nils-herrmann/clean_scirepeval huggingface dataset:
Multicenter study of brain volume abnormalities in children and adolescent-onset psychosis.

The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of "schizophrenia" or "other psychosis" showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents.
Favorable outcome after complete resection in elderly soft tissue sarcoma patients: Japanese Musculoskeletal Oncology Group study.

The surgical management of soft tissue sarcoma (STS) in elderly patients has only been addressed in a few studies. The objective of the current study was to assess surgical outcomes in patients with STS aged 70 years and older and the association of older age with the survival after complete resection.



A retrospective analysis was conducted in 158 elderly patients with localized STS who visited 11 institutions participating in Japanese Musculoskeletal Oncology Group between 1995 and 2006 and were treated by surgical resection. Univariate and multivariate analyses were performed to identify prognostic factors.



Median follow-up period was 38 months. Histologically high-grade tumors were detected in 71% of the patients. Wide resection with adequate margins was performed in 66% of the cases. Systemic chemotherapy was performed in only 5 patients. Univariate analysis identified histological grade and gender as statistically significant prognostic factors for sarcoma-specific survival. Multivariate analysis did not identify significant prognostic factors for sarcoma-specific survival, although high grade sarcoma emerged as a potentially significant prognostic factor (P = 0.050). Local recurrence was detected in 19% of the patients. Multivariate analysis of local recurrence-free survival showed that tumor site and surgical margins were statistically significant prognostic factors.



Older age was not identified as a prognostic factor for sarcoma-specific survival, which is not consistent with the findings of previous studies showing that older age was associated with decreased sarcoma-specific survival. Complete resection should be indicated and can lead to optimal treatment outcome for properly selected elderly patients.
Elevated pulmonary artery systolic pressures are associated with a lower risk of atrial fibrillation following lung transplantation.

Atrial fibrillation (AF) is common after open-chest procedures, but the etiology remains poorly understood. Lung transplant procedures allow for the study of novel contributing factors.



Records of lung transplant procedures performed at a single center between 2002 and 2009 were reviewed.



Of 174 patients, 27 (16%) had AF a median 6 days post-surgery. Post-operative AF patients less often had right ventricular hypertrophy (RVH) by either electrocardiogram (0 versus 14%, P=.042) or echocardiography (19% versus 47%, P=.006), and had lower pulmonary artery systolic pressures (PASP) (39 ± 12 versus 51 ± 22, P=.005). After multivariable adjustment, every 10-mm Hg increase in PASP was associated with a 31% reduction in the odds of post-operative AF (OR 0.69, 95% CI 0.49-0.98, P=.035). A higher pulmonary pressure was the only predictor independently associated with less post-operative AF.



Higher PASP was associated with a lower risk of AF after lung transplantation.
Mortality from diseases other than cancer following low doses of ionizing radiation: results from the 15-Country Study of nuclear industry workers.

Ionizing radiation at very high (radio-therapeutic) dose levels can cause diseases other than cancer, particularly heart diseases. There is increasing evidence that doses of the order of a few sievert (Sv) may also increase the risk of non-cancer diseases. It is not known, however, whether such effects also occur following the lower doses and dose rates of public health concern.



We used data from an international (15-country) nuclear workers cohort study to evaluate whether mortality from diseases other than cancer is related to low doses of external ionizing radiation. Analyses included 275 312 workers with adequate information on socioeconomic status, over 4 million person-years of follow-up and an average cumulative radiation dose of 20.7 mSv; 11 255 workers had died of non-cancer diseases.



The excess relative risk (ERR) per Sv was 0.24 [95% CI (confidence intervals) -0.23, 0.78] for mortality from all non-cancer diseases and 0.09 (95% CI -0.43, 0.70) for circulatory diseases. Higher risk estimates were observed for mortality from respiratory and digestive diseases, but confidence intervals included zero. Increased risks were observed among the younger workers (attained age <50 years, identified post hoc) for all groupings of non-cancer causes of death, including external causes. It is unclear therefore whether these findings reflect real effects of radiation, random variation or residual confounding.



The most informative low-dose radiation study to date provides little evidence for a relationship between mortality from non-malignant diseases and radiation dose. However, we cannot rule out risks per unit dose of the same order of magnitude as found in studies at higher doses.
Adrenocorticotrophic hormone (ACTH) responsiveness to ghrelin increases after 6 months of ketoconazole use in patients with Cushing's disease: comparison with GH-releasing peptide-6 (GHRP-6).

In Cushing's disease (CD), adrenocorticotrophic hormone (ACTH)/cortisol responses to growth hormone secretagogues (GHS), such as ghrelin and GHRP-6, are exaggerated. The effect of clinical treatment of hypercortisolism with ketoconazole on ACTH secretion in CD is controversial. There are no studies evaluating ACTH/cortisol responses to GHS after prolonged ketoconazole use in these patients.



To compare ghrelin- and GHRP-6-induced ACTH/cortisol release before and after ketoconazole treatment in patients with CD.



Eight untreated patients with CD (BMI: 28.5 +/- 0.8 kg/m(2)) were evaluated before and after 3 and 6 months of ketoconazole treatment and compared with 11 controls (BMI: 25.0 +/- 0.8).



After ketoconazole use, mean urinary free cortisol values decreased significantly (before: 613.6 +/- 95.2 nmol/24 h; 3rd month: 170.0 +/- 27.9; 6th month: 107.9 +/- 30.1). The same was observed with basal serum cortisol (before: 612.5 +/- 69.0 nmol/l; 3rd month: 463.5 +/- 44.1; 6th month: 402.8 +/- 44.1) and ghrelin- and GHRP-6-stimulated peak cortisol levels (before: 1183.6 +/- 137.9 and 1045.7 +/- 132.4; 3rd month: 637.3 +/- 69.0 and 767.0 +/- 91.0; 6th month: 689.8 +/- 74.5 and 571.1 +/- 71.7 respectively). An increase in basal ACTH (before: 11.2 +/- 1.6 pmol/l; 6th month: 19.4 +/- 2.7) and in ghrelin-stimulated peak ACTH values occurred after 6 months (before: 59.8 +/- 15.4; 6th month: 112.0 +/- 11.2). GHRP-6-induced ACTH release also increased (before: 60.7 +/- 17.2; 6th month: 78.5 +/- 12.1), although not significantly.



The rise in basal ACTH levels during ketoconazole treatment in CD could be because of the activation of normal corticotrophs, which were earlier suppressed by hypercortisolism. The enhanced ACTH responses to ghrelin after ketoconazole in CD could also be due to activation of the hypothalamic-pituitary-adrenal axis and/or to an increase in GHS-receptors expression in the corticotroph adenoma, consequent to reductions in circulating glucocorticoids.
Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects

The aim of this study was to investigate whether dynamic strength training modifies the control of lipolysis, with particular attention paid to the involvement of the antilipolytic adrenergic alpha 2A receptor (ADRA2A) pathway. Twelve obese men (age: 47.4±2.8 years; BMI: 32.7±0.9) were investigated during a 210-min euglycaemic–hyperinsulinaemic clamp conducted before and after 3 months of dynamic strength training. Before and during the third hour of the clamp, the lipolytic effect of a perfusion of isoproterenol or adrenaline (epinephrine) alone or associated with the ADRA2A antagonist phentolamine was evaluated using the microdialysis method of measuring extracellular glycerol concentration (EGC) in subcutaneous abdominal adipose tissue (SCAAT). In addition, biopsies of SCAAT were carried out before and after training to determine mRNA levels The training increased insulin sensitivity in adipose tissue. The decrease of EGC was more pronounced during the clamp conducted after the training period than during the clamp done in pre-training conditions. Before and after the training, catecholamines induced an increase in EGC, the increase being lower during the clamp on each occasion. The isoproterenol-induced increase in EGC was higher after the training. Adrenaline-induced lipolysis was potentiated by phentolamine after but not before the training. There were no training-induced changes in mRNA levels of key genes of the lipolytic pathway in SCAAT. In obese subjects, dynamic strength training improves whole-body and adipose tissue insulin responsiveness. It increases responsiveness to the adrenergic beta receptor stimulation of lipolysis and to the antilipolytic action of catecholamines mediated by ADRA2As.
Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin's lymphoma: a randomized controlled trial.

The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia, infection, and cytotoxic chemotherapy administration was studied in a randomized trial in patients receiving intensive weekly chemotherapy for non-Hodgkin's lymphoma (NHL). Eighty patients (aged 16 to 71 years) with high-grade NHL (Kiel) of any stage were randomized to receive VAPEC-B chemotherapy alone (39 patients) or with G-CSF administered as a daily subcutaneous dose of 230 micrograms/m2 (41 patients). Prophylactic ketoconazole and cotrimoxazole were administered to all patients throughout treatment. The protocol specified identical dose modification and antibiotic treatment criteria bor both groups. Neutropenia (absolute neutrophil count [ANC] less than 1.0 x 10(9)/L) occurred in 15 of 41 (37%) of the G-CSF-treated patients and in 33 of 39 (85%) of the controls, giving a relative risk for control patients of 2.31 (95% confidence interval [CI], [1.51, 3.54]; P = .00001). Fever (greater than or equal to 37.5 degrees C) with neutropenia (ANC less than 1.0 x 10(9)/L) occurred in 9 of 41 (22%) of the G-CSF group and in 17 of 39 (44%) of the controls (relative risk for control, 2.26; 95% CI [1.01, 5.06]; P = .04). There were fewer treatment delays, with shorter duration (P = .01) in patients receiving G-CSF. Chemotherapy doses were reduced in 4 of 41 (10%) of the G-CSF patients and 13 of 39 (33%) of the controls (P = .01). The dose intensity of cytotoxic chemotherapy was significantly increased in patients receiving G-CSF (median of 95% in G-CSF group compared with 83% in control patients). Three vascular deaths occurred in the G-CSF group. Delays in the control group most commonly resulted from neutropenia (19 patients, compared with 2 patients in the G-CSF-treated group, P = .000007). Severe mucositis was the major dose-limiting toxicity in G-CSF-treated patients, but did not occur more frequently than in controls (15 patients in each group). Overall, patients randomized to receive G-CSF achieved a greater dose intensity than control patients, but this did not result in significant differences in drug toxicity (other than neutropenia), intravenous antibiotic usage, or hospitalization between the two groups.
The high incidence of the emergence of entecavir-resistant mutants among patients infected with lamivudine-resistant hepatitis B virus.

Hepatitis B virus (HBV) infection remains to be one of the most prevailing infection in the world, causing chronic liver diseases. Although lamivudine has been effective to suppress HBV replication, longer durations of administration can lead to the emergence of drug-resistant mutant viruses, followed by reactivation of hepatic inflammation (breakthrough hepatitis). Moreover, the optimal period of administration as well as the effects of anti-viral nucleot(s)ide such as lamivudine, adefovir, and entecavir, has not been established. To evaluate the efficacy of the anti-viral effects of entecavir for lamivudine-resistant HBV, we administered entecavir sequentially in four patients with chronic HBV infection, who demonstrated the emergence of lamivudine-resistant HBV and histological active hepatitis. The antiviral effects were evaluated by the serum viral loads and biochemical laboratory data. After follow-up periods of more than 36 months, we found high incidence in the emergence of entecavir resistant mutants (3/4, i.e., 75%). An additional mutation at the 184th amino acid, different from the previously reported lamivudine-resistant mutations (80th, 180th, and 204th), seemed to have a close relationship with the induction of entecavir-resistant mutants at least for Japanese HBV genotype C. Our observation draws attention to the possibility that the usage of entecavir for lamivudine-resistant HBV could promptly induce entecavir-resistant mutations in addition to lamivudine-resistance.
A phase 1 study of tazarotene in adults with advanced cancer

Tazarotene is an acetylenic retinoid which is metabolised to tazarotenic acid and which binds selectively to the retinoid receptors RARβ and RARγ. The safety, toxicity and pharmacokinetics of oral tazarotene were determined over 12 weeks of treatment in 34 patients with advanced cancer. Commonly seen toxicities were mucocutaneous symptoms, musculoskeletal pain and headache. Dose-limiting toxicities were hypercalcaemia, hypertriglyceridaemia and musculoskeletal pain. The maximum tolerated dose of tazarotene in this schedule is 25.2 mg day−1. Plasma concentrations of tazarotenic acid were found to peak rapidly within 1–3 h of dosing and thereafter declined quickly. The Cmax and AUC values on day 0, and weeks 2 and 4 were similar indicating no drug accumulation. The dose-normalised Cmax and AUC values at different dose levels and different study days appeared to be similar indicating linear pharmacokinetics. No objective responses were seen, although stable disease was seen in six out of eight evaluable patients receiving the three highest dose levels of tazarotene (16.8, 25.2 or 33.4 mg day−1). We conclude that oral tazarotene is well tolerated when administered daily for 12 weeks, has a favourable toxicity profile compared with other retinoids and merits further investigation as an anticancer therapy.
Causes of death in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.

This study analyzed the causes of death in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.



Both implantable cardioverter-defibrillators (ICDs) and antiarrhythmic drugs (AADs) are used as mainstays of treatment for life-threatening ventricular arrhythmias in patients who have survived either ventricular fibrillation or sustained ventricular tachycardia with hemodynamic compromise and serious symptoms. The AVID Trial compared the effectiveness of these two therapies. Survival was better with the ICD. Assessment of the cause of death should help to determine the mechanism of improvement in survival with the ICD.



Of 1,016 patients enrolled in the AVID Trial, 202 patients died. The mode of death was determined by the unblinded Principal Investigator and independently by an Events Committee, which reviewed materials meticulously blinded with respect to treatment. Deaths were classified as cardiac or noncardiac. Cardiac deaths were further classified as arrhythmic or nonarrhythmic, and causes of noncardiac death were identified.



Deaths were more frequent in patients treated with an AAD (n = 122), compared with patients treated with the ICD (n = 80), unadjusted p < 0.001, p = 0.012 adjusted for sequential monitoring. In AVID, 157 deaths were cardiac, and 79 were arrhythmic. The major effect of the ICD was to prevent arrhythmic death (AAD = 55, ICD = 24, nominal unadjusted p < 0.001). Nonarrhythmic cardiac deaths were equal (AAD = 39, ICD = 39). Patients treated with an AAD had a slightly greater incidence of noncardiac deaths (28 vs. 17, p = 0.053), primarily due to pulmonary and renal causes.



The ICD is more effective than an AAD in reducing arrhythmic cardiac death, while nonarrhythmic cardiac death is unchanged. Of note, apparent arrhythmic death still seems to constitute 38% of all cardiac deaths despite treatment with an ICD. However, the ICD remains superior to an AAD in prolonging survival after life-threatening arrhythmias.
Gene expression is differentially regulated in skeletal muscle and circulating immune cells in response to an acute bout of high-load strength exercise

High-intensity exercise induces many metabolic responses. In is unknown whether the response in the peripheral blood mononuclear cells (PBMCs) reflects the response in skeletal muscle and whether mRNA expression after exercise can be modulated by nutritional intake. The aims were to (i) investigate the effect of dairy proteins on acute responses to exercise in skeletal muscle and PBMCs measuring gene expression and (ii) compare this response in young and older subjects. We performed two separate studies in young (20–40 years) and older subjects (≥70 years). Subjects were randomly allocated to a milk group or a whey group. Supplements were provided immediately after a standardized exercise session. We measured mRNA expression of selected genes after a standardized breakfast and 60/120 min after finishing the exercise, using RT-qPCR. We observed no significant differences in mRNA expression between the milk and the whey group; thus, we merged both groups for further analysis. The mRNA expression of IL6, TNF, and CCL2 in skeletal muscle increased significantly after exercise compared with smaller or no increase, in mRNA expression in PBMCs in all participants. The mRNA expression of IL1RN, IL8, and IL10 increased significantly in skeletal muscle and PBMCs. Some mRNA transcripts were differently regulated in older compared to younger participants in PBMCs. An acute bout of heavy-load strength exercise, followed by protein supplementation, caused overlapping, but also unique, responses in skeletal muscle and PBMCs, suggesting tissue-specific functions in response to exercise. However, no different effects of the different protein supplements were observed. Altered mRNA expressions in PBMCs of older participants may affect regenerative mechanisms.
Long-term follow-up of a randomized Phase II study of cisplatin/5-FU concurrent chemoradiotherapy for esophageal cancer (KROSG0101/JROSG021).

Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed.



Eligible patients were <75 years old and performance status 0-2, and had Stages II-IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m(2) Days 1 and 29 and 5-fluorouracil 700 mg/m(2) Days 1-5 and 29-33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m(2) Days 1-5, 8-12, 29-33 and 36-40, and 5-fluorouracil 250 mg/m(2) Days 1-14 and 29-42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms.



Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22-48%), while those for arm B were 44 and 22% (11-35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment.



Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.
A validation study of new risk grouping criteria for postoperative treatment in stage IB cervical cancers without high-risk factors: rethinking the Gynecologic Oncology Group criteria.

The aim of this study was to verify whether the Gynecologic Oncology Group (GOG) criteria are valid in a different cohort of patients and to investigate simplified new criteria tailoring adjuvant radiation therapy in patients with intermediate-risk factors after radical hysterectomy.



We analyzed the data of 332 patients with FIGO stage IB cervical cancer who underwent radical hysterectomy between 1994 and 2007. Two hundred and twenty-five patients without high-risk factors (lymph node metastasis, parametrial invasion, or positive surgical margins) were identified and were classified into low-risk and high-risk groups according to the GOG criteria and new criteria based on combinations of intermediate-risk factors (large tumor size, deep stromal invasion, lymph-vascular space invasion). We evaluated the prognostic significance of both criteria.



We identified 140 low-risk patients and 85 high-risk patients in the application of the GOG criteria. Low-risk patients had significantly better disease-free survival (DFS) (P=0.001) and overall survival (OS) (P=0.013) than high-risk patients. There were 145 low-risk patients and 80 high-risk patients on applying the new criteria. Low-risk patients had significantly better DFS (P=0.001) and OS (P=0.013) than high-risk patients. The receiver operating characteristic (ROC) curves showed that both criteria had similar performance for predicting which patients would have help from adjuvant therapy.



This study demonstrated that the GOG criteria were still valid in the different population, the simplified new criteria were convenient to apply in practice, and the performance of the new criteria was as good as the GOGs.