nils-herrmann/clean_scirepeval huggingface dataset:
Treatment Enhances Ultradian Rhythms of CSF Monoamine Metabolites in Patients with Major Depressive Episodes

Unipolar and bipolar depressions show abnormal behavioral manifestations of ultradian (less than 24 h) rhythms, but abnormal rhythms of the central neurotransmitters thought to be important for depression pathophysiology (eg dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eye-movement sleep and hormonal rhythms), we hypothesized that depression-related changes in ultradian oscillations of DA and 5-HT might be revealed during antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for 24 h in 13 patients experiencing major depressive episodes (MDE) before and after treatment for 5 weeks with sertraline or bupropion were assayed for levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio was calculated. Data were analyzed in the frequency domain using Fourier transforms and multivariate permutation testing. Antidepressant treatments were associated with decreased variance for 5-HIAA, increased variance for HVA, and markedly increased variance for the HVA : 5-HIAA ratio (p<0.05, p<0.02, and p<0.003, respectively). With treatment, the correlations between 5-HIAA and HVA weakened (p=0.06). Power spectral density (PSD—the Fourier magnitude squared) of the 5-HIAA signals at periods of 1.75 and 3.7 h (both p<0.05) decreased, while circadian cycling of HVA levels (p<0.05) and of the ratio (p<0.005) increased after treatment. The PSD of the full-length HVA : 5-HIAA ratio series after treatment increased in rapid variability (20–103 min periods, p<0.05). Spectrographic windowing demonstrated a focal span of enhanced HVA : 5-HIAA ratio variability following antidepressant treatment, in an approximately 84-min period through the evening (p<0.05). Periodic neurotransmitter relationships in depressed patients were altered by treatment in this analysis of a small data set. This may represent a baseline abnormality in the regulation of periodic functions involved in the depression pathophysiology, but it could also be due to an unrelated antidepressant effect. Further studies including comparisons with healthy subject data are in progress.
Joint association of coffee consumption and other factors to the risk of type 2 diabetes: a prospective study in Finland

To examine joint associations of coffee consumption and other factors (including physical activity, obesity and alcohol consumption) with the risk of type 2 diabetes.Prospective follow-up study.In all, 10 188 Finnish men and 11 197 women aged 35–74 years without a history of stroke, coronary heart disease or diabetes at baseline.A self-administered questionnaire data on coffee, tea, alcohol and other food consumption, physical activity, smoking, socio-economic factors and medical history, together with measured height, weight and blood pressure using standardized protocol.During a mean follow-up of 13.4 years, there were 964 incident cases of type 2 diabetes. Multivariate-adjusted (age, study year, systolic blood pressure, education, smoking, physical activity, body mass index (BMI) and fruit, vegetable, sausage, bread, alcohol and tea consumption) hazard ratio of type 2 diabetes in participants who drank 0–2, 3–6 and ⩾7 cups of coffee were 1.00, 0.77 and 0.66 (P=0.022 for trend) in men, 1.00, 0.71 and 0.52 (P=0.001 for trend) in women, and 1.00, 0.75 and 0.61 (P<0.001 for trend) in men and women combined (adjusted also for sex), respectively. This inverse association was consistent in subjects with any joint levels of physical activity and BMI, and in alcohol drinkers and non-drinkers. Among obese and inactive people, coffee drinking of seven cups or more daily reduced the risk of type 2 diabetes to half.Coffee drinking was associated with a reduced risk of type 2 diabetes in both men and women, and this association was observed regardless of the levels of physical activity, BMI and alcohol consumption.
Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma

Allogeneic SCT is an effective therapy for lymphoma. Reduced-intensity conditioning (RIC) reduces non-relapse mortality (NRM) associated with myeloablative conditioning but relapse rates are high when performed in active disease. This study was designed to explore the safety and outcome of ibritumomab tiuxetan (Zevalin) combined with RIC in patients with advanced lymphoma. The study included 12 patients, median age 54 years (37–62), with a median of four prior treatments (2–6) and active disease documented on PET–CT. Zevalin 0.4 mCi/kg was given on day −14 and fludarabine combined with BU (n=6) or melphalan (n=6) was started on day −6. GVHD prevention was tapered 3 months after SCT to augment the graft-versus-lymphoma effect. All patients engrafted, a median of 14 days after SCT. Eighty-three percent achieved CR/PR. With a median follow-up of 21 months (12–37), 2-year PFS is 33%. Only three patients relapsed; cumulative incidence 25%. NRM was 42%, predominantly due to acute GVHD. Zevalin–RIC is feasible with consistent engraftment, acceptable organ toxicity, but high rates of acute GVHD. The low incidence of relapse suggests augmented anti-lymphoma effect. Zevalin–RIC merits further study. Better results may be achieved in patients earlier in disease course and with longer duration of immune-suppression.
Prognostic influence of Barrett's oesophagus and Helicobacter pylori infection on healing of erosive gastro-oesophageal reflux disease (GORD) and symptom resolution in non-erosive GORD: report from the ProGORD study.

Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase.



Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett's oesophagus (BO). Data from 6215 patients were included in the "intention to treat" analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4-8 weeks for endoscopic healing while NERD patients received 20 mg for 2-4 weeks for resolution of heartburn symptoms.



Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in Helicobacter pylori negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only H pylori infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for H pylori positive and H pylori negative, respectively; p = 0.03).



The presence of Barrett's mucosa, as well as severe mucosal damage, exerts a negative impact on healing. H pylori infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.
Assessment of venous thromboembolism risk and adequacy of prophylaxis in selected acute care medical centres in Arabian Gulf States: results from the ENDORSE study.

To assess the prevalence of venous thromboembolism (VTE) risk in acutely ill surgical and medical patients in selected acute care centres in the Arabian Gulf States, and to determine the proportion of at-risk patients who received effective prophylaxis in accordance with 2004 American College of Chest Physicians (ACCP) guidelines.



Eight hospitals from 3 countries (Kuwait, Kingdom of Saudi Arabia, and United Arab Emirates) contributed to the global ENDORSE (Epidemiological International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study. Medical records were reviewed for all the in-patients aged ≥40 years admitted to medical wards, and in patients aged ≥18 admitted to surgical wards. The VTE risk and recommended prophylaxis were assessed according to the 2004 ACCP guidelines.



Of 1,291 evaluable patients, 801 were considered at risk of VTE; 391 (48.8%) surgical patients and 410 (51.2%) medical patients. Of the 801 patients, 322 (40.2%) received ACCP-recommended VTE prophylaxis; 159 (40.7%) of surgical patients and 163 (39.8%) of medical patients.



The data showed that VTE prophylaxis was underutilized in high-risk hospitalized patients. We recommend that active measures should be implemented in acute care centres in these Arabian Gulf countries to ensure identification of patients at risk of VTE and institute the appropriate prophylaxis.
Pneumothorax in cystic fibrosis: prevalence and outcomes in Scotland.

Pneumothorax is a feared complication of cystic fibrosis. With improved survival into adult life the incidence of pneumothorax is expected to increase. The optimal management of these patients is unclear.



Case review of patients from the three Scottish adult CF centres.



A total of 22 episodes of pneumothorax occurred in 20 patients over a 12year period. 2 patients died as a result of the pneumothorax. 16 pneumothoraces were treated by insertion of an intercostal drain and 8 by observation. 8 patients suffered a prolonged air leak. 5 patients were treated with pleurodesis. Pneumothorax was associated with a small decline in lung function which persisted for at least 1year.



Pneumothorax can present a challenge to treat in adult CF. However successful outcomes can be achieved even in cases of prolonged air leaks. Current national guidelines help in selecting optimal pleural interventions.
Effects of low-frequency cranial electrostimulation on the rest-activity rhythm and salivary cortisol in Alzheimer's disease.

In previous studies, cranial electrostimulation (CES) had positive effects on sleep in depressed patients and in patients with vascular dementia. The present study examined the effects of low-frequency CES on the rest-activity rhythm and cortisol levels of patients with probable Alzheimer's disease (AD).



It was hypothesised that a decreased level of cortisol would parallel a positive effect of low-frequency CES on nocturnal restlessness. Sixteen AD patients were randomly assigned to an experimental group (n = 8) or a control group (n = 8). The experimental group was treated with CES, whereas the control group received sham stimulation, for 30 minutes a day, during 6 weeks. The rest-activity rhythm was assessed by actigraphy. Cortisol was measured repeatedly in the saliva throughout the day by means of salivette tubes.



Low-frequency CES did not improve the rest-activity rhythm in AD patients. Moreover, both groups showed an increase instead of a decrease in the level of cortisol.



These preliminary results suggest that low-frequency CES has no positive effect on the rest-activity rhythm in AD patients. An alternative research design with high-frequency CES in AD is discussed.
A two-step approach to myeloablative haploidentical transplantation: low nonrelapse mortality and high survival confirmed in patients with earlier stage disease.

Haploidentical hematopoietic stem cell transplantation (HSCT) is an attractive alternative donor option based on the rapid availability of an acceptable donor for most patients and decreased cost compared with costs of other alternative donor strategies. The safety of haploidentical HSCT has increased in recent years, making it ethically feasible to offer to patients with earlier stage disease. We developed a 2-step approach to haploidentical HSCT that separates the lymphoid and myeloid portions of the graft, allowing fixed T cell dosing to improve consistency in outcome comparisons. In the initial 2-step trial, the subset of patients without morphologic disease at HSCT had high rates of disease-free survival. To confirm these results, 28 additional patients without evidence of their disease were treated and are now 15 to 45 (median, 31) months past HSCT. To date, the 2-year cumulative incidence of nonrelapse mortality is 3.6%, with only 1 patient dying of nonrelapse causes, confirming the safety of this approach. Based on low regimen toxicity, the probabilities of disease-free and overall survival at 2 years are 74% and 77%, respectively, consistent with the findings in the initial trial and supporting the use of this approach in earlier stage patients lacking a matched related donor.
Clinical effects of a nine-month web-based intervention in subacute non-specific low back pain patients: a randomized controlled trial.

To test the clinical effect of a web-based lower back pain intervention on quality of life and selected lower back pain outcomes.



A prospective single-blinded randomized intervention.



Occupational preventive service.



One hundred office workers with non-specific subacute lower back pain.



The 50 intervention group subjects were educated daily about sitting correctly and asked to perform exercises shown by video demonstrations on the university website. The exercise routines included strengthening, mobility and stretching exercises focused on the postural stability muscles. The 50 control group subjects only received standard occupational care.



Outcomes were measured by the EuroQol questionnaire five dimensions three levels, the Oswestry Disability Index, and the StarT Back Screening Tool questionnaires. At nine months, the intervention group outcomes were compared to the baseline data and the control group outcomes.



For 97% (n = 45) of the experimental group quality of life (clinical utility) improved significantly; 3.58 times greater than the control group. Oswestry Disability Index showed an odds ratio (OR) of 5.42 with a 37% (n = 17) change for the intervention group with respect to the control group. With regard to the StarT Back Screening Tool, 76% (n = 35) of the intervention group improved their clinical state (odds ratio = 3.04 with respect to the control group improvement). Logistic regression analysis revealed positive changes in EuroQol questionnaire, increasing the likelihood of observing positive changes in StarT Back Screening Tool (OR = 15.5) and Oswestry Disability Index (OR = 4.5).



The intervention showed clinical improvements in quality of life and selected lower back pain outcomes in the experimental group compared to the control group.
Does Anxiety Cause Freezing of Gait in Parkinson's Disease?

Individuals with Parkinson's disease (PD) commonly experience freezing of gait under time constraints, in narrow spaces, and in the dark. One commonality between these different situations is that they may all provoke anxiety, yet anxiety has never been directly examined as a cause of FOG. In this study, virtual reality was used to induce anxiety and evaluate whether it directly causes FOG. Fourteen patients with PD and freezing of gait (Freezers) and 17 PD without freezing of gait (Non-Freezers) were instructed to walk in two virtual environments: (i) across a plank that was located on the ground (LOW), (ii) across a plank above a deep pit (HIGH). Multiple synchronized motion capture cameras updated participants' movement through the virtual environment in real-time, while their gait was recorded. Anxiety levels were evaluated after each trial using self-assessment manikins. Freezers performed the experiment on two separate occasions (in their ON and OFF state). Freezers reported higher levels of anxiety compared to Non-Freezers (p < 0.001) and all patients reported greater levels of anxiety when walking across the HIGH plank compared to the LOW (p < 0.001). Freezers experienced significantly more freezing of gait episodes (p = 0.013) and spent a significantly greater percentage of each trial frozen (p = 0.005) when crossing the HIGH plank. This finding was even more pronounced when comparing Freezers in their OFF state. Freezers also had greater step length variability in the HIGH compared to the LOW condition, while the step length variability in Non-Freezers did not change. In conclusion, this was the first study to directly compare freezing of gait in anxious and non-anxious situations. These results present strong evidence that anxiety is an important mechanism underlying freezing of gait and supports the notion that the limbic system may have a profound contribution to freezing in PD.
Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions.

To determine the role of CD154-CD40 interactions in the B cell overactivity exhibited by patients with active systemic lupus erythematosus (SLE), CD19+ peripheral B cells were examined before and after treatment with humanized anti-CD154 mAb (BG9588, 5c8). Before treatment, SLE patients manifested activated B cells that expressed CD154, CD69, CD38, CD5, and CD27. Cells expressing CD38, CD5, or CD27 disappeared from the periphery during treatment with anti-CD154 mAb, and cells expressing CD69 and CD154 disappeared from the periphery during the post-treatment period. Before treatment, active-SLE patients had circulating CD38 (bright) Ig-secreting cells that were not found in normal individuals. Disappearance of this plasma cell subset during treatment was associated with decreases in anti-double-stranded DNA (anti-dsDNA) Ab levels, proteinuria, and SLE disease activity index. Consistent with this finding, peripheral B cells cultured in vitro spontaneously proliferated and secreted Ig in a manner that was inhibited by anti-CD154 mAb. Finally, the CD38(+/++)IgD(+), CD38(+++), and CD38(+)IgD(-) B cell subsets present in the peripheral blood also disappeared following treatment with humanized anti-CD154. Together, these results indicate that patients with active lupus nephritis exhibit abnormalities in the peripheral B cell compartment that are consistent with intensive germinal center activity, are driven via CD154-CD40 interactions, and may reflect or contribute to the propensity of these patients to produce autoantibodies.
Predictors and outcomes of acute kidney injury after thoracic aortic endograft repair.

This study analyzed the incidence and the predictive factors of postoperative acute kidney injury (AKI) after thoracic endovascular aortic repair (TEVAR) and evaluated the effect of AKI on postoperative survival.



Between November 2000 and April 2011, all consecutive patients undergoing TEVAR of the descending thoracic or thoracoabdominal aorta were enrolled at four teaching hospitals. Estimated glomerular filtration rate (eGFR) was evaluated during the entire hospitalization. AKI was defined by the RIFLE (Risk, Injury, Failure, Loss of function, End-stage renal disease) consensus criteria.



The study included 171 patients (80% men) who were a mean age of 69±14 years (range, 18-87 years). AKI occurred in 24 patients (14%). Independent predictors of postoperative AKI were preoperative depressed eGFR, thoracoabdominal extent, and postoperative transfusion. Patients with AKI experienced major postoperative complications (P=.001), longer hospitalization (P=.008), and higher hospital mortality (29% vs 4%; P<.001). Kaplan-Meier analysis showed a survival of 82%, 51%, and 51% at 1, 3, and 5 years for patients who developed AKI, which was significantly worse than the 99%, 89%, and 80% for patients who did not experience AKI (P=.001).



Preoperative poor renal function, blood transfusions, and the thoracoabdominal extent of the aortic disease were the most important predictors for AKI.
A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia.

At present, there is no method available to predict response to farnesyltransferase inhibitors (FTIs). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1/APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy using a "leave one out" cross validation (LOOCV; 96%). RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair. The utility of this classifier for predicting response to tipifarnib was validated in an independent set of 58 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (154 vs 56 days; P < .001), which was independent of other covariates, including a previously described prognostic gene expression classifier. Therefore, these data indicate that a 2-gene expression assay may have utility in categorizing a population of patients with AML who are more likely to respond to tipifarnib.
Association of the HLA-DRB1 epitope LA(67, 74) with rheumatoid arthritis and citrullinated vimentin binding.

Although rheumatoid arthritis (RA) has long been associated with an HLA-DRB1 shared epitope, a systematic search for other epitopes has never been conducted. In addition, the relationship between these epitopes and the binding of citrullinated autoantigens has not been investigated. We developed a program that can analyze HLA data for all possible epitopes of up to 5 amino acids and used this program to assess the shared epitope hypothesis in RA.



We analyzed high-resolution data from the International Histocompatibility Working Group, which included a group of 488 patients with RA and a group of 448 racially and ethnically balanced control subjects, for all combinations of up to 5 amino acids among polymorphic HLA-DRB1 positions 8-93. Statistical significance was determined by chi-square and Fisher's exact tests, with a false discovery rate correction.



Three residues (V(11), H(13), and L(67)) were found to have the highest degree of association with RA susceptibility (P < 10(-11)), and D(70) was found to correlate best with RA resistance (P = 2 × 10(-11)). Of >2 million epitopes examined, LA(67, 74) exhibited the highest correlation with RA susceptibility (P = 2 × 10(-20); odds ratio 4.07 [95% confidence interval 3.07-5.39]). HLA alleles containing the LA(67, 74) epitope exhibited significantly greater binding to citrullinated vimentin(65-77) than did alleles containing D(70). Only 1 allele (DRB1*16:02) contained both LA(67, 74) and D(70); it bound citrullinated vimentin weakly and was not associated with RA.



The findings of these studies confirm the importance of HLA-DRB1 amino acids in pocket 4 for the binding of citrullinated autoantigens and susceptibility to RA.