nils-herrmann/clean_scirepeval huggingface dataset:
Hypermethylation in the ZBTB20 gene is associated with major depressive disorder

Although genetic variation is believed to contribute to an individual’s susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder. Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression. We show that major depressive disorder is associated with significant hypermethylation within the coding region of ZBTB20, and is replicated in an independent cohort of 356 unrelated case-control individuals. The twins with major depressive disorder also show increased global variation in methylation in comparison with their unaffected co-twins. ZBTB20 plays an essential role in the specification of the Cornu Ammonis-1 field identity in the developing hippocampus, a region previously implicated in the development of major depressive disorder. Our results suggest that aberrant methylation profiles affecting the hippocampus are associated with major depressive disorder and show the potential of the epigenetic twin model in neuro-psychiatric disease.
Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4+ T-cell response: a randomized controlled trial.

Despite virally suppressive combination antiretroviral therapy (cART), some HIV-infected patients exhibit suboptimal CD4(+) T-cell recovery. This study aimed to determine the effect of intensification of cART with raltegravir or addition of hyperimmune bovine colostrum (HIBC) on CD4(+) T-cell count in such patients.



We randomized 75 patients to 4 treatment groups to receive raltegravir, HIBC, placebo, or both raltegravir and HIBC in a factorial, double-blind study. The primary endpoint was time-weighted mean change in CD4(+) T-cell count from baseline to week 24. T-cell activation (CD38(+) and HLA-DR(+)), plasma markers of microbial translocation (lipopolysaccharide, 16S rDNA), monocyte activation (soluble (s) CD14), and HIV-RNA (lowest level of detection 4 copies/mL) were monitored. Analysis was performed using linear regression methods.



Compared with placebo, the addition of neither raltegravir nor HIBC to cART for 24 weeks resulted in a significant change in CD4(+) T-cell count (mean difference, 95% confidence interval [CI]: 3.09 cells/μL, -14.27; 20.45, P = .724 and 9.43 cells/μL, -7.81; 26.68, P = .279, respectively, intention to treat). There was no significant interaction between HIBC and raltegravir (P = .275). No correlation was found between CD4(+) T-cell count and plasma lipopolysaccharide, 16S rDNA, sCD14, or HIV-RNA.



The determinants of poor CD4(+) T-cell recovery following cART require further investigation.
Enhanced prefrontal function with pharmacotherapy on a response inhibition task in adolescent bipolar disorder.

The aim of the current study is to determine whether pharmacotherapy normalizes cognitive circuitry function supporting voluntary behavioral inhibition in adolescent bipolar disorder.



Healthy controls and unmedicated patients with DSM-IV adolescent bipolar disorder in manic, mixed, or hypomanic episodes were matched on demographics and IQ (n = 13 per group; mean age = 14.4 ± 2.4 years). Functional magnetic resonance imaging studies were performed at baseline and after 14 weeks, during which time patients with adolescent bipolar disorder were treated initially with second-generation antipsychotics (SGAs) followed by lamotrigine monotherapy. The primary outcome measure was a Response Inhibition Task, which involved a planned motor response, already "on the way" to execution, that had to be voluntarily inhibited by the subjects in the trials in which a stop signal was presented. There were 6 blocks, each with a predominant rate of either "go" or "stop" trials. The study was conducted from June 2006 through July 2009.



All patients showed significant improvement (P < .001) in both the manic and depressive symptoms from baseline. Behavioral data showed that accuracy improved over 14 weeks in patients and healthy controls. Significant time by group interaction effects for the difference between stop versus go blocks showed greater increases of activation in prefrontal (left inferior and middle frontal gyri and medial frontal gyrus bilaterally) and temporal (left superior temporal gyrus and right middle temporal gyrus) regions and greater decreases in activation in right putamen and bilateral thalamus at follow-up in the adolescent bipolar disorder group than in healthy controls. Increased ventrolateral prefrontal cortex function was related to clinical treatment response.



Treatment with SGAs followed by lamotrigine monotherapy enhanced prefrontal and temporal lobe activity during a Response Inhibition Task demonstrating the reversal of disorder-relevant neural circuitry dysfunction in patients with adolescent bipolar disorder. Patient performance was not slowed down with this treatment regimen.
Shortened acquisition time or reduced-activity dose for gated myocardial perfusion SPECT with new reconstruction algorithm

To confirm that shortened acquisition time or reduced-activity dose in single-photon emission computed tomography (SPECT) myocardial perfusion imaging reconstructed with Astonish software (AS) does not compromise image quality or diagnostic accuracy. One hundred patients referred for SPECT myocardial perfusion imaging were prospectively studied. The patients were randomly selected to receive the full-dose protocol (group A, n = 54) or the half-dose protocol (group B, n = 46). The patients of group A underwent a 2-day stress/rest protocol. After half-time acquisition, they underwent a full-time acquisition for stress and rest SPECT. Group B underwent a 1-day stress/rest protocol. During peak stress, all patients received an intravenous injection of 99mTc-methoxyisobutylisonitrile (MIBI; 5.2 ± 0.6 mCi). After the full-time stress acquisition, the patients underwent a double-time stress acquisition. If the stress image showed a defect, a patient received 99mTc-MIBI (19.5 ± 1.7 mCi) at rest on the same day. The rest SPECT acquisition protocol was the same in both groups. The low count (LC) and high count (HC) were acquired for each patient. AS and filtered back projection (FBP) reconstructed each set of raw data. Image quality of perfusion was assessed on a four-point scale. Perfusion parameters and function parameters were calculated by quantitative perfusion SPECT and quantitative gated SPECT. Mean image quality for LC-AS and HC-AS (3.5 ± 0.5 and 3.7 ± 0.5, respectively) was superior to HC-FBP (3.1 ± 0.4) in group A (for all, p < 0.001). LC-AS and HC-AS (3.5 ± 0.5 and 3.6 ± 0.5, respectively) in group B were superior to HC-FBP (3.1 ± 0.3) (for all, p < 0.001). LC-AS, HC-AS and LC-FBP showed high diagnostic concordance with HC-FBP (kappa value was 0.92, 0.92, and 0.94, respectively; all p < 0.001). Cardiac SPECT studies can be acquired with half of the scan time or reduced radioactivity dose and reconstructed by using the AS algorithm without compromising image quality.
Anxiety in women "at risk' of developing breast cancer.

Do family history clinics offering counselling, surveillance and preventative programmes alleviate or exacerbate anxiety in women at a high risk of developing breast cancer? In this study risk perceptions and anxiety of 99 'at risk' women participating in the Tamoxifen Prevention Trial were compared with those of 87 'at risk' women not attending any specialist clinic who were recruited from the National Breast Screening Programme (NBSP). Most anxiety was found in NBSP women with a family history. Women attending the family history clinic and participating in the trial had anxiety scores comparable with 86 women recruited from the NBSP who did not have a family history. We conclude that such specialist clinics do not see a selected group of the most anxious 'at risk' women nor does participation in tamoxifen prevention programmes appear to increase anxiety.
Cognitive impairment in Spinocerebellar ataxia type
10

Cognitive and psychiatric dysfunction has been described in several neurodegenerative diseases but has not been systematically evaluated in spinocerebellar ataxia type 10 (SCA10).



The aim of the present study was to investigate the core cognitive features in a large cohort of Brazilian patients with SCA10, comparing the results against a healthy control group.



Twenty-eight SCA10 and 28 healthy subjects were prospectively assessed regarding cognitive function and psychiatric disorders at the Movement Disorders Unit of the Federal University of Paraná between February 2012 and October 2014.



The SCA10 group had worse depression scores, as well as cognitive performance, when compared to healthy individuals.



Our study showed mild cognitive and mood dysfunctions in patients with SCA10, consistent with the symptoms reported in the Cerebellar Cognitive Affective Syndrome described by Schmahmann JD in 1998. The description of these findings is an important clinical phenomenon that may guide physicians in specific disease management and improve quality of life of these patients.
Treatment of depression and anxiety with internet-based cognitive behavior therapy in patients with a recent myocardial infarction (U-CARE Heart): study protocol for a randomized controlled trial

Major depression and depressive symptoms are common in patients with a recent myocardial infarction (MI), and depression is associated with adverse cardiovascular outcomes. Anxiety post-MI is less studied, but occurs commonly in patients with heart disease, and is also considered a risk factor for recurrence of cardiac events. Cognitive behavior therapy (CBT) is an established therapy for depression and anxiety disorders. To the best of our knowledge, there have not been any studies to determine if internet-based CBT (iCBT) can reduce the symptoms of depression and anxiety in patients with a recent MI. The main aim of the U-CARE Heart trial is to evaluate an iCBT intervention for patients with a recent MI.



This is a randomized, controlled, prospective study with a multicenter design. A total of 500 participants will be randomized at a 1:1 ratio, around two months after an acute MI, to either iCBT or to a control group. Both groups will receive an optimal standard of care according to guidelines. The intervention consists of a self-help program delivered via the internet with individual online support from a psychologist. Treatment duration is 14 weeks. The primary outcome is change in patients' self-rated anxiety and depression symptoms from baseline to end of treatment. An internal pilot study was conducted indicating sufficient levels of study acceptability and engagement in treatment.



The present study is designed to evaluate an iCBT intervention targeting symptoms of depression and anxiety in a post-MI population. If effective, iCBT has several advantages, and will potentially be implemented as an easily accessible treatment option added to modern standard of care.
Radiographic validation of manual functional analysis of temporomandibular joint osteoarthritis.

The finding of osteoarthritis of temporomandibular joint (TMJ) obtained by clinical diagnosis, i.e. manual functional analysis (MFA) and the finding obtained by magnetic resonance imaging (MRI) as the gold standard were compared in 30 patients (mean age 52.6) diagnosed with osteoarthritis, selected out of 140 consecutive patients diagnosed with a TMJ disorder by MRI. The clinical parameters were symptoms of pain in the TMJ region, crepitations, and absence of clicking, which was confirmed by manual examinations as part of MFA. A positive MRI finding included flattening, subchondral degenerative changes with or without intact cortical bone, osteophytes and subchondral degenerative cysts of joint surfaces. The validity of MFA for osteoarthritis was as follows: sensitivity 0.38, specificity 0.91, positive predictive value (PPV) 0.77 and negative predictive value (NPV) 0.65. MRI examination revealed disk displacement (DD) without reduction in 12 (40.00%) patients and DD with reduction in one (3.33%) patient. The finding of passive compressions for the osteoarthritis diagnosis depending on DD showed sensitivity of 0.29, specificity of 0.95, PPV 0.67 and NPV 0.78. Although MFA significantly improves validity of clinical diagnosis when differentiating a myogenic from TMJ disorder, clinical determination of osteoarthritis is not satisfactory. Nonspecific clinical signs and symptoms accompanied by predominant pain in the TMJ on dynamic but not on passive manual examinations cannot help differentiate DD from osteoarthritis.
Primary chemotherapy with doxorubicin and paclitaxel in patients with early breast cancer: final results of a multicenter phase II study

To assess the efficacy and safety of primary systemic treatment with doxorubicin and paclitaxel in patients with early breast cancer. Forty patients with newly diagnosed, histologically confirmed breast cancer (T2, N0–1, M0) received primary chemotherapy with doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) in 3-week intervals for up to four courses. A total of 151 cycles were administered. The clinical response rate as assessed by sonographic measurement was 70%, and complete remissions of the primary tumor occurred in two patients. Eight patients (20%) had histologically confirmed complete responses. Predominant toxicity was myelosuppression with grade 3/4 neutropenia in 70% of patients. Non-hematological toxicity was generally moderate. Grade 4 non-hematological toxicities were not observed and grade 3 toxicity was reported with alopecia (98%) and stomatitis (10%). The combination of doxorubicin and paclitaxel is safe and highly active in patients with early breast cancer. The evaluated schedule is suitable for phase III studies.
A Resource Management Architecture for Metacomputing Systems

Metacomputing systems are intended to support remote and/or concurrent use of geographically distributed computational resources. Resource management in such systems is complicated by five concerns that do not typically arise in other situations: site autonomy and heterogeneous substrates at the resources, and application requirements for policy extensibility, co-allocation, and online control. We describe a resource management architecture that addresses these concerns. This architecture distributes the resource management problem among distinct local manager, resource broker, and resource co-allocator components, and defines an extensible resource specification language to exchange information about requirements. We describe how these techniques have been implemented in the context of the Globus metacomputing toolkit and used to implement a variety of different resource management strategies. We report on our experiences applying our techniques in a large testbed, GUSTO, incorporating 15 sites, 330 computers, and 3600 processors.
Transcriptome-wide studies of merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival.

Merkel cell carcinoma (MCC) is a polyomavirus-associated skin cancer that is frequently lethal and lacks established prognostic biomarkers. This study sought to identify biomarkers that improve prognostic accuracy and provide insight into MCC biology.



Gene expression profiles of 35 MCC tumors were clustered based on prognosis. The cluster of genes overexpressed in good-prognosis tumors was tested for biologic process enrichment. Relevant mRNA expression differences were confirmed by quantitative polymerase chain reaction and immunohistochemistry. An independent set of 146 nonoverlapping MCC tumors (median follow-up, 25 months among 116 living patients) was employed for biomarker validation. Univariate and multivariate Cox regression analyses were performed.



Immune response gene signatures were prominent in patients with good prognoses. In particular, genes associated with cytotoxic CD8+ lymphocytes were overexpressed in tumors from patients with favorable prognoses. In the independent validation set, cases with robust intratumoral CD8+ lymphocyte infiltration had improved outcomes (100% MCC-specific survival, n = 26) compared with instances characterized by sparse infiltration (60% survival, n = 120). Only stage and intratumoral CD8 infiltration (but not age, sex, or CD8+ lymphocytes localized to the tumor-stroma interface) were significant in both univariate and multivariate Cox regression analyses. Notably, traditional histologic identification of tumor-infiltrating lymphocytes was not a significant independent predictor of survival.



Intratumoral CD8+ lymphocyte infiltration can be readily assessed on paraffin-embedded tissue, is independently associated with improved MCC-specific survival, and therefore, may provide prognostic information that enhances established MCC staging protocols.
Additive value of severe diastolic dysfunction and contractile reserve in the identification of responders to cardiac resynchronization therapy.

The identification of responders remains challenging in cardiac resynchronization therapy (CRT). In this study we assessed the role of myocardial contractile reserve (CR) during dobutamine stress echocardiography (DSE) and resting severe diastolic dysfunction for identifying responders to CRT.



Sixty-nine patients (59% with ischaemic aetiology, ejection fraction: 26 ± 5%) referred for CRT underwent high-dose DSE. Contractile reserve was evaluated using a pressure-volume relationship, defined as systolic cuff pressure/end-systolic volume index difference between rest and peak DSE. We defined severe diastolic dysfunction as the presence of restrictive patterns and/or E/E' > 15. We divided the patients into four groups as follows: presence (CR+) or absence (CR-) of myocardial CR and presence (Diast+) or absence (Diast-) of severe diastolic dysfunction. Patients with CR+ Diast- showed higher percentage of clinical responders (91 vs. 46%, P= 0.002) and echocardiographic responders (90 vs. 25%, P= 0.001) to CRT, compared with patients with CR- Diast+. By log-rank analysis, event-free survival was significantly poorer in patients with CR- Diast+ (log rank = 18.36, P= 0.0004).



Heart failure patients with severe diastolic dysfunction and absence of myocardial CR during DSE had a poorer clinical and echocardiographic response to CRT. The associated evaluations of diastolic function and CR had an additive value in the identification of responders to CRT.
Housing First for Long-Term Shelter Dwellers with Psychiatric Disabilities in a Suburban County: A Four-Year Study of Housing Access and Retention

First is an effective intervention that ends and prevents homelessness for individuals with severe mental illness and co-occurring addictions. By providing permanent, independent housing without prerequisites for sobriety and treatment, and by offering support services through consumer-driven Assertive Community Treatment teams, Housing First removes some of the major obstacles to obtaining and maintaining housing for consumers who are chronically homeless. In this study, consumers diagnosed with severe mental illness and who had the longest histories of shelter use in a suburban county were randomly assigned to either one of two Housing First programs or to a treatment-as-usual control group. Participants assigned to Housing First were placed in permanent housing at higher rates than the treatment-as-usual group and, over the course of four years, the majority of consumers placed by both Housing First agencies were able to maintain permanent, independent housing. Results also highlight that providers new to Housing First must be aware of ways in which their practices may deviate from the essential features of Housing First, particularly with respect to enrolling eligible consumers on a first-come, first-served basis and separating clinical issues from tenant or housing responsibilities. Finally, other aspects of successfully implementing a Housing First program are discussed.
Validation of post-operative atrial fibrillation in the Western Denmark Heart Registry.

Post-operative new-onset atrial fibrillation and flutter (POAF) is associated with increased morbidity and mortality following cardiac surgery. Registers and databases are important data sources for observational studies in this research area; hence, the aim was to assess the data validity of the POAF diagnosis in the Western Denmark Heart Registry (WDHR).



We studied a 25% random sample (n = 1,381) from a cohort of 5,532 patients who underwent coronary artery bypass grafting, valve surgery or combinations between 1 January 2011 and 31 December 2013. Registrations of POAF diagnoses in the WDHR were compared with the actual clinical course as documented in the medical records. The positive predictive value for new-onset POAF in the WDHR was calculated.



A positive predictive value of 82.5% (95% confidence interval: 78.8-85.7) was found with a sensitivity and specificity of 75.2% and 90.9%, respectively.



A diagnosis of new-onset POAF in the WDHR is relatively valid and may be used for contemporary epidemiological studies. Improvements may optimise the registry's validity even further, emphasising the importance of continuous validation and maintenance of the registry.



none.
Cross Validation of Experts Versus Registration Methods for Target Localization in Deep Brain Stimulation

In the last five years, Deep Brain Stimulation (DBS) has become the most popular and effective surgical technique for the treatent of Parkinson's disease (PD). The Subthalamic Nucleus (STN) is the usual target involved when applying DBS. Unfortunately, the STN is in general not visible in common medical imaging modalities. Therefore, atlas-based segmentation is commonly considered to locate it in the images. In this paper, we propose a scheme that allows both, to perform a comparison between different registration algorithms and to evaluate their ability to locate the STN automatically. Using this scheme we can evaluate the expert variability against the error of the algorithms and we demonstrate that automatic STN location is possible and as accurate as the methods currently used.