nils-herrmann/clean_scirepeval huggingface dataset:
A Randomized, Placebo-Controlled Study of Memantine as Adjunctive Treatment in Patients with Schizophrenia

Memantine, an uncompetitive antagonist of glutamate receptors of the N-methyl-D-aspartate type is approved for the treatment of moderate to severe Alzheimer's disease. A growing body of evidence supports a link between the glutamatergic neurotransmission and schizophrenia. The purpose of this study (MEM-MD-29) was to examine the efficacy and safety of memantine as an adjunctive treatment to atypical antipsychotics in patients with persistent residual psychopathology of schizophrenia. In this double-blind, placebo-controlled study, participants were assigned to receive 20 mg/day memantine (n=70) or placebo (n=68), in addition to continuing treatment with atypical antipsychotics, for 8 weeks. The primary efficacy measure was the total score on the Positive and Negative Symptom Scale (PANSS). Secondary measures were positive and negative PANSS scores, PANSS responders, Calgary Depression Scale for Schizophrenia (CDSS), Clinical Global Impression of Severity (CGI-S), Clinical Global Impression of Improvement (CGI-I), and Brief Assessment of Cognition in Schizophrenia (BACS). Missing data were imputed using the last observation carried forward (LOCF) approach. Safety was assessed by means of physical examination, clinical laboratory evaluation, recording of adverse events (AEs), and measures of extrapyramidal symptoms. At end point, total PANSS scores did not differ between the memantine and the placebo group (p=0.570, LOCF). A similar outcome was observed for all secondary measures. The frequency of serious AEs in the memantine vs placebo group was 8.7 vs 6.0%; treatment discontinuations because of AEs occurred in 11.6 and 3.0% of patients in these groups, respectively. Memantine showed no efficacy as an adjunctive therapy in schizophrenia patients with residual psychopathology and was associated with a higher incidence of AEs than placebo.
Effects of Short-Term Hypocaloric Diet on Sympatho-Vagal Interaction Assessed by Spectral Analysis of Heart Rate and Blood Pressure Variability during Stress Tests in Obese Hypertensive Patients

We examined the effects of a short-term low-calorie diet on the activity of the autonomic nervous system during stress tests in obese patients with hypertension by analysis of heart rate and blood pressure variability. Eighteen obese inpatients with essential hypertension were given a regular-calorie diet (1,600 kcal, NaCl 7 g) for 4 days, and then a low-calorie diet (1,100 kcal, NaCl 7 g) for 11 days. During both the regular-calorie diet and low-calorie diet, power spectral analysis of heart rate and blood pressure variability at rest and during mental arithmetic test, deep breathing test, isometric handgrip test or cold pressor test was performed. Body weight and 24-h ambulatory blood pressure were significantly lower during the low-calorie diet than during the regular-calorie diet. Systolic and diastolic blood pressure significantly increased over the handgrip test and cold pressor test during both diets. The low frequency component (LF) of systolic blood pressure, a marker of sympathetic activity to the vasculature, during the deep breathing test and cold pressor test were significantly lower on the low-calorie diet than the regular-calorie diet. The blood leptin concentration was also significantly lower on the low-calorie diet than the regular-calorie diet. The decrease in body weight was positively correlated with the decrease in blood leptin concentration. The LF/high frequency component (HF) ratio of the RR interval at rest on the regular-calorie diet was negatively correlated with the decrease in blood leptin concentration. These results suggest that the autonomic nervous function assessed by analysis of heart rate and blood pressure variability during stress tests may be improved by weight loss due to a short-term low-calorie diet in obese patients with hypertension.
Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case–control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43–1.96); P=1.1 × 10−10). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10−7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.
Validating computationally predicted TMS stimulation areas using direct electrical stimulation in patients with brain tumors near precentral regions

The spatial extent of transcranial magnetic stimulation (TMS) is of paramount interest for all studies employing this method. It is generally assumed that the induced electric field is the crucial parameter to determine which cortical regions are excited. While it is difficult to directly measure the electric field, one usually relies on computational models to estimate the electric field distribution. Direct electrical stimulation (DES) is a local brain stimulation method generally considered the gold standard to map structure-function relationships in the brain. Its application is typically limited to patients undergoing brain surgery. In this study we compare the computationally predicted stimulation area in TMS with the DES area in six patients with tumors near precentral regions. We combine a motor evoked potential (MEP) mapping experiment for both TMS and DES with realistic individual finite element method (FEM) simulations of the electric field distribution during TMS and DES. On average, stimulation areas in TMS and DES show an overlap of up to 80%, thus validating our computational physiology approach to estimate TMS excitation volumes. Our results can help in understanding the spatial spread of TMS effects and in optimizing stimulation protocols to more specifically target certain cortical regions based on computational modeling.
The trouble with ubiquitous technology pushers

The idea has seized our imaginations with all the force of a logical necessity. In fact, you could almost say that the idea is the idea of logical necessity — the necessity of embedding little bits of silicon logic in everything around us. What was once the feverish dream of spooks and spies — to plant a “bug” in every object — has been enlarged and re-shaped into the millennial dream of ubiquitous computing. In this new dream, of course, the idea of a bug in every object carries various unpleasant overtones. But there are also overtones in the larger and better-promoted notion of ubiquitous computing, despite the fact that our ears are not yet attuned to them.
Validation in Spanish of a screening questionnaire for the detection of psoriatic arthritis in patients with psoriasis.

A patient self-administered questionnaire [PsA Screening and Evaluation (PASE)] has been developed and validated in English, but has not been tried in Spanish speaking populations. This study aimed to adapt and validate PASE in Spanish to screen Spanish speaking psoriasis patients for signs and symptoms of inflammatory arthritis.



Initial translation from English to Spanish (forward translation) was performed by two independent translators and the resulting versions were synthesized during a consensus meeting. The questionnaire was tried in a pilot study and resulted in a change in the agreement scale for a frequency scale with wording adaptation [Spanish PASE (PASE-S)].



One hundred and eleven patients were screened with PASE-S; 25 with PsA (without previous treatments), 23 with psoriasis, 22 with psoriasis and OA and 41 with OA without psoriasis. The diagnosis of psoriasis was performed by a dermatologist, and a rheumatologist determined the diagnosis of PsA or OA. Patients with PsA had statistically significant higher symptoms, function and total PASE-S scores compared with those without PsA. Receiver operator curves showed an area under the curve of 0.79 (95% CI 0.69, 0.89) for the total score. A cut-off value ≥34 showed sensitivity of 76%, and specificity of 74.4% for the diagnosis of PsA.



The validated PASE questionnaire is a self-administered tool that can be used to screen for PsA among patients with psoriasis in a Spanish speaking population. PASE was able to distinguish between symptoms of PsA and OA.
A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group Study.

Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC).



Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800 mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed.



Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and seven PRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months. Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS.



Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.
Juvenile conduct disorder as a risk factor for trauma exposure and posttraumatic stress disorder.

Juvenile conduct disorder (CD) is a well-documented risk factor for posttraumatic stress disorder (PTSD). This study examines the mechanisms underlying this relationship by using data from 3,315 twin pairs in the Vietnam Era Twin Registry. Results indicate the number of conduct disorder symptoms increased risk of trauma exposure and PTSD in a dose-response fashion. This increased risk was mediated in part by the positive association between CD and lifestyle factors and was not due to confounding by shared genetic or familial vulnerability. The findings suggest CD increases risk for trauma exposure and PTSD among male veterans through direct and indirect mechanisms. Veterans who have a history of CD are at high risk for trauma exposure and development of PTSD.
Pilot trial of autologous dendritic cells loaded with tumor lysate(s) from allogeneic tumor cell lines in patients with metastatic medullary thyroid carcinoma.

Immunotherapy with autologous dendritic cells (DCs) loaded with tumor lysate(s) from allogeneic tumor cell lines is a novel strategy to induce immune responses in cancer patients. We report on a pilot trial of autologous DCs pulsed with tumor cell lysate derived from allogeneic medullary thyroid carcinoma (MTC) cell lines in patients with metastatic MTC. The purpose of this study was to assess the safety, resulting immune responses and clinical activity of the DCs. DCs were injected into a groin lymph node at 3-week intervals. Monitoring included serial calcitonin tumor marker measurements, radiological imaging and immunological in vitro tests (T-cell interferon-gamma detection assay, T-cell cytotoxicity assay). Ten patients (median age 47 years, range 29-77) were enrolled. DC vaccinations were well-tolerated and safe. After a median follow-up of 11 months, (range 7-26), 3 (30%) of 10 patients had stable disease, while 7 (70%) of the patients progressed during treatment. In 2 patients with stable disease, calcitonin decreased below treatment levels, paralleled by a T-cell-mediated immune response. Notably, treatment with DCs pulsed with a combination of different tumor cell lysates was followed by a calcitonin decrease in 4 patients who had previously experienced a calcitonin increase during monotherapy with DCs pulsed with a single lysate. Allogeneic tumor cell lysate-based DC immunotherapy is well-tolerated and safe. Combined treatment with different tumor cell lysate-pulsed DCs increases the likelihood of a calcitonin tumor marker response and should therefore be preferred over monotherapy with DCs pulsed with a single lysate.
Optimal Management of High-Risk T1G3 Bladder Cancer: A Decision Analysis

Controversy exists about the most appropriate treatment for high-risk superficial (stage T1; grade G3) bladder cancer. Immediate cystectomy offers the best chance for survival but may be associated with an impaired quality of life compared with conservative therapy. We estimated life expectancy (LE) and quality-adjusted life expectancy (QALE) for both of these treatments for men and women of different ages and comorbidity levels.



We evaluated two treatment strategies for high-risk, T1G3 bladder cancer using a decision-analytic Markov model: (1) Immediate cystectomy with neobladder creation versus (2) conservative management with intravesical bacillus Calmette-Guérin (BCG) and delayed cystectomy in individuals with resistant or progressive disease. Probabilities and utilities were derived from published literature where available, and otherwise from expert opinion. Extensive sensitivity analyses were conducted to identify variables most likely to influence the decision. Structural sensitivity analyses modifying the base case definition and the triggers for cystectomy in the conservative therapy arm were also explored. Probabilistic sensitivity analysis was used to assess the joint uncertainty of all variables simultaneously and the uncertainty in the base case results. External validation of model outputs was performed by comparing model-predicted survival rates with independent published literature. The mean LE of a 60-y-old male was 14.3 y for immediate cystectomy and 13.6 y with conservative management. With the addition of utilities, the immediate cystectomy strategy yielded a mean QALE of 12.32 y and remained preferred over conservative therapy by 0.35 y. Worsening patient comorbidity diminished the benefit of early cystectomy but altered the LE-based preferred treatment only for patients over age 70 y and the QALE-based preferred treatment for patients over age 65 y. Sensitivity analyses revealed that patients over the age of 70 y or those strongly averse to loss of sexual function, gastrointestinal dysfunction, or life without a bladder have a higher QALE with conservative therapy. The results of structural or probabilistic sensitivity analyses did not change the preferred treatment option. Model-predicted overall and disease-specific survival rates were similar to those reported in published studies, suggesting external validity.



Our model is, to our knowledge, the first of its kind in bladder cancer, and demonstrated that younger patients with high-risk T1G3 bladder had a higher LE and QALE with immediate cystectomy. The decision to pursue immediate cystectomy versus conservative therapy should be based on discussions that consider patient age, comorbid status, and an individual's preference for particular postcystectomy health states. Patients over the age of 70 y or those who place high value on sexual function, gastrointestinal function, or bladder preservation may benefit from a more conservative initial therapeutic approach.
Intravesical instillation of Adriamycin for bladder tumors

In the present series of trials, Adriamycin (ADM) intravesical instillation therapy was found to be effective against tumors of papillary morphology measuring <10 mm in diameter that were of low pathological stage and low histological grade. The rate of complete disappearance increased in proportion to the concentration of ADM and the duration of retention of the drug, although the efficacy rates were almost the same in each trial. On the other hand, side effects on the bladder were reduced when the instilled solution was lower in concentration and the retention time was short.
An Expanded Version of the Multnomah Community Ability Scale: Anchors and Interview Probes for the Assessment of Adults with Serious Mental Illness

Objective clinical assessments are important in psychiatric settings to assess patients' functioning and the outcome of rehabilitation interventions. We developed anchors of the Multnomah Community Ability Scale (MCAS) and tested the inter-rater reliability of the expanded instrument. Twenty patients receiving psychiatric rehabilitation services participated in a structured interview and were rated by two raters. Intraclass correlation coefficients were .96 for the total and .87–.99 for the subscale scores. The expanded MCAS can serve as a reliable assessment tool.
Acellular cadaveric dermis decreases the inflammatory response in capsule formation in reconstructive breast surgery.

Acellular cadaveric dermis in implant-based breast reconstruction provides an alternative to total submuscular placement. To date, there has been no detailed in vivo human analysis of the histopathologic sequelae of acellular cadaveric dermis in implant-based breast reconstruction. Based on clinical observations, we hypothesize that acellular cadaveric dermis decreases the inflammatory response and foreign body reaction normally seen around breast implants.



Twenty patients underwent tissue expander reconstruction using the "dual-plane" acellular cadaveric dermis technique (AlloDerm). During implant exchange, intraoperative biopsy specimens were obtained of (1) biointegrated acellular cadaveric dermis and (2) native subpectoral capsule (internal control). Histopathologic analysis was performed. Masked biopsy specimens were scored semiquantitatively by an experienced histopathologist to reflect observed granulation tissue formation, vessel proliferation, chronic inflammatory changes, capsule fibrosis, fibroblast cellularity, and foreign body giant cell inflammatory reaction. Scores were analyzed statistically using the Wilcoxon signed rank test.



Acellular cadaveric dermis (AlloDerm) had statistically diminished levels for all parameters compared with corresponding native breast capsules (p<0.001).



This represents the first detailed histopathologic comparative analysis between biointegrated acellular cadaveric dermis and native capsules in implant-based breast reconstruction. These histopathologic findings suggest that certain properties intrinsic to acellular cadaveric dermis may limit capsule formation by diminishing inflammatory changes that initiate capsule formation. Further investigation is needed to determine whether acellular cadaveric dermis reduces the incidence of breast capsular contracture.
Phase I and pharmacokinetic study of tirapazamine (SR 4233) administered every three weeks.

Tirapazamine (SR 4233; 3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) is a bioreductive agent exhibiting up to 200 x greater toxicity for hypoxic cells as compared to oxygenated cells. In murine studies, a selective increase in tumor kill was observed when tirapazamine was coadministered with other agents, notably cisplatin. A Phase I study of single-agent tirapazamine administered i.v. every 3 weeks was conducted to determine the toxicity of a schedule for use with systemic chemotherapy. A total of 28 patients were given 50 courses of tirapazamine at doses ranging from 36-450 mg/m2. No tumor responses were observed. Reversible deafness and tinnitus were dose-limiting, with ototoxicity observed in 1 of 6 patients treated at 330 mg/m2, 1 of 4 patients treated at 390 mg/m2, and 3 of 3 patients treated at 450 mg/m2. Muscle cramps, nausea, and vomiting were also observed. Pharmacokinetic studies revealed a greater than dose-proportional increase in the area under the plasma concentration x time curve (AUCs) of the two major metabolites. Patients who developed ototoxicity generally showed higher plasma AUC values for the parent drug and metabolites. The mean plasma tirapazamine AUC at 330 mg/m2 was 1026.5 microgram/ml x min (range 863. 8-1252.3), but no pharmacokinetic data are available for the solitary patient who developed otoxicity at this dose level. These AUC values were in the (estimated) range required for therapeutic effect in murine studies. Ototoxicity was not observed when the AUC of tirapazamine was equal to or less than 1252 microgram/ml x min. The dose of 330 mg/m2 was therefore chosen as an appropriate level for combination chemotherapy studies.
Accounting for data dependencies within a hierarchical dirichlet process mixture model

We propose a hierarchical nonparametric topic model, based on the hierarchical Dirichlet process (HDP), that accounts for dependencies among the data. The HDP mixture models are useful for discovering an unknown semantic structure (i.e., topics) from a set of unstructured data such as a corpus of documents. For simplicity, HDP makes an exchangeability assumption that any permutation of the data points would result in the same joint probability of the data being generated. This exchangeability assumption poses a problem for some domains where there are clear and strong dependencies among the data. A model that allows for non-exchangeability of data can capture these dependencies and assign higher probabilities to clusters that account for data dependencies, for example, inferring topics that reflect the temporal patterns of the data. Our model incorporates the distance dependent Chinese restaurant process (ddCRP), which clusters data with an inherent bias toward clusters of data points that are near to one another, into a hierarchical construction analogous to the HDP, and we call this new prior the distance dependent Chinese restaurant franchise (ddCRF). When tested with temporal datasets, the ddCRF mixture model shows clear improvements in data fit compared to the HDP in terms of heldout likelihood and complexity. The resulting set of topics shows the sequential emergence and disappearance patterns of topics.