nils-herrmann/clean_scirepeval huggingface dataset:
First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001).

We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans.



Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed.



Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively.



This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1.
The effect of C-reactive protein reduction with a highly specific antisense oligonucleotide on atrial fibrillation assessed using beat-to-beat pacemaker Holter follow-up

C-reactive protein (CRP) is known to be strongly associated with atrial fibrillation (AF). However, it is not clear if CRP is a causal factor for AF. ISIS-CRPRx is a novel antisense oligonucleotide that reduces CRP production by specifically inhibiting mRNA translation. The effect of ISIS-CRPRx on AF was evaluated. A double-blind phase II trial of ISIS-CRPRx in patients with paroxysmal AF and DDDRP permanent pacemakers (PPMs) with advanced atrial and ventricular Holters allowing beat-to-beat arrhythmia follow-up. Twenty six patients were screened and seven patients dosed with ISIS-CRPRx. After 4 weeks of baseline assessment, patients were randomly assigned to two treatment periods of either placebo then ISIS-CRPRx or ISIS-CRPRx then placebo. All patients were followed up for 8 weeks after the active treatment period. There was a 63.7 % (95 % CI 38.4 to 78.6 %, p = 0.003) relative reduction in CRP on treatment with ISIS-CRPRx versus baseline. Sensitivity analyses demonstrated a consistent treatment effect. The primary end-point was change in AF burden assessed by PPM. There was no significant difference in AF burden on treatment with ISIS-CRPRx versus baseline (OR 1.6, 95 % CI −2.42 to 5.62, p = 0.37). ISIS CRPRx was safe and well tolerated and there were no serious adverse events. Treatment with ISIS-CRPRx did not reduce AF burden in patients with paroxysmal AF and PPMs, despite a large relative reduction in CRP. In this population, highly specific CRP reduction had no clinically discernable effect upon paroxysmal AF. However, average levels of CRP at baseline were relatively low, so it remains possible that AF patients with higher levels of CRP may benefit from CRP-directed therapy.
The Effect of Orem's Self-Care Model on Quality of Life in Patients with Migraine: a Randomized Clinical Trial.

Many aspects of the lives of migraineurs are commonly affected by the condition, including occupational affairs, social and family life, responsibilities and ultimately the quality of life. This study was designed to determine the effect of orem's self-care nursing model on quality of life in patients with a migraine. This study was carried out in Tehran, Iran. According to the pre-post design of the randomized clinical trial, 88 patients were selected. After obtaining approval from the ethics committee of the Baqiyatallah Medical Sciences University's Research Deputy; Patients who signed the informed consent aged 20-55 years and without any more disease or disability affecting the quality of life were selected and randomly assigned to a group. Data collection tools were a demographic questionnaire, general health survey short form (SF36), and Orem cognition form and self-care checklist. Self-care model were held as four 30-45 minutes training sessions based on self-care deficit needs for the experimental group. The quality of life scores was measured in two stages, before and three months after intervention then were compared in both groups. Data were analyzed with statistical software SPSS and use of descriptive analysis tests, Chi-square, Mann-Whitney u and Wilcoxon. The final analysis was performed on 43 experimental and 40 controls. No significant difference was detected in the two groups in terms of demographic variables (P>0.05). All dimensions of quality of life including physical functioning, physical role limitation, body pain, general health, vitality, social functioning and emotional role limitation and mental health in the experimental group showed a significant increase after intervention compared to the control group (P<0.05). It was concluded that performing Orem's self-care nursing model improves function and overall quality of life and reduces the high cost of a migraine and migraine-related disability to individuals and society.
A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of osmotic-controlled release oral delivery system methylphenidate HCl in adults with attention-deficit/hyperactivity disorder in Japan.

To evaluate the safety and efficacy of osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) HCl in adults with attention-deficit/hyperactivity disorder (ADHD).



In this study, 284 adults with ADHD were randomized to OROS MPH or placebo. During the 4-week titration period, patients were titrated from a starting dose of 18 mg once daily to an individually-optimized dose of up to 72 mg once daily in weekly 18-mg increments. Patients continued on their individualized dose during the 4-week efficacy assessment period. The primary efficacy endpoint was change in DSM-IV Total ADHD Symptoms subscale score of Conners' Adult ADHD Rating Scale-Observer: Screening Version (CAARS-O:SV) from baseline to endpoint.



The mean change in DSM-IV Total ADHD Symptoms subscale score of CAARS-O:SV was significantly larger with OROS MPH compared with placebo (P < 0.0001, ANCOVA). Similar results were observed for the majority of secondary endpoints, including CAARS-O:SV total score and other subscale scores. Although treatment-emergent adverse events were reported more frequently in the OROS MPH group (81.8%) versus the placebo group (53.9%), OROS-MPH showed a well-tolerated safety profile overall.



OROS MPH in a dose range of 18-72 mg once daily was effective and well-tolerated in adult patients with ADHD.
Impact of the condolence letter on the experience of bereaved families after a death in intensive care: study protocol for a randomized controlled trial.

As intensive care mortality is high, end of life is a subject of major concern for intensivists. In this context, relatives are particularly vulnerable and prone to post-ICU syndrome, in the form of high levels of anxiety, depression, post-traumatic stress, and complicated grief. Grieving families suffer from a feeling of abandonment and evoke the need to get back in touch with the team to ask questions and remove doubts, but very few actually do. Aiding families during the grieving process is an important aspect of palliative care. A condolence letter represents an opportunity to recognize the pain of the family member and the strong tie that linked the family member to the ICU team, and to offer additional information if necessary. The goal of the study is to measure the impact of the condolence letter on the experience of bereaved families after a death in the ICU. Our hypothesis is that a post-death follow-up in the form of a condolence letter sent by the ICU physician who was in charge of the patient may help to reduce the risks of presenting symptoms of anxiety/depression, post-traumatic stress, and complicated grief.



This is a randomized, controlled, multicenter study. Research will compare two groups of bereaved family members: one group that does not receive a condolence letter (control) and one group that receives a condolence letter 15 days after the death (intervention). Each of the 22 participating centers will include 12 relatives. Participating relatives will be followed up by phone with a call at 1 month and one at 6 months to complete questionnaires, permitting evaluation of post-ICU burden. The main outcome is anxiety and depression measured at 1 month. Other outcomes include evaluation of quality of dying and death, post-traumatic stress, and complicated grief.



This study will allow us to assess if sending a condolence letter can reduce the risks of presenting symptoms of anxiety and depression, complicated grief, and symptoms of post-traumatic stress disorder after the death of a loved one in the ICU.
The MI bundle: enabling network and structural biology in genome visualization tools

Prioritization of candidate genes emanating from large-scale screens requires integrated analyses at the genomics, molecular, network and structural biology levels. We have extended the Integrated Genome Browser (IGB) to facilitate these tasks. The graphical user interface greatly simplifies building disease networks and zooming in at atomic resolution to identify variations in molecular complexes that may affect molecular interactions in the context of genomic data. All results are summarized in genome tracks and can be visualized and analyzed at the transcript level.



The MI Bundle is a plugin for the IGB. The plugin, help, video and tutorial are available at http://cru.genomics.iit.it/igbmibundle/ and https://github.com/CRUiit/igb-mi-bundle/wiki. The source code is released under the Apache License, Version 2.



arnaud.ceol@iit.it



Supplementary data are available at Bioinformatics online.
Impact of HMG-CoA reductase inhibitors on the incidence of polyomavirus-associated nephropathy in renal transplant recipients with human BK polyomavirus viremia.

Up to 20% of renal transplant recipients (RTR) will develop human BK polyomavirus (BKPyV) viremia. BKPyV viremia is a pre-requisite of polyomavirus-associated nephropathy (PyVAN). Risk of BKPyV infections increases with immunosuppression. Currently, the only effective therapy against PyVAN is reductions in immunosuppression, but this may increase the risk of rejection. In vitro data have shown that pravastatin dramatically decreased caveolin-1 expression in human renal proximal tubular epithelial cells (HRPTEC) and suppressed BKPyV infection in these cells. Based on these data, we postulated that statin therapy may prevent the progression of BKPyV viremia to PyVAN.



A multicenter, retrospective study was conducted in adult RTR transplanted between July 2005 and March 2012. All patients with documented BKPyV viremia (viral load >500 copies/mL on 2 consecutive tests) were included. Group I consisted of patients taking a statin before the BKPyV viremia diagnosis (n = 32), and Group II had no statin exposure before or after the BKPyV viremia diagnosis (n = 36). The primary endpoint was the incidence of PyVAN.



Demographic data, transplant characteristics, and the degree of immunosuppression (i.e., induction/maintenance therapies, rejection treatment) were similar between the groups, with the exception of more diabetics in Group I. The incidence of PyVAN was comparable between the 2 groups (Group I = 28.1% vs. Group II = 41.7%; P = 0.312).



Despite the proven in vitro effectiveness of pravastatin preventing BKPyV infection in HRPTEC, statins at doses maximized for cholesterol lowering, in RTR with BKPyV viremia, did not prevent progression to PyVAN.
Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: A bold FMRI study

Oral naltrexone reduces heavy drinking, but is less consistent as an abstinence promoter, whereas once-monthly extended-release naltrexone (XR-NTX) also maintains abstinence. The present study sought to determine if alcohol cue reactivity is attenuated by XR-NTX. Twenty-eight detoxified alcohol-dependent adult male and female volunteers received a single i.m. injection of either XR-NTX or placebo under double-blind conditions. An fMRI/cue reactivity procedure was conducted immediately before and two weeks after injection. At baseline, alcohol-related visual and olfactory cues elicited significant increases in orbital and cingulate gyri, inferior frontal and middle frontal gyri. Subsequently, brain activation was significantly altered in XR-NTX-treated individuals. These affected brain regions are associated with the integration of emotion, cognition, reward, punishment, and learning/memory, suggesting that XR-NTX attenuates the salience of alcohol-related cues. Such an effect on brain function may interrupt the processes associated with "slips" and relapse, which may account for XR-NTX's ability to maintain abstinence.
Long-term association between self-reported signs and symptoms and heart failure hospitalizations: the Atherosclerosis Risk In Communities (ARIC) Study.

Although studies of the accuracy of heart failure (HF) classification scoring systems are available, few have examined their performance when restricted to self-reported items.



We evaluated the association between a simplified version of the Gothenburg score, a validated HF score comprised of cardiac and pulmonary signs and symptoms and medication use, and incident HF hospitalizations in 15,430 Atherosclerosis Risk in Communities (ARIC) Study participants. Gothenburg scores (range: 0-3) were constructed using self-reported items obtained at study baseline (1987-89). Incident HF hospitalization over 14.7 years of follow-up was defined as the first identified hospitalization with an ICD-9 discharge code of 428 (n = 1,668). Self-reported Gothenburg scores demonstrated very high agreement with the original metric comprised of self-reported and clinical measures and were directly associated with incident HF hospitalizations: [score = 1: hazard rate ratio (HRR) = 1.23 (1.07-1.42); score = 2: HRR = 2.17 (1.92-2.43); score = 3: HRR = 3.98 (3.37-4.70)].



In a population-based cohort, self-reported Gothenburg criteria items were associated with hospitalized HF over a prolonged follow-up time. The association was also consistent across groups defined by sex and race, suggesting that this simple score deserves further study as a screening tool for the identification of individuals at high risk of HF in resource-limited settings.
Validation of the Korean version of the EORTC QLQ-C30

This study evaluated the Korean version of the EORTC QLQ-C30 (version 3.0) in terms of psychometric properties and its validation. One hundred and seventy patients completed three questionnaires EORTC QLQ-C30, the Beck depression inventory (BDI), and a brief pain inventory (BPI). Multitrait scaling analyses demonstrated that all scales met multidimensional conceptualization criteria, in terms of convergence and discrimination validity. Cronbach's α coefficients for eight multiple-item scales were greater than 0.70, with the exception of cognitive functioning. All interscale correlations were statistically significant in the expected direction (p < 0.01). Multivariate analyses showed that physical and emotional functioning were significant explanatory variables for the global quality-of-life (QOL) scale (regression coefficients: 0.36, p < 0.001; and 0.37, p < 0.001; respectively). All scales were significantly associated with pain severity and interference of the BPI, and with the cognitive-affective and somatic scales of the BDI. The emotional-functioning scale was substantially correlated with the cognitive-affective scale and somatic scale of the BDI. These results demonstrate that the Korean version of the EORTC QLQ-C30 is a valid instrument for evaluating Korean-speaking patients with cancer, and can be used to distinguish clearly between subgroups of patients of differing performance status.
Hemostatic changes in pediatric neurosurgical patients as evaluated by thrombelastograph.

Thromboembolic events are a known complication in neurosurgical patients. There is evidence to suggest that a hypercoagulable state may develop perioperatively. Thrombelastograph (TEG) coagulation analysis is a reliable method of evaluating hypercoagulability. We evaluated coagulation by using TEG data in pediatric neurosurgical patients undergoing craniotomy to determine whether a hypercoagulable state develops intraoperatively or postoperatively. Thirty children undergoing craniotomy for removal of a tumor or seizure focus were studied. Blood was analyzed with TEG) data by using native and celite techniques, at three time points for each patient: preoperatively after induction of anesthesia; intraoperatively during closure of the dura; and on the first postoperative day. Compared with preoperative indices, closing and postoperative celite TEG values were indicative of hypercoagulability with shortened coagulation time values (P < 0.001), prolonged alpha angle divergence values (P < 0.001), and above-normal TEG coagulation indices (P < or = 0.002). Reaction time values were shortened, and maximal amplitude of clot strength values were prolonged but did not reach statistical significance. Hypercoagulation develops early after resection of brain tissue in pediatric neurosurgical patients as assessed by using TEG data. Further studies are needed to determine the clinical significance of this hypercoagulable state.



Hypercoagulability in postoperative neurosurgical patients has been demonstrated in the adult population, but few studies have dealt with the pediatric population. We found that children undergoing craniotomy for focal resection, lobectomy, and hemispherectomy are hypercoagulable as detected by thrombelastograph coagulation analysis. Further studies are needed to determine whether this is clinically significant.
Safety and immunovirologic outcomes with maraviroc combination regimens in patients with a history of past treatment failures and virologic resistance in Brazil: an open-label, multicenter phase 3b study.

Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, experience in regimens containing newer antiretroviral agents is limited. The primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. Of 638 patients screened, 206 were treated and 125 completed the study. Approximately 70% were male; the mean age was 43.2 years. Most patients (65.0%) received an OBT combination of protease inhibitor plus nucleoside reverse transcriptase inhibitor. Adverse event (AE) and treatment-related AE incidence was 91.3% and 36.9%, respectively. The most common AEs were diarrhea, nasopharyngitis, and headache. Serious AEs and treatment-related serious AEs occurred in 16.5% and 4.4% of patients. Only eight patients (3.9%) discontinued due to AEs. Few AIDS-defining events were observed (4.9%). The proportion of patients with viral load <400 copies/ml increased from 2.4% at baseline to 43.9% at week 8, remaining >40% until week 48. At the end of treatment, 26.7% of patients had a viral load <400 copies/ml. Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/μl. In conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.
Bedside Glucose Monitoring—Is it Safe? A New, Regulatory-Compliant Risk Assessment Evaluation Protocol in Critically Ill Patient Care Settings*

New data have emerged from ambulatory and acute care settings about adverse patient events, including death, attributable to erroneous blood glucose meter measurements and leading to questions over their use in critically ill patients. The U.S. Food and Drug Administration published new, more stringent guidelines for glucose meter manufacturers to evaluate the performance of blood glucose meters in critically ill patient settings. The primary objective of this international, multicenter, multidisciplinary clinical study was to develop and apply a rigorous clinical accuracy assessment algorithm, using four distinct statistical tools, to evaluate the clinical accuracy of a blood glucose monitoring system in critically ill patients.



Observational study.



Five international medical and surgical ICUs.



All patients admitted to critical care settings in the centers.



None.



Glucose measurements were performed on 1,698 critically ill patients with 257 different clinical conditions and complex treatment regimens. The clinical accuracy assessment algorithm comprised four statistical tools to assess the performance of the study blood glucose monitoring system compared with laboratory reference methods traceable to a definitive standard. Based on POCT12-A3, the Clinical Laboratory Standards Institute standard for hospitals about hospital glucose meter procedures and performance, and Parkes error grid clinical accuracy performance criteria, no clinically significant differences were observed due to patient condition or therapy, with 96.1% and 99.3% glucose results meeting the respective criteria. Stratified sensitivity and specificity analysis (10 mg/dL glucose intervals, 50-150 mg/dL) demonstrated high sensitivity (mean = 95.2%, SD = ± 0.02) and specificity (mean = 95. 8%, SD = ± 0.03). Monte Carlo simulation modeling of the study blood glucose monitoring system showed low probability of category 2 and category 3 insulin dosing error, category 2 = 2.3% (41/1,815) and category 3 = 1.8% (32/1,815), respectively. Patient trend analysis demonstrated 99.1% (223/225) concordance in characterizing hypoglycemic patients.



The multicomponent, clinical accuracy assessment algorithm demonstrated that the blood glucose monitoring system was acceptable for use in critically ill patient settings when compared to the central laboratory reference method. This clinical accuracy assessment algorithm is an effective tool for comprehensively assessing the validity of whole blood glucose measurement in critically ill patient care settings.
A Bounded Storage Algorithm for Copying Cyclic Structures

A new algorithm is presented which copies cyclic list structures using bounded workspace and linear time. Unlike a previous similar algorithm, this one makes no assumptions about the storage allocation system in use and uses only operations likely to be available in a high-level language. The distinctive feature of this algorithm is a technique for traversing the structure twice, using the same spanning tree in each case, first from left to right and then from right to left.