nils-herrmann/clean_scirepeval huggingface dataset:
Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years.

Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months.



A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival.



Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival.



There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.
The relationship between HAART use and sexual activity among HIV-positive women of reproductive age in Brazil, South Africa, and Uganda.

The purpose of this study was to determine whether current HAART use is associated with recent sexual intercourse among HIV-infected women (18-49 years) from Brazil, South Africa and Uganda. We conducted an analysis of survey data from a cross-sectional study, which enrolled 179 HIV-infected women receiving regular care from the Mbarara Hospital HIV Clinic in Uganda (n=85); the Perinatal HIV Research Unit in Soweto, South Africa (n=50); and the IPEC-Fiocruz cohort in Rio de Janeiro, Brazil (n=44). The primary outcome was sexual intercourse in the previous month. Secondary outcomes were protected sex and contraceptive use. We found that overall, 46% reported recent sexual intercourse. After adjusting for covariates, recent sexual intercourse was not associated with HAART use (AOR: 0.76; 95%CI: 0.34-1.72); however, it was significantly associated with being currently married, wanting to have more children and having higher HAART optimism. Among women reporting recent sexual intercourse (n=83), HAART users were significantly more likely to practice protected sex (crude OR: 3.64; 95%CI: 1.41-9.38) and non-significantly more likely to use contraceptive methods (crude OR: 2.15; 95%CI: 0.77-5.99). In summary, self-reported recent sexual intercourse is not more likely among women on HAART. Moreover, sexually active HAART users may be more likely to practice protected sex and use contraceptives.
Flk1+ and VE-Cadherin+ Endothelial Cells Derived from iPSCs Recapitulates Vascular Development during Differentiation and Display Similar Angiogenic Potential as ESC-Derived Cells

Induced pluripotent stem (iPS) cells have emerged as a source of potentially unlimited supply of autologous endothelial cells (ECs) for vascularization. However, the regenerative function of these cells relative to adult ECs and ECs derived from embryonic stem (ES) cells is unknown. The objective was to define the differentiation characteristics and vascularization potential of Fetal liver kinase (Flk)1(+) and Vascular Endothelial (VE)-cadherin(+) ECs derived identically from mouse (m)ES and miPS cells.



Naive mES and miPS cells cultured in type IV collagen (IV Col) in defined media for 5 days induced the formation of adherent cell populations, which demonstrated similar expression of Flk1 and VE-cadherin and the emergence of EC progenies. FACS purification resulted in 100% Flk1(+) VE-cadherin(+) cells from both mES and miPS cells. Emergence of Flk1(+)VE-cadherin(+) cells entailed expression of the vascular developmental transcription factor Er71, which bound identically to Flk1, VE-cadherin, and CD31 promoters in both populations. Immunostaining with anti-VE-cadherin and anti-CD31 antibodies and microscopy demonstrated the endothelial nature of these cells. Each cell population (unlike mature ECs) organized into well-developed vascular structures in vitro and incorporated into CD31(+) neovessels in matrigel plugs implanted in nude mice in vivo.



Thus, iPS cell-derived Flk1(+)VE-cadherin(+) cells expressing the Er71 are as angiogenic as mES cell-derived cells and incorporate into CD31(+) neovessels. Their vessel forming capacity highlights the potential of autologous iPS cells-derived EC progeny for therapeutic angiogenesis.
Effects of selective serotonin reuptake and dual serotonergic-noradrenergic reuptake treatments on memory and mental processing speed in patients with major depressive disorder.

Patients with major depressive disorder (MDD) usually suffer from altered cognitive functions of episodic memory, working memory, mental processing speed and motor response. Diverse studies suggest that different antidepressant agents may improve cognitive functions in patients with MDD. The aim of this work is to study the effects of serotonergic reuptake inhibitors (SSRIs) and serotonergic-noradrenergic reuptake inhibitors (SNRIs) treatments to improve the performance on memory tasks and mental processing speed in MDD. Seventy-three subjects meeting criteria for major depressive disorder were assessed with the Hamilton depression rating scale and a neuropsychological battery. The subjects were medicated with escitalopram (n=36) or duloxetine (n=37) for 24 weeks. At the end of the trial, the subjects were assessed again with the same neuropsychological battery used prior to the treatment. Both treatments improved importantly the episodic memory and to a lesser extent, working memory, mental processing speed and motor performance. Our results suggest that cognition is partially independent from improvement in clinical symptoms. Both groups achieved remission rates in the HAM-D-17 after 24 weeks of treatment, but SNRI was superior to SSRI at improving episodic and working memory. Our work indicates that the superiority of SNRI over the SSRI at episodic memory improvement is clinically relevant.
Tolerability, pharmacodynamics, and pharmacokinetics studies of depsipeptide (romidepsin) in patients with acute myelogenous leukemia or advanced myelodysplastic syndromes.

Epigenetic modulation of gene expression plays an important role in cancer, including leukemia. Furthermore, histone deacetylase inhibitors may induce the reexpression or repression of genes critical for normal hematopoiesis. The purpose of this study was to evaluate the toxicity, pharmacokinetic profile, and selected pharmacodynamic properties of the histone deacetylase inhibitor depsipeptide in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML).



Depsipeptide was administered to MDS or AML patients at a (solid tumor) phase I dose of 18 mg/m(2) i.v. on days 1 and 5 every 3 weeks. Toxicities and clinical activity were monitored and pharmacokinetic and pharmacodynamic studies were done.



Twelve patients (nine with AML, three with MDS) received one to five cycles of depsipeptide. The most common grade 3/4 toxicities were febrile neutropenia/infection (five patients), neutropenia/thrombocytopenia (nine patients), nausea (nine patients), and asymptomatic hypophosphatemia (three patients). No clinically significant cardiac toxicity was observed. The best response of 11 assessed patients was one complete remission in a patient with AML, stable disease in six patients, and progression of disease in four patients. Exploratory laboratory studies showed modest but rapid increases in apoptosis and changes in myeloid maturation marker expression. Histone H3 and H4 acetylation levels were evaluated in five patients; no consistent changes were observed.



Depsipeptide therapy can be administered with acceptable short-term toxicity. However, gastrointestinal symptoms and fatigue seem to be treatment-limiting after multiple cycles. Depsipeptide monotherapy has limited clinical activity in unselected AML/MDS patients.
A Robust Password-based Authentication Scheme for Heterogeneous Sensor Networks

User authentication is a critical security function for computer systems that allow legitimate users remote access over an insecure communication network. In this paper, we propose a new password-based authentication scheme for heterogeneous sensor networks that consist of sensor nodes of different types. The proposed scheme allows legitimate users to query sensor data at any sensor node in the network, provides not only mutual authentication but also key agreement between a user and a sensor node, and adopts fuzzy identity-based encryption for gateway nodes and high-end sensor nodes. Additionally, our analysis shows that the proposed scheme is immune to some of the most notorious attacks, such as replay attacks, forgery attacks, offline-dictionary attacks, stolen smart card attacks, insider attacks, and many other potential breaches of security.
Multidetector CT enteroclysis versus barium enteroclysis with methylcellulose in patients with suspected small bowel disease

The purpose of this study was to evaluate the diagnostic accuracy of multidetector-CT enteroclysis (MDCT-E) versus barium enteroclysis with methylcellulose (BE) in clinically selected patients with suspected small bowel disease. We prospectively studied 52 patients who underwent unenhanced and contrast-enhanced multidetector CT (16 rows) after administration of 2–2.5 l of methylcellulose by naso-jejunal tube. BE was performed after administration of barium 60% w/v (200–250 ml) and methylcellulose (1–2 l). Patients with radiological signs of Crohn’s disease were classified into the following subtypes: active, fibrostenotic, fistulising/perforating, reparative or regenerative subtypes. Twenty-eight patients also underwent endoscopy. The radiological prevalent subtype was the active subtype. The sensitivity, specificity and diagnostic accuracy of MDCT-E versus BE was 83%, 100% and 89%, respectively. BE showed five false negative CT cases due to early Crohn’s disease; endoscopy confirmed positive cases of the CT and the BE, but showed one false negative case of the BE. Together, MDCT enteroclysis and BE permitted the diagnosis of Crohn’s disease in 30 patients, adhesions in one patient, lymphoma in two patients and carcinoid tumours in two patients. In conclusion, MDCT-E permits good representation of pathological patterns. Early stages of Crohn’s disease are better evaluated by BE.
Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors

DNA electroporation has been demonstrated in preclinical models to be a promising strategy to improve cancer immunity, especially when combined with other genetic vaccines in heterologous prime-boost protocols. We report the results of 2 multicenter phase 1 trials involving adult cancer patients (n=33) with stage II-IV disease. Patients were vaccinated with V930 alone, a DNA vaccine containing equal amounts of plasmids expressing the extracellular and trans-membrane domains of human HER2, and a plasmid expressing CEA fused to the B subunit of Escherichia coli heat labile toxin (Study 1), or a heterologous prime-boost vaccination approach with V930 followed by V932, a dicistronic adenovirus subtype-6 viral vector vaccine coding for the same antigens (Study 2). The use of the V930 vaccination with electroporation alone or in combination with V932 was well-tolerated without any serious adverse events. In both studies, the most common vaccine-related side effects were injection site reactions and arthralgias. No measurable cell-mediated immune response (CMI) to CEA or HER2 was detected in patients by ELISPOT; however, a significant increase of both cell-mediated immunity and antibody titer against the bacterial heat labile toxin were observed upon vaccination. V930 vaccination alone or in combination with V932 was well tolerated without any vaccine-related serious adverse effects, and was able to induce measurable immune responses against bacterial antigen. However, the prime-boost strategy did not appear to augment any detectable CMI responses against either CEA or HER2. Study 1 – ClinicalTrials.gov, NCT00250419 ; Study 2 – ClinicalTrials.gov, NCT00647114 .
HIV incidence and sexually transmitted disease prevalence associated with condom use: a population study in Rakai, Uganda.

Evidence of condom effectiveness for HIV and sexually transmitted disease (STD) prevention is based primarily on high-risk populations. We examined condom effectiveness in a general population with high HIV prevalence in rural Africa.



Data were from a randomized community trial in Rakai, Uganda. Condom usage information was obtained prospectively from 17,264 sexually active individuals aged 15-59 years over a period of 30 months. HIV incidence and STD prevalence was determined for consistent and irregular condom users, compared to non-users. Adjusted rate ratios (RR) of HIV acquisition were estimated by Poisson multivariate regression, and odds ratios of STDs estimated by logistic regression.



Only 4.4% reported consistent condom use and 16.5% reported inconsistent use during the prior year. Condom use was higher among males, and younger, unmarried and better educated individuals, and those reporting multiple sex partners or extramarital relationships. Consistent condom use significantly reduced HIV incidence [RR, 0.37; 95% confidence interval (CI), 0.15-0.88], syphilis [odds ratio (OR), 0.71; 95% CI, 0.53-0.94] and gonorrhea/Chlamydia (OR, 0.50; 95% CI, 0.25-0.97) after adjustment for socio-demographic and behavioral characteristics. Irregular condom use was not protective against HIV or STD and was associated with increased gonorrhea/Chlamydia risk (OR, 1.44; 95% CI, 1.06-1.99). The population attributable fraction of consistent use for prevention of HIV was -4.5% (95% CI, -8.3 to 0.0), due to the low prevalence of consistent use in the population.



Consistent condom use provides protection from HIV and STDs, whereas inconsistent use is not protective. Programs must emphasize consistent condom use for HIV and STD prevention.
Effect of tranexamic acid on early postvitrectomy diabetic haemorrhage; a randomised clinical trial.

To evaluate the effect of tranexamic acid on early postvitrectomy haemorrhage in diabetic patients.



In a clinical trial, 62 diabetic patients scheduled for vitrectomy were randomly assigned to two groups. The treatment group (32 eyes) received two doses of tranexamic acid (10 mg/kg) shortly before and after the operation intravenously, continued orally for 4 days (20 mg/kg/8 hours). The control group (30 eyes) received no medication. Both media clarity and visual acuity were compared during 4 weeks.



Four weeks after surgery visual acuity was low (< or =1 metre counting fingers) in 21.4%, moderate (>1 metre counting fingers but<20/200) in 14.3%, and good (> or =20/200) in 64.3% of the treated group. Corresponding figures in the control group were 26.1%, 26.1%, and 47.8%, respectively. These differences were of no statistical significance. The ratio of mild to severe vitreous haemorrhage during the first 4 days and after 4 weeks was 79% to 21% and 82% to 18% in the treatment group and 76.7% to 23.3% and 78.3% to 21.7% in the control group respectively, which showed no statistically significant difference.



Tranexamic acid, with the method of administration in this study, had no effect on reducing early postvitrectomy haemorrhage in diabetic patients.
Application of objective clinical human reliability analysis (OCHRA) in assessment of technical performance in laparoscopic rectal cancer surgery

Laparoscopic rectal resection is technically challenging, with outcomes dependent upon technical performance. No robust objective assessment tool exists for laparoscopic rectal resection surgery. This study aimed to investigate the application of the objective clinical human reliability analysis (OCHRA) technique for assessing technical performance of laparoscopic rectal surgery and explore the validity and reliability of this technique. Laparoscopic rectal cancer resection operations were described in the format of a hierarchical task analysis. Potential technical errors were defined. The OCHRA technique was used to identify technical errors enacted in videos of twenty consecutive laparoscopic rectal cancer resection operations from a single site. The procedural task, spatial location, and circumstances of all identified errors were logged. Clinical validity was assessed through correlation with clinical outcomes; reliability was assessed by test–retest. A total of 335 execution errors identified, with a median 15 per operation. More errors were observed during pelvic tasks compared with abdominal tasks (p < 0.001). Within the pelvis, more errors were observed during dissection on the right side than the left (p = 0.03). Test–retest confirmed reliability (r = 0.97, p < 0.001). A significant correlation was observed between error frequency and mesorectal specimen quality (r s = 0.52, p = 0.02) and with blood loss (r s = 0.609, p = 0.004). OCHRA offers a valid and reliable method for evaluating technical performance of laparoscopic rectal surgery.
Predicting the duration of antiviral treatment needed to suppress plasma HIV-1 RNA.

Effective therapeutic interventions and clinical care of adults infected with HIV-1 require an understanding of factors that influence time of response to antiretroviral therapy. We have studied a cohort of 118 HIV-1-infected subjects naive to antiretroviral therapy and have correlated the time of response to treatment with a series of virological and immunological measures, including levels of viral load in blood and lymph node, percent of CD4 T cells in lymph nodes, and CD4 T-cell count in blood at study entry. Suppression of viremia below the limit of detection, 50 HIV-1 RNA copies/mL of plasma, served as a benchmark for a successful virological response. We employed these correlations to predict the length of treatment required to attain a virological response in each patient. Baseline plasma viremia emerged as the factor most tightly correlated with the duration of treatment required, allowing us to estimate the required time as a function of this one measure.
Ankle-brachial index improves the classification of cardiovascular risk: PERART/ARTPER Study.

The sensitivity of cardiovascular risk functions is low because many cardiovascular events occur in low- or intermediate-risk patients. The aim of the present study was to evaluate how the ankle-brachial index (ABI) reclassifies these patients.



We conducted a descriptive, transversal, multicenter study (28 centers) of 3171 randomly selected patients aged >49 years. We studied demographic variables, clinical history and cardiovascular risk factors, ABI (defined as pathologic if <0.9) and 10-year cardiovascular risk with the Framingham-Wilson, REGICOR and SCORE equations, dividing risk into three categories: low (Framingham<10%, REGICOR<5% and SCORE<2.5%, intermediate (10-19.9%, 5-9.9% and 2.5-4.9%, respectively) and high (≥20%, ≥10% and ≥5%, respectively). Low- or intermediate-risk patients were reclassified as high-risk if they presented ABI <0.9.



We compared patients with ABI <0.9 and patients with ABI ≥0.9 and found the former were significantly older, more frequently men, had a worse history and more cardiovascular risk factors, and included more high-risk patients than when the classification used Framingham-Wilson (42.7% vs. 18.5%), REGICOR (25.8% vs. 9.3%) and SCORE (42.2% vs. 15.9%) equations. In men, using ABI led to a 5.8% increase in the high-risk category versus Framingham-Wilson, a 19.1% increase versus REGICOR and a 4.4% increase versus SCORE. In women, the increases were 78.6% versus Framingham-Wilson, 151.6% versus REGICOR and 50.0% versus SCORE.



The ABI reclassifies a substantial proportion of patients towards the high-risk category. This is particularly marked in women and by comparison with REGICOR scores.
A combination strategy for enhancing linkage to and retention in HIV care among adults newly diagnosed with HIV in Mozambique: study protocol for a site-randomized implementation science study

Despite the extraordinary scale up of HIV prevention, care and treatment services in sub-Saharan Africa (SSA) over the past decade, the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum. Data from "real-life" settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum.



We are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy (CIS) using feasible, evidence-based, and practical interventions-including (1) point-of-care (POC) CD4 count testing, (2) accelerated antiretroviral therapy initiation for eligible individuals, and (3) SMS reminders for linkage to and retention in care-as compared to the standard of care (SOC) in Mozambique in improving linkage and retention among adults following HIV diagnosis. A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives (CIS + FI) compared to the CIS without FI on study outcomes. Randomization is done at the level of the study site, defined as a primary health facility. Five sites are included from the City of Maputo and five from Inhambane Province. Target enrollment is a total of 2,250 adults: 750 in the SOC arm, 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm (average of 150 participants per site). Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test. Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted.



Study findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a "real-life" service delivery system in a SSA country severely impacted by HIV.