nils-herrmann/clean_scirepeval huggingface dataset:
T-cell enumeration from dried blood spots by quantifying rearranged T-cell receptor-beta genes.

Significant hurdles remain to large-scale implementation of medical interventions in the developing world due to the lack of a modern diagnostic infrastructure. This is especially pertinent to the international roll-out of antiretroviral drugs to treat HIV, which ideally includes a CD4 T-cell count to determine eligibility. We designed a novel technique to estimate mature T-cell numbers by calculating the amount of rearranged T-cell receptor beta genes from dried blood spots of HIV-infected individuals in the United States and Uganda. It was observed that the rearranged T-cell receptor beta count correlated well with total lymphocyte counts from both study populations (Baltimore R=0.602, Uganda R=0.497; p<0.001) and the ability for this measurement to determine antiretroviral initiation was similar to total lymphocyte counts, which can be used to determine eligibility in HIV+children. This technique as well as other dried blood spot based technologies could increase the diagnostic and monitoring capabilities in resource-limited settings.
Multidisciplinary rehabilitation treatment of patients with chronic low back pain: a prognostic model for its outcome.

(1) To determine if treatment outcome in chronic low back pain can be predicted by a predefined multivariate prognostic model based on consistent predictors from the literature and (2) to explore the value of potentially prognostic factors further.



Data were derived from a randomized controlled trial on the effect of a multidisciplinary rehabilitation program for chronic low back pain compared with usual care. The primary outcome measure was the Roland and Morris Disability Questionnaire and secondary outcomes were the Physical and Mental Component Summary Scales, derived from the Short Form Health Survey. Outcomes were expressed as the differences between baseline and follow-up (8 wk and 6 mo) values. A confirmatory and an exploratory model were defined. Baseline predictors included in the confirmatory model were pain intensity, work status, and Multidimensional Pain Inventory subgroup membership. The exploratory model included sick leave, compensation, depression, and fear-avoidance beliefs. Statistical analysis was performed using multiple linear regression analysis.



One hundred and sixty-three patients participated in the study. More pain was prognostic for more improvement in the rehabilitation group. No value was found for work status or the Multidimensional Pain Inventory subgroups. For the exploratory model, more depression and fear-avoidance beliefs predicted more improvement after rehabilitation. The explained variance ranged from 18.5% to 43.8% depending on the length of follow-up evaluation, the treatment group, and the outcome variable of interest.



The results of this study do not support the construction of a clinical prediction model. Future confirmative studies of homogeneous rehabilitation treatments and outcome measures are needed to shed more light on relevant prognostic factors.
Assessment of sexual function in patients with cancer undergoing radiotherapy--a single centre prospective study.

The main objective was to delineate the rates and clinical course of sexual function and depression in cancer patients undergoing radiotherapy.



Forty-eight male and 90 female radiotherapy-naive outpatients with breast or pelvic cancer completed the International Index of Erectile Function (IIEF) or the Female Sexual Function Index (FSFI), and the Hamilton Depression Scale (HDS) prior to (phase 1), at the end of (phase 2) and 12 months after radiotherapy (phase 3).



Overall, the majority of patients (93.8% of males and 80% of females) experienced intense sexual dysfunction. At presentation, males reported severe erectile dysfunction that was significantly associated with age. However, only in sexual desire was the difference between baseline and phase 3 significant. In females, an improvement was observed in all parameters of FSFI between phase 1 and 3. Females with stage III disease achieved lower scores in almost all parameters of FSFI than those with stage II. Finally, although a quarter of patients reported elevated depression scores, depression was not related to sexual function.



A significant proportion of cancer patients experience intense levels of sexual dysfunction and depression throughout radiotherapy and the subsequent year. Pelvic radiotherapy affected sexual function to a higher degree than did breast radiotherapy.
Multicenter clinical assessment of the Raumedic Neurovent-P intracranial pressure sensor: a report by the BrainIT group.

The aim of this study was to evaluate the robustness and zero-drift of an intracranial pressure sensor, Neurovent-P (Raumedic AG, Münchberg, Germany), when used in the clinical environment.



A prospective multicenter trial, conforming to the International Organization for Standardization 14155 Standard, was conducted in 6 European BrainIT centers between July 2005 and December 2006. Ninety-nine catheters were used. The study was observational, followed by a centralized sensor bench test after catheter removal.



The mean recorded value before probe insertion was 0.17 +/- 1.1 mm Hg. Readings outside the range +/-1 mm Hg were recorded in only 3 centers on a total of 15 catheters. Complications were minimal and mainly related to the insertion bolt. The mean recorded pressure value at removal was 0.8 +/- 2.2 mm Hg. No relationship was identified between postremoval reading and length of monitoring. The postremoval bench test indicated the probability of a system failure, defined as a drift of more than 3 mm Hg, at a range between 12 and 17%.



The Neurovent-P catheter performed well in clinical use in terms of robustness. The majority of technical complications were associated with the bolt fixation technology. Adverse events were rare and clinically nonsignificant. Despite the earlier reported excellent bench test zero-drift rates, under the more demanding clinical conditions, zero-drift rate remains a concern with catheter tip strain gauge technology. This performance is similar, and not superior, to other intracranial pressure devices.
Safety and efficacy of NAD depleting cancer drugs: results of a phase I clinical trial of CHS 828 and overview of published data

Depletion of cellular nicotinamide adenine dinucleotide (NAD) by inhibition of its synthesis is a new pharmacological principle for cancer treatment currently in early phases of clinical development. We present new and previously published data on the safety and efficacy of these drugs based on early clinical trials. A phase I clinical trial of CHS 828 in patients with advanced solid tumours was performed. Published clinical trials on NAD depleting drugs for cancer treatment were summarised for safety and efficacy. Seven patients with previously treated solid tumours received oral administration of CHS 828 in the dose range 20–80 mg once weekly for 3 weeks in 4 weeks cycles. Toxicity was dominated by gastrointestinal symptoms including nausea, vomiting, diarrhoea, constipation, subileus and gastric ulcer. One patient had thrombocytopenia grade 2. There were two cases each of grade 3–4 hyperuricemia and hypokalemia. Safety and efficacy of the NAD depleting drugs CHS 828 and FK866 have been reported from four phase I clinical trials, including a total of 97 patients with previously treated solid tumours. Outstanding toxicity reported was thrombocytopenia and various gastrointestinal symptoms. No objective tumour remission has been observed in the total of 104 patients treated in the above early trials. Critical toxicity from NAD depleting cancer drugs to consider in future trials seems to be thrombocytopenia and various gastrointestinal symptoms. Efficacy of NAD depleting drugs when used alone is expected to be low.
Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384.

Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized.



Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4(+), CD4(+) naive and memory, CD4(+) activation, CD8(+), CD8(+) activation, B, and natural killer cells among patients in different baseline CD4(+) strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113.



Patients in the lower baseline CD4(+) strata did not achieve total CD4(+) cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4(+) cell count increases were similar. Ratios of CD4(+) naive-memory cell counts and CD4(+):CD8(+) cell counts remained significantly reduced in patients with lower baseline CD4(+) cell counts (<or=350 cells/mm(3)). These immune imbalances were most notable for those initiating ART with a baseline CD4(+) cell count <or=200 cells/mm(3), even after adjustment for baseline plasma HIV RNA levels.



After nearly 3 years of ART, T cell subsets in patients with baseline CD4(+) cell counts >350 cells/mm(3) achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with <or=350 CD4(+) cells/mm(3) generally did not regain normal CD4(+) naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm(3) and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4(+) cell counts.
Changes in metabolic toxicity after switching from stavudine/didanosine to tenofovir/lamivudine--a Staccato trial substudy.

Stavudine is widely used in Thailand and is associated with mitochondrial toxicity. Here, we evaluated the effect of switching from stavudine/didanosine to tenofovir/lamivudine on measures of metabolic and mitochondrial toxicity in Thai patients.



Thirty-five Thai patients with full HIV RNA suppression were switched from stavudine/didanosine to tenofovir/lamivudine while receiving saquinavir/ritonavir 1600/100 mg once daily. Patients were assessed at the time of switch and 24 and 48 weeks after for lipids, liver enzymes, lactate, mitochondrial DNA content and limb/total fat mass by dual energy X-ray absorptiometry (DEXA) scanning.



Forty-eight weeks after the switch, there were significant reductions in lipids and lactate, but no change in liver enzymes. There was reversal of lipoatrophy, as shown by rises in limb fat mass (+0.38 kg, P = 0.006) and total fat mass (+0.69 kg, P = 0.02) on DEXA scan. Patients perceived weight improvement, but did not report reversal of lipoatrophy of individual body parts. The mitochondrial DNA/nuclear DNA ratio rose (+1.06, P < 0.0001).



After the nucleoside reverse transcriptase inhibitor switch, reversal of mitochondrial toxicity was consistent with switch studies of mainly Caucasian patients, although the peripheral mononuclear cell mitochondrial DNA rise exceeded previous reports.
Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system?

To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1).  In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smoking, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted.



IGF-1 declined significantly by almost 25% among men aged >75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of -1.6 (- 2.2 to -0.9)% for an increment of one drink per day. There was no evidence for an effect of either smoking or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of -31.5 (- 49.1 to -7.9)% for an increment of one serving per day.



The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system.
Muscle atrophy and changes in spinal morphology: is the lumbar spine vulnerable after prolonged bed-rest?

prospective longitudinal study.



to evaluate the effect of bed-rest on the lumbar musculature and soft-tissues.



earlier work has suggested that the risk of low back injury is higher after overnight bed-rest or spaceflight. Changes in spinal morphology and atrophy in musculature important in stabilizing the spine could be responsible for this, but there are limited data on how the lumbar musculature and vertebral structures are affected during bed-rest.



nine male subjects underwent 60-days head-down tilt bed-rest as part of the second Berlin Bed-Rest Study. Disc volume, intervertebral spinal length, intervertebral lordosis angle, and disc height were measured on sagittal plane magnetic resonance images. Axial magnetic resonance images were used to measure cross-sectional areas (CSAs) of the multifidus (MF), erector spinae, quadratus lumborum, and psoas from L1 to L5. Subjects completed low back pain (LBP) questionnaires for the first 7-days after bed-rest.



increases in disc volume, spinal length (greatest at lower lumbar spine), loss of the lower lumbar lordosis, and move to a more lordotic position at the upper lumbar spine (P < 0.0097) were seen. The CSAs of all muscles changed (P < 0.002), with the rate of atrophy greatest at L4 and L5 in MF (P < 0.002) and at L1 and L2 in the erector spinae (P = 0.0006). Atrophy of the quadratus lumborum was consistent throughout the muscle (P = 0.15), but CSA of psoas muscle increased (P < 0.0001). Subjects who reported LBP after bed-rest showed, before reambulation, greater increases in posterior disc height, and greater losses of MF CSA at L4 and L5 than subjects who did not report pain (all P < 0.085).



these results provide evidence that changes in the lumbar discs during bed-rest and selective atrophy of the MF muscle may be important factors in the occurrence of LBP after prolonged bed-rest.
Antibiotic Prophylaxis Using Third Generation Cephalosporins Can Reduce the Risk of Early Rebleeding in the First Acute Gastroesophageal Variceal Hemorrhage: A Prospective Randomized Study

Bacterial infection may be a critical trigger for variceal bleeding. Antibiotic prophylaxis can prevent rebleeding in patients with acute gastroesophageal variceal bleeding (GEVB). The aim of the study was to compare prophylactic third generation cephalosporins with on-demand antibiotics for the prevention of gastroesophageal variceal rebleeding. In a prospective trial, patients with the first acute GEVB were randomly assigned to receive prophylactic antibiotics (intravenous cefotaxime 2 g q 8 hr for 7 days, prophylactic antibiotics group) or to receive the same antibiotics only when infection became evident (on-demand group). Sixty-two patients in the prophylactic group and 58 patients in the on-demand group were included for analysis. Antibiotic prophylaxis decreased infection (3.2% vs. 15.5%, p=0.026). The actuarial rebleeding rate in the prophylactic group was significantly lower than that in the on-demand group (33.9% vs. 62.1%, p=0.004). The difference of rebleeding rate was mostly due to early rebleeding within 6 weeks (4.8% vs. 20.7%, p=0.012). On multivariate analysis, antibiotic prophylaxis (relative hazard: 0.248, 95% confidence interval (CI): 0.067-0.919, p=0.037) and bacterial infection (relative hazard: 3.901, 95% CI: 1.053-14.448, p=0.042) were two independent determinants of early rebleeding. In conclusion, antibiotic prophylaxis using third generation cephalosporins can prevent bacterial infection and early rebleeding in patients with the first acute GEVB.
Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study

The objective of this clinical study was to assess the potential benefit of a dietary supplement, NP 06-1, on joint health in overweight and normal weight adults diagnosed with osteoarthritis.



An 8-week placebo-controlled, randomized, double-blind study was conducted with four groups comparing the effects of NP 06-1 to placebo on overweight and normal weight subjects diagnosed with primary osteoarthritis of the knee. NP 06-1 (a combination of two botanical extracts; Phellodendron amurense bark and Citrus sinensis peel) or matching placebo were given in a dose of two capsules (370 mg each) twice daily. The outcome measures were the Lequesne Algofunctional Index (LAI) for joint pain and movement as well as biomarkers of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]).



Eighty (80) subjects were enrolled and 45 subjects completed the study. No serious adverse events were reported. The mean total LAI scores at baseline for the four groups ranged from 11.4 to 12.4 (SD 1.2 to 2.4). Treatment for 8 weeks resulted in a statistical improvement in the LAI score in the overweight treatment group compared to placebo (6.3 +/- 2.3 vs 11.8 +/- 1.5; p < 0.0001). At 8 weeks, a similar result was observed in the normal weight groups (7.7 +/- 1.4 vs 9.9 +/- 0.9; p < 0.0001). There was a reduction in CRP levels with treatment in the overweight treatment group at 8 weeks (-0.62 +/- 0.2; 49%) compared to baseline (p < 0.001) and to placebo (p < 0.001). For the normal weight participants, there were significant reductions in CRP compared to baseline, but not to the matched placebo group. Both overweight and normal weight treatment groups lost a significant amount of weight compared to their placebo groups. The overweight treatment group lost an average of 5% body weight after 8 weeks. There was no significant change in ESR in any of the groups.



In this pilot study, NP 06-1 had beneficial effects on symptoms of osteoarthritis of the knee as measured using LAI scores and had anti-inflammatory effects as measured using CRP. Administration of NP 06-1 was also associated with weight loss, which may have been a contributing factor to the other benefits.
Analytical validation of the Oncotype DX prostate cancer assay – a clinical RT-PCR assay optimized for prostate needle biopsies

The Oncotype DX® Prostate Cancer Assay is a multi-gene RT-PCR expression assay that was developed for use with fixed paraffin-embedded (FPE) diagnostic prostate needle biopsies containing as little as 1 mm of prostate tumor in the greatest dimension. The assay measures expression of 12 cancer-related genes representing four biological pathways and 5 reference genes which are algorithmically combined to calculate the Genomic Prostate Score (GPS). This biopsy-based assay has been analytically and subsequently clinically validated as a predictor of aggressive prostate cancer. The aim of this study was to validate the analytical performance of the Oncotype DX Prostate Cancer Assay using predefined acceptance criteria. The lowest quartile of RNA yields from prostate needle biopsies (six 5 μm sections) was between 19 and 34 ng. Analytical validation of the process requiring as little as 5 ng of RNA met all pre-defined acceptance criteria. Amplification efficiencies, analytical sensitivity, and accuracy of gene assays were measured by serially diluting an RNA sample and analyzing features of the linear regression between RNA expression measured by the crossing point (Cp) versus the log2 of the RNA input per PCR assay well. Gene assays were shown to accurately measure expression over a wide range of inputs (from as low as 0.005 ng to 320 ng). Analytical accuracy was excellent with average biases at qPCR inputs representative of patient samples <9.7% across all assays while amplification efficiencies were within ±6% of the median. Assessments of reproducibility and precision were performed by testing 10 prostate cancer RNA samples over multiple instruments, reagent lots, operators, days (precision), and RNA input levels (reproducibility) using appropriately parameterized linear mixed models. The standard deviations for analytical precision and reproducibility were 1.86 and 2.11 GPS units (100-unit scale) respectively. The Oncotype DX Prostate Cancer Assay, a clinical RT-PCR assay specifically designed for use with prostate needle biopsies, has been analytically validated using very limited RNA inputs. The assay requirements and analytical performance will provide physicians with test results from a robust and reliable assay which will enable improved treatment decisions for men diagnosed with early-stage prostate cancer.
Circadian variation in patient characteristics and outcomes in ST-segment elevation myocardial infarction.

A morning peak in ST-segment elevation myocardial infarction (STEMI) has been described. The authors explored the relationship between variation of symptom onset, patient characteristics, and outcomes in two worldwide fibrinolytic trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by time of symptom onset: early (06:00 to 13:59 h), late-day (14:00 to 21:59 h), overnight (22:00 to 05:59 h). The authors correlated timing with patient characteristics and outcomes (adjusted for thrombolysis in myocardial infarction [TIMI] risk score) first in InTIME II-TIMI 17 trial (N = 15 031), and confirmed in the ExTRACT-TIMI 25 trial (N = 20 461). Timing was similar in the derivation (early 49%, late-day 30%, and overnight 21%; p < .001) and validation set (48%, 31%, and 21%, respectively; p < .001). Some patient characteristics consistently varied with time of symptom onset. Patients in the early cohort were older with poorer renal function. The late-day group had more smokers with higher initial heart rate and systolic blood pressure. Those with overnight symptom onset had higher rates of obesity, prior myocardial infarction, and treatment delays. Prior use of aspirin and beta-blockers was also highest in the overnight group. Relative to the early cohort, adjusted mortality was higher with late-day onset (derivation odds ratio [OR]: 1.19, p = .04; validation OR: 1.18, p = .01), but there was no excess in mortality overnight compared with early (derivation OR: .97, p = .72; validation OR: 1.01, p = .90). Composite endpoints followed similar patterns. This study indicates that circadian patterns in onset of STEMI continue to exist with patient characteristics differing by time of day. Despite a potential physiologic resistance to morning thrombolysis, outcomes were best in the early cohort, intermediate overnight, and worst with late-day symptom onset. Efforts to reduce smoking and improve control of blood pressure could reduce the number of patients with late-day onset of STEMI who experience the worst outcomes.