nils-herrmann/clean_scirepeval huggingface dataset:
Safety and Tolerability of the Treatment of Youth-Onset Type 2 Diabetes

Data related to the safety and tolerability of treatments for pediatric type 2 diabetes are limited. The TODAY clinical trial assessed severe adverse events (SAEs) and targeted nonsevere adverse events (AEs) before and after treatment failure, which was the primary outcome (PO).



Obese 10- to 17-year-olds (N = 699) with type 2 diabetes for <2 years and hemoglobin A1c (A1C) ≤ 8% on metformin monotherapy were randomized to one of three treatments: metformin, metformin plus rosiglitazone (M + R), or metformin plus lifestyle program (M + L). Participants were followed for 2-6.5 years.



Gastrointestinal (GI) disturbance was the most common AE (41%) and was lower in the M + R group (P = 0.018). Other common AEs included anemia (20% before PO, 14% after PO), abnormal liver transaminases (16, 15%), excessive weight gain (7, 9%), and psychological events (10, 18%); the AEs were similar across treatments. Permanent medication reductions/discontinuations occurred most often because of abnormal liver transaminases and were lowest in the M + R group (P = 0.005). Treatment-emergent SAEs were uncommon and similar across treatments. Most (98%) were unrelated or unlikely related to the study intervention. There were no deaths and only 18 targeted SAEs (diabetic ketoacidosis, n = 12; severe hypoglycemia, n = 5; lactic acidosis, n = 1). There were 62 pregnancies occurring in 45 participants, and 6 infants had congenital anomalies.



The TODAY study represents extensive experience managing type 2 diabetes in youth and found that the three treatment approaches were generally safe and well tolerated. Adding rosiglitazone to metformin may reduce GI side effects and hepatotoxicity.
Can Patients' Likelihood of Benefiting from Primary Chemotherapy for Breast Cancer Be Predicted Before Commencement of Treatment?

Primary chemotherapy is commonly used in patients with breast cancer to downstage the primary tumour prior to surgery. There is a need to establish, prior to commencement of chemotherapy, predictors of clinical and pathological response, which may then be surrogate markers for patient survival and thus allow identification of patients who are most likely to benefit from such treatment.  A total of 104 patients with large and locally advanced breast cancers received an anthracycline/docetaxel-based regimen prior to surgery. Immunohistochemistry was carried out on pre-treatment core biopsies of the tumour to detect hormone receptors (oestrogen-ER; progesterone-PR), a proliferation marker (MIB-1), the oncoprotein Bcl-2, an extracellular matrix degradation enzyme (cathepsin D), p53, and an oestrogen associated protein (pS2). Both clinical and pathological response were assessed following completion of chemotherapy.  Patients whose tumours did not express oestrogen receptor (p= 0.02) or did not express Bcl-2 (p < 0.01) had a better pathological response in a univariate analysis. However, in a multivariate model, it was only the absence of detectable Bcl-2 protein that predicted a better pathological response (p= 0.001).  This study has identified that patients whose breast cancers are most likely to experience the greatest degree of tumour destruction by primary chemotherapy do not express either oestrogen receptors or Bcl-2. This may have important implications in the selection of patients with breast cancer for primary chemotherapy who are most likely to gain a survival benefit.
The Paris Cardiovascular Risk Factor Prevention Trial. Effects of two years of intervention in a population of young men.

The Paris Cardiovascular Risk Factor Prevention Trial was designed to determine whether individualised intervention could induce a reduction in the coronary risk factor levels in young men. Three thousand three hundred and thirty-six men aged 25 to 35, working in the 160 sections of a large Parisian administration, were examined. The section were randomly allocated to a control and an intervention group. Advice concerning diet, cigarette smoking, and physical activity was provided repeatedly to the subjects in the intervention group. Two years after the first intervention, the first 1292 subjects who entered the study, whether from the intervention or the control group, were recalled; 86% of the intervention group and 84% of the control group responded. The changes in weight, blood pressure, and cigarette smoking in the intervention group, corrected for changes in the control group, were respectively -0.4 kg (p = 0.06), -1.4 mm Hg (p less than 0.05), and -1.2 cigarettes (p less than 0.01). There was no difference between the two groups in serum cholesterol change. Most of these results concerning young men are in agreement with recently reported results of community intervention programmes in middle-aged men.
Treatment patterns in major depressive disorder after an inadequate response to first-line antidepressant treatment

The aim of the study was to determine the most common pharmacological strategies used in the management of major depressive disorder (MDD) after an inadequate response to first-line antidepressant treatment in clinical practice.



Multicenter, non-interventional study in adult outpatients with a DSM-IV-TR diagnosis of MDD and inadequate response to first-line antidepressant medication. Multiple logistic regression analyses were performed to identify independent factors associated with the adoption of a specific second-line strategy.



A total of 273 patients were analyzed (mean age: 46.8 years, 67.8% female). Baseline mean Montgomery-Asberg Depression Rating Scale total score was 32.1 (95%CI 31.2-32.9). The most common strategies were: switching antidepressant medication (39.6%), augmentation (18.8%), and combination therapy (17.9%). Atypical antipsychotic drugs were the most commonly used agent for augmenting antidepressant effect. The presence of psychotic symptoms and the number of previous major depressive episodes were associated with the adoption of augmenting strategy (OR = 3.2 and 1.2, respectively).



The switch to another antidepressant agent was the most common second-line therapeutic approach. Psychiatrists chose augmentation based on a worse patients' clinical profile (number of previous episodes and presence of psychotic symptoms).
The molecular signature of endometriosis-associated endometrioid ovarian cancer differs significantly from endometriosis-independent endometrioid ovarian cancer.

To determine whether endometriosis-associated endometrioid cancer (EAOC) is a specific entity compared with endometrioid cancer not associated with endometriosis (OC).



Case-control study.



University hospital research laboratory.



Seven patients with endometriosis-associated ovarian cancer EAOC and five patients each with OC, ovarian endometriosis, and benign ovaries.



Ovarian tissue samples were collected from surgical procedures.



We hybridized cRNA samples to the Affymetrix HG-U133A microarray chip. Representative genes were validated by real time polymerase chain reaction.


RESULT(S)
We identified two main groups of genes: The first group contained the genes SICA2, CCL14, and TDGF1. These genes were equally regulated in endometriosis and EAOC but not in OC and benign ovaries. The second group contained the genes StAR, SPINT1, Keratin 8, FoxM1B, FOLR1, CRABP1, and Claudin 7. They were equally regulated in EAOC and OC but not in ovarian endometriosis and benign ovaries.


CONCLUSION(S)
That the first group is composed of the cytokines SICA2 and CCL14 and the growth factor TDGF1 indicates that the regulation of the autoimmune system and of inflammatory cytokines may be very important in the etiology of endometriosis and EAOC. That the second group is composed of genes that play a central role in cell-cell interaction, differentiation, and cell proliferation indicates that they may be important in the development of ovarian cancer in women with endometriosis.
Stimulation of the Noradrenergic System during Memory Formation Impairs Extinction Learning but not the Disruption of Reconsolidation

The noradrenergic system plays a critical role in the ‘consolidation’ of emotional memory. If we are to target ‘reconsolidation’ in patients with anxiety disorders, the noradrenergic strengthening of fear memory should not impair the disruption of reconsolidation. In Experiment I, we addressed this issue using a differential fear conditioning procedure allowing selective reactivation of one of two fear associations. First, we strengthened fear memory by administering an α2-adrenergic receptor antagonist (ie, yohimbine HCl; double-blind placebo-controlled study) 30 min before acquisition (time for peak value yohimbine HCl <1 h). Next, the reconsolidation of one of the fear associations was manipulated by administering a β-adrenergic receptor antagonist (ie, propranolol HCl) 90 min before its selective reactivation (time for peak value propranolol HCl <2 h). In Experiment II, we administered propranolol HCl after reactivation of the memory to rule out a possible effect of the pharmacological manipulation on the memory retrieval itself. The excessive release of noradrenaline during memory formation not only delayed the process of extinction 48 h later, but also triggered broader fear generalization. Yet, the β-adrenergic receptor blocker during reconsolidation selectively ‘neutralized’ the fear-arousing aspects of the noradrenergic-strengthened memory and undermined the generalization of fear. We observed a similar reduction in fear responding when propranolol HCl was administered after reactivation of the memory. The present findings demonstrate the involvement of noradrenergic modulation in the formation as well as generalization of human fear memory. Given that the noradrenergic strengthening of fear memory impaired extinction learning but not the disruption of reconsolidation, our findings may have implications for the treatment of anxiety disorders.
Association of out-of-hospital advanced airway management with outcomes after traumatic brain injury and hemorrhagic shock in the ROC hypertonic saline trial.

Prior studies suggest adverse associations between out-of-hospital advanced airway management (AAM) and patient outcomes after major trauma. This secondary analysis of data from the Resuscitation Outcomes Consortium Hypertonic Saline Trial evaluated associations between out-of-hospital AAM and outcomes in patients suffering isolated severe traumatic brain injury (TBI) or haemorrhagic shock.



This multicentre study included adults with severe TBI (GCS ≤8) or haemorrhagic shock (SBP ≤70 mm Hg, or (SBP 71-90 mm Hg and heart rate ≥108 bpm)). We compared patients receiving out-of-hospital AAM with those receiving emergency department AAM. We evaluated the associations between airway strategy and patient outcomes (28-day mortality, and 6-month poor neurologic or functional outcome) and airway strategy, adjusting for confounders. Analysis was stratified by (1) patients with isolated severe TBI and (2) patients with haemorrhagic shock with or without severe TBI.



Of 2135 patients, we studied 1116 TBI and 528 shock; excluding 491 who died in the field, did not receive AAM or had missing data. In the shock cohort, out-of-hospital AAM was associated with increased 28-day mortality (adjusted OR 5.14; 95% CI 2.42 to 10.90). In TBI, out-of-hospital AAM showed a tendency towards increased 28-day mortality (adjusted OR 1.57; 95% CI 0.93 to 2.64) and 6-month poor functional outcome (1.63; 1.00 to 2.68), but these differences were not statistically significant. Out-of-hospital AAM was associated with poorer 6-month TBI neurologic outcome (1.80; 1.09 to 2.96).



Out-of-hospital AAM was associated with increased mortality after haemorrhagic shock. The adverse association between out-of-hospital AAM and injury outcome is most pronounced in patients with haemorrhagic shock.
Association between plasma nitric oxide metabolites levels and negative symptoms of schizophrenia: a pilot study.

Nitric oxide (NO) is involved in pathophysiology of psychiatric disorders such as depression and schizophrenia. We hypothesize that plasma levels of NO and its metabolites (NO(x)) are decreased in patients with schizophrenia. To examine the hypothesis, we compared plasma NO(x) levels between 30 schizophrenic patients (M/F: 18/12, age: 38 +/- 15 years) and age- and sex-matched 30 healthy controls (M/F: 18/12, age: 41 +/- 19 years), and we also examined the effects of risperidone on plasma NO(x) levels in schizophrenic patients. The baseline plasma NO(x) levels were significantly lower in the schizophrenia group (1.85 +/- 0.70 microM) than those in control group (3.37 +/- 2.27 microM). A significantly negative correlation was found between plasma NO(x) levels and PANSS-N scores before risperidone administration (rho = -0.385, p = 0.0416). Treatment with risperidone significantly increased the plasma NO(x) levels by 8 weeks (before; 1.85 +/- 0.70 microM, after; 2.25 +/- 1.00 microM, p = 0.0491). These results suggest that NO might be one of the candidates factors which are associated with the pathophysiology of negative symptoms of schizophrenia.
The relationship between hypotension, cerebral flow, and the surgical field during endoscopic sinus surgery.

Hypotensive anesthesia is often used in endoscopic sinus surgery (ESS) to improve surgical visibility; however, its safety and efficacy in this role are yet to be justified. This study aimed to evaluate the effect of hypotensive anesthesia on both real-time middle cerebral artery blood flow velocity (Vmca) and the severity of surgical bleeding in patients undergoing ESS.



Prospective, observational cohort study.



Thirty-two patients undergoing hypotensive anesthesia for ESS at a single tertiary institution during February 2011 to July 2012 were recruited for the study. Transcranial Doppler ultrasonography measured periodic Vmca, which were time-matched for hemodynamic and respiratory factors. One-minute video segments corresponding with each Vmca reading were randomized and distributed to two blinded observers for bleeding assessment.



Three hundred and fifty-six data time points were recorded for systolic, diastolic, and mean arterial blood pressure (MAP), pulse rate, respiratory rate, end-tidal carbon dioxide concentration, Vmca, and bleeding assessment score (BAS). A direct relationship exists between MAP and Vmca (r = 0.77, P < .0001) as well as MAP and BAS (r = 0.36, P < .0001). MAP levels above 60 mm Hg maintained at least 50% of baseline Vmca flow in almost 90% of all time points.



Hypotensive anesthesia is an effective method of controlling intraoperative bleeding during endoscopic sinus surgery; however the effect is clinically small in low MAP ranges. In otherwise healthy patients undergoing ESS with general anesthesia, reducing MAP to below 60 mm Hg may increase the risk of cerebral ischemia.
Prospective use of EuroSCORE for the short-term risk evaluation of consecutive cardiac surgery candidates: are there any differences in prediction of perioperative risk versus risk of nonsurgical treatments?

In the era of modern medicine, the relevance of perioperative risk stratification with respect to the practice of cardiac surgeons and cardiologists worldwide has increased.



This study aims at estimating the validity of a preoperative risk stratification model EuroSCORE in predicting short-term mortality in Czech adult cardiac population.



All consecutive patients (n = 460) presented to cardiac surgeons as surgery candidates during a six-month period were enrolled in this study. The Additive and logistic EuroSCORE were used for the risk assessment. The operative mortality, as well as the mortality within 30 days from discharge were recorded. The observed and predicted mortality derived from the EuroSCORE were compared.



Fifty-seven percent of the patients underwent cardiac surgery, while 43% was refused for surgery by the cardiac surgeon. There was no significant difference between the observed and predicted mortality in both subgroups. EuroSCORE showed good discriminatory ability in predicting short-term mortality (C statistic 0.755 vs. 0.762 for the surgery subgroup and 0.695 vs. 0.716 for the refused subgroup).



The EuroSCORE has a good discriminatory ability in predicting early mortality after cardiac surgery as well as in patients rejected for cardiac surgery. Both EuroSCORE risk prediction model forms are a suitable mortality predictor in Czech cardiac patients.
Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study.

Polyunsaturated n-3 fatty acids have been shown to inhibit the growth and metastasis of tumors. This double-blind, randomized study was designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can improve metabolic parameters, decrease chemical indices of inflammation, enhance quality of life, and extend disease free interval and survival time for dogs treated for lymphoblastic lymphoma with doxorubicin chemotherapy.



Thirty-two dogs with lymphoma were randomized to receive one of two diets supplemented with menhaden fish oil and arginine (experimental diet) or an otherwise identical diet supplemented with soybean oil (control diet). Diets were fed before and after remission was attained with up to five dosages of doxorubicin. Parameters examined included blood concentrations of glucose, lactic acid, and insulin in response to glucose and diet tolerance tests; alpha-1 acid glycoprotein; tumor necrosis factor; interleukin-6; body weight; amino acid profiles; resting energy expenditure; disease free interval (DFI); survival time (ST); and clinical performance scores.



Dogs fed the experimental diet had significantly (P < 0.05) higher mean serum levels of the n-3 fatty acids docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) compared with controls. Higher serum levels of C22:6 and C20:5 were associated with lesser (P < 0.05) plasma lactic acid responses to intravenous glucose and diet tolerance testing. Increasing C22:6 levels were significantly (P < 0.05) associated with longer DFI and ST for dogs with Stage III lymphoma fed the experimental diet.



Fatty acids of the n-3 series normalize elevated blood lactic acid in a dose-dependent manner, resulting in an increase in DFI and ST for dogs with lymphoma.
Applicability of current diagnostic algorithms in geriatric patients suspected of new, slow onset heart failure.

referral for echocardiography for all geriatric outpatients suspected of heart failure (HF) is not feasible. Diagnostic algorithms could be helpful.



to investigate whether available diagnostic algorithms accurately identify (older) patients (aged 70 years or over) eligible for echocardiography, with acceptable numbers of false-negatives.



algorithms (European Society of Cardiology (ESC)) guideline, National Institute for Health and Clinical Excellence (NICE) guideline, multidisciplinary guideline the Netherlands (NL) and algorithm by Mant et al. were validated in 203 geriatric patients (mean age 82 ± 6 years, 30% men) suspected of new, slow onset HF. HF was adjudicated by an outcome panel. Applicability of algorithms was evaluated by calculating proportion of patients (i) referred for echocardiography, (ii) with HF among referred patients and (iii) without HF in the non-referred.



ninety-two (45%) patients had HF. Applying algorithms resulted in referral for echocardiography in 52% (normal NT-proBNP; ESC), 72% (normal ECG; ESC), 56% (NICE), 93% (NL) and 70% (Mant) of all patients, diagnosing HF in 78, 56, 76, 49 and 62% of those referred, respectively. In patients not referred for echocardiography HF was absent in 90, 82, 93, 100 and 95%, respectively.



the ESC NT-proBNP (<400 pg/ml)-based algorithm combines the lowest number of referrals for echocardiography (of whom 78% has HF) with a limited number (10%) of false negatives in the non-referred.
Platelet aggregation, eicosanoid production and thrombogenic ratio in individuals at high cardiovascular risk consuming meat enriched in walnut paste. A crossover, placebo-controlled study.

Walnut consumption produces beneficial cardiovascular effects. The aim of the present study is to compare the effects of meat enriched in walnut paste (WM) and low-fat meat (LM) consumptions on platelet aggregation, plasma thromboxane A2 (TXA2, measured as TXB2), prostacyclin I2 (PGI2, as 6-keto-PGF1alpha) and the thrombogenic ratio (TXB2/6-keto-PGF1alpha) in volunteers at high CVD risk. Twenty-two adults were placed on a random, non-blinded crossover study involving two test periods (five portions WM/week for 5 week; five portions LM/week for 5 week) separated by a 4- to 6-week washout period. The participants were asked to complete a diet record throughout the study. Platelet aggregation, plasma TXB2, 6-keto-PGF1alpha production and the TXB2/6-keto-PGF1alpha ratio were determined at baseline and at weeks 3 and 5 for the two dietary periods. The WM diet contains a lower SFA content, a higher concentration of PUFA and a more favourable n-6/n-3 ratio than the LM diet. Significant time x treatment interactions were observed for TXB2 (P = 0.048) and the TXB2/6-keto-PGF1alpha ratio (P = 0.028). The WM diet significantly increased the level of 6-keto-PGF1alpha (P = 0.037) and decreased the TXB2/6-keto-PGF1alpha ratio (P = 0.048). At week 5, significant differences (P < 0.05) between treatments were found for maximum aggregation rate, TXB2 values and the TXB2/6-keto-PGF1alpha ratio. The effects on TXB2 and the TXB2/6-keto-PGF1alpha ratio were time-course dependent (P = 0.019 and 0.011, respectively). The WM and LM diets reduced TXB2 levels most (P = 0.050) in obese individuals, while the TXB2/6-keto-PGF1alpha ratio decreased most (P = 0.066) in volunteers whose serum cholesterol levels were > or = 2200 mg/l. The WM diet should be considered a functional meat because it improves the thrombogenic status mainly in individuals with high-cholesterol levels or high BMI.
Type-oriented Intraoperative and Adjuvant Chemotherapy and Survival after Curative Resection of Advanced Gastric Cancer

= 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n= 13); or UFT 600 mg/day (P2 group, n= 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n= 17), H1 (n= 12), and H2 (n= 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.