nils-herrmann/clean_scirepeval huggingface dataset:
Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials.

Tumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines.



A total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs.



TIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P < 0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20-1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-).



We confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.
Autologous adipose tissue-derived stem cells for the treatment of Crohn's fistula: a phase I clinical study.

The present study was designed to evaluate the safety and potential of adipose tissue-derived stem cells (ASCs) for the treatment of Crohn's fistula. In this dose escalation study, patients were sequentially enrolled into three dosing groups with at least three patients per group. The first three patients (group 1) were given 1 × 10(7) cells/ml. After 4 weeks, this dose was deemed safe, and so an additional four patients (group 2) were given 2 × 10(7) cells/ml. Four weeks later, after which this second dose was deemed safe, a third and final group of three patients were given 4 × 10(7) cells/ml. Each patient was followed for a minimum of 8 weeks. Patients who showed complete healing at week 8 were followed up for an additional 6 months. Efficacy endpoint was complete healing at week 8 after injection, defined as complete closure of the fistula track and internal and external openings without drainage or signs of inflammation. There were no grade 3 or 4 severity adverse events, and there were no adverse events related to the study drug. Two patients in group 2, treated with 2 × 10(7) ASCs/ml, showed complete healing at week 8 after injection. Of the three patients enrolled in group 3, treated with 4 × 10(7) ASCs/ml, one showed complete healing. Outcome in another patient was assessed as partial healing due to incomplete closure of the external opening, although the inside of fistula track was filled considerably and there was no drainage. All three patients with complete healing at week 8 showed a sustained effect without recurrence 8 months after injection. In conclusion, this study demonstrates the tolerability, safety, and potential efficacy of ASCs for the treatment of Crohn's fistula and provides support for further clinical study.
High prevalence of lipoatrophy among patients on stavudine-containing first-line antiretroviral therapy regimens in Rwanda.

This study was conducted among individuals placed on WHO-recommended first-line antiretroviral therapy (ART) at two urban health centres in Kigali, Rwanda, in order to determine (a) the overall prevalence of lipodystrophy and (b) the risk factors for lipoatropy. Consecutive individuals on ART for >1 year were systematically subjected to a standardised case definition-based questionnaire and clinical assessment. Of a total of 409 individuals, 370 (90%) were on an ART regimen containing stavudine (d4T), whilst the rest were receiving a zidovudine (AZT)-containing regimen. Lipodystrophy was apparent in 140 individuals (34%), of whom 40 (9.8%) had isolated lipoatrophy, 20 (4.9%) had isolated lipohypertrophy and 80 (19.6%) had mixed patterns. Fifty-six percent of patients reported the effects as disturbing. The prevalence of lipoatrophy was more than three times higher when taking d4T compared with AZT-containing regimens (31.4% vs. 10.3%). Being female, d4T-based ART, baseline body mass index >or=25 kg/m(2) or baseline CD4 count >or=150 cells/microl and increasing duration of ART were all significantly associated with lipoatrophy. Lipoatrophy appears to be an important long-term complication of WHO-recommended first-line ART regimens. These data highlight the urgent need for access to more affordable and less toxic ART regimens in resource-limited settings.
Impaired visual recognition of biological motion in schizophrenia

Motion perception deficits have been suggested to be an important feature of schizophrenia but the behavioral consequences of such deficits are unknown. Biological motion refers to the movements generated by living beings. The human visual system rapidly and effortlessly detects and extracts socially relevant information from biological motion. A deficit in biological motion perception may have significant consequences for detecting and interpreting social information.



Schizophrenia patients and matched healthy controls were tested on two visual tasks: recognition of human activity portrayed in point-light animations (biological motion task) and a perceptual control task involving detection of a grouped figure against the background noise (global-form task). Both tasks required detection of a global form against background noise but only the biological motion task required the extraction of motion-related information.



Schizophrenia patients performed as well as the controls in the global-form task, but were significantly impaired on the biological motion task. In addition, deficits in biological motion perception correlated with impaired social functioning as measured by the Zigler social competence scale [Zigler, E., Levine, J. (1981). Premorbid competence in schizophrenia: what is being measured? Journal of Consulting and Clinical Psychology, 49, 96-105.].



The deficit in biological motion processing, which may be related to the previously documented deficit in global motion processing, could contribute to abnormal social functioning in schizophrenia.
Altered Nitric Oxide Bioavailability Contributes to Diesel Exhaust Inhalation‐Induced Cardiovascular Dysfunction in Man

Diesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects.



In 2 randomized double-blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air.  Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 μg/min) and sodium nitroprusside (SNP; 2 to 8 μg/min) in the presence of the NO clamp (NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) 8 μg/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow).  Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenous l-NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68±48 versus 41±32 nmol/L; P=0.006) despite similar l-NMMA-induced reductions in basal blood flow (-20.6±14.7% versus -21.1±14.6%; P=0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose-dependent vasodilatation that was not affected by diesel exhaust inhalation (P>0.05 for both). Following exposure to diesel exhaust, l-NMMA caused a greater increase in blood pressure (P=0.048) and central arterial stiffness (P=0.007), but reductions in cardiac output and increases in systemic vascular resistance (P>0.05 for both) were similar to those seen with filtered air.



Diesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability.
Community based integrated intervention for prevention and management of chronic obstructive pulmonary disease (COPD) in Guangdong, China: cluster randomised controlled trial

To evaluate the effects of a community based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China.



Cluster randomised controlled trial.



Eight healthcare units in two communities.



Of 1062 people aged 40-89, 872 (101 with COPD and 771 without COPD) who fulfilled the inclusion and exclusion criteria were allocated to the intervention or the usual care programmes.



Participants randomly assigned to integrated intervention (systematic health education, intensive and individualised intervention, treatment, and rehabilitation) or usual care.



Annual rate of decline in forced expiratory rate in one second (FEV(1)) before use of bronchodilator.



Annual rate of decline in FEV(1) was significantly lower in the intervention community than the control community, with an adjusted difference of 19 ml/year (95% confidence interval 3 to 36) and 0.9% (0.1% to 1.8%) of predicted values (all P<0.05), as well as a lower annual rate of decline in FEV(1)/FVC (forced vital capacity) ratio (adjusted difference 0.6% (0.1% to 1.2%) P=0.029). There were also higher rates of smoking cessation (21% v 8%, P<0.004) and lower cumulative death rates from all causes (1% v 3%, P<0.009) in the intervention community than in the control community during the four year follow-up. Improvements in knowledge of COPD and smoking hazards, outdoor air quality, environmental tobacco smoke, and working conditions were also achieved (all P<0.05). The difference in cumulative incidence rate of COPD (both around 4%) and cumulative death rate from COPD (2% v 11%) did not reach significance between the two communities.



A community based integrated intervention can have a significant impact on the prevention and management of COPD, mainly reflected in the annual rate of decline in FEV(1).
Effects of stepwise ablation of chronic atrial fibrillation on atrial electrical and mechanical properties.

This study sought to evaluate the effects of stepwise catheter ablation of chronic atrial fibrillation (AF) on atrial electrical and mechanical properties.



Although stepwise catheter ablation of chronic AF is associated with acute arrhythmia termination and a favorable clinical outcome, atrial tissue damage following the procedure has not been evaluated.



Forty patients who had previously undergone catheter ablation of chronic AF were studied. In the index procedure, termination of AF was achieved by catheter ablation alone in 36 of 40 patients (90%). Electroanatomical mapping was performed in sinus rhythm > or =1 month after the index procedure, during which the surface area of scar (bipolar voltage of <0.05 mV), low-voltage tissue (<0.5 mV), and atrial propagation were evaluated. Left atrial (LA) mechanical function was assessed by transthoracic echocardiography.



Electroanatomical mapping showed areas of scar and low-voltage accounting for 31% +/- 12% and 32% +/- 17% of the total LA surface area respectively, with the ablated pulmonary vein region accounting for 20% +/- 4% of the LA surface area. The area of scar outside the pulmonary vein region represented 14% +/- 12% of the LA surface area using the initial randomized ablation strategy, and 6% +/- 8% (p = 0.02) using a specific ablation strategy. Atrial conduction was diversely affected by ablation with a wide range of LA conduction times observed (range 100 to 360 ms). The LA contraction was shown in all patients by the presence of late diastolic mitral flow (37 +/- 15 cm/s) and a mean LA active emptying fraction of 18 +/- 11%. At 9 +/- 5 months of follow-up, 39 patients (98%) were in sinus rhythm.



Stepwise ablation achieving sinus rhythm in patients with chronic AF has a significant impact on LA electrical activity but is associated with recovery of LA function.
Comfort levels of nursing students regarding clinical assignment to a patient with AIDS.

For educators, preparing nursing students for the care of persons with AIDS is an important responsibility. A review of the literature suggests that many nursing students are fearful of occupational transmission of HIV and that educational interventions may improve the students' attitudes toward caring for patients with AIDS. The author administered Form A of the Nursing Care Comfort scale to a sample of 122 baccalaureate students. Findings revealed variations in comfort levels relative to specific nursing skills.
Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study.

Although the incidence of the postthrombotic syndrome (PTS) has been addressed in patients with symptomatic deep vein thrombosis (DVT), less information is available on the incidence in patients who develop asymptomatic DVT after major hip or knee arthroplasty.



To determine whether symptomatic PTS occurs more frequently in patients who develop DVT after hip or knee arthroplasty than those who are free of DVT and to provide an estimate of the incidence of PTS in patients who had undergone major hip or knee arthroplasty and had proximal DVT, distal (calf) DVT, or no DVT.



A cross-sectional study conducted at the Hamilton Health Sciences Corporation, Hamilton, Ontario, and the Academic Medical Centre, Amsterdam, the Netherlands.



Two hundred fifty-five subjects who had undergone major hip or knee arthroplasty 2 to 7 years previously and had routine predischarge venography showing proximal DVT (n = 25), distal DVT (n = 66), or no DVT (n = 164) were enrolled from March 1993 through December 1998. The presence of symptomatic PTS confirmed by the presence of objectively confirmed venous valvular incompetence was ascertained.



The rates of PTS were low and not significantly different among the 3 subgroups: 1 (4.0%, 95% confidence interval [CI] = 0.1%-20.4%) of 25 patients with proximal DVT, 4 (6.1%, 95% CI = 1.7%-14.8%) of 66 patients with distal DVT, and 7 (4.3%, 95% CI = 1.7%-8.6%) of 164 patients with no DVT.



Symptomatic PTS is an uncommon complaint after major hip or knee arthroplasty. Patients who develop postoperative proximal or distal DVT and who receive 6 to 12 weeks of anticoagulant therapy are not predisposed to PTS.
Impaired skin capillary recruitment in essential hypertension is caused by both functional and structural capillary rarefaction.

Capillary rarefaction occurs in many tissues in patients with essential hypertension and may contribute to an increased vascular resistance and impaired muscle metabolism. Rarefaction may be caused by a structural (anatomic) absence of capillaries, functional nonperfusion, or both. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of subjects with essential hypertension. We examined skin capillary density with video microscopy before and during maximization of the number of perfused capillaries by venous congestion (structural capillary number) and before and during postocclusive reactive hyperemia (capillary recruitment, which may have a structural and/or functional basis). The study group was composed of 26 patients with never-treated essential hypertension and 26 normotensive control subjects. In both groups, intermittently perfused capillaries in the resting state were an important functional reserve for recruitment during postocclusive hyperemia. Recruitment of perfused capillaries during postocclusive reactive hyperemia was decreased in the hypertensive subjects compared with normotensive control subjects (47.9+/-6.8 versus 55.3+/-8.2 capillaries/mm(2), respectively; P<0.01). During venous occlusion, maximal capillary density was significantly lower in the hypertensive subjects than in the control subjects (52.5+/-6.6 versus 57.2+/-8.6 capillaries/mm(2), respectively; P<0.05), suggesting structural rarefaction. However, in the hypertensive subjects compared with the normotensive subjects, a smaller proportion of the maximal number of capillaries was perfused during postocclusive hyperemia (91.6+/-7.5% versus 97.2+/-2.7%, respectively; P<0.05), suggesting an additional functional impairment of capillary recruitment. If the difference in capillary numbers during venous congestion ( approximately 4.6 capillaries/mm(2)) truly reflects the structural difference between the normotensive and hypertensive subjects, then, at most, 62% (4.6/7.4x100%) of the difference in capillary numbers during postocclusive hyperemia ( approximately 7.4 capillaries/mm(2)) can be explained by structural defects, and at least 38% can be explained by functional defects. In conclusion, in patients with essential hypertension, recruitment of perfused capillaries is impaired, which can be explained by both functional and structural rarefaction.
Transvaginal three-dimensional color power Doppler ultrasound and cervical MVD measurement in the detection of cervical intraepithelial neoplasia.

To explore the potential correlation between three-dimensional color power Doppler ultrasound (3D-CPA) parameters and high-grade cervical lesions and early cervical cancer microvessel density (MVD) and investigate the role of transvaginal three-dimensional power Doppler ultrasonography in the detection of cervical intraepithelial neoplasia.



Totally 90 subjects were randomly divided into three groups: the control group (n = 30, including patients with chronic cervicitis), the high-grade cervical intraepithelial neoplasia (CIN) group (n = 30, mainly CIN II-III), and the early cervical cancer group (stage Ia-IIa) (n = 30). All patients received preoperative 3D-CPA, and the cervical blood flow was graded. The cervical and intra-mass parameters including vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were measured. The immunohistochemistry of the anti-CD34 monoclonal antibody was performed for the post-operative specimens obtained from each group. The MVD of the tumors was calculated. The difference of each parameter was compared among these three groups, and the correlations between the ultrasound vascular parameters and MVD were analyzed. The high-grade CIN group was followed up for 6 months after the loop electrosurgical excision procedure (LEEP) conization surgery with 3D-CPA.



Compared with the other two groups, the early cervical cancer group had significantly higher VI, FI, and VFI parameters (p < 0.01). Compared with the control group, all of the three parameters of the high-grade CIN group were significantly higher (p < 0.01). The MVD values increased from the control group to the high-grade CIN group, and in turn to the cervical cancer group, with significant differences between each pair (p < 0.05). MVD was positively correlated with the ultrasound parameters VI and VFI (r = 0.723, r = 0.692). There were significant differences among the three groups in terms of vascular morphology and type. However, the ultrasound parameters and vascular types were not significantly different between the postoperative CIN group and the control group.



3D-CPA can be used to assess blood flow in the cervix. It is particularly useful for the early diagnosis of cervical cancer and CIN and for the postoperative follow-up of CIN.
Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer.

The National Epirubicin Adjuvant Trial (NEAT) and the BR9601 trial examined the efficacy of anthracyclines in the adjuvant treatment of early breast cancer.



In NEAT, we compared four cycles of epirubicin followed by four cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) with six cycles of CMF alone. In the BR9601 trial, we compared four cycles of epirubicin followed by four cycles of CMF, with eight cycles of CMF alone every 3 weeks. The primary end points were relapse-free and overall survival. The secondary end points were adverse effects, dose intensity, and quality of life.



The two trials included 2391 women with early breast cancer; the median follow-up was 48 months. Relapse-free and overall survival rates were significantly higher in the epirubicin-CMF groups than in the CMF-alone groups (2-year relapse-free survival, 91% vs. 85%; 5-year relapse-free survival, 76% vs. 69%; 2-year overall survival, 95% vs. 92%; 5-year overall survival, 82% vs. 75%; P<0.001 by the log-rank test for all comparisons). Hazard ratios for relapse (or death without relapse) (0.69; 95% confidence interval [CI], 0.58 to 0.82; P<0.001) and death from any cause (0.67; 95% CI, 0.55 to 0.82; P<0.001) favored epirubicin plus CMF over CMF alone. Independent prognostic factors were nodal status, tumor grade, tumor size, and estrogen-receptor status (P<0.001 for all four factors) and the presence or absence of vascular or lymphatic invasion (P=0.01). These factors did not significantly interact with the effect of epirubicin plus CMF. The overall incidence of adverse effects was significantly higher with epirubicin plus CMF than with CMF alone but did not significantly affect the delivered-dose intensity or the quality of life.



Epirubicin plus CMF is superior to CMF alone as adjuvant treatment for early breast cancer.
Use of B-type natriuretic peptide in the risk stratification of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the leading infectious cause of death in developed countries. Risk stratification has previously been difficult.



Markers of cardiac stress (B-type natriuretic peptide, BNP) and inflammation (C-reactive protein, white blood cell count, procalcitonin) as well as the pneumonia severity index (PSI) were determined in 302 consecutive patients presenting to the emergency department (ED) with CAP. The accuracy of these parameters to predict death was evaluated as the primary endpoint. Prediction of treatment failure was considered as the secondary endpoint.



B-type natriuretic peptide levels increased with rising disease severity as classified by the PSI (P = 0.015). BNP levels were significantly higher in nonsurvivors compared to survivors [median 439.2 (IQR 137.1-1384.6) vs. 114.3 (51.3-359.6) pg mL(-1), P < 0.001]. In a receiver operating characteristic analysis for the prediction of survival the area under the curve (AUC) for BNP was comparable to the AUC of the PSI (0.75 vs. 0.71, P = 0.52). Importantly, the combination of BNP and the PSI significantly improved the prognostic accuracy of the PSI alone (AUC 0.78 vs. 0.71; P = 0.02). The optimal cut-off for BNP was 279 pg mL(-1). The accuracy of BNP to predict treatment failure was identical to the accuracy to predict death (AUC 0.75).



In patients with CAP, BNP levels are powerful and independent predictors of death and treatment failure. When used in conjunction with the PSI, BNP levels significantly improve the risk prediction when compared with the PSI alone.