 patients.

Cardiovascular magnetic resonance imaging (cmr) is an accurate technique for assessing ventricular function, myocardial perfusion and viability; its development remains limited mainly because of logistical and time constraints.Data regarding optimization of a dedicated stress cmr workflow are needed.Aims this study aimed to describe the optimization of a dedicated workflow, and to assess the feasibility and safety of stress cmr in a large registry of>35,000 patients.Methods a large single-centre french registry of vasodilator stress cmr included consecutive patients referred between 2008 and 2019 for the detection of inducible ischaemia.Stress cmr was performed at 1.5 tesla using dipyridamole.Clinical and demographic data, test quality, cmr findings, haemodynamic data and complications were recorded prospectively.A locally optimized workflow was described and evaluated.Results among the 35,862 patients referred for vasodilator stress cmr (mean age 68.9±11.8 years; 64.1% male), the stress cmr protocol was completed in 35,013 (97.6%) patients; 144 (0.3%) patients with missing baseline data were excluded.The mean examination duration was 27±5min, with image quality optimal in 90.8%, suboptimal in 7.1% and poor in 0.5% of cases.Images were diagnostic in 97.9% of patients.No patients died during or immediately after cmr.Fifty-six (0.16%) patients had severe complications.The incidence of non-severe complications was low (1.5%), whereas minor symptoms occurred frequently (35.5%).The presence of ischaemia was associated with a higher incidence of severe complications, non-severe complications and minor symptoms (all p 35,000 referral patients with known or suspected cad showed that stress cmr was feasible in clinical routine practice, with high diagnostic image quality and an excellent safety profile.Inducible ischaemia was associated with severe complications, non-severe complications and minor symptoms.

Journal: Archives of cardiovascular diseases (2021)
Publication types: Journal Article