nils-herrmann/clean_scirepeval huggingface dataset:
The right hemisphere supports but does not replace left hemisphere auditory function in patients with persisting aphasia.

In this study, we used magnetoencephalography and a mismatch paradigm to investigate speech processing in stroke patients with auditory comprehension deficits and age-matched control subjects. We probed connectivity within and between the two temporal lobes in response to phonemic (different word) and acoustic (same word) oddballs using dynamic causal modelling. We found stronger modulation of self-connections as a function of phonemic differences for control subjects versus aphasics in left primary auditory cortex and bilateral superior temporal gyrus. The patients showed stronger modulation of connections from right primary auditory cortex to right superior temporal gyrus (feed-forward) and from left primary auditory cortex to right primary auditory cortex (interhemispheric). This differential connectivity can be explained on the basis of a predictive coding theory which suggests increased prediction error and decreased sensitivity to phonemic boundaries in the aphasics' speech network in both hemispheres. Within the aphasics, we also found behavioural correlates with connection strengths: a negative correlation between phonemic perception and an inter-hemispheric connection (left superior temporal gyrus to right superior temporal gyrus), and positive correlation between semantic performance and a feedback connection (right superior temporal gyrus to right primary auditory cortex). Our results suggest that aphasics with impaired speech comprehension have less veridical speech representations in both temporal lobes, and rely more on the right hemisphere auditory regions, particularly right superior temporal gyrus, for processing speech. Despite this presumed compensatory shift in network connectivity, the patients remain significantly impaired.
Casting with Skewed Ejection Direction

Casting is a manufacturing process in which liquid is poured into a cast (mould) that has a cavity with the shape of the object to be manufactured. The liquid then hardens, after which the cast is removed. We address geometric problems concerning the removal of the cast. A cast consists of two parts, one of which retracts in a given direction carrying the object with it. Afterwards, the object will be ejected from the retracted cast part. In this paper, we give necessary and sufficient conditions to test the feasibility of the cast part retraction and object ejection, where retraction and ejection directions need not be the same. For polyhedral objects, we show that the test can be performed in O(n log n) time and the cast parts can be constructed within the same time bound. The complexity of the cast parts constructed is worst-case optimal. We also give a polynomial time algorithm for finding a feasible pair of retraction and ejection directions for a given polyhedral object.
Quantifying muscle tone in spinal cord injury patients using isokinetic dynamometric techniques

The torque generated during a passive movement of the knee joint was used to quantify muscle tone in normal able-bodied subjects and spastic and flaccid spinal cord injury (SCI) subjects using a computerized isokinetic dynamometer. Maximum peak (Tmax) and the sum of four consecutive peaks (Tsum) were calculated for each velocity (30, 60, 120°/s) and for each phase (flexing or extending) separately and compared statistically using a one-way ANOVA. Statistical significance between groups was found in Tmax FLEXION (FLX) at 60 and 120°/s. Scheffe's tests revealed that the spastic group was significantly less than both the flaccid and normal groups, although the flaccid and normal groups were not significantly different from each other. The slopes of the linear regression curve of the torque-velocity data were found and compared statistically using a t-test for parallelism. In all parameters, the data increased in a linear fashion with increasing velocity of knee motion. The slope of the regression curve for the spastic group was significantly lower than that of the normal group for Tmax and was significantly lower than that of the flaccid group for Tsum while the slopes for the flaccid and normal groups were not significantly different. The ability of the entire set of variables to classify subjects into three groups (normal, spastic, and flaccid) was tested using discriminant analysis. By taking into account 7 of the 12 original variables, this multivariate technique correctly classified 100% of the spastic, 90% of the normal, but only 67% of the flaccid subjects. Separation of observations was between spastic and normal subjects was good, except for only one case. This feature could be useful when dealing with assessment of individual responses to therapeutic interventions aimed at modification of spasticity.
Different effects of eicosapentaenoic acid and olive oil on blood pressure, intracellular free platelet calcium, and plasma lipids in patients with essential hypertension

In a randomized, double-blind, crossover study our specific aim was to examine the effects of a dietary fish oil or olive oil supplementation on blood pressure, intracellular free platelet calcium, plasma lipoproteins, and circulating vasoactive substances such as norepinephrine, epinephrine, and renin in patients with essential hypertension. Ten hypertensive patients (WHO classes I, II) were randomly assigned to receive 9 g fish oil or 9 g olive oil daily for 6 weeks after a 4-week baseline period. The 6-week treatment periods were separated by a 4-week wash-out. During treatment with fish oil diastolic blood pressure decreased from 103±1 to 98±2 mmHg (P<0.05) but did not change significantly during olive oil intake. Systolic blood pressure was not affected by either treatment. Intracellular free platelet calcium decreased in patients receiving fish oil (from 102±8 nM to 86±6 nM, P < 0.05) but was not significantly altered by olive oil treatment. In contrast, the dose-response curve for thrombin-induced intracellular free platelet calcium was not altered by the fish oil enriched diet. Plasma triglycerides decreased by approximately 40% in the fish oil group while low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and total cholesterol were not altered. Renin activity, norepinphrine, and epinephrine in plasma were not influenced by fish oil supplementation. We conclude that a moderate increase in dietary fish oil reduces diastolic blood pressure, intracellular free platelet calcium, and plasma triglycerides in patients with essential hypertension. The decrease in basal intracellular free platelet calcium concentration does not seem to be due to a diminished responsiveness of the calcium messenger system to thrombin.
A phase I trial of PR-104, a nitrogen mustard prodrug activated by both hypoxia and aldo-keto reductase 1C3, in patients with solid tumors

PR-104 is a “pre-prodrug” designed to be activated to a dinitrobenzamide nitrogen mustard cytotoxin by nitroreduction in hypoxic regions of tumors. This study was conducted to establish the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and pharmacokinetics (PK) of PR-104 in patients with advanced solid tumors. Patients with solid tumors refractory or not amenable to conventional treatment were evaluated in a dose-escalation trial of PR-104 administered as a 1-h intravenous (IV) infusion every 3 weeks. The plasma PK of PR-104 and its primary metabolite, PR-104A, were evaluated. Twenty-seven patients received a median of two cycles of PR-104 in doses ranging from 135 to 1,400 mg/m2. The MTD of PR-104 as a single-dose infusion every 3 weeks was established as 1,100 mg/m2. One of six patients treated at 1,100 mg/m2 experienced DLT of grade 3 fatigue. Above the MTD, the DLTs at 1,400 mg/m2 were febrile neutropenia and infection with normal absolute neutrophil count. No objective responses were observed, although reductions in tumor size were observed in patients treated at doses ≥550 mg/m2. The plasma PK of PR-104 demonstrated rapid conversion to PR-104A, with approximately dose-linear PK of both species. PR-104 was well tolerated at a dose of 1,100 mg/m2 administered as an IV infusion every 3 weeks. The area under the PR-104A plasma concentration–time curve at this dose exceeded that required for activity in human tumor cell cultures and xenograft models. The recommended dose of PR-104 as a single agent for phase II trials is 1,100 mg/m2 and further trials are underway.
Transesophageal Doppler echocardiography evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation.

Transesophageal echocardiography allows the evaluation of proximal coronary artery anatomy and coronary blood flow velocity (CBFV). To assess the potential of transesophageal echocardiography in evaluating CBFV and its variations induced by coronary-active drugs, we studied 15 patients by high-quality pulsed wave Doppler recordings of CBFV. In these patients, transesophageal Doppler evaluation of CBFV was performed before, 2 minutes after cessation of dipyridamole infusion (0.56 mg/kg in 4 minutes), and 2 minutes after aminophylline infusion (240 mg injected 4 minutes after cessation of dipyridamole infusion). The following CBFV parameters were evaluated at each of the three steps of the study protocol: maximal and mean diastolic velocities and maximal and mean systolic velocities. Furthermore, the following indexes of coronary flow reserve were evaluated: the ratio between maximal diastolic velocity recorded after and before dipyridamole administration and the ratio between mean diastolic velocity recorded after and before dipyridamole administration. Nine of the 15 patients had a normal left anterior descending coronary artery (group A), whereas the remaining six had significant (less than or equal to 75%) stenosis (group B). In group A patients, all CBFV parameters increased significantly during dipyridamole infusion and returned to near baseline values after aminophylline infusion. In group B patients, on the other hand, none of the CBFV parameters increased after dipyridamole infusion. Dipyridamole/baseline maximal diastolic velocity and mean diastolic velocity ratios were, respectively, 3.22 +/- 0.96 and 3.04 +/- 0.88 in group A and 1.46 +/- 0.45 (p less than 0.01 versus group A) and 1.48 +/- 0.49 (p less than 0.01 versus group A) in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Post mastectomy adjuvant radiotherapy in breast cancer: a comparision of three hypofractionated protocols.

To compare three hypofractionated protocols in postmastectomy cancinoma breast in terms of local control, toxicity and work load.



A total of three hundred patients suffering from cancer breast stage T2-4, N any were randomized into three arms after mastectomy. All the patients were treated with four fields on Co60 i.e. two tangential portals for chest wall, one anterior supraclavicular and axillary field and a posterior axillary boost and were randomized into three arms i.e. 2700 CGy in 5 fractions (one week) arm A, 3500 CGy in 10 fractions (2 weeks) arm B and 4000 CGy in 15 fractions (3 weeks) arm C. Skin, cardiac, pulmonary and haematological toxicities and lymphoedema were compared in addition to local control and work load.



The locoregional relapses were 11%, 12% and 10% in arms A, B and C respectively. 26%, 24% and 28% patients developed metastatic disease and 17%, 18% and 20% died in the three arms. G3 and G4 skin toxicities were 37%, 28% and 14%. G2 and G3 lymphedoema was 21%, 22% and 27%. Cardiac toxicity was 5%, 6% and 5% while pulmonary toxicity was 4%, 5% and 5% respectively. All the differences except skin toxicity were statistically insignificant. There were no cases of haematological depression or rib fractures.



All the three short protocols were equally effective in locoregional disease control and toxicity was also comparable. They were helpful in reducing the work load and can be safely recommended for routine clinical use.
Insulin detemir improves glycaemic control without weight gain in insulin-naïve patients with type 2 diabetes: subgroup analysis from the PREDICTIVE study.

Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation (PREDICTIVE) is a multi-national, open-label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. This post hoc subanalysis evaluates insulin-naïve patients on oral antidiabetic drugs (OADs) who were initiated on insulin detemir as basal therapy (+/- OADs).



The European cohort of the PREDICTIVE study currently includes 20,531 patients (12,981 with type 2 diabetes) who were prescribed insulin detemir and followed up for 12, 26 or 52 weeks. Here, we report data from a subgroup of 2377 OAD-treated, insulin-naïve type 2 diabetes patients for a mean follow-up of 14.4 weeks. Patients were prescribed insulin detemir as basal therapy (+/- OADs) by their physician, as part of routine clinical care. Results were reported in comparison with baseline observations.



One serious adverse drug reaction was reported, which was a major hypoglycaemic episode. Treatment with insulin detemir (+/- OADs) significantly reduced mean haemoglobin A(1c) (HbA(1c)) (-1.3%; p < 0.0001), fasting glucose (-3.7 mmol/l; p < 0.0001), and within-patient fasting glucose variability (-0.5 mmol/l; p < 0.0001). In the majority of patients (82%), these improvements in glycaemic control were achieved with once daily administration of insulin detemir. There was a small reduction in mean body weight (-0.7 kg; p < 0.0001), which was most apparent in patients with a higher body mass index (BMI) at baseline. A significant negative relationship between weight change and baseline BMI was observed (greater the BMI, greater the weight reduction). Multiple regression analysis showed that BMI and HbA(1c) at baseline, and change in HbA(1c), were all predictors for weight change (p < 0.0001 for all), with BMI being the strongest predictor.



Patients with type 2 diabetes naïve to insulin can be effectively treated with once-daily insulin detemir (+/- OADs) to achieve improved glycaemic control with no adverse effect on weight and a low risk of hypoglycaemia. These short-term results are consistent with the findings of clinical trials.
The paradox of NKp46+ natural killer cells: drivers of severe hepatitis C virus-induced pathology but in-vivo resistance to interferon α treatment

There is evidence that natural killer (NK) cells help control persistent viral infections including hepatitis C virus (HCV). The phenotype and function of blood and intrahepatic NK cells, in steady state and after interferon (IFN) α treatment has not been fully elucidated.



We performed a comparison of NK cells derived from blood and intrahepatic compartments in multiple paired samples from patients with a variety of chronic liver diseases. Furthermore, we obtained serial paired samples from an average of five time points in HCV patients treated with IFNα.



Liver NK cells demonstrate a distinct activated phenotype compared to blood manifested as downregulation of the NK cell activation receptors CD16, NKG2D, and NKp30; with increased spontaneous degranulation and IFN production. In contrast, NKp46 expression was not downregulated. Indeed, NKp46-rich NK populations were the most activated, correlating closely with the severity of liver inflammation. Following initiation of IFNα treatment there was a significant increase in the proportion of intrahepatic NK cells at days 1 and 3. NKp46-rich NK populations demonstrated no reserve activation capacity with IFNα treatment and were associated with poor viral control on treatment and treatment failure.



NKp46 marks out pathologically activated NK cells, which may result from a loss of homeostatic control of activating receptor expression in HCV. Paradoxically these pathological NK cells do not appear to be involved in viral control in IFNα-treated individuals and, indeed, predict slower rates of viral clearance.
Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study.

The anti-EGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. We assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients.



For this randomised, open-label, phase 3 head-to-head study, we enrolled patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type KRAS exon 2 status. Using a computer-generated randomisation sequence, we assigned patients (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m(2); 250 mg/m(2) once a week thereafter). The primary endpoint was overall survival assessed for non-inferiority (retention of ≥ 50% of the cetuximab treatment effect; historical hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care alone of 0.55). The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. Recruitment for this trial is closed. 
Between Feb 2, 2010, and July 19, 2012, we enrolled and randomly allocated 1010 patients, 999 of whom began study treatment: 499 received panitumumab and 500 received cetuximab. For the primary analysis of overall survival, panitumumab was non-inferior to cetuximab (Z score -3.19; p=0.0007). Median overall survival was 10.4 months (95% CI 9.4-11.6) with panitumumab and 10.0 months (9.3-11.0) with cetuximab (HR 0.97; 95% CI 0.84-1.11). Panitumumab retained 105.7% (81.9-129.5) of the effect of cetuximab on overall survival seen in this study. The incidence of adverse events of any grade and grade 3-4 was similar across treatment groups. Grade 3-4 skin toxicity occurred in 62 (13%) patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence of grade 3-4 infusion reactions was lower with panitumumab than with cetuximab (one [<0.5%] patient vs nine [2%] patients), and the occurrence of grade 3-4 hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). We recorded one treatment-related fatal adverse event: a lung infection in a patient given cetuximab.



Our findings show that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients. Both agents had toxicity profiles that were to be expected. In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 3-4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment.
Validation of SAG/RBX2/ROC2 E3 ubiquitin ligase as an anticancer and radiosensitizing target.

Sensitive to apoptosis gene (SAG; also known as RBX2 or ROC2) was originally cloned as a redox-inducible antioxidant protein and was later characterized as a RING component of SCF E3 ubiquitin ligases. SAG overexpression inhibits apoptosis induced by many stimuli both in vitro and in vivo. SAG mRNA was overexpressed in human lung tumor tissues with a correlation to poor patient survival. To investigate whether SAG serves as an anticancer target, we determined the effect of SAG silencing on cell proliferation, survival, and radiosensitivity.



SAG protein expression in human tumors was evaluated by immunohistochemical staining using tumor tissue arrays. SAG expression in cancer cells was knocked down by siRNA silencing. The anticancer effects of SAG silencing were evaluated by in vitro assays for cell growth and survival and by an in vivo orthotopic xenograft tumor model. Radiosensitization by SAG silencing of human cancer cells was determined by clonogenic survival assay. Apoptosis induction was evaluated by fluorescence-activated cell sorting analysis, caspase-3 activation assay, and Western blotting of apoptosis-associated proteins.



SAG was overexpressed in multiple human tumor tissues compared with their normal counterparts. SAG silencing selectively inhibited cancer cell proliferation, suppressed in vivo tumor growth, and sensitized radiation-resistant cancer cells to radiation. Mechanistically, SAG silencing induced apoptosis with accumulation of NOXA, whereas SAG overexpression reduced NOXA levels and shortened NOXA protein half-life.



The findings showed that SAG E3 ubiquitin ligase plays an essential role in cancer cell proliferation and tumor growth and may serve as a promising anticancer and radiosensitizing target.
Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer

We conducted a phase II trial of 5-fluorouracil and oxaliplatin combination chemotherapy as a second-line treatment in unresectable/metastatic biliary tract cancer patients who had failed gemcitabine-based chemotherapy. Patients treated with gemcitabine-based palliative treatment were enrolled in this study. Patients were received modified FOLFOX3 (mFOLFOX3) consists of oxaliplatin 85 mg/m2 (day 1) and leucovorin 30 mg (days 1, 2) followed by 5-fluorouracil 1,500 mg/m2 (days 1, 2) every 2 weeks. Between March 2010 and June 2012, a total of 30 patients were enrolled in this study. Twenty-eight patients were measurable for treatment response. One achieved complete response, and one a partial response was observed. Overall response rate was 7.1 % (95 % confidence interval 0.9–23.5 %). The median progression-free survival was 1.6 months, and the median overall survival was 4.4 months. Grade 3–4 hematologic toxicities included neutropenia (6.7 %) and thrombocytopenia (3.4 %). The most common non-hematologic toxicity was neuropathy (22.2 %). However, the most common grade 3–4 non-hematologic toxicity was hyperbilirubinemia (5.0 %). There was one treatment-related death due to neutropenic infection. mFOLFOX3 as a second-line regimen has modest effect and tolerable toxicity in unresectable/metastatic biliary tract cancer patients who have been treated previously via gemcitabine-based chemotherapy.
Where the action is: monitoring local trends in sexual behaviour.

To assess the role in an overall monitoring strategy of the PLACE method of estimating local trends in sexual behaviour among individuals at social venues in areas at increased risk of HIV transmission.



Public venues identified by community informants as places where people meet new sexual partners were visited and characterised in Karaganda, Kazakhstan, in 2002 and 2003, and in a township in South Africa in 2000 and 2003. At a subset of venues, a representative sample of individuals socialising at the venue were interviewed about their sexual behaviour. The age distribution and partnerships rates of those socialising at these venues were compared by year and with national data from Kazakhstan and South Africa obtained via household surveys.



Women and men socialising at venues were younger and had higher rates of new and concurrent partnerships than men and women interviewed in national household surveys. There was little apparent change in sexual behaviour between 2002 and 2003 in Karaganda. In the South African township, there was a reduction in sexual partnerships and an increase in condom use, possibly due to a local AIDS prevention programme.



Findings from the PLACE method supplement national data on sexual behaviours with data from key populations in high transmission areas, inform local targeting of interventions, and, when subsequent rounds of PLACE are implemented, can evaluate change in target populations.