nils-herrmann/clean_scirepeval huggingface dataset:
Lymphocyte cytosolic protein 1 is a chronic lymphocytic leukemia membrane-associated antigen critical to niche homing.

Membrane antigens are critical to the pathogenesis of chronic lymphocytic leukemia (CLL) as they facilitate microenvironment homing, proliferation, and survival. Targeting the CLL membrane and associated signaling patterns is a current focus of therapeutic development. Many tumor membrane targets are simultaneously targeted by humoral immunity, thus forming recognizable immunoglobulin responses. We sought to use this immune response to identify novel membrane-associated targets for CLL. Using a novel strategy, we interrogated CLL membrane-specific autologous immunoglobulin G reactivity. Our analysis unveiled lymphocyte cytosolic protein 1 (LCP1), a lymphocyte-specific target that is highly expressed in CLL. LCP1 plays a critical role in B-cell biology by crosslinking F-actin filaments, thereby solidifying cytoskeletal structures and providing a scaffold for critical signaling pathways. Small interfering RNA knockdown of LCP1 blocked migration toward CXCL12 in transwell assays and to bone marrow in an in vivo xenotransplant model, confirming a role for LCP1 in leukemia migration. Furthermore, we demonstrate that the Bruton's tyrosine kinase inhibitor ibrutinib or the PI3K inhibitor idelalisib block B-cell receptor induced activation of LCP1. Our data demonstrate a novel strategy to identify cancer membrane target antigens using humoral anti-tumor immunity. In addition, we identify LCP1 as a membrane-associated target in CLL with confirmed pathogenic significance. This clinical trial was registered at clinicaltrials.gov; study ID number: OSU-0025 OSU-0156.
Mobile-bearing versus fixed-bearing total knee implants. Results of a series of 100 randomised cases after 9 years follow-up.

Mobile-bearing total knee arthroplasty (TKA) implants were developed as an alternative to fixed-bearing implants because of their theoretical advantages related to wear and range of motion. For all that, none of the short-term and medium-term studies published so far have reported a significant clinical improvement related to these mobile bearings. The goal of this study was to compare the outcomes of fixed and mobile bearings in the same type of TKA model after a longer follow-up.



This series initially comprised 100 patients with a mean age of 73 years who were operated by a single surgeon. The patients were randomised to receive either a fixed bearing TKA implant or a mobile one; their outcomes evaluated after a mean of 9 years (7.2-12.2) follow-up. Twenty-two patients died before the final review, 15 were lost to follow-up and 2 were excluded. This resulted in 30 patients with a mobile-bearing knee and 31 with a fixed-bearing knee being available for analysis.



There were no significant clinical differences between the groups receiving a fixed or mobile bearing in terms of the range of motion, subjective outcomes or validated outcomes measured, such as the self-reported Oxford or the IKS. Conversely, there was a significantly higher rate of osteolysis in the fixed-bearing group, but it was not clinically relevant.



This study, which has the longest published follow-up, confirms the results found in the seven randomised studies published up to now: there are no significant differences in the clinical outcomes between fixed-bearing and mobile-bearing inserts of the same TKA model. Although the mobile bearing knees had a better radiographic appearance, this did not translate to better clinical outcomes. In practice, the superiority of mobile bearings is solely theoretical.
Short-burst oxygen therapy for COPD patients: a 6-month randomised, controlled study.

Short-burst oxygen therapy (SBOT) remains widely advocated for patients with chronic obstructive pulmonary disease (COPD), despite a lack of supporting evidence. The aim of this randomised, double-blind, placebo-controlled, parallel group study was to determine whether SBOT improves health-related quality of life (HRQL) or reduces acute healthcare utilisation in patients discharged following an acute exacerbation of COPD. Consecutive patients were screened; 78 of 331 were eligible for randomisation to cylinder oxygen, cylinder air or usual care following discharge. Patients were elderly with high acute healthcare utilisation, forced expiratory volume in one second of <1 L and had dyspnoea limiting daily activity but were not hypoxaemic at rest. Over the 6-month study period, there were no significant differences between patient groups in HRQL (Chronic Respiratory Questionnaire (CRQ), 36-item Short-Form Health Survey, Hospital Anxiety and Depression Scale) except for CRQ emotion domain. There were no significant differences in acute healthcare utilisation. Time to readmission was greatest in the usual care group. Cylinder use was high initially, but rapidly fell to very low levels within weeks in both cylinder oxygen and air groups. In conclusion, the availability of short-burst oxygen therapy for chronic obstructive pulmonary disease patients discharged from hospital following an acute exacerbation did not improve health-related quality of life or reduce acute healthcare utilisation. These results provide no support for the widespread use of short-burst oxygen therapy.
The effects of telmisartan on the nuclear factor of activated T lymphocytes signalling pathway in hypertensive patients

Previous studies provide links between the nuclear factor of activated T lymphocytes (NFAT) signalling pathway and the development of hypertension. Our preliminary studies indicate that telmisartan can block Kv1.3 potassium channels and effectively inhibit potassium current densities, along with Kv1.3 mRNA and protein expression levels. This paper aims to investigate whether telmisartan has an inhibitory effect on the NFAT signalling pathway after activation and proliferation of peripheral blood T lymphocytes in Kazakh patients with essential hypertension (EH) from Xinjiang, China.



T lymphocytes were isolated using the immunomagnetic cell sorting method (MACS). The mRNA expression of NFATc1, IL-6 and TNF-α was measured by quantitative polymerase chain reaction (qRT-PCR) and relative protein levels were evaluated by Western blot. T cell samples from 50 hypertensive Kazakh patients from Xinjiang were randomly divided into control, telmisartan, cyclosporin A (CsA), VIVIT, and 4-aminopytidine (4-AP) groups. Peripheral blood T lymphocytes were first activated and proliferated in vitro, then incubated for 48 h under different treatment conditions before determination of protein and mRNA expression of NFATc1, IL-6, and TNF-α by Western blot and qRT-PCR analyses, respectively.



There were no significant differences in cardiovascular risk factors among the patients with samples assigned to the five groups (p > 0.05). Expression of NFATc1, IL-6, and TNF-α mRNA and protein was significantly reduced in T lymphocytes in all treatment groups (telmisartan, CsA, VIVIT, and 4-AP) compared with controls.



Antihypertensive function and inhibitory effects of telmisartan on the T lymphocyte NFAT signalling pathway are unlikely to affect the normal immune function of hypertensive patients. Telmisartan may exert anti-inflammatory effects by inhibition of the NFAT signalling pathway in the T lymphocytes of hypertensive patients.
Influence of a six month endurance exercise program on the immune function of prostate cancer patients undergoing Antiandrogen- or Chemotherapy: design and rationale of the ProImmun study

Exercise seems to minimize prostate cancer specific mortality risk and treatment related side effects like fatigue and incontinence. However the influence of physical activity on the immunological level remains uncertain. Even prostate cancer patients undergoing palliative treatment often have a relatively long life span compared to other cancer entities. To optimize exercise programs and their outcomes it is essential to investigate the underlying mechanisms. Further, it is important to discriminate between different exercise protocols and therapy regimes. The ProImmun study is a prospective multicenter patient preference randomized controlled trial investigating the influence of a 24 week endurance exercise program in 80–100 prostate cancer patients by comparing patients undergoing Antiandrogen therapy combined with exercise (AE), Antiandrogen therapy without exercise (A), Chemotherapy with exercise(CE) or Chemotherapy without exercise (C). The primary outcome of the study is a change in prostate cancer relevant cytokines and hormones (IL-6, MIF, IGF-1, Testosterone). Secondary endpoints are immune cell ratios, oxidative stress and antioxidative capacity levels, VO2 peak, fatigue and quality of life. Patients of the intervention group exercise five times per week, while two sessions are supervised. During the supervised sessions patients (AE and CE) exercise for 33 minutes on a bicycle ergometer at 70-75% of their VO2 peak. To assess long term effects and sustainability of the intervention two follow-up assessments are arranged 12 and 18 month after the intervention. The ProImmun study is the first trial which primarily investigates immunological effects of a six month endurance exercise program in prostate cancer patients during palliative care. Separating patients treated with Antiandrogen therapy from those who are additionally treated with Chemotherapy might allow a more specific view on the influence of endurance training interventions and the impact of different therapy protocols on the immune function.
Quantitative I-123 mIBG SPECT in differentiating abnormal and normal mIBG myocardial uptake.

The purpose of this study was to evaluate global quantitation of cardiac uptake on I-123 mIBG SPECT.



The study included a pilot group of 67 subjects and a validation group of 1,051 subjects. SPECT images were reconstructed by filtered backprojection, ordered subsets expectation maximization, and deconvolution of septal penetration, respectively. SPECT heart-to-mediastinum ratio (H/M) was calculated by comparing the mean counts between heart and mediastinum volumes of interest drawn on transaxial images. Receiver operating characteristic (ROC) analysis was used to assess the capability of each SPECT method to differentiate the heart disease subjects from controls in comparison with that of the planar H/M.



In the validation group, the areas under the ROC curves were not significantly different between the SPECT and planar H/M. Order subsets expectation maximization had significantly larger area under the ROC curve than the other two SPECT methods.



H/M obtained from I-123 mIBG SPECT was equivalent to the planar H/M for differentiating between subjects with normal and abnormal mIBG uptake. Global quantification of cardiac I-123 mIBG SPECT may represent a viable alternative to the planar H/M.
Correction: The Nerve Growth Factor Receptor CD271 Is Crucial to Maintain Tumorigenicity and Stem-Like Properties of Melanoma Cells

Large-scale genomic analyses of patient cohorts have revealed extensive heterogeneity between individual tumors, contributing to treatment failure and drug resistance. In malignant melanoma, heterogeneity is thought to arise as a consequence of the differentiation of melanoma-initiating cells that are defined by cell-surface markers like CD271 or CD133.



Here we confirmed that the nerve growth factor receptor (CD271) is a crucial determinant of tumorigenicity, stem-like properties, heterogeneity and plasticity in melanoma cells. Stable shRNA mediated knock-down of CD271 in patient-derived melanoma cells abrogated their tumor-initiating and colony-forming capacity. A genome-wide expression profiling and gene-set enrichment analysis revealed novel connections of CD271 with melanoma-associated genes like CD133 and points to a neural crest stem cell (NCSC) signature lost upon CD271 knock-down. In a meta-analysis we have determined a shared set of 271 differentially regulated genes, linking CD271 to SOX10, a marker that specifies the neural crest. To dissect the connection of CD271 and CD133 we have analyzed 10 patient-derived melanoma-cell strains for cell-surface expression of both markers compared to established cell lines MeWo and A375. We found CD271+ cells in the majority of cell strains analyzed as well as in a set of 16 different patient-derived melanoma metastases. Strikingly, only 2/12 cell strains harbored a CD133+ sub-set that in addition comprised a fraction of cells of a CD271+/CD133+ phenotype. Those cells were found in the label-retaining fraction and in vitro deduced from CD271+ but not CD271 knock-down cells.



Our present study provides a deeper insight into the regulation of melanoma cell properties and points CD271 out as a regulator of several melanoma-associated genes. Further, our data strongly suggest that CD271 is a crucial determinant of stem-like properties of melanoma cells like colony-formation and tumorigenicity.
B-type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea.

B-Type natriuretic peptide (BNP) is a neurohormone secreted from the cardiac ventricles in response to volume expansion and pressure overload. We have recently demonstrated that BNP can differentiate congestive heart failure (CHF) from other causes of dyspnea in patients presenting to the emergency department. In this study, we assess whether BNP levels drawn in patients presenting with dyspnea to the ED were a predictor of future cardiac events.



In 325 patients presenting with dyspnea to the ED, BNP levels were determined. Patients were then followed up for 6 months to determine the following end points: death (cardiac and noncardiac), hospital admissions (cardiac), and repeat ED visits for CHF. Receiver operating characteristic (ROC) curves, relative risks (RRs), and Kaplan-Meier plots were used to assess the ability of BNP levels to predict future cardiac events.



The area under the ROC curve using BNP to detect a CHF end point-a CHF death, hospital admission, or repeat ED visit-was 0.870 (95% confidence interval [CI] 0.826 to 0.915). A BNP value of 480 pg/mL had a sensitivity of 68%, specificity of 88%, and an accuracy of 85% for predicting a subsequent CHF end point. The area under the ROC curve using BNP to detect death from CHF was 0.881 (95% CI 0.807 to 0.954) and for any cardiac death was 0.877 (95% CI 0.822 to 0.933). BNP was not associated with death from noncardiac causes. Using Kaplan-Meier plots for all CHF events, rising BNP levels were associated with a progressively worse prognosis. Patients with BNP levels more than 480 pg/mL had a 51% 6-month cumulative probability of a CHF event. Alternatively, patients with BNP levels less than 230 pg/mL had an excellent prognosis with only 2.5% incidence of CHF end points. The RR of 6-month CHF death in patients with BNP levels more than 230 pg/mL was 24.1. The RR of 6-month noncardiac death with BNP levels more than 230 pg/mL was 1.1. BNP levels were also predictive of CHF events in subsets of patients with positive CHF histories and ED diagnoses.



In this study population, BNP levels measured in patients presenting with dyspnea to the ED are highly predictive of cardiac events over the next 6 months.
Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study

Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.



In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3.



More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein.



In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage.
Combat Exposure and Risk for Suicidal Thoughts and Behaviors Among Military Personnel and Veterans: A Systematic Review and Meta-Analysis.

Due to seemingly mixed empirical results, questions persist about the possible role of deployments and combat exposure. We conducted a narrative review and meta-analysis of 22 published studies to integrate findings regarding the relationship of deployment-related predictors (i.e., deployment, deployment to a combat zone, combat experience, and exposure to specific combat events) with suicide-related outcomes (i.e., suicide ideation, attempt, and death). Across all predictors and outcomes, the combined effect was small and positive, r = .08 [0.04, 0.13], and marked by significant heterogeneity, I2  = 99.9%, Q(21)=4880.16, p < .0001, corresponding to a 25% increased risk for suicide-related outcomes among those who have deployed. Studies examining the relationship between exposure to killing and atrocities (k = 5) showed the largest combined effect, r = .12 [0.08, 0.17], and less heterogeneity, I2  = 84.4%, Q(4)=34.96, p < .0001, corresponding to a 43% increased risk for suicide-related outcomes among those exposed to killing or atrocity. Implications for theory, research, and clinical practice are discussed.
The DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression.

The Depression Outcomes Study of Exercise (DOSE) was a randomized clinical trial to determine whether exercise is an efficacious treatment for mild to moderate major depressive disorder (MDD) in adults ages 20 to 45 years. The specific hypotheses under investigation were (1) active exercise is an efficacious monotherapy for mild to moderate levels of MDD, and (2) there is a dose-response relation between the exercise amount and reduction in depressive symptoms. The primary outcome measure was the Hamilton Rating Scale for Depression (HRSD) collected weekly over 12 weeks. Secondary outcome measures were the Inventory of Depressive Symptoms (clinician and self-report), HRSD scores at 24 weeks, cardiorespiratory fitness, self-efficacy, and quality of life. Eighty men and women who were diagnosed with a Structured Clinical Interview for Depression and who had mild (HRSD 12-16) to moderate (HRSD 17-25) MDD were randomized to one of five doses of exercise: 7.0 kcal/kg/week in 3 days/week; 7.0 kcal/kg/week in 5 days/week; 17.5 kcal/kg/week in 3 days/week; 17.5 kcal/kg/week in 5 days/week; or 3 days/week of stretching and flexibility exercises for 15 to 20 min/session. Participants exercised under supervision in our laboratory over the course of 12 weeks. Symptoms of depression were measured weekly by trained clinical raters blinded to the participant's treatment assignment. The design of the study restricted participant characteristics to mild to moderate MDD and controlled exercise features to permit the evaluation of exercise as a sole treatment for depression. This study is the first to examine dose-response effects of exercise in participants diagnosed with MDD.
Results of primary central nervous system lymphoma treated by radiation and chemotherapy: Retrospective analysis of twelve institutions in the Tokai district of Japan, 1995–1999

We analyzed the therapeutic results and prognostic factors of 46 primary central nervous system lymphoma (PCNSL) patients who were treated at twelve institutions in the Tokai district of Japan between 1995 and 1999. We compared the results with those of a Japanese nationwide survey performed in the past. We sent each institution a questionnaire about the state of patients' disease, pathological type, method and doses of radiotherapy, regimen and intensity of chemotherapy, and patients' prognoses. The range of patients' ages was 33 to 93 years (median, 61 years). Thirty-one were men and 15 were women. The most prevalent histology was diffuse large B cell type (33 patients). We used the Kaplan-Meier method to calculate the survival rate and Cox's proportional hazards model to analyze the prognostic factors. The five-year cumulative survival rate was 25%, and the median survival time was 22.7 months. The five-year disease-free survival rate was 23%. In monovariate analysis, patients who were both younger than 60 years old and had a WHO performance status (PS) score equal to or less than 2 showed a better survival rate. Furthermore, the patients receiving systemic chemotherapy showed a significantly better local control rate. In addition, patients who received systemic chemotherapy achieved a higher complete remission rate than those not receiving it. However, no factors that significantly influenced survival rate were identified in multivariate analysis. We demonstrated that the therapeutic outcome of PCNSL patients has recently improved. In particular, patients with good PS showed better local control than those with poor PS. However, we could not identify any significant prognostic factors in PCNSL patients.
Radiographic and metabolic response rates following image-guided stereotactic radiotherapy for lung tumors.

To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors.



Thirty-nine tumors were treated prospectively with SBRT (dose=48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0=67%; T2N0=25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses.



At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks.



SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.