nils-herrmann/clean_scirepeval huggingface dataset:
Computer-assisted quantification of interstitial lung disease associated with rheumatoid arthritis: preliminary technical validation.

To validate a threshold-based prototype software application (MeVis PULMO 3D) for quantification of chronic interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) using variable threshold settings for segmentation of diseased lung areas.



Twenty-two patients with rheumatoid arthritis were included and underwent thin-section CT (4x1.25mm collimation). CT scans were assessed by two observers for extent of ILD (EoILD), and twice by MeVis PULMO 3D for each protocol. MeVis PULMO 3D used four segmentation threshold (ST) settings (ST=-740, -780, -800 and -840HU). Pulmonary function tests were obtained in all patients. Statistical evaluation used 95% limits of agreement (LoA) and linear regression analysis.



There was total concordance between the software measurements. Interobserver agreement was good (LoA=-28.36 to 17.58%). EoILD by readers correlated strongly with DL(CO) (r=-0.702, p<0.0001) and moderately with FVC (r=-0.523, p=0.018). There was close correlation between readers and MeVis PULMO 3D with best results for ST <780HU (EoILD vs. MeVis PULMO 3D: r=0.650 for ST=-800 and -840HU, respectively; p=0.002). MeVis PULMO 3D correlated best with DL(CO) at ST of -800HU (r=-0.44, -0.49, -0.58 and -0.57 for ST=-740, -780, -800 and -840, respectively; p=0.007-0.05) and moderately with FVC (r=-0.44, -0.51, -0.59 and -0.45 for ST=-740, -780, -800 and -840), respectively; p=0.007-0.05).



The MeVis PULMO 3D system used holds promise to become a valuable instrument for quantification of chronic ILD in patients with RA when using the threshold value of -800HU, with evidence of the closest correlations, both with human observers and physiologic impairment.
Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo

NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are 'primed' with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(t)ides (sequential NUC therapy), an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB.
An Outbreak of Lymphocutaneous Sporotrichosis among Mine-Workers in South Africa

The largest outbreak of sporotrichosis occurred between 1938 and 1947 in the gold mines of Witwatersrand in South Africa. Here, we describe an outbreak of lymphocutaneous sporotrichosis that was investigated in a South African gold mine in 2011.



Employees working at a reopened section of the mine were recruited for a descriptive cross-sectional study. Informed consent was sought for interview, clinical examination and medical record review. Specimens were collected from participants with active or partially-healed lymphocutaneous lesions. Environmental samples were collected from underground mine levels. Sporothrix isolates were identified by sequencing of the internal transcribed spacer region of the ribosomal gene and the nuclear calmodulin gene.



Of 87 male miners, 81 (93%) were interviewed and examined, of whom 29 (36%) had skin lesions; specimens were collected from 17 (59%). Sporotrichosis was laboratory-confirmed among 10 patients and seven had clinically-compatible lesions. Of 42 miners with known HIV status, 11 (26%) were HIV-infected. No cases of disseminated disease were detected. Participants with ≤ 3 years' mining experience had a four times greater odds of developing sporotrichosis than those who had been employed for >3 years (adjusted OR 4.0, 95% CI 1.2-13.1). Isolates from 8 patients were identified as Sporothrix schenckii sensu stricto by calmodulin gene sequencing while environmental isolates were identified as Sporothrix mexicana.



S. schenckii sensu stricto was identified as the causative pathogen. Although genetically distinct species were isolated from clinical and environmental sources, it is likely that the source was contaminated soil and untreated wood underground. No cases occurred following recommendations to close sections of the mine, treat timber and encourage consistent use of personal protective equipment. Sporotrichosis is a potentially re-emerging disease where traditional, rather than heavily mechanised, mining techniques are used. Surveillance should be instituted at sentinel locations.
Circadian activity rhythms and mortality: the study of osteoporotic fractures.

To determine whether circadian activity rhythms are associated with mortality in community-dwelling older women.



Prospective study of mortality.



A cohort study of health and aging.



Three thousand twenty-seven community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84).



Activity data were collected using wrist actigraphy for a minimum of three 24-hour periods, and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), midline estimating statistic of rhythm (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained.



Over an average of 4.1 years of follow-up, there were 444 (14.7%) deaths. There was an inverse association between peak activity height and all-cause mortality rates, with higher mortality rates observed in the lowest activity quartile (hazard ratio (HR)=2.18, 95% confidence interval (CI)=1.63-2.92) than in the highest quartile after adjusting for age, clinic site, race, body mass index, cognitive function, exercise, instrumental activity of daily living impairments, depression, medications, alcohol, smoking, self-reported health status, married status, and comorbidities. A greater risk of mortality from all causes was observed for those in the lowest quartiles of mesor (HR=1.71, 95% CI=1.29-2.27) and rhythm robustness (HR=1.97, 95% CI=1.50-2.60) than for those in the highest quartiles. Greater mortality from cancer (HR=2.09, 95% CI=1.04-4.22) and stroke (HR=2.64, 95% CI=1.11-6.30) was observed for later peak activity (after 4:33 p.m.; >1.5 SD from mean) than for the mean peak range (2:50-4:33 p.m.).



Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g., physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in older adults.
Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls.

An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan.



To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD.



Randomized double-blind crossover study.



Outpatient clinic.



Twenty-seven medication-free patients with remitted MDD (18 women and 9 men; mean +/- SD age, 39.8 +/- 12.7 years) and 19 controls (10 women and 9 men; mean +/- SD age, 34.4 +/- 11.5 years).



We induced TD by administering capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing hydrous lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD. Magnetic resonance images were obtained for all participants.



Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD. Behavioral assessments used a modified (24-item) version of the Hamilton Depression Rating Scale.



Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P<.001). Compared with sham depletion, TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex, medial thalamus, anterior and posterior cingulate cortices, and ventral striatum in patients with remitted MDD but not in controls.



The pattern of TD-induced regional cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific, serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD.
Telomere attrition and candidate gene mutations preceding monosomy 7 in aplastic anemia.

The pathophysiology of severe aplastic anemia (SAA) is immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs). Most patients respond to immunosuppressive therapies, but a minority transform to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), frequently associated with monosomy 7 (-7). Thirteen SAA patients were analyzed for acquired mutations in myeloid cells at the time of evolution to -7, and all had a dominant HSPC clone bearing specific acquired mutations. However, mutations in genes associated with MDS/AML were present in only 4 cases. Patients who evolved to MDS and AML showed marked progressive telomere attrition before the emergence of -7. Single telomere length analysis confirmed accumulation of short telomere fragments of individual chromosomes. Our results indicate that accelerated telomere attrition in the setting of a decreased HSPC pool is characteristic of early myeloid oncogenesis, specifically chromosome 7 loss, in MDS/AML after SAA, and provides a possible mechanism for development of aneuploidy.
Real-life effectiveness of budesonide/formoterol maintenance and reliever therapy in asthma patients across Asia: SMARTASIA study

The use of budesonide/formoterol in a single inhaler for both maintenance and reliever therapy is a recommended option for treatment of persistent asthma not responding well to inhaled corticosteroid (ICS) alone.



This was a multi-centre open-label study on patients whose asthma condition remained inadequately controlled by various asthma treatments other than budesonide/formoterol. After a 2-week run-in period, eligible patients underwent a 12-week treatment period with budesonide/formoterol (Symbicort SMART(®), 160/4.5 μg) twice daily plus as needed. Patient's asthma control and quality of life were assessed using the 5-item Asthma Control Questionnaire (ACQ-5) and the standardized Asthma Quality of Life Questionnaire (AQLQ-S), respectively.



A total of 862 eligible asthma patients who have had asthma for a mean duration of 10.73 ± 12.03 years entered a 12-week treatment with budesonide/formoterol maintenance and reliever therapy. During treatment, ACQ-5 score improved significantly by 0.58 ± 0.93 (95% CI, 0.51 to 0.64, P < 0.0001) from the baseline level of 1.62 ± 1.00. ) score improved by 0.70 ± 0.89 (95% CI, 0.64 to 0.76, P < 0.0001) from baseline. Asthma symptom score was also reduced significantly (P < 0.0001); between run-in and treatment periods, night- and day-time symptom scores were reduced by 0.32 ± 0.54 (95% CI, 0.28 to 0.35) and 0.30 ± 0.52 (95% CI, 0.27 to 0.34), respectively. The percentage of nights with awakenings due to asthma symptoms was reduced by 11.09 ± 26.13% (95% CI, 9.34 to 12.85%), while the percentage of asthma-control and symptom-free days increased by 20.90 ± 34.40% (95% CI, 18.59 to 23.21%) and 23.89 ± 34.62% (95% CI, 21.56 to 26.21%), respectively (P < 0.0001). Together with the improvement in asthma control, the number of night- and day-time inhalations of as-needed reliever medication decreased by 0.30 ± 0.82 (95% CI, 0.24 to 0.35) inhalations and 0.30 ± 0.97 (95% CI, 0.23 to 0.36) inhalations, respectively (P < 0.0001). No unexpected adverse events were reported.



During treatment of inadequately controlled asthmatic patients with budesonide/formoterol maintenance and reliever therapy, significant improvement in patients' asthma control and reductions in asthma symptoms and as-needed medication use was observed. Patients' quality of life was improved and the treatment was well tolerated.
The Painfulness of Active, but not Sham, Transcranial Magnetic Stimulation Decreases Rapidly Over Time: Results From the Double-Blind Phase of the OPT-TMS Trial

Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) over several weeks is an FDA approved treatment for major depression. Although rTMS is generally safe when administered using the FDA guidelines, there are a number of side effects that can make it difficult for patients to complete a course of rTMS. Many patients report that rTMS is painful, although patients appear to accommodate to the initial painfulness. The reduction in pain is hypothesized to be due to prefrontal stimulation and is not solely explained by accommodation to the stimulation.



In a recent 4 site randomized controlled trial (using an active electrical sham stimulation system) investigating the antidepressant effects of daily left dorsolateral prefrontal rTMS (Optimization of TMS, or OPT-TMS), the procedural painfulness of TMS was assessed before and after each treatment session. Computerized visual analog scale ratings were gathered before and after each TMS session in the OPT-TMS trial. Stimulation was delivered with an iron core figure-8 coil (Neuronetics) with the following parameters: 10 Hz, 120% MT (EMG-defined), 4 s pulse train, 26 s inter-train interval, 3000 pulses per session, one 37.5 min session per day. After each session, procedural pain (pain at the beginning of the TMS session, pain toward the middle, and pain toward then end of the session) ratings were collected at all 4 sites. From the 199 patients randomized, we had usable data from 142 subjects for the initial 15 TMS sessions (double-blind phase) delivered over 3 weeks (142 × 2 × 15 = 4260 rating sessions).



The painfulness of real TMS was initially higher than that of the active sham condition. Over the 15 treatment sessions, subjective reports of the painfulness of rTMS (during the beginning, middle and end of the session) decreased significantly 37% from baseline in those receiving active TMS, with no change in painfulness in those receiving sham. This reduction, although greatest in the first few days, continued steadily over the 3 weeks. Overall, there was a decay rate of 1.56 VAS points per session in subjective painfulness of the procedure in those receiving active TMS.



The procedural pain of left, prefrontal rTMS decreases over time, independently of other emotional changes, and only in those receiving active TMS. These data suggest that actual TMS stimulation of prefrontal cortex maybe related to the reduction in pain, and that it is not a non-specific accommodation to pain. This painfulness reduction softly corresponds with later clinical outcome. Further work is needed to better understand this phenomenon and whether acute within-session or over time painfulness changes might be used as short-term biomarkers of antidepressant response.
D ivergent Effects of Beta-Blocker Therapy on Self-Estimated and Objectively Scored Activities of Daily Living

To identify factors that influence changes in the activities of daily living (ADL) assessed by a standardized scoring system, ADL-20, and factors affecting the self-estimate of the changes in ADL, we conducted a 1-yr follow-up study of 1,163 outpatients aged 50 yr or older. The follow-up rate was 83.1 % . A decrease in the ADL score was associated with advancing age and a lower prescription rate of ,9-blockers. Analysis of the modalities of ADL revealed an association between a decreasing mobility score and a lower
Polyethylene glycol loxenatide injections added to metformin effectively improve glycemic control and exhibit favorable safety in type 2 diabetic patients.

The aim of the present study was to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) injections in Chinese type 2 diabetic (T2D) patients.



The present multicenter randomized double-blind parallel placebo-controlled clinical trial enrolled patients who had been treated with a stable dose of metformin (≥1500 mg/day) for ≥12 weeks and had an HbA1c level between 7% and 11%. Subjects were randomly divided into three groups (1: 1: 1) and were treated with once weekly subcutaneous injections of either placebo or 100 or 200 μg PEX168 for 12 weeks. All subjects continued to receive metformin daily.



After 12 weeks treatment, the adjusted least-squares mean of HbA1c reductions from baseline values in the 100 and 200 μg PEX168 groups were significantly higher than in the placebo group (-1.02% [95% confidence interval {CI} -1.33, -0.71), -1.36% [95% CI -1.68, -1.04], and 0.13% [95% CI -0.20, 0.45], respectively; P < 0.05). After treatment, 50% and 60.5% of subjects in the 100 and 200 μg PEX168 groups, respectively, achieved HbA1c levels <7% (P < 0.01 for both vs placebo [HbA1c 11.1%]). The most frequent adverse reactions in the PEX168 groups were mild to moderate dose-dependent gastrointestinal reactions. There were no reports of hypoglycemia or pancreatitis in any of the groups.



Continuous 12 week treatment with PEX168 showed excellent safety and efficacy in T2D patients whose glucose was not well controlled with metformin alone.
Depression, mood, stress, and Th1/Th2 immune balance in primary breast cancer patients undergoing classical massage therapy

Cancer patients frequently suffer from psychological comorbidities such as depression and elevated stress. Previous studies could demonstrate that cancer patients benefit from massage therapy on the physical and psychological level. This pilot study investigates the effects of massage on depression, mood, perceived stress, and the Th1/Th2 ratio in breast cancer patients. Thirty-four breast cancer patients were randomly assigned to a massage group (n = 17) and a control group (n = 17). Patients of the massage group received two 30-min classical massages per week for 5 weeks. At baseline, at the end of the intervention period, and 6 weeks after the end of intervention, patients of both groups completed the Perceived Stress Questionnaire (PSQ), the Patient Health Questionnaire (PHQ), and the Berlin Mood Questionnaire (BFS) and blood was withdrawn for determining cytokine concentrations and the Th1/Th2 ratio. Twenty-nine patients were included in the statistical analysis. Depression (PHQ) and anxious depression (BSF) were significantly reduced immediately after massage compared to the control group. Stress (PSQ) and elevated mood (BSF) did not show significant alterations after massage therapy. Changes of cytokine concentrations and Th1/Th2 ratio were insignificant as well, although there was a slight shift towards Th1 in the massage group over time. Massage therapy is an efficient treatment for reducing depression in breast cancer patients. Insignificant results concerning immunological parameters, stress, and mood indicate that further research is needed to determine psychological and immunological changes under massage therapy.
Outcomes in elderly patients with acute coronary syndromes randomized to enoxaparin vs. unfractionated heparin: results from the SYNERGY trial.

Elderly patients are at high risk from non-ST-segment elevation acute coronary syndromes (NSTE ACS) as well as from treatment-related complications. Age-associated changes in physiology may alter the risk and benefit expected from therapy. The SYNERGY database was used to study the influence of age on treatment outcomes with enoxaparin vs. unfractionated heparin (UFH) in patients with high-risk NSTE ACS.



Age was analysed as a continuous and categorical variable (<65, 65-74, and >or=75 years, and <75 and >or=75 years) for descriptive purposes. Logistic regression was used to adjust the outcomes of 30-day death, death or myocardial infarction (MI), and major bleeding for baseline characteristics. Odds ratios compared outcomes by age and by treatment within age groups. Model interaction terms were used to test for statistically different outcomes by treatment and age. Overall, 9977 randomized patients had age information, of whom 25.5% (2540) were >or=75 years of age. Elderly patients (>or=75 years) had more cardiovascular risk factors, prior cardiac disease, and higher acuity at presentation. After adjustment, advanced age (per 10 years) was associated with 30-day death or MI [risk odds ratios (ROR): 1.14, P = 0.002], 30-day death (ROR: 1.54, P < 0.0001), and 1-year death (ROR: 1.47, P < 0.0001), as well with TIMI major bleeding (ROR: 1.21, P = 0.001), GUSTO severe bleeding (ROR: 1.20, P = 0.047), and transfusion (ROR: 1.04, P = 0.324). Although there was a higher rate of GUSTO severe bleeding noted with enoxaparin in elderly patients, the overall relationships between treatment (UFH or enoxaparin) and outcomes did not vary significantly as a function of the patient's age.



Although higher rates of adverse events are seen in the oldest subgroup (age >or=75 years) treated with enoxaparin, statistical comparisons confirm similar efficacy and safety of enoxaparin and UFH across age subgroups as was demonstrated overall in SYNERGY.
Trends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999-2005.

The purpose of this study was to assess changes in the prevalence of preexisting diabetes (diabetes antedating pregnancy) and gestational diabetes mellitus (GDM) from 1999 through 2005.



In this retrospective study of 175,249 women aged 13-58 years with 209,287 singleton deliveries of >or=20 weeks' gestation from 1999 through 2005 in all Kaiser Permanente hospitals in southern California, information from clinical databases and birth certificates was used to estimate the prevalence of preexisting diabetes and GDM.



Preexisting diabetes was identified in 2,784 (1.3%) of all pregnancies, rising from an age- and race/ethnicity-adjusted prevalence of 0.81 per 100 in 1999 to 1.82 per 100 in 2005 (P(trend) < 0.001). Significant increases were observed in all age-groups and all racial/ethnic groups. After women with preexisting diabetes were excluded, GDM was identified in 15,121 (7.6%) of 199,298 screened pregnancies. The age- and race/ethnicity-adjusted GDM prevalence remained constant at 7.5 per 100 in 1999 to 7.4 per 100 in 2005 (P(trend) = 0.07). Among all deliveries to women with either form of diabetes, 10% were due to preexisting diabetes in 1999, rising to 21% in 2005, with GDM accounting for the remainder.



The stable prevalence of GDM and increase in the prevalence of preexisting diabetes were independent of changes in the age and race/ethnicity of the population. The increase in preexisting diabetes, particularly among younger women early in their reproductive years, is of concern.