nils-herrmann/clean_scirepeval huggingface dataset:
A randomized pilot trial comparing cyclosporine and azathioprine for maintenance therapy in diffuse lupus nephritis over four years.

There is not agreement about the best maintenance treatment for patients with diffuse lupus nephritis. This multicenter, randomized trial compared the safety and efficacy of cyclosporine and azathioprine. Seventy-five patients with diffuse proliferative lupus were given three intravenous methylprednisolone pulses followed by prednisone and oral cyclophosphamide for a median of 90 d. Subsequently, patients were randomly assigned either to cyclosporine or to azathioprine for 2 yr (core study). Treatment continued for up to 4 yr (follow-up study). The primary outcome measure was the incidence of disease flares. Secondary end points were proteinuria per day, creatinine clearance, and adverse effects. Seven flares occurred in the cyclosporine group, and eight occurred in the azathioprine group. At the end of the core study, mean proteinuria decreased from 2.8 +/- 3.57 to 0.4 +/- 0.85 g/d (P < 0.0001) in the cyclosporine group and from 2.2 +/- 1.94 to 0.5 +/- 0.78 g/d (P < 0.0002) in the azathioprine group. After 4 yr, mean proteinuria was 0.2 +/- 0.24 and 0.3 +/- 0.33 g/d, respectively. At the core study end and at the follow-up completion, creatinine clearance and BP levels did not change significantly from baseline in either group. Five of 36 patients who were receiving cyclosporine and four of the 33 who were receiving azathioprine stopped the treatment because of adverse effects. For patients with diffuse proliferative lupus nephritis, azathioprine or cyclosporine combined with corticosteroids demonstrated equal efficacy in the prevention of flares.
A six-month, placebo-controlled trial of d-cycloserine co-administered with conventional antipsychotics in schizophrenia patients

d-Cycloserine, a partial agonist at the glycine site of the N-methyl-d-aspartate receptor, has demonstrated inconsistent efficacy for negative and cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come from studies using d-cycloserine at a dose of 50 mg/day added to conventional antipsychotics in trials of 8 weeks duration or less. To assess the efficacy for negative symptoms and cognitive impairment of d-cycloserine augmentation of conventional antipsychotics in a 6-month trial. Fifty-five schizophrenia patients with prominent negative symptoms, treated with conventional antipsychotics, were randomly assigned to treatment with d-cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group design. Twenty-six subjects completed the 6-month trial; drop-out rates did not differ between treatment groups. d-Cycloserine treatment did not differ from placebo treatment on any primary outcome measure at 8 or 24 weeks, including response of negative symptoms and performance on a cognitive battery. Serum d-cycloserine concentrations did not correlate with response of negative symptoms. d-Cycloserine did not exhibit therapeutic effects in this trial, possibly reflecting the high drop-out rate, a narrow range of therapeutic serum concentrations, a modest magnitude of therapeutic effect for the selected outcome measures, or loss of efficacy over time. Because d-cycloserine is a partial agonist with relatively low affinity for the glycine site, the magnitude of potential therapeutic effect may be smaller than that achieved by the higher-affinity full agonists, glycine and d-serine.
Differential temporal activation of oxy- and deoxy-hemodynamic signals in optical imaging using functional near-infrared spectroscopy (fNIRS)

Optical imaging of the brain based on near-infrared spectroscopy (NIRS) can provide real-time measurements of the hemodynamic signals that represent metabolic demands of the underlying neural tissues. Functional imaging based on NIRS (fNIRS) can detect both oxyhemoglobin (oxy-Hb) and deoxy-hemoglobin (deoxy-Hb) levels related to neural metabolic activity, whereas BOLD fMRI (blood-oxygen-level dependent functional magnetic resonance imaging) can only detect signals related to deoxy-Hb. Thus, during task execution, only fNIRS can determine the differential temporal activation/deactivation of oxy-Hb and deoxy-Hb hemodynamic signals as the blood-oxygen demand changes. We have previously shown that as metabolic demand increases, temporal changes in oxy-Hb and deoxy-Hb levels can be temporally decoupled (i.e., oxy-Hb level can decrease while deoxy-Hb level increases) rather than being coupled, in which case both would increase or decrease simultaneously [1-5]. In order to account for the observed differential temporal decoupling of oxy-Hb and deoxy-Hb levels, we hypothesize that as oxygen demand increases, the delivery of blood oxygen cannot keep up with the demand of the neural tissues, resulting in decreased oxy-Hb and increased deoxy-Hb levels. This study provides experimental evidence that validates the above hypothesis.
Investigation of rheumatoid arthritis susceptibility genes identifies association of AFF3 and CD226 variants with response to anti-tumour necrosis factor treatment

Anti-tumour necrosis factor (anti-TNF) therapy has proved to be highly successful in treating rheumatoid arthritis (RA), although 30-40% of patients have little or no response. The authors hypothesise that this may be genetically determined. In other complex diseases, susceptibility genes have been shown to influence treatment response. The aim of the current study was to investigate the association of markers within confirmed RA susceptibility loci with the response to anti-TNF treatment.



Eighteen single nucleotide polymorphisms (SNPs) mapping to 11 genetic loci were genotyped in 1012 patients with RA receiving treatment with etanercept, infliximab or adalimumab. Multivariate linear regression analyses were performed using the absolute change in 28 joint count disease activity score (DAS28) between baseline and 6-month follow-up as the outcome variable, adjusting for confounders. p Values <0.05 were considered statistically significant and associated markers were genotyped in an additional 322 samples. Analysis was performed in the combined cohort of 1334 subjects with RA treated with anti-TNF.



In the combined analysis, SNPs mapping to AFF3 and CD226 had a statistically significant association with the response to anti-TNF treatment under an additive model. The G allele at rs10865035, mapping to AFF3, was associated with an improved response to anti-TNF treatment (coefficient -0.14 (95% CI -0.25 to -0.03), p=0.015). At the CD226 SNP rs763361, the C allele conferred reduced response to treatment (coefficient 0.11 (95% CI 0.00 to 0.22), p=0.048).



These results suggest that AFF3 and CD226, two confirmed RA susceptibility genes, have an additional role in influencing the response to anti-TNF treatment.
24-month follow-up of multiple sclerosis patients treated with cyclophosphamide

15 patients with remitting-progressive multiple sclerosis received a course of intravenous cyclophosphamide followed by a booster dose every 60 days for 2 years. There were no severe short or medium term side effects. Half of the patients presented clinical stabilization and substantially unchanged Kurtzke rating at 2 year follow-up. Since the aim was stabilization only, our findings argue for continuation of the study in young patients with very short shift. 15 pazienti affetti da sclerosi multipla remittente-progressiva, sono stati sottoposti a ciclo di CTX endovena con richiami ogni sessanta giorni. Non ci sono stati pesanti effetti collaterali a breve e medio termine. A due anni di follow-up il 50% dei pazienti ha mostrato una stabilizzazione della malattia. I dati orientano per una continuazione dello studio su pazienti con giovane età e passaggio dalla forma remittente a remittente-progressiva da breve tempo.
Continuing decrease in coronary heart disease mortality in Sweden

Deaths from coronary heart disease (CHD) have been decreasing in most Western countries over the last few decades. In contrast, a flattening of the decrease in mortality has been recently reported among younger age groups in some countries. We aimed to determine whether the decrease in CHD mortality is flattening among Swedish young adults.



We examined trends in CHD mortality in Sweden between 1987 and 2009 among persons aged 35 to 84 years using CHD mortality data from the Swedish National Register on Cause of Death. Annual percent changes in rates were examined using Joinpoint software.



Overall, CHD mortality rates decreased by 67.4% in men and 65.1% in women. Among men aged 35-54 years, there was a modest early attenuation from a marked initial decrease. In the oldest women aged 75-84 years, an attenuation in the mortality decrease was observed from 1989 to 1992, followed by a decrease, as in all other age groups.



In Sweden, coronary heart disease deaths are still falling. We were unable to confirm a flattening of the decline in young people. Death rates continue to decline in men and women across all age groups, albeit at a slower pace in younger men since 1991. Continued careful monitoring of CHD mortality trends in Sweden is required, particularly among young adults.
Clinical interest of bone texture analysis in osteoporosis: a case control multicenter study

We demonstrate the clinical interest of bone texture analysis with a new high resolution X-ray device. We have found that the combination of BMD and texture parameter values provided a better assessment of the fracture risk than that obtainable solely by BMD measurement. Osteoporosis is characterized by BMD and trabecular bone microarchitecture. We have developed a new high-resolution X-ray device with direct digitization. The aim of this study was to demonstrate in a multicenter case control study the clinical interest of bone texture analysis with this new device. In this cross-sectional multicenter case-control population study in post-menopausal women, 159 osteoporotic fractures were compared with 219 control cases. Images were obtained on calcaneus with a direct digital X-ray device (BMA™, D3A Medical Systems). Co-occurrence, run-length matrices and the fractal parameter Hmean were evaluated. BMD was measured at the lumbar spine (LS), femoral neck (FN) and total hip (TH) by DXA. The three texture parameters were significantly lower in osteoporotic fracture cases than in control cases. These differences persisted after adjustment for TH BMD. Receiver operating characteristic curves were used to compare the discriminant capacity of texture parameters and BMD measurements for fracture. The highest areas under curve (AUC) were 0.721 for TH BMD and 0.706 for Hmean (AUC THBMD vs. AUC Hmean, p = NS). We determined the threshold between high and low Hmean parameter values and then the odds ratios (OR) of fracture for low Hmean, for BMD ≤2.5 SD in the T-score and for combinations of both parameters. The OR of fracture for low H was 2.72 (95% CI, 1.36–5.4). For a FN BMD ≤ −2.5 SD, the OR of 4.78 (2.19–10.43) shifted to 14.06 (4.41–44.85) adding H. These data confirmed the clinical interest of the combination of BMD and texture parameters to improve the assessment of the risk of fracture other that obtainable by the sole BMD measurement.
Effects of activity modification on the patients with osteoarthritis of the knee.

A prospective randomized clinical trial was conducted on 162 patients of osteoarthritis of knee were included in the study. The patients were divided into two groups- Group A and Group B. The Group A was treated with shortwave diathermy, exercise, naproxen and activity modification and the Group B was treated with shortwave diathermy, exercise and naproxen. Improvement was found more in Group A than Group B after 4th week (95% CI was -2.59 to 6.56). Then it was found that the improvement was gradually increased in Group A than Group B and finally, it was found that there was highly significant improvement in Group A than Group B after 6th week (95% CI was -3.45 to -0.70). This study suggests that activity modification play an important role for the treatment of the patients with osteoarthritis of knee.
Fluticasone furoate/vilanterol 200/25 mcg in Asian asthma patients: a randomized trial.

This study investigated the efficacy and safety of the inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combination fluticasone furoate (FF)/vilanterol (VI) in Asian asthma patients.



A 12-week, double-blind, double-dummy, active-comparator, parallel-group, multicenter study. 309 Asian asthma patients (≥12 years, uncontrolled with high-strength ICS or mid-dose ICS/LABA) were randomized (1:1) and included in the intent-to-treat population; 155 received once-daily FF/VI 200/25 mcg and 154 received twice-daily fluticasone propionate (FP) 500 mcg. The primary endpoint was change from baseline in daily evening peak expiratory flow (PEF) averaged over 12 weeks. Secondary endpoints were mean change from baseline in % rescue-free 24-h periods, daily morning PEF, % symptom-free 24-h periods, and overall Asthma Quality of Life Questionnaire score. Safety assessments were performed.



For change from baseline in daily evening PEF, the adjusted mean treatment difference for FF/VI versus FP of 28.5 L/min (95% confidence interval [CI]: 20.1, 36.9) was clinically and statistically significant (p < 0.001). For change from baseline in % rescue-free 24-h periods, the adjusted mean treatment difference (1.0%; 95% CI: -7.3, 9.2) was not statistically significant (p = 0.821). Statistical significance could not be inferred for the remaining endpoints due to the statistical hierarchy employed. Incidence of on-treatment adverse events was similar with FF/VI (26%; 3% treatment-related; n = 1 serious) and FP (27%; 3% treatment-related; n = 2 serious); none were fatal. No further safety concerns were identified.



FF/VI improved evening PEF over 12 weeks versus FP in Asian patients, with a similar safety profile. The results are generally consistent with a global study comparing the same treatments.
The role of urine prostate cancer antigen 3 mRNA levels in the diagnosis of prostate cancer among Hong Kong Chinese patients.

To establish and verify the utility of measuring urine prostate cancer antigen 3 (PCA3) mRNA levels in the diagnosis of prostate cancer among Hong Kong Chinese patients.



Cross-sectional study.



Urology Unit of a regional hospital in Hong Kong.



This study was carried out in two parts. In the first part, 102 post-prostatic massage urine samples were collected from patients with known prostate cancer (38 patients) and controls (64 patients, with normal digital rectal examination and serum prostate-specific antigen <4 ng/mL). The urine levels of PCA3 and prostate-specific antigen mRNA were measured and the best cut-off point for differentiating cancer was determined. In the second part of the study, post-prostatic massage urine samples from 47 patients with clinically suspected prostate cancer were collected prior to prostate biopsy. The performance of PCA3 as a diagnostic aid for cancer was then assessed using the aforementioned cut-off value.



In the first part of the study, the best cut-off for the PCA3 ratio (defined as the ratio of the Ct value of PCA3/PSA mRNA) was 1.127. Applying this cut-off to the 47 patients with clinically suspected prostate cancer and no history of previous prostate biopsy, the sensitivity and specificity of PCA3 for diagnosing prostate cancer were 71% and 92%, respectively.



The post-prostatic massage urine PCA3 level shows utility for diagnosing prostate cancer in patients with elevated prostate-specific antigen levels that could facilitate decisions to undertake prostate biopsy and avoid unnecessary biopsies.
Measuring patient satisfaction with exercise therapy for knee osteoarthritis: evaluating the utility of the physiotherapy outpatient survey.

To assess patient satisfaction with exercise for knee osteoarthritis (OA).



A convenience sample of 27 patients recruited to a randomized controlled trial (RCT) comparing open kinetic chain and closed kinetic chain exercises for knee OA were reassessed at nine months post-randomization. Clinical outcomes included self-report and physical performance measures of function and pain severity. Patients also completed the Physiotherapy Outpatient Survey (POPS), which is a multi-dimensional measure of patient satisfaction with physiotherapy.



There was no significant difference in satisfaction between the two intervention groups. Overall mean satisfaction for the entire cohort was 4.07 of a maximum score of 5 (standard deviation (SD) = 0.52). Lower levels of satisfaction with outcome (mean = 3.56, SD = 0.8) were reported compared with other domains of expectations, communication, organization and the therapist (mean = 3.79-4.49; SDs = 0.42-0.92). Both intervention groups improved from baseline on clinical outcomes of pain, self-report function and walking distance, with no significant differences between the two groups.



High levels of satisfaction were reported in this subsample of knee OA patients participating in an RCT evaluating the effects of different exercise approaches for knee OA. Satisfaction varied depending on the satisfaction domain, with lower satisfaction with outcome compared with other aspects of care. The POPS questionnaire can be used to measure the multi-dimensional aspects of satisfaction with physiotherapy.
Severe adverse events during second-line tuberculosis treatment in the context of high HIV Co-infection in South Africa: a retrospective cohort study

According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa.



We reviewed medical records of the six-month intensive treatment phase for rifampicin-resistant (RR) TB patients registered May 2012 - December 2014. Patients contributed follow-up time until death, loss from treatment, censoring (6 months) or data extraction. A standardized regimen of kanamycin, moxifloxacin, ethionamide, terizidone, and pyrazinamide was used according to national guidelines. AEs were graded using the AIDS Clinical Trial Group scale. We present subhazard ratios from competing risk analysis for time to severe AE, accounting for mortality and loss from treatment.



Across the two sites, 578 eligible patient files were reviewed. 36.7 % were categorized as low weight (≤50 kg) at DR-TB initiation. 76.0 % had no history of TB treatment prior to the current episode of RR TB. 26.8 % were diagnosed with RR TB while hospitalized, indicating poor clinical condition. 82.5 % of patients were also HIV positive, of whom 43.8 % were on ART prior to RR TB treatment and 32.1 % initiated ART with or after RR TB treatment. Median CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs were captured for 204 patients (35.3 %) and 110 patients (19.0 %) had at least one severe AE reported. Patients with at least one AE experienced a median of 3 (IQR: 2-4) AEs per patient. HIV-positive patients with CD4 counts ≤100 cells/mm3 and those newly initiating ART were more likely to experience a severe AE (sHR: 2.76, 95 % CI: 1.30-5.84 and sHR: 3.07, 95 % CI: 1.46-6.46, respectively).



Severe AE are common during the first 6 months of RR TB treatment and HIV-positive patients newly initiating ART have the highest subdistribution hazard ratio for severe AE, accounting for the competing risks of death and loss from treatment.
MDCT angiography for detection of pulmonary emboli: comparison between equi-iodine doses of iomeprol 400 mgI/mL and iodixanol 320 mgI/mL.

To compare iomeprol 400 and iodixanol 320 in pulmonary artery MDCTA in subjects with suspected pulmonary embolism.



Eighty randomized subjects received equi-iodine intravenous doses (48 g) of iomeprol 400 (n=40) or iodixanol 320 (n=40), via power injector at 4 mL/s. Four-row (35 subjects) and 64-row (45 subjects) scanners were used. Lumen attenuation was determined on-site and by two off-site blinded readers in the main, lobar, segmental and subsegmental pulmonary arteries. Statistical comparison between groups was performed for demographics and lumen attenuation.



There were no between-group differences (p>0.05) in demographics. Pulmonary artery attenuation was significantly (p<or=0.03) higher with iomeprol 400 for all readers. Attenuation quality was excellent in more patients after iomeprol 400 than after iodixanol-320 (80% vs. 62.5%; 82.5% vs. 77.5%; off-site readers 1 and 2, respectively). No safety concerns were noted.



The greater iodine delivery rate achievable with iomeprol 400 compared to iodixanol-320 at equi-iodine dose and injection rate permits consistently greater attenuation at all levels of the pulmonary arterial tree.
Fas Ligand mRNA Levels of Circulating Leukocytes Reflect Endothelial Dysfunction in Hyperlipidemic but Not in Non-Hyperlipidemic Patients

To find a novel marker for identifying patients at high-risk for endothelial dysfunction among patients with atherosclerosis, we examined the correlation between mRNA levels of Fas ligand (FasL), an apoptosis-inducing factor, in circulating leukocytes and clinical parameters in these patients. FasL mRNA levels of circulating leukocytes were measured with the TaqMan-PCR method. A negative correlation was observed between brachial artery flow-mediated dilatation (%FMD) and FasL mRNA levels of leukocytes in hyperlipidemic but not in non-hyperlipidemic patients. %FMD was more impaired in patients with a high level of FasL mRNA than in those with a low level of FasL mRNA. Interestingly, the improvement of %FMD by treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (simvastatin) was greater in the group showing a decrease in FasL mRNA than in the group with no such decrease. Additionally, simvastatin suppressed the FasL mRNA expression in leukocytes and decreased plasma oxidized low-density lipoprotein (OxLDL) levels. Furthermore, the supernatant of cultured leukocytes from hyperlipidemic patients induced cell death in Jurkat T cells, which was neutralized by an antibody against FasL. These findings suggest that high FasL mRNA expression in circulating leukocytes may be a marker of high-risk for endothelial dysfunction in hyperlipidemic but not in non-hyperlipidemic patients. This information may provide a novel basis for targeting of statin therapy in patients with vulnerable plaques.
Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer.

MicroRNA (miRNA) opens up a new field for molecular diagnosis of cancer. However, the role of circulating miRNAs in plasma/serum in cancer diagnosis is not clear. The aim of this study was to investigate whether plasma miRNAs can be used as biomarkers for the early detection of colorectal carcinoma (CRC). We measured the levels of 12 miRNAs (miR-134, -146a, -17-3p, -181d, -191, -221, -222, -223, -25, -29a, -320a and -92a) in plasma samples from patients with advanced colorectal neoplasia (carcinomas and advanced adenomas) and healthy controls using real-time RT-PCR. We found that plasma miR-29a and miR-92a have significant diagnostic value for advanced neoplasia. MiR-29a yielded an AUC (the areas under the ROC curve) of 0.844 and miR-92a yielded an AUC of 0.838 in discriminating CRC from controls. More importantly, these 2 miRNAs also could discriminate advanced adenomas from controls and yielded an AUC of 0.769 for miR-29a and 0.749 for miR-92a. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.883 with 83.0% sensitivity and 84.7% specificity in discriminating CRC, and AUC of 0.773 with 73.0% sensitivity and 79.7% specificity in discriminating advanced adenomas. Collectively, these data suggest that plasma miR-29a and miR-92a have strong potential as novel noninvasive biomarkers for early detection of CRC.