nils-herrmann/clean_scirepeval huggingface dataset:
Phase II study of ipilimumab monotherapy in Japanese patients with advanced melanoma

Ipilimumab is designed to block cytotoxic T-lymphocyte antigen-4 to augment antitumor T cell responses. In studies of predominantly Caucasian patients with advanced melanoma, ipilimumab was associated with durable response, long-term survival benefit, and a manageable safety profile. This phase II study assessed the safety of ipilimumab in Japanese patients with unresectable stage III or IV melanoma. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. The database lock for the original analysis was in August 2014. Overall survival, progression-free survival, and data on deaths were based on an updated, follow-up analysis (database lock April 2015). Data are reported from 20 patients. Fifteen patients (75 %) received all four doses of ipilimumab during induction. Twelve patients (60 %) had at least one drug-related adverse event (AE), and no patients discontinued due to a drug-related AE. There were no deaths related to study drug. The most common drug-related AEs were rash (n = 7), pyrexia (n = 3), increased aspartate aminotransferase (AST; n = 3), and increased alanine aminotransferase (ALT; n = 3). Twelve patients (60 %) reported immune-related AEs (irAEs); most frequent were skin (n = 9) and liver (n = 3) disorders. Grade 3 irAEs were ALT and AST elevation (n = 2) and diabetes mellitus (n = 1). Two patients had a partial response and two had stable disease, yielding a 20 % disease control rate. Median overall survival and progression-free survival were 8.71 and 2.74 months, respectively. Ipilimumab 3 mg/kg had a manageable AE profile in this Japanese patient population with clinical outcomes similar to that in Caucasian patients. NCT01990859.
Image Prototype Similarity Matching for Lymph Node Hemopathology

This paper describes general aspects of an automated expert system for Lymph Node Hemopathology, which utilizes methods of segmentation and classification for performing image prototype similarity matching (IPSM). The expert system consists of a set of representative prototype images of a large number of histologic features required to differentiate different lymph node pathologies. A queiy case, which may consist of one or more images, is compared against each prototype set and is assigned a degree of similarity by calculating a distance metric in a multidimensional feature space. Introductory motivation to this problem is presented together with technical details of the lowlevel segmentation algorithms utilized. As a representative application, results are presented for cases which are dominated by cytologic characteristics.
Validity and reliability of the Internalized Stigma of Smoking Inventory: An exploration of shame, isolation, and discrimination in smokers with mental health diagnoses.

De-normalization of smoking as a public health strategy may create shame and isolation in vulnerable groups unable to quit. To examine the nature and impact of smoking stigma, we developed the Internalized Stigma of Smoking Inventory (ISSI), tested its validity and reliability, and explored factors that may contribute to smoking stigma.



We evaluated the ISSI in a sample of smokers with mental health diagnoses (N = 956), using exploratory and confirmatory factor analysis, and assessed construct validity.



Results reduced the ISSI to eight items with three subscales: smoking self-stigma related to shame, felt stigma related to social isolation, and discrimination experiences. Discrimination was the most commonly endorsed of the three subscales. A multivariate generalized linear model predicted 21-30% of the variance in the smoking stigma subscales. Self-stigma was greatest among those intending to quit; felt stigma was highest among those experiencing stigma in other domains, namely ethnicity and mental illness-based; and smoking-related discrimination was highest among women, Caucasians, and those with more education.



Smoking stigma may compound stigma experiences in other areas. Aspects of smoking stigma in the domains of shame, isolation, and discrimination were related to modeled stigma responses, particularly readiness to quit and cigarette addiction, and were found to be more salient for groups where tobacco use is least prevalent.



The ISSI measure is useful for quantifying smoking-related stigma in multiple domains.
Validity and Reliability of Using a Self-Lavaging Device for Cytology and HPV Testing for Cervical Cancer Screening: Findings from a Pilot Study

Self-sampling could increase cervical cancer screening uptake. While methods have been identified for human papillomavirus (HPV) testing, to date, self-sampling has not provided adequate specimens for cytology. We piloted the validity and reliability of using a self-lavaging device for cervical cytology and HPV testing. We enrolled 198 women in New York City in 2008-2009 from three ambulatory clinics where they received cervical cancer screening. All were asked to use the Delphi Screener™ to self-lavage 1-3 months after clinician-collected index cytological smear (100 normal; 98 abnormal). Women with abnormal cytology results from either specimen underwent colposcopy; 10 women with normal results from both specimens also underwent colposcopy. We calculated sensitivity of self-collected cytology to detect histologically confirmed high grade lesions (cervical intraepithelial neoplasia, CIN, 2+); specificity for histology-negative (CIN 1 or lower), paired cytology negative, or a third cytology negative; and kappa for paired results. One hundred and ninety-seven (99.5%) women self-collected a lavage. Seventy-five percent had moderate to excellent cellularity, two specimens were unsatisfactory for cytology. Seven of 167 (4%) women with definitive results had CIN2+; one had normal and six abnormal cytology results with the self-lavage (sensitivity = 86%, 95% Confidence Interval, CI: 42, 100). The kappa for paired cytology was low (0.36; 95% CI: 0.25, 0.47) primarily due to clinician specimens with atypical squamous cells of undetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) coded as normal using Screener specimens. However, three cases of HSIL were coded as ASC-US and one as normal using Screener specimens. Seventy-three women had paired high-risk HPV tests with a kappa of 0.66 (95% CI: 0.49, 0.84). Based on these preliminary findings, a larger study to estimate the performance of the Screener for co-testing cytology and HPV or for HPV testing with cytology triage is warranted.
Adjuvant chemotherapy is associated with improved overall survival in pelvic node-positive penile cancer after lymph node dissection: a multi-institutional study.

We determined whether adjuvant chemotherapy (AC) would be associated with improved survival after lymph node dissection (LND) for patients with penile cancer (PeCa) who have positive pelvic lymph nodes (PPLNs).



We retrospectively identified patients across 4 centers with penile squamous cell carcinoma who underwent LND from 1978 to 2013 and were found to have PPLNs. Patients who received chemotherapy before surgery or in the presence of recurrent disease were excluded. Cox regression was used to evaluate the association of AC with overall survival (OS), which was estimated using the Kaplan-Meier method. Differences in OS were determined with the log-rank test.



During the study period, 141 patients who underwent LND for PeCa had PPLNs, and 84 of them met inclusion criteria. Median number of PPLNs was 2 (interquartile range [IQR]: 4-7), with 10% of cases occurring bilaterally and 55% having pelvic extranodal extension. AC was used in 36 (43%) patients. Patients who received AC were younger (P = 0.014), had less-aggressive penile tumor pathology (P<0.01), were less likely to receive adjuvant radiation (P<0.01), had less bilateral inguinal disease (P = 0.019), and had more inguinal extranodal extension (P = 0.042). Median follow-up was 12.1 months. Estimated median OS was 21.7 months (IQR: 11.8-104) in patients who received AC vs. 10.1 (IQR: 5.6-48.1) in those who did not (P = 0.048). AC was independently associated with improved OS on multivariate analysis (hazard ratio: 0.40; 95% CI: 0.19-0.87; P = 0.021).



AC is associated with improved OS in patients with PeCa who have PPLNs after LND. Prospective studies are needed to demonstrate causality.
Integrated bio-behavioural HIV surveillance surveys among female sex workers in Sudan, 2011–2012

To assess HIV and syphilis prevalence, HIV-related behaviours and testing for HIV in female sex workers (FSW) in Sudan.



Bio-behavioural surveys using respondent-driven sampling were carried out among FSW in the capital cities of 14 states in Sudan in 2011-2012. HIV and syphilis testing was done by rapid tests.



4220 FSW aged 15-49 years were recruited. The median age of recruited women varied from 21 to 28 years per site. The highest HIV prevalence was measured at two sites in the eastern zone (5.0% and 7.7%), while in the other zones it ranged from 0% to 1.5%. Syphilis prevalence ranged from 1.5% in the northern zone to 8.9% in the eastern zone. Ever having been tested for HIV was reported by 4.4%-23.9% of FSW across all sites. Condom use at last sex with a client varied from 4.7% to 55.1%, while consistent condom use with clients in the month preceding the surveys was reported by 0.7%-24.5% of FSW. The highest reporting of ever injecting drugs was measured at a site in the western zone (5.0%).



The surveys' findings indicate that the highest burden of HIV in FSW is in the eastern states of the country. Condom use and HIV testing data demonstrate the need for HIV interventions that should focus on HIV testing and risk reduction strategies that include stronger condom promotion programmes in FSW and their clients.
Extrafine Beclomethasone/formoterol compared to Fluticasone/salmeterol Combination Therapy in COPD

The study evaluated the efficacy of beclomethasone dipropionate/formoterol fumarate (BDP/FF) extrafine combination versus fluticasone propionate/salmeterol (FP/S) combination in COPD patients.



The trial was a 12-week multicentre, randomised, double-blind, double dummy study; 419 patients with moderate/severe COPD were randomised to BDP/FF 200/12 μg or FP/S 500/50 μg twice daily. The primary objective was to demonstrate the equivalence between treatments in terms of Transition Dyspnoea Index (TDI) score and the superiority of BDP/FF in terms of change from pre-dose in the first 30 minutes in forced expiratory volume in the first second (FEV1). Secondary endpoints included lung function, symptom scores, symptom-free days and use of rescue medication, St. George's Respiratory Questionnaire, six minute walking test and COPD exacerbations.



BDP/FF was equivalent to FP/S in terms of TDI score and superior in terms of FEV1 change from pre-dose (p < 0.001). There were no significant differences between treatments in secondary outcome measures, confirming overall comparability in terms of efficacy and tolerability. Moreover, a clinically relevant improvement (>4 units) in SGRQ was detected in the BDP/FF group only.



BDP/FF extrafine combination provides COPD patients with an equivalent improvement of dyspnoea and a faster bronchodilation in comparison to FP/S.
Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.



One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microg daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period.



Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months).



The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.
Danqi Piantang Jiaonang (DJ), a traditional Chinese medicine, in poststroke recovery.

Stroke is a leading cause of death and disability worldwide. Despite improvements in acute stroke treatment, many patients only make a partial or poor recovery. Therefore, there is a need for treatments that would further improve outcome. Danqi Piantang Jiaonang (DJ; NeuroAid), a traditional Chinese medicine widely used in China to improve recovery after stroke, has been compared with another traditional Chinese medicine in 2 unpublished randomized clinical trials. The results of these studies were pooled and reanalyzed to assess efficacy and safety.



Six hundred five subjects were randomized in 2 randomized double-blinded, controlled trials to receive either DJ or Buchang Naoxintong Jiaonang. Subjects were treated for 1 month.  patients with recent (from 10 days to 6 months) ischemic stroke; (2) patients satisfying Western diagnostic standards for stroke and traditional Chinese medicine standards for diagnosis of apoplexy; and (3) Diagnostic Therapeutic Effects of Apoplexy score >/=10.



The functional outcome, measured by the Comprehensive Function Score component of the Diagnostic Therapeutic Effects of Apoplexy scale, showed a statistically significant superiority of DJ over the control treatment group (relative risk, 2.4; 95% CI, 1.28 to 4.51; P=0.007). Tolerance was excellent in both groups.



The pooled analysis of 2 unpublished trials of DJ, a traditional Chinese medicine currently approved in China to improve neurological recovery after stroke, shows good tolerability and superiority of DJ over another traditional Chinese medicine also approved for stroke. A large double-blind randomized clinical trial is required to further assess the safety and efficacy of DJ.
Is Early Reversal of Defunctioning Ileostomy a Shorter, Easier and Less Expensive Operation?

A defunctioning loop ileostomy mitigates the consequences of anastomotic leak from low rectal anastomosis but it is associated with significant morbidity. In this study, the outcome of early reversal of defunctioning ileostomy during the same admission with the primary operation was assessed. This randomized study was carried out at York Teaching Hospital during the period 2003–2007. All patients with defunctioning ileostomy were considered for an early second operation if they had an uneventful recovery and were in good general condition. Patients on steroids, at high cardiorespiratory risk and those experiencing any postoperative complication were excluded. Eligible patients with satisfactory gastrografin enema on postoperative day 6 were randomized to early versus late reversal at 6–8 weeks. Outcome measures were ease of closure as assessed by a visual analog scale by the operating surgeon, all postoperative complications, duration of the operation, total length of hospital stay and associated costs. Thirty-nine consecutive patients were assessed for eligibility and finally 26 were included in the study. Sixteen patients underwent early reversal. The median(interquartile range (IQR)) age was 62(22) years. Early reversal was significantly superior in terms of ease of abdominal wall closure, ease of reversal (p < 0.01 each), duration of the operation (median(IQR) 20(13) vs. 40(9) min, p < 0.01) and costs of stoma care (median(IQR) 27(9) vs. 311(108) £, p < 0.01). There were no major (grade III/IV) complications in either group. Total length of hospital stay was similar between groups. In carefully selected patients, early reversal of defunctioning ileostomy is feasible, technically easier and has shorter operative time which can also lead to significant cost savings.
Neurofeedback Training with Virtual Reality for Inattention and Impulsiveness

In this research, the effectiveness of neurofeedback, along with virtual reality (VR), in reducing the level of inattention and impulsiveness was investigated. Twenty-eight male participants, aged 14-18, with social problems, took part in this study. They were separated into three groups: a control group, a VR group, and a non-VR group. The VR and non-VR groups underwent eight sessions of neurofeedback training over 2 weeks, while the control group just waited during the same period. The VR group used a head-mounted display (HMD) and a head tracker, which let them look around the virtual world. Conversely, the non-VR group used only a computer monitor with a fixed viewpoint. All participants performed a continuous performance task (CPT) before and after the complete training session. The results showed that both the VR and non-VR groups achieved better scores in the CPT after the training session, while the control group showed no significant difference. Compared with the other groups, the VR group presented a tendency to get better results, suggesting that immersive VR is applicable to neurofeedback for the rehabilitation of inattention and impulsiveness.
Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation) trial.

We hypothesized that human atrial fibrillation (AF) may be sustained by localized sources (electrical rotors and focal impulses), whose elimination (focal impulse and rotor modulation [FIRM]) may improve outcome from AF ablation.



Catheter ablation for AF is a promising therapy, whose success is limited in part by uncertainty in the mechanisms that sustain AF. We developed a computational approach to map whether AF is sustained by several meandering waves (the prevailing hypothesis) or localized sources, then prospectively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome.



We recruited 92 subjects during 107 consecutive ablation procedures for paroxysmal or persistent (72%) AF. Cases were prospectively treated, in a 2-arm 1:2 design, by ablation at sources (FIRM-guided) followed by conventional ablation (n = 36), or conventional ablation alone (n = 71; FIRM-blinded).



Localized rotors or focal impulses were detected in 98 (97%) of 101 cases with sustained AF, each exhibiting 2.1 ± 1.0 sources. The acute endpoint (AF termination or consistent slowing) was achieved in 86% of FIRM-guided cases versus 20% of FIRM-blinded cases (p < 0.001). FIRM ablation alone at the primary source terminated AF in a median 2.5 min (interquartile range: 1.0 to 3.1 min). Total ablation time did not differ between groups (57.8 ± 22.8 min vs. 52.1 ± 17.8 min, p = 0.16). During a median 273 days (interquartile range: 132 to 681 days) after a single procedure, FIRM-guided cases had higher freedom from AF (82.4% vs. 44.9%; p < 0.001) after a single procedure than FIRM-blinded cases with rigorous, often implanted, electrocardiography monitoring. Adverse events did not differ between groups.



Localized electrical rotors and focal impulse sources are prevalent sustaining mechanisms for human AF. FIRM ablation at patient-specific sources acutely terminated or slowed AF, and improved outcome. These results offer a novel mechanistic framework and treatment paradigm for AF. (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation [CONFIRM]; NCT01008722).
Acid-suppression Therapy Offers Varied Laryngopharyngeal and Esophageal Symptom Relief in Laryngopharyngeal Reflux Patients

It is widely accepted that laryngopharyngeal reflux requires more aggressive and prolonged therapy than gastro-esophageal reflux disease. Otolaryngologists often observe that laryngopharyngeal symptoms, such as throat clearing, hoarseness, cough, and globus pharyngeus, are slower to resolve than esophageal symptoms, such as heartburn and regurgitation. The aim of this was to provide empirical evidence to support this observation and to carry out a detailed investigation of the differences between these symptoms. Forty-five patients with laryngopharyngeal and esophageal symptoms received acid-suppression therapy that involved the continuous administration of a proton-pump inhibitor for up to 6 months. We investigated the differences in response to acid-suppression therapy between patients suffering from laryngopharyngeal and esophageal symptoms, respectively, who received upper gastrointestinal endoscopy and were assayed for serum Helicobacter pylori antibodies. The significance of the rate of symptom improvement was estimated by Kaplan–Meier analysis and the logrank test. Laryngopharyngeal symptoms improved significantly more slowly than esophageal symptoms following acid-suppression therapy (49.8 vs. 78.3%, 60 days after the start of acid suppression; P = 0.003). These differences were observed both in patients with erosive esophagitis (P = 0.008) and in H. pylori-seronegative patients (P = 0.001).
Immediate effects of lumbar spine manipulation on the resting and contraction thickness of transversus abdominis in asymptomatic individuals.

Randomized, blinded, controlled crossover trial.



To determine if thrust joint manipulation (TJM) to the lumbar spine would result in changes to the resting and contraction thickness of transversus abdominis (TrA) in healthy individuals.



Recent studies have demonstrated an immediate decrease in resting thickness and an increase in contraction thickness in TrA following lumbar TJM in patients with low back pain (LBP) who met a clinical prediction rule (CPR) for spinal manipulation. This observed phenomenon has not been investigated in healthy individuals.



Thirty-five healthy participants were randomly assigned to receive a TJM or sham manipulation treatment. All participants received instruction on how to produce an isolated concentric contraction of the TrA that involved visual ultrasound imaging biofeedback. Data were analyzed using ultrasound imaging to measure changes in thickness of the TrA at rest and during contraction, following the administration of each treatment.



There were no interactions observed between treatment and time for TrA muscle thickness at rest (P = .351) and during the contracted state (P = .761).



Our results indicate that TJM to the lumbar spine does not appear to affect the resting or contraction thickness of TrA in healthy individuals. These findings are in contrast to previous research in which patients with LBP who met a CPR demonstrated an immediate decrease in resting thickness and an increase in contraction thickness in TrA following lumbar TJM.