nils-herrmann/clean_scirepeval huggingface dataset:
Attitudes of People in the UK with HIV Who Are Antiretroviral (ART) Naïve to Starting ART at High CD4 Counts for Potential Health Benefit or to Prevent HIV Transmission

To assess if a strategy of early ART to prevent HIV transmission is acceptable to ART naïve people with HIV with high CD4 counts.



ASTRA is a UK multicentre, cross sectional study of 3258 HIV outpatients in 2011/12. A self-completed questionnaire collected sociodemographic, behavioral and health data, and attitudes to ART; CD4 count was recorded from clinical records.



ART naïve participants with CD4 ≥350 cells/µL (n = 281) were asked to agree/disagree/undecided with the statements (i) I would want to start treatment now if this would slightly reduce my risk of getting a serious illness, and (ii) I would want to start treatment now if this would make me less infectious to a sexual partner, even if there was no benefit to my own health.



Participants were 85% MSM, 76% white, 11% women. Of 281 participants, 49.5% and 45.2% agreed they would start ART for reasons (i) and (ii) respectively; 62.6% agreed with either (i) or (ii); 12.5% agreed with neither; 24.9% were uncertain. Factors independently associated (p<0.1) with agreement to (i) were: lower CD4, more recent HIV diagnosis, physical symptoms, not being depressed, greater financial hardship, and with agreement to (ii) were: being heterosexual, more recent HIV diagnosis, being sexually active.



A strategy of starting ART at high CD4 counts is likely to be acceptable to the majority of HIV-diagnosed individuals. Almost half with CD4 >350 would start ART to reduce infectiousness, even if treatment did not benefit their own health. However a significant minority would not like to start ART either for modest health benefit or to reduce infectivity. Any change in approach to ART initiation must take account of individual preferences. Transmission models of potential benefit of early ART should consider that ART uptake may be lower than that seen with low CD4 counts.
Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study.

Several laboratory and epidemiological studies have inversely linked endogenous vitamin D and the risk of breast cancer. The acquisition of vitamin D over time on the relative risk (RR) of the disease development is not known. In a longitudinal study, we evaluated the association between vitamin D levels at pregnancy over time with the risk of breast cancer, and pregnancy-associated breast cancer.



The risk for subsequent development of breast cancer associated with serum 25-hydroxyvitamin (25-OHD) levels was assessed for consecutive (1st and 2nd pregnancy) samples of 100 cases, with mean lag times (micro(t)) of 7.4 and 4.6 years between sampling and the diagnosis, and matched (parity, age, year, season) controls. Pregnancy-associated breast cancer (PABC, 111 case-control pairs, micro(t)=1 year) risk was also studied. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the lowest quintile as the reference.



Serum 25-OHD level was not associated with an increased risk neither at the 1st nor at the 2nd pregnancy samples (OR=1.4, 95%CI 0.6-3.4; OR 1.4, 95%CI 0.7-2.8, respectively), but was associated with an increased risk of PABC (OR=2.7, 95%CI 1.04-6.7).



Generally, vitamin D may not be related to breast cancer risk but the increased PABC risk fits the association of vitamin D with the most aggressive cancers, and warrants caution with vitamin D supplementation during pregnancy.
Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study.

Elotuzumab, an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system, and thus might have clinical benefit in the treatment of myeloma. In phase 1 of this phase 1b-2 study, 82% of patients with relapsed multiple myeloma who were given elotuzumab plus lenalidomide and dexamethasone achieved an overall response. Here we report the final phase 2 results.



We did this randomised, multicentre, open-label, dose-escalation study (1703) at 17 hospitals in the USA, Canada, France, and Germany. Patients aged at least 18 years with confirmed, relapsed multiple myeloma, Eastern Cooperative Oncology Group performance status 0-2, and one to three previous therapies but no previous lenalidomide were eligible for phase 2. We randomly assigned patients (1:1) to either 10 mg/kg or 20 mg/kg intravenous elotuzumab plus oral lenalidomide (25 mg) and dexamethasone (40 mg). We stratified patients on the basis of the number of previous therapies (one versus two or three), and status of previous treatment with immunomodulatory drugs (yes or no), and used permuted block randomisation with a block size of four. Treatment was given in 28-day cycles until disease progression or unacceptable toxic effects occurred (elotuzumab was given on days 1, 8, 15, and 22 for cycles 1 to 2 and days 1 and 15 for subsequent cycles; lenalidomide was given on days 1-21 and dexamethasone once per week). The primary endpoint was the proportion of patients who achieved an objective response according to International Myeloma Working Group criteria. Primary analyses were done in the intention-to-treat population, and safety was analysed in all patients who received at least one dose of study drugs. 
Between Jan 4, 2010, and Dec 21, 2010, we recruited and randomly assigned 73 patients to elotuzumab (36 to 10 mg/kg, 37 to 20 mg/kg). At data cutoff (Jan 16, 2014), 13 patients remained on treatment (six on 10 mg/kg, seven on 20 mg/kg). 61 (84%) patients achieved an objective response (33 [92%] with 10 mg/kg, 28 [76%] with 20 mg/kg); 31 (42%) a very good partial response (17 [47%] with 10 mg/kg, 14 [38%] with 20 mg/kg); and 20 (27%) a partial response (10 [28%] with 10 mg/kg, 10 [27%] with 20 mg/kg). The most common treatment-emergent adverse events of any grade were diarrhoea (48 [66%]), muscle spasms (45 [62%]), and fatigue (41 [56%]). 57 (78%) patients had grade 3-4 events, the most common of which were lymphopenia (15 [21%]) and neutropenia (14 [19%]). Three deaths occurred, none related to the study drugs.



Elotuzumab combined with lenalidomide and dexamethasone in patients with relapsed multiple myeloma showed acceptable safety and efficacy that seems better than that previously noted with lenalidomide and dexamethasone only. Phase 3 trials are in progress.



Bristol-Myers Squibb, AbbVie Biotherapeutics.
Liquid Fermentation of Ganoderma applanatum and Antioxidant Activity of Exopolysaccharides

The medium composition and fermentation conditions of Ganoderma applanatum(GA) strain were optimized by the liquid shake flask fermentation, and the antioxidant activity of exopolysaccharides was investigated. The results showed that the optimal conditions of the liquid fermentation of GA strain were as follows: Carbon source was corn powder, nitrogen source was soy powder, the initial pH was 6.0, the inoculum size was 8％, the fermentation temperature was 32(o)C, the fermentation time was 7 d. The exopolysaccharides of GA strain could scavenge hydroxyl radicals(HR) and superoxide anion radicals(SAR), and the concentration of exopolysaccharides was positively related to the antioxidant activity.
N-terminal Pro-B-type natriuretic peptide and its correlation to haemodialysis-induced myocardial stunning.

Haemodialysis (HD) is able to induce recurrent myocardial ischemia and segmental left-ventricular dysfunction (myocardial stunning). The association of N-terminal Pro-B-type natriuretic peptide (NTpro-BNP) with HD-induced myocardial stunning is unclear.



In 70 prevalent HD patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. The extent to which pre-dialysis NTpro-BNP was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint.



The median Ntpro-BNP concentration in this cohort was 2,154 pg/ml (IQR 1,224-3,014). Patients experiencing HD-induced myocardial stunning at either time point displayed elevated NTpro-BNP values (2,418 pg/ml, IQR, 1,583-3,474 vs. 1,751 pg/ml, IQR (536-2,029), p = 0.02). NTpro-BNP levels did not differ between patients showing HD-induced stunning at baseline and those developing stunning during the observational period (p = 0.8). NTpro-BNP levels drawn at the beginning of the dialysis session achieved a poor diagnostic accuracy for the detection of myocardial stunning (area under the ROC curve 0.61, 95% CI 0.45-0.77), but provided an accurate rule out for myocardial stunning during the subsequent year (AUC 0.85, 95% CI 0.70-0.99). The calculated cut-off of 1,570 pg/ml achieved a sensitivity of 66% and a specificity of 78% for the exclusion of myocardial stunning at any time point. In logistic regression analysis, only low NTpro-BNP levels (OR 0.92 for every additional 100 pg/ml, 95% CI 0.85-0.99, p = 0.03) were significantly associated with absence of myocardial stunning at any time point.



Predialytic NTpro-BNP levels fail to adequately diagnose current dialysis-induced myocardial stunning, but help to identify patients with a propensity to develop dialysis-induced myocardial stunning at any time during the next 12 months.
Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes.

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)). The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold.
Adrenal suppression with inhaled budesonide and fluticasone propionate given by large volume spacer to asthmatic children.

The aim of this study was to compare the systemic bioactivity of inhaled budesonide (B) and fluticasone propionate (F), each given by large volume spacer, on a microgram equivalent basis in asthmatic children.



Ten stable asthmatic children of mean age 11 years and forced expiratory volume in one second (FEV1) 81.6% predicted, who were receiving treatment with < or = 400 micrograms/day of inhaled corticosteroid, were studied in a placebo controlled single blind (investigator blind) randomised crossover design comparing single doses of inhaled budesonide and fluticasone propionate 400 micrograms, 800 micrograms, and 1250 micrograms. Doses were given at 20.00 hours with mouth rinsing and an overnight 12 hour urine sample was collected for estimation of free cortisol and creatinine excretion.



The results of overnight 12 hour urinary cortisol output (nmol/12 hours) showed suppression with all doses of fluticasone propionate (as geometric means): F400 micrograms (11.99), F800 micrograms (6.49), F1250 micrograms (7.00) compared with placebo (24.43), whereas budesonide caused no suppression at any dose. A comparison of the drugs showed that there were differences at 800 micrograms and 1250 micrograms levels for urinary cortisol: B800 micrograms versus F800 micrograms (2.65-fold, 95% CI 1.26 to 5.58), B1250 micrograms versus F1250 micrograms (2.94-fold, 95% CI 1.67 to 5.15). The results for the cortisol/creatinine ratio were similar to that of urinary cortisol, with fluticasone causing suppression at all doses and with differences between the drugs at 800 micrograms and 1250 micrograms.



Single doses of inhaled fluticasone produce greater systemic bioactivity than budesonide when given by large volume spacer on a microgram equivalent basis in asthmatic children. The systemic bioactivity of fluticasone, like budesonide, is due mainly to lung bioavailability.
Assessment of the perioperative hemodynamics and right ventricular performance of lung cancer patients using a continuous cardiac output monitoring system: comparison between video-assisted thoracic surgery and muscle-sparing thoracotomy.

This prospective study was conducted to assess the influences of hemodynamics and right ventricular (RV) performance after lobectomy by video-assisted thoracic surgery (VATS) and that by muscle-sparing thoracotomy (MST) using a continuous cardiac output (CCO) monitoring system.



Between October 2002 and April 2004, 16 patients (VATS, 8; MST, 8) who underwent lobectomy with mediastinal lymphadenectomy were enrolled in this study. Changes in hemodynamics and RV performance were evaluated preoperatively and for 36 hours postoperatively.



There were significant differences in operative blood loss (BL) and postoperative maxCPK/m(2) between VATS and MST groups. Postoperative values were expressed as a percentage of the preoperative values. For 36 hours perioperatively, the mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP) and total pulmonary resistance index (TPRI) decreased to greater extents in the VATS group than in the MST group. There were no significant differences between the two groups in RV performance including the continuous cardiac index (CCI), RV ejection fraction (RVEF), RV end-diastolic volume index (RVEDVI) and RV stroke index (SI) postoperatively.



Considering our previous report about postoperative RV performance using the VATS procedure and posterolateral thoracotomy procedure, this study suggests that pulmonary resection using either VATS or MST could be employed as minimally invasive surgery.
Levetiracetam in children with refractory epilepsy: Lack of correlation between plasma concentration and efficacy

The goals of this study are to evaluate the efficacy and tolerability of levetiracetam (LEV) as add-on therapy in children with refractory epilepsies and to determine the value of LEV blood level monitoring in this population.



Sixty-nine children (39 males and 30 females) treated with LEV between 2006 and 2007 were selected. Their medical files were reviewed for LEV efficacy and tolerability. In a subgroup of children currently taking LEV, plasma concentrations were determined by high performance liquid chromatography by ultraviolet detection (HPLC-UV) method and correlated with the given dose per kilo as well as clinical response.



Fifty-one patients (74%) had a more than 50% reduction in seizure frequency with 16 patients (23%) becoming seizure free on LEV. Eighteen (26%) patients had a less than 50% reduction in seizure frequency. Adverse events due to LEV ranged from mild to moderate in only 18 patients (26%). The most frequently observed were drowsiness, behavioral difficulties, increase in seizure frequency and headaches. The majority (60.5%) of the responders received doses between 10 and 50mg/kg/day and had a plasma concentration (PC) between 5 and 40microg/ml. However, we found no clear correlation between PC and efficacy.



Levetiracetam given twice a day in children with refractory epilepsy reduces seizure frequency in all types of epilepsy. In children, LEV is a broad spectrum anticonvulsant with a favourable safety profile.
Measurement of coping and stress responses in women with breast cancer.

The development of the Responses to Stress Questionnaire-cancer version (RSQ-CV) to assess coping with and responses to the stress of breast cancer is described. The RSQ-CV was completed by 232 women with breast cancer near the time of their diagnosis. Confirmatory factor analyses verified a model that includes three voluntary coping factors (primary control engagement coping, secondary control engagement coping, disengagement coping) and two involuntary stress response factors (involuntary engagement, involuntary disengagement). Internal consistency reliability, and stability over 12 weeks for the five factors were adequate to excellent. Convergent and discriminant validity was examined through correlations with measures of intrusive thoughts, avoidance, and dimensions of perceived control. Significant correlations with symptoms of anxiety and depression are also reported. Applications of the RSQ-CV for research with breast cancer patients are discussed.
Effect of community-based voluntary counselling and testing on HIV incidence and social and behavioural outcomes (NIMH Project Accept; HPTN 043): a cluster-randomised trial.

Although several interventions have shown reduced HIV incidence in clinical trials, the community-level effect of effective interventions on the epidemic when scaled up is unknown. We investigated whether a multicomponent, multilevel social and behavioural prevention strategy could reduce HIV incidence, increase HIV testing, reduce HIV risk behaviour, and change social and behavioural norms.



For this phase 3 cluster-randomised controlled trial, 34 communities in four sites in Africa and 14 communities in Thailand were randomly allocated in matched pairs to receive 36 months of community-based voluntary counselling and testing for HIV (intervention group) or standard counselling and testing alone (control group) between January, 2001, and December, 2011. The intervention was designed to make testing more accessible in communities, engage communities through outreach, and provide support services after testing. Randomisation was done by a computer-generated code and was not masked. Data were collected at baseline (n=14 567) and after intervention (n=56.683) by cross-sectional random surveys of community residents aged 18-32 years. The primary outcome was HIV incidence and was estimated with a cross-sectional multi-assay algorithm and antiretroviral drug screening assay. Thailand was excluded from incidence analyses because of low HIV prevalence. 
The estimated incidence of HIV in the intervention group was 1.52% versus 1.81% in the control group with an estimated reduction in HIV incidence of 13.9% (relative risk [RR] 0.86, 95% CI 0.73-1.02; p=0.082). HIV incidence was significantly reduced in women older than 24 years (RR=0.70, 0.54-0.90; p=0.0085), but not in other age or sex subgroups. Community-based voluntary counselling and testing increased testing rates by 25% overall (12-39; p=0.0003), by 45% (25-69; p<0·0001) in men and 15% (3-28; p=0.013) in women. No overall effect on sexual risk behaviour was recorded. Social norms regarding HIV testing were improved by 6% (95% CI 3-9) in communities in the intervention group.



These results are sufficiently robust, especially when taking into consideration the combined results of modest reductions in HIV incidence combined with increases in HIV testing and reductions in HIV risk behaviour, to recommend the Project Accept approach as an integral part of all interventions (including treatment as prevention) to reduce HIV transmission at the community level.



US National Institute of Mental Health, the Division of AIDS of the US National Institute of Allergy and Infectious Diseases, and the Office of AIDS Research of the US National Institutes of Health.
Improvement of signal-to-noise ratio using iterative reconstruction in a 99mTc-ECD split-dose injection protocol

Split-dose injection using technetium-99m ethyl cysteinate dimer (99mTc-ECD) and consecutive SPET measurements performed before and after acetazolamide (ACZ) loading was used to estimate the cerebral perfusion reserve. The disadvantage of the split-dose method is that the signal-to-noise ratio (S/N) of ACZ-loaded images is decreased by subtraction of the 1st SPET data (rest) from the 2nd SPET data (ACZ loaded). To improve the S/N of reconstructed images, we implemented an iterative reconstruction algorithm including the term of remaining radioactivity in the brain from the 1st injection. It was expected that this method (the "addition method") would improve the S/N of rest and ACZ images compared with the conventional subtraction method owing to exclusion of the subtraction process. To evaluate the effect of statistical noise, we estimated the percentage coefficient of variation (%COV) as a function of total photon counts (from 1.35 to 86.5 Mcounts/slice) by Monte Carlo simulation with equal-volume split-dose injection. The %COV of the 2nd SPET study was higher than that of the 1st (e.g. 50.3% for the 1st and 80.5% for the 2nd at a total count of 2.70 Mcounts/slice) when using the conventional subtraction method. By contrast, the %COV of the 1st and 2nd SPET studies was almost equivalent (e.g. 43.1% for the 1st and 41.4% for the 2nd at a total count of 2.70 Mcounts/slice) when using the addition method. We also determined the optimal injection dose ratio of the 2nd to the 1st SPET study, which provides the equivalent %COV value between the 1st and 2nd images. With the subtraction method, the optimal injection dose ratio of the 2nd to the 1st SPET study was approximately 2.0, while with the addition method it was approximately 1.0. The absolute value of %COV at the optimal injection dose was about 54% and 43% with the subtraction method and the addition method, respectively. The addition method gave a lower %COV value than the subtraction method even at the optimal injection dose ratio. In a clinical study, the addition method provided better quality images than the subtraction method. The ROI values of rest images estimated by the subtraction method were close to the results obtained with the addition method (ROIsub=1.01 ROIadd−0.312, r=0.999). The ROI values of the ACZ images estimated by the subtraction method also agreed with the results obtained using the addition method, but the correlation was slightly worse (ROIsub=1.03 ROIadd−2.23, r=0.995). Quantitative ROI values were quite similar between the methods. Our results demonstrated that the quality of reconstructed rest and ACZ-loaded images were significantly better with the addition method than with the conventional subtraction method. We conclude that the proposed method will be useful as a practical reconstruction algorithm to improve the S/N in an equal-volume split-dose injection protocol using 99mTc-ECD.