nils-herrmann/clean_scirepeval huggingface dataset:
Can geometric indices of heart rate variability predict improvement in autonomic modulation after resistance training in chronic obstructive pulmonary disease?

Chronic obstructive pulmonary disease (COPD) is associated with autonomic dysfunctions that can be evaluated through heart rate variability (HRV). Resistance training promotes improvement in autonomic modulation; however, studies that evaluate this scenario using geometric indices, which include nonlinear evaluation, thus providing more accurate information for physiological interpretation of HRV, are unknown. This study aimed to investigate the influence of resistance training on autonomic modulation, using geometric indices of HRV, and peripheral muscle strength in individuals with COPD. Fourteen volunteers with COPD were submitted to resistance training consisting of 24 sessions lasting 60 min each, with a frequency of three times a week. The intensity was determined as 60% of one maximum repetition and was progressively increased until 80% for the upper and lower limbs. The HRV and dynamometry were performed at two moments, the beginning and the end of the experimental protocol. Significant increases were observed in the RRtri (4·81 ± 1·60 versus 6·55 ± 2·69, P = 0·033), TINN (65·36 ± 35·49 versus 101·07 ± 63·34, P = 0·028), SD1 (7·48 ± 3·17 versus 11·04 ± 6·45, P = 0·038) and SD2 (22·30 ± 8·56 versus 32·92 ± 18·78, P = 0·022) indices after the resistance training. Visual analysis of the Poincare plot demonstrated greater dispersion beat-to-beat and in the long-term interval between consecutive heart beats. Regarding muscle strength, there was a significant increase in the shoulder abduction and knee flexion. In conclusion, geometric indices of HRV can predict improvement in autonomic modulation after resistance training in individuals with COPD; improvement in peripheral muscle strength in patients with COPD was also observed.
Use and Acceptance of Electronic Communication by Patients With Multiple Sclerosis: A Multicenter Questionnaire Study

The number of multiple sclerosis (MS) information websites, online communities, and Web-based health education programs has been increasing. However, MS patients' willingness to use new ways of communication, such as websites, mobile phone application, short message service, or email with their physician, remains unknown.



We designed a questionnaire to evaluate the a priori use of electronic communication methods by MS patients and to assess their acceptance of such tools for communication with their health care providers.



We received complete data from 586 MS patients aged between 17 and 73 years. Respondents were surveyed in outpatient clinics across Germany using a novel paper-and-pencil questionnaire. In addition to demographics, the survey items queried frequency of use of, familiarity with, and comfort with using computers, websites, email, and mobile phones.



About 90% of all MS patients used a personal computer (534/586) and the Internet (527/586) at least once a week, 87.0% (510/586) communicated by email, and 85.6% (488/570) communicated by mobile phone. When asked about their comfort with using electronic communication methods for communication with health care providers, 20.5% (120/586) accepted communication by mobile Internet application or short message service via mobile phone, 41.0% (240/586) by websites, 54.3% (318/586) by email service, and 67.8% (397/586) by at least one type of electronic communication. The level of a priori use was the best predictor for the acceptance of electronic communication with health care providers. Patients who reported already searching online for health information (odds ratio 2.4, P < .001) and who had already communicated with a physician through a website (odds ratio 3.3, P = .03) reported higher acceptance for Web-based communication. Patients who already scheduled appointments with their mobile phones (odds ratio 2.1, P = .002) were more likely to accept the use of mobile phone applications or short message service for communicating with their physician.



The majority of MS patients seen at specialist centers already use modern communication technology regularly. New forms of electronic communication appear to have high levels of acceptance for exchanging information about MS between patients and health care providers. Such methods should be integrated into eHealth services such as electronic health records and patient relationship management systems.
CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs.

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population that shares certain characteristics including an aberrant myeloid phenotype and the ability to suppress T cells. MDSCs have been predominantly studied in malignant diseases and findings suggest involvement in tumor-associated immune suppression. Chronic lymphocytic leukemia (CLL) is the leukemia with the highest incidence among adults. Immune defects occur already at early disease stages and impact the clinical course. We assessed presence, frequency, association to other immune parameters, and functional properties of circulating CD14(+) cells lacking HLA-DR expression (HLA-DR(lo)) in patients with untreated CLL. These monocytic cells represent one of the best-defined human MDSC subsets. Frequency of CD14(+)HLA-DR(lo) cells was significantly increased in CLL patients. Furthermore, MDSCs suppressed in vitro T-cell activation and induced suppressive regulatory T cells (TRegs). The MDSC-mediated modulation of T cells could be attributed to their increased indoleamine 2,3-dioxygenase (IDO) activity. CLL cells induced IDO(hi) MDSCs from healthy donor monocytes suggesting bidirectional crosstalk between CLL-cells, MDSCs, and TRegs. Overall, we identified a MDSC population that expands in CLL. The exact mechanisms responsible for such accumulation remain to be elucidated and it will be of interest to test whether antagonizing suppressive functions of CLL MDSCs could represent a mean for enhancing immune responses.
Rationale and design of the Kanyini guidelines adherence with the polypill (Kanyini-GAP) study: a randomised controlled trial of a polypill-based strategy amongst Indigenous and non Indigenous people at high cardiovascular risk

The Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP) Study aims to examine whether a polypill-based strategy (using a single capsule containing aspirin, a statin and two blood pressure-lowering agents) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline-indicated therapies, and lower blood pressure and cholesterol levels.



The study is an open, randomised, controlled, multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practices and Aboriginal Medical Services, followed for an average of 18 months. The participants will be randomised to one of two versions of the polypill, the version chosen by the treating health professional according to clinical features of the patient, or to usual care. The primary study outcomes will be changes, from baseline measures, in serum cholesterol and systolic blood pressure and self-reported current use of aspirin, a statin and at least two blood pressure lowering agents. Secondary study outcomes include cardiovascular events, renal outcomes, self-reported barriers to indicated therapy, prescription of indicated therapy, occurrence of serious adverse events and changes in quality-of-life. The trial will be supplemented by formal economic and process evaluations.



The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated.
Long-Term Caregiver Mental Health Outcomes Following a Predominately Online Intervention for Adolescents With Complicated Mild to Severe Traumatic Brain Injury.

To examine the efficacy of counselor-assisted problem solving (CAPS) in improving long-term caregiver psychological functioning following traumatic brain injury (TBI) in adolescents.



This randomized clinical trial compared CAPS (n = 65), a predominantly online problem-solving intervention, with an Internet resource comparison (n = 67) program. Families of adolescents with TBI completed a baseline assessment and follow-up assessments 6, 12, and 18 months later. General linear mixed models were used to examine longitudinal changes in caregiver global psychological distress, depressive symptoms, and caregiving self-efficacy. Family income and injury severity were examined as moderators of treatment efficacy.



Family income moderated long-term changes in caregiver psychological distress. For lower-income caregivers, the CAPS intervention was associated with lower levels of psychological distress at 6, 12, and 18 months post baseline.



These findings support the utility of Web-based interventions in improving long-term caregiver psychological distress, particularly for lower-income families.
Renin-angiotensin system genes and exercise training-induced changes in sodium excretion in African American hypertensives.

To determine whether angiotensin-converting enzyme (ACE) and angiotensinogen (ACT) genotypes could predict changes in urinary sodium excretion in response to short-term aerobic exercise training (AEX).



Longitudinal intervention.



The study was conducted at the University of Maryland at College Park and at Baltimore, and the University of Pittsburgh General Clinical Research Center.



31 (age 53 +/- 2 years) sedentary, hypertensive (146 +/- 2/88 +/- 2 mm Hg) African Americans.



Aerobic exercise training (AEX) consisted of seven or eight consecutive days, 50 minutes per day, at 65% of heart rate reserve. Participants underwent a 24-hour period of ambulatory blood pressure (BP) monitoring and urine collection at baseline and 14-18 hours after the last exercise session.



Angiotensiongen (AGT) M235T and ACE I/D genotype and sodium excretion and ambulatory BP.



Average sodium excretion for the entire group independent of genotype increased after AEX (108 +/- 9 vs 143 +/- 12 mEq/day, P=.003). Sodium excretion significantly increased after exercise training in the ACE II (114 +/- 22 vs 169 +/- 39 mEq/day, P=.04), but not in the ID (100 +/- 8 vs 133 +/- 17 mEq/day, P=.12) or DD (113 +/- 18 vs 138 +/- 11 mEq/day, P=.13) genotype groups. In the II genotype group, the increase in sodium excretion was significantly and inversely correlated with decreases in 24-hour diastolic (r= -.88, P=.02) and mean (r= -.95, P=.004) BP. The ACT TT and MT+MM genotype groups similarly increased their sodium excretion by 34 +/- 16 (P=.05) and 37 +/- 17 (P=.05) mEq/day respectively.



These results suggest that African American hypertensives with the ACE II genotype may be more susceptible to sodium balance and BP changes with exercise training compared with those with the ID and DD genotypes.
Geriatric Assessment to Predict Survival and Risk of Serious Adverse Events in Elderly Newly Diagnosed Multiple Myeloma Patients: A Multicenter Study in China

Elderly multiple myeloma (MM) patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival (OS) time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM.



We retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013. A geriatric assessment had been performed to assess comorbidities, cognitive, and physical status for these patients. The primary endpoint was to evaluate different physical states of elderly patients with OS time and treatment-related side effects.



An additive scoring system (range: 0-5), based on age, Katz's Activity of Daily Living (ADL) and Lawton's Instrumental Activity of Daily Living (IADL) ≤5 and Charlson Comorbidity Index (CCI) was developed to identify three groups: fit (score = 0); intermediate-fitness (score = 1); and frail (score ≥2). The 3-year OS was 63% in fit patients, 63% in intermediate-fitness patients, and 49% in frail patients ≥3 hematologic adverse events (AEs) were documented in 45 (35.4%) fit, 34 (34%) intermediate-fitness, and 121 (30.2%) frail patients. The risk of a grade ≥3 hematologic AEs was not significantly increase in intermediate-fitness (hazard ratios [HR]: 0.99, 95% confidence interval [CI]: 0.54-1.47, P = 1.000) and in frail patients (HR: 1.16, 95% CI: 0.70-1.93, P = 0.558) compared with fit ones.



MM occurs earlier in life and being advanced when the diagnosis is made in the mainland of China. The overall survival in frailty with International Staging System (ISS) II/III was the worst in all patients.
Ancestral gene synteny reconstruction improves extant species scaffolding

We exploit the methodological similarity between ancestral genome reconstruction and extant genome scaffolding. We present a method, called ARt-DeCo that constructs neighborhood relationships between genes or contigs, in both ancestral and extant genomes, in a phylogenetic context. It is able to handle dozens of complete genomes, including genes with complex histories, by using gene phylogenies reconciled with a species tree, that is, annotated with speciation, duplication and loss events. Reconstructed ancestral or extant synteny comes with a support computed from an exhaustive exploration of the solution space. We compare our method with a previously published one that follows the same goal on a small number of genomes with universal unicopy genes. Then we test it on the whole Ensembl database, by proposing partial ancestral genome structures, as well as a more complete scaffolding for many partially assembled genomes on 69 eukaryote species. We carefully analyze a couple of extant adjacencies proposed by our method, and show that they are indeed real links in the extant genomes, that were missing in the current assembly. On a reduced data set of 39 eutherian mammals, we estimate the precision and sensitivity of ARt-DeCo by simulating a fragmentation in some well assembled genomes, and measure how many adjacencies are recovered. We find a very high precision, while the sensitivity depends on the quality of the data and on the proximity of closely related genomes.
Effects of the acyl coenzyme A:cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions.

Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis.



This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level <125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was approximately 200 mm3, and the least squares mean change at end of treatment was 0.7 mm3 for placebo and 7.7, 4.1, and 4.8 mm3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted P=0.17 [unadjusted P=0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (P=NS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (P<0.05 in all groups).



Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in LDL cholesterol.
Prognostically significant cytotoxic T cell clones are stimulated after thalidomide therapy in patients with multiple myeloma.

The expanded T cell clones are associated with a prolonged survival in patients with multiple myeloma. We sought to confirm this prognostic significance in a multicenter patient cohort and investigate the effect of thalidomide on clones and T regulatory cells (T(regs)). Blood was collected from 120 patients enrolled in a Phase III trial of maintenance therapy +/- thalidomide after autologous stem cell transplantation. TCR Vbeta repertoire analysis identified T cell expansions in 48% of patients pre-transplant and 68% after 8-month maintenance. T cell expansions, previously shown to be clonal, were predominantly CD8+ (93%) and all 24 TCR Vbeta families tested were represented. Thalidomide therapy was associated with a significant increase in the incidence of patients with multiple expansions (49% vs. 23%; chi2 = 6.8; p = 0.01). The presence of expansions regardless of therapy was associated with a significantly longer median progression free survival (PFS) (32.1 vs. 17.6 months; chi2 = 5.6; p = 0.02) and overall survival (OS) (chi2 = 3.9; p < 0.05). Median PFS in the thalidomide arm was 50.9 months for patients with expansions and 28.3 months for patients without expansions (chi2 = 19.4; p = 0.0002). Thalidomide did not appear to modulate T(reg) numbers. Expanded T cell clones are prognostically significant and have an impact on progression after thalidomide therapy in a proportion of patients.
Regulation of soluble guanylyl cyclase by phosphorylation

In vitro kinase assays revealed that the α1, but not the β1, subunit of sGC is a PKG substrate and that the phosphorylation site is located within the first 360 residues of the α1. A constitutively active form of PKG stimulated incorporation of 32P into the α1 subunit in vivo. In addition, PKG could be detected in sGC immunoprecipitates, suggesting that the two proteins interact in cells. Serine to alanine mutation of putative PKG sites revealed that Ser64 is the main phosphorylation site for PKG. After generating a phospho-specific antibody for Ser64, we could demonstrate that phosphorylation of endogenous sGC on Ser64 increases in cells and tissues exposed to NO. Phosphorylation of sGC in cells following SNP stimulation was blocked by the peptide inhibitor of PKG, DT-3. Wild-type (wt) sGC when co-expressed in COS cells with a constitutively active form of PKG exhibited lower basal and NOstimulated cGMP accumulation. In contrast, the S64A α1/ β1 sGC was resistant to the PKG-induced reduction in activity. Moreover, co-cultures of endothelial cells with smooth muscle expressing a phosphorylation-resistant form of sGC, exhibited higher levels of cGMP (both basally and following stimulation with bradykinin) compared to co-cultures expressing wild-type sGC. Phosphorylation of the α1 subunit did not alter its ability to form heterodimers with β1. Using purified sGC and mutants, we observed that the S64D α1 phosphomimetic/β1 dimer exhibited lower Vmax; moreover, the decrease in Km after NO stimulation was less pronounced in S64D α1/β1 compared to wt sGC. Expression of a phosphorylation deficient form of sGC showed reduced desensitization to acute NO exposure and allowed for greater VASP phosphorylation.
Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity.

Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity.



Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women.



Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m² and smallest in women with BMI >30 kg/m². Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI.



During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.
Phase II study of carboplatin (CBDCA) in refractory multiple myeloma

Nineteen patients with multiple myeloma resistant to standard alkylating agent therapy or to the VAD regimen received carboplatin at a planned daily dose of 100 mg/M2 on four successive days. Two patients erroneously received a four-fold higher drug dose resulting in bone marrow aplasia and death without antitumor effect in one patient with post-mortem examination. No anti-tumor effect was observed among 15 patients evaluable for response (two lacked follow-up examination of tumor markers). Major toxicities were hematologic and included grade ≥ III, leukopenia in 9, thrombocytopenia in 6 and anemia in 3 of the 17 evaluable patients. Their median survival was 9 months. These results indicate that carboplatin is inactive in refractory multiple myeloma.
Attitudes to early rheumatoid arthritis: changing patterns. Results of a survey.

To determine if rheumatologists have changed their views on diagnosis and treatment of early rheumatoid arthritis (RA).



Three consecutive questionnaires were sent out to international rheumatologists in 1997, 2000, and 2003. The following aspects of early RA were covered: definition; patient referral time; diagnostic means; follow up intervals; and treatment strategies. All initial participants who responded to at least one of the follow up surveys were included in the analysis.



RA is now defined by a smaller number of affected joints (monarthritis: 9.8% respondents in 1997 v 17.4% in 2003), and shorter symptom duration (<3 months: 65.5% in 1997 v 85.8% in 2003). Early referrals (<6 weeks) increased (8.9% in 1997 v 17.4% in 2003). Serological test for diagnosis was mostly rheumatoid factor (100% in 2003), but anti-CCP was already used by 17.4% in 2003. Follow up of patients with early RA intensified (every 2 weeks: 16.1% in 1997 v 30.4% in 2003; every month: 47.8% in 2003 v 64.3% in 1997). Treatment with disease modifying antirheumatic drugs (DMARDs) mainly comprised methotrexate, sulfasalazine, and antimalarial drugs. Leflunomide was among the two favourite DMARDs of 10.9% in 2003, whereas no biological agent was so. In 2003, 46.7% respondents started treatment with DMARDs if RA was suspected (30.9% in 1997); no one waited for erosions to occur (7.3% in 1997).



The data obtained in this study suggest that the concept of diagnosing and treating RA early is accepted by a large proportion of the rheumatological community.