nils-herrmann/clean_scirepeval huggingface dataset:
A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle

Insulin-sensitive tissues (muscle, liver) of individuals with obesity and type 2 diabetes mellitus are in a state of low-grade inflammation, characterised by increased Toll-like receptor (TLR) expression and TLR-driven signalling. However, the cause of this mild inflammatory state is unclear. We tested the hypothesis that a prolonged mild increase in plasma NEFA will increase TLR expression and TLR-driven signalling (nuclear factor κB [NFκB] and mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean healthy individuals. Twelve lean, normal-glucose-tolerant participants were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid followed by a euglycaemic–hyperinsulinaemic clamp. Vastus lateralis muscle biopsies were performed before and during the clamp. Lipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and inhibitor of κB kinase-NFκB (CHUK [IKKA], c-REL [REL] and p65 [RELA, NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased extracellular signal-regulated kinase (ERK) phosphorylation (p < 0.05) and tended to reduce the content of inhibitor of kappa Bα (p = 0.09). The muscle content of most diacylglycerol, ceramide and acylcarnitine species was unaffected. In summary, insulin resistance induced by prolonged low-dose lipid infusion occurs together with increased TLR-driven inflammatory signalling and impaired insulin-stimulated IRS-1 tyrosine phosphorylation. A sustained, mild elevation in plasma NEFA is sufficient to increase TLR expression and TLR-driven signalling (NFκB and MAPK) in lean individuals. The activation of this pathway by NEFA may be involved in the pathogenesis of insulin resistance in humans.
Possible implication of thiopurine S-methyltransferase in occurrence of infectious episodes during maintenance therapy for childhood lymphoblastic leukemia with mercaptopurine

6-Mercaptopurine (6-MP) is metabolized by thiopurine S-methyltransferase (TPMT), an enzyme subject to genetic polymorphism. We investigated the relationships between the TPMT locus (TPMT activity and genotype) and the pharmacological response to 6-MP during maintenance therapy of 78 children with acute lymphoblastic leukemia (ALL). For each patient, 6-MP dosage, leukocyte counts and occurrence of infectious episodes were monitored on an 8 week basis. Higher 6-MP dosage was associated with higher TPMT activity (P = 0.03) and higher average leukocyte counts (P < 0.01). Eight patients (10%) carrying a TPMT mutant genotype (one homozygous and seven heterozygous) received lower 6-MP doses (average: 48 vs 65 mg/m2/day; P = 0.02) and had on average lower leukocyte counts (2834 vs 3398 cells/mm3; P = 0.003) than patients carrying the wild-type TPMT genotype. Higher occurrence of infectious episodes graded 2 or 3 was correlated with higher 6-MP dosage (P < 0.01) but no difference was observed between TPMT mutants and TPMT wild-type patients. Patients who received 6-MP dosage above the group median (62 mg/m2/day) or having a TPMT activity above the group median (21.5 nmol/h/ml) had a higher percentage of 8 week periods with infectious episodes requiring treatment (34% vs 17% and 33% vs 19%, respectively) than those with 6-MP dose or TPMT activity below the group median (P < 0.01). In the last 25 patients enrolled in the study, steady-state erythrocyte thioguanine nucleotide (TGN) concentrations were associated with lower leukocyte counts (P = 0.01) but not with a higher occurrence of infectious episodes. In contrast, higher steady-state erythrocyte methylmercaptopurine nucleotide (MeMPN) concentrations were associated with higher 6-MP dosage (P < 0.01) and higher occurrence of infectious episodes (P < 0.001). In conclusion, during maintenance therapy of ALL, children with higher TPMT activity receive a higher 6-MP dosage and may have infectious episodes caused by metabolism of 6-MP into methylmercaptopurine nucleotides.
Modulation of training by single-session transcranial direct current stimulation to the intact motor cortex enhances motor skill acquisition of the paretic hand.

Mechanisms of skill learning are paramount components for stroke recovery. Recent noninvasive brain stimulation studies demonstrated that decreasing activity in the contralesional motor cortex might be beneficial, providing transient functional improvements after stroke. The more crucial question, however, is whether this intervention can also enhance the acquisition of complex motor tasks, yielding longer-lasting functional improvements. In the present study, we tested the capacity of cathodal transcranial direct current stimulation (tDCS) applied over the contralesional motor cortex during training to enhance the acquisition and retention of complex sequential finger movements of the paretic hand.



Twelve well-recovered chronic patients with subcortical stroke attended 2 training sessions during which either cathodal tDCS or a sham intervention were applied to the contralesional motor cortex in a double-blind, crossover design. Two different motor sequences, matched for their degree of complexity, were tested in a counterbalanced order during as well as 90 minutes and 24 hours after the intervention. Potential underlying mechanisms were evaluated with transcranial magnetic stimulation.



tDCS facilitated the acquisition of a new motor skill compared with sham stimulation (P=0.04) yielding better task retention results. A significant correlation was observed between the tDCS-induced improvement during training and the tDCS-induced changes of intracortical inhibition (R(2)=0.63).



These results indicate that tDCS is a promising tool to improve not only motor behavior, but also procedural learning. They further underline the potential of noninvasive brain stimulation as an adjuvant treatment for long-term recovery, at least in patients with mild functional impairment after stroke.
A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours

On the basis of preclinical studies of NC-6004, a cisplatin-incorporated micellar formulation, we hypothesised that NC-6004 could show lower toxicity than cisplatin and show greater anti-tumour activity in phase I study.A total of 17 patients were recruited in a range of advanced solid tumour types. NC-6004 was administered intravenously (i.v.) every 3 weeks. The dose escalation started at 10 mg m−2 and was increased up to 120 mg m−2 according to the accelerated titration method and modified Fibonacci method.One dose-limiting toxicity (DLT) occurred in a patient who was given 90 mg m−2 of NC-6004, otherwise any significant cisplatin-related toxicity was not observed or generally mild toxicity was observed. Despite the implementation of post-hydration and pre-medication regimen, renal impairment and hypersensitivity reactions still developed at 120 mg m−2, which led to the conclusion that the maximum tolerated dose was 120 mg m−2, and the recommended dose was 90 mg m−2, although DLT was not defined as per protocol. Stable disease was observed in seven patients. The maximum concentration and area under the concentration–time curve of ultrafilterable platinum at 120 mg m−2 NC-6004 were 34-fold smaller and 8.5-fold larger, respectively, than those for cisplatin.The delayed and sustained release of cisplatin after i.v. administration contributes to the low toxicity of NC-6004.
Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy

The aim of the present phase II study was to evaluate the efficacy of combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) in patients with recurrent urothelial cancer who had been treated with cisplatin-based chemotherapy.  Eligible patients were those with histologically confirmed urothelial cancer who had progressed or relapsed after cisplatin-based chemotherapy. The PIN regimen consisted of paclitaxel 175 mg/m2 on day 1; ifosfamide 4.5 g/m2 divided over days 1, 2, and 3; and nedaplatin 70 mg/m2 on day 1; PIN was given every 28 days.  Among the 32 patients enrolled in the study (median age, 66 years), complete and partial responses were obtained in 5 patients and 19 patients, respectively, with an overall response rate of 75% (95% confidence interval [CI], 59–91%). The median time to progression was 8 months (range, 0–50+ months) and the median survival was 22 months (range, 4–52+ months). The 1- and 2-year overall survival rates were 53.7 and 42.9%, respectively. All patients experienced Grade 3 or 4 neutropenia, while Grade 3 or 4 thrombocytopenia was seen in 8 patients; Grade 3 or 4 anemia was seen in 6 patients; Grade 3 neuropathy was observed in 1 patient, for whom the PIN therapy was discontinued. There were no treatment-related deaths.  The PIN combination was highly active and tolerable in previously treated patients with urothelial cancer as a second-line treatment.
Echocardiographic predictors of an adverse response to a nifedipine trial in primary pulmonary hypertension: diminished left ventricular size and leftward ventricular septal bowing.

The clinical course in primary pulmonary hypertension (PPH) is improved by calcium channel blocker therapy in those with a favorable hemodynamic response during a trial of high-dose oral nifedipine. Although trials of nifedipine are performed only in patients who demonstrate pulmonary vasodilator reserve to short-acting agents, this response does not predict the safety of nifedipine treatment, which can result in severe first-dose hypotension and death.



To identify echocardiographic parameters that predict first-dose nifedipine-induced hypotension in patients with PPH.



The pretrial echocardiograms of 23 consecutive PPH patients (mean age, 42.3 +/- 13 years; 77% female) undergoing evaluation of pulmonary vasodilator reserve with nifedipine were analyzed. Patients were classified as those who suffered first-dose nifedipine hypotension (group 1) and those who did not (group 2). Echocardiographic measures of chamber size and septal geometry in the two groups were compared.



Five measures reflecting diminished left ventricular (LV) size and leftward ventricular septal bowing were found to be associated with nifedipine hypotension: LV transverse diameter in systole (LVDs; p = 0.007), LV transverse diameter in diastole (LVDd; p = 0.05), LV area in systole (LVAs; p = 0.009), LV area in diastole (LVAd; p = 0.03), the ratio of RV to LVAs (p = 0. 02), and leftward ventricular septal bowing (p = 0.01). The LV dimensions found to best predict nifedipine-induced hypotension were LVDs < 2.7 cm, LVDd < 4.0 cm, LVAs < 15.5 cm(2), and LVAd < 20.0 cm(2).



Readily available echocardiographic parameters in patients with PPH are predictive of nifedipine-induced hypotension, and can be used to select patients in whom a trial of nifedipine should be avoided.
Psychometric evaluation of the EORTC QLQ-PR25 questionnaire in assessing health-related quality of life in prostate cancer survivors: a curate’s egg

The EORTC QLQ-PR25 was primarily developed to measure disease-specific health-related quality of life (HRQoL) of prostate cancer (PCa) patients undergoing active treatment. The growing number of cancer survivors has focussed interest on assessing survivors’ HRQoL. We evaluated psychometric properties of the EORTC QLQ-PR25 questionnaire amongst PCa survivors. A postal questionnaire, including the QLQ-PR25, was administered to 6559 PCa survivors 2–18 years post-diagnosis, identified through population-based cancer registries in Ireland; 3348 participated. The QLQ-PR25 has been suggested to have five multi-item subscales measuring urinary (US), bowel (BS) and hormone treatment-related symptoms (TS), sexual activity (SA) and sexual functioning (SF), and a single item measuring bother due to using incontinence aids (IA). Reliability analysis, divergent validity, discriminant validity (compared to EORTC QLQ-C30, DASS-21 and EuroQoL EQ-5D-5L), and exploratory and confirmatory factor analysis (EFA, CFA) were undertaken. The percentage of survivors completing QLQ-PR25 subscales was: US-79 %; IA-20 %; BS-83 %; TS-86 %; SA-87 %; and SF-26 %. Reliability was acceptable (Cronbach’s α > 0.7) for three subscales (US, SA, SF). The instrument discriminated well between clinically distinct groups, especially those defined by primary treatment(s) and stage at diagnosis. The SA and SF subscales showed good discriminant validity compared to QLQ-C30, DASS-21 and EQ-5D-5L; other subscales did not. EFA reproduced a near fit to the proposed factor structure. CFA confirmed this. This is the largest ever QLQ-PR25 validation study. When used in PCa survivors, although the proposed factor structure was confirmed, some of the subscales (e.g. BS and TS) showed poor reliability, a lack of discriminant validity and moderate levels of item non-response.
Olanzapine plus carbamazepine v. carbamazepine alone in treating manic episodes.

Combinations of olanzapine and carbamazepine are often used in clinical practice in the management of mania.



To assess the efficacy and safety of olanzapine plus carbamazepine in mixed and manic bipolar episodes.



Randomised, double-blind, 6-week trial of olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day; n=58) v. placebo plus carbamazepine (n=60) followed by open-label, 20-week olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day, n=86), with change in manic symptoms as main outcome measure. Safety and pharmacokinetics were also evaluated.



There were no significant differences (baseline to endpoint) in efficacy measures between treatment groups, but at 6 weeks triglyceride levels were significantly higher (P=0.008) and potentially clinically significant weight gain (>or=7%) occurred more frequently (24.6% v. 3.4%, P=0.002) in the combined olanzapine and carbamazepine group. Carbamazepine reduced olanzapine concentrations but olanzapine had no effect on carbamazepine concentrations.



The combination of olanzapine and carbamazepine did not have superior efficacy to carbamazepine alone. The increases in weight and triglycerides observed during combination treatment are a matter of concern.
NUTRITION AND DIETETICS FOR NURSES

Come with us to read a new book that is coming recently. Yeah, this is a new coming book that many people really want to read will you be one of them? Of course, you should be. It will not make you feel so hard to enjoy your life. Even some people think that reading is a hard to do, you must be sure that you can do it. Hard will be felt when you have no ideas about what kind of book to read. Or sometimes, your reading material is not interesting enough.
Design of Static Resilient WDM Mesh Networks with Multiple Heuristic Criteria

We present a heuristic method to optimize the capacity of a WDM mesh network assigning working and protection capacity to a set of static optical-connection requests under the linkdisjoint constraint. The method can be applied to networks supporting either dedicated or shared path-protection. Routing and fiber and wavelength assignment (RFWA) are jointly performed for all the lightpaths with the aim of minimizing the number of fibers in the network. The employment of multiple prioritized heuristic criteria and an efficient link disjoint paths search algorithm are proposed. With less computational effort, the proposed heuristic approach allows to obtain good suboptimal results compared to the exact integer-linear-programming optimization. After introducing our design approach, we discuss the optimization of particular case-study networks under various condition and compare the results.
Customized Feedback to Patients and Providers Failed to Improve Safety or Quality of Diabetes Care

To assess whether providing customized clinical information to patients and physicians improves safety or quality of diabetes care.



Study subjects included 123 primary care physicians and 3,703 eligible adult diabetic patients with elevated A1C or LDL cholesterol, who were randomly assigned to receive customized feedback of clinical information as follows: 1) patient only, 2) physician only, 3) both the patient and physician, or 4) neither patient nor physician. In the intervention groups, patients received customized mailed information or physicians received printed, prioritized lists of patients with recommended clinical actions and performance feedback. Hierarchical models were used to accommodate group random assignment.



Study interventions did not improve A1C test ordering (P = 0.35) and negatively affected LDL cholesterol test ordering (P < 0.001) in the 12 months postintervention. Interventions had no effect on LDL cholesterol values (P = 0.64), which improved in all groups over time. Interventions had a borderline unfavorable effect on A1C values among those with baseline A1C >or=7% (P = 0.10) and an unfavorable effect on A1C values among those with baseline A1C >or=8% (P < 0.01). Interventions did not reduce risky prescribing events or increase treatment intensification. Time to next visit was longer in all intervention groups compared with that for the control group (P < 0.05).



Providing customized decision support to physicians and/or patients did not improve quality or safety of diabetes care and worsened A1C control in patients with baseline A1C >or=8%. Future researchers should consider providing point-of-care decision support with redesign of office systems and/or incentives to increase appropriate actions in response to decision-support information.
Immunotherapy with autologous antigen presenting cells for the treatment of androgen independent prostate cancer

Prostate cancer is an excellent target for an active vaccine-based approach based on the fact that prostate cancer cells express unique proteins which serve as highly specific targets. APC8015 (Provenge) is one such investigational therapeutic vaccine that uses autologous antigen presenting cells (APCs) loaded with a recombinant fusion protein of prostatic acid phosphatase linked to a molecule that specifically targets a receptor expressed on the surface of human APCs. Clinical trial outcomes have demonstrated activity in patients with androgen independent prostate cancer.
Development and validation of an asthma knowledge test for children 8-10 years of age.

Although there are many instruments available to measure asthma knowledge in adult populations, a search of the literature identified the lack of valid and reliable instruments to assess the asthma knowledge of pre-adolescent children. The aim of this study was to develop and validate an asthma knowledge test for children 8-10 years of age.



Three strategies were used to achieve the study objective: develop and design the asthma knowledge test; establish the content validity of test items; and conduct a pilot study to examine the validity, reliability and user friendliness of the instrument in a sample of 151 primary school children.



A 24-item asthma knowledge test was developed based on selected items from the Newcastle Asthma Knowledge Questionnaire and supplemented with items from other instruments. Test items were worded to ensure they could be understood by 8- to 10-year-old children, and content validity confirmed by an expert panel. A pilot study demonstrated that the test was user friendly, generated responses that reflected varying degrees of item difficulty and produced scores on the test that discriminated between 'known groups'.



Findings from this study indicate that an asthma knowledge test designed for primary school-age children has considerable promise. With further refinement and testing, this test will provide a valid and reliable measure of asthma knowledge in children with and without asthma that can be used in a wide range of childhood asthma studies.
Addressing intimacy and partner communication after breast cancer: a randomized controlled group intervention

While quality of life for most breast cancer survivors (BCS) returns to normal by 1 year post-treatment, problems in sexual function and intimacy often persist. The present study tested the efficacy of a 6-week psycho-educational group intervention in improving BCS’s sexual well-being. We conducted a mailed survey of BCS 1–5 years post-diagnosis to identify a sample of women who reported moderately severe problems in body image, sexual function or partner communication, and were deemed eligible for the randomized intervention trial. Using a pre-randomized design, 70% (n = 284) were assigned to a 6-week psycho-educational group intervention and 30% (n = 127) were assigned to a control condition (print material only); however, only 83 BCS agreed to participate in the intervention. Four months post-intervention, the intervention and control groups were not significantly different on the primary outcome of emotional functioning; however, BCS randomized to the intervention group were more likely to report improvements in relationship adjustment and communication as well as increased satisfaction with sex compared to controls. Members of the intervention group who were the least satisfied with their sexual relationship appeared to improve the most. Although modest in its effects, this intervention can be delivered in standard clinical settings. Having an identified treatment may help reduce physician reluctance to ask BCS about problems in intimacy and as appropriate, refer them for timely help.
Randomized cross-over trial to investigate the efficacy of a two-week physiotherapy programme with repetitive exercises of cueing to reduce the severity of freezing of gait in patients with Parkinson's disease.

To investigate the efficacy of a two-week programme of repetitive exercise with cueing and movement strategies upon freezing of gait in people with Parkinson's disease.



Randomized cross-over trial.



Specialist clinic for Parkinson's disease.



A total of 22 patients with Parkinson's disease and freezing while other symptoms had favorably responded to dopaminergic treatment.



Patients were randomized into a four-week cross-over trial, and received either treatment (Group 1) or no treatment (Group 2) during Period 1, and switched during Period 2. Treatment consisted of a two-week programme during which the patients exercised cueing, and movement strategies together with a physiotherapist.



The primary outcome measure was a freezing score assessed from blinded and random ratings of video recordings. The secondary outcome measure was a patient-reported freezing questionnaire. Mean differences between the treatment periods (treatment arms) were evaluated for treatment (period) effects. Sums of treatment periods were evaluated for carry-over effects.



The programme led to a significant treatment effect in the freezing score of 3.0 improvement (95% confidence interval 0.9-5.0; p < 0.01). No carry-over or period effects were detected. The questionnaire revealed a period effect, so groups were compared after Period 1, where a significant difference was found (15.0 vs. 11.7; p < 0.05).



The two-week physiotherapy programme reduced the severity of freezing in patients with Parkinson's disease.