nils-herrmann/clean_scirepeval huggingface dataset:
Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor dormancy and mastectomy-driven acceleration of the metastatic process.

The aim of this study was to better understand human breast cancer biology by studying how the timing of metastasis following primary resection is affected by adjuvant CMF (cyclophoshamide, methotrexate, 5-fluorouracil) chemotherapy.



Discrete hazards of recurrence and recurrence risk reductions for treated patients relative to controls were analyzed for all patients enrolled in two separate randomized clinical trials [study 1 (386 women): no further treatment versus 12 cycles of CMF; study 2 (459 women): six versus 12 cycles of CMF] and a historical group (396 women: surgery alone) of axillary node-positive patients undergoing mastectomy.



(i) Nearly all CMF benefit occurs during the first 4 years following resection/chemotherapy. (ii) The CMF recurrence rate reduction is largely restricted to two specific spans. These temporally separate recurrence clusters occur during the first and third year of follow-up, while the second-year recurrences are weakly affected. (iii) Prolonging adjuvant treatment from 6 to 12 months partially alters this recurrence timing, without appreciably affecting the overall recurrence rate. (iv) These effects upon the dynamics of post-resection occurrence are menopausal status-independent.



At least two different therapeutically vulnerable proliferative events, resulting in clinical appearance of two metastasis temporally distinct clusters of post-resection cancer recurrence, apparently occur during the administration of adjuvant chemotherapy. Metastases that transpire outside of these temporal windows are refractory to adjuvant therapy. The dynamics of both post-treatment recurrence risk and CMF effectiveness are similar for both pre- and postmenopausal women, suggesting that post-resection mechanisms by which chemotherapy prevents metastases are similar, but of different magnitude in pre- and postmenopausal women. These findings are consistent with a metastasis model that includes tumor dormancy in specific micrometastatic phases (single cells and avascular foci) and with the acceleration of the metastatic process by the surgical resection of the primary breast cancer.
Radial extracorporeal shock wave therapy (rESWT) in the treatment of spasticity in cerebral palsy: a randomized, placebo-controlled clinical trial.

The aim of this study was to evaluate the efficacy and safety of radial extracorporeal shock wave therapy (rESWT) in the treatment of spasticity in patients with cerebral palsy.



Fifteen patients with spastic cerebral palsy, 12 men and 3 women, aged 10-46 years (mean age 31). The 15 patients presented 40 spastic muscles that were divided in three groups using a computerized random-number generator. The first group, received rESWT in spastic muscle. The second group received rESWT in spastic muscle + rESWT in antagonist muscle. The third group received placebo. Range of motion and Ashworth Scale were performed. This study is a randomized, placebo-controlled clinical trial. The patients were treated in 3 sessions at intervals of one week.



There are significant differences between groups treated with rESWT and group placebo. A significant decrease in the Ashworth Scale, an increase in the range of motion, were observed in all patients that were treated with rESWT. Positive results were maintained for at least 2 months after treatment.



The treatment with rESWT is more effective than placebo in decreasing spasticity of patients with CP.
A realistic approach to teaching systems anlaysis at the small or medium-sized college

It is difficult for the small or medium sized college to offer and staff the broad spectrum of system analysis and design courses that some curriculum designers are currently recommending. This article proposes a single senior level capstone course in systems analysis and design to partially solve this problem. The course, carefully designed and orchestrated, will teach the essentials of systems analysis and structured design and still develop the interpersonal skills necessary to produce a well-trained systems analyst.  There are a variety of approaches to teaching systems analysis in colleges and universities. These range from not offering a course to offering as many as seven courses. In fact, a reasonably strong case can be made for the extreme of offering a sequence of seven courses in the area of systems analysis. Dinerstein  presents such a case. Clearly, at least one course should be offered. A recent study by Archer [i] reveals that business and industry list systems analysis as the most important course in a list of typical computer science courses offered in the small college. Table ~ summarizes these findings.
Copeptin Predicts Mortality in Critically Ill Patients

Critically ill patients admitted to a medical intensive care unit exhibit a high mortality rate irrespective of the cause of admission. Besides its role in fluid and electrolyte balance, vasopressin has been described as a stress hormone. Copeptin, the C-terminal portion of provasopressin mirrors vasopressin levels and has been described as a reliable biomarker for the individual's stress level and was associated with outcome in various disease entities. The aim of this study was to analyze whether circulating levels of copeptin at ICU admission are associated with 30-day mortality.



In this single-center prospective observational study including 225 consecutive patients admitted to a tertiary medical ICU at a university hospital, blood was taken at ICU admission and copeptin levels were measured using a commercially available automated sandwich immunofluorescent assay.



Median acute physiology and chronic health evaluation II score was 20 and 30-day mortality was 25%. Median copeptin admission levels were significantly higher in non-survivors as compared with survivors (77.6 IQR 30.7-179.3 pmol/L versus 45.6 IQR 19.6-109.6 pmol/L; p = 0.025). Patients with serum levels of copeptin in the third tertile at admission had a 2.4-fold (95% CI 1.2-4.6; p = 0.01) increased mortality risk as compared to patients in the first tertile. When analyzing patients according to cause of admission, copeptin was only predictive of 30-day mortality in patients admitted due to medical causes as opposed to those admitted after cardiac surgery, as medical patients with levels of copeptin in the highest tertile had a 3.3-fold (95% CI 1.66.8, p = 0.002) risk of dying independent from APACHE II score, primary diagnosis, vasopressor use and need for mechanical ventilation.



Circulating levels of copeptin at ICU admission independently predict 30-day mortality in patients admitted to a medical ICU.
Randomized comparison of everolimus- and paclitaxel-eluting stents. 2-year follow-up from the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV trial.

We sought to determine whether the differences in outcomes present between everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV trial at 1 year were sustained with longer-term follow-up.



In the SPIRIT IV trial, patients undergoing percutaneous coronary intervention who were randomized to EES compared with PES experienced lower 1-year rates of target lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target lesion revascularization [TLR]), with significant reductions in the individual rates of MI, TLR, and stent thrombosis.



We prospectively randomized 3,687 patients with up to 3 noncomplex previously untreated native coronary artery lesions to EES versus PES at 66 U.S. sites. Follow-up through 2 years is complete in 3,578 patents (97.0%).



Treatment with EES compared with PES reduced the 2-year rates of TLF (6.9% vs. 9.9%, p = 0.003), all MI (2.5% vs. 3.9%, p = 0.02), Q-wave MI (0.1% vs. 0.8%, p = 0.002), stent thrombosis (0.4% vs. 1.2%, p = 0.008), and ischemia-driven TLR (4.5% vs. 6.9%, p = 0.004), with nonsignificantly different rates of all-cause and cardiac mortality. Between 1 year and 2 years, there were no significant differences in adverse event rates between the 2 stent types.



In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, the benefits of EES compared with those of PES present at 1 year were sustained at 2 years.
Effects of 3-week Outpatient Pulmonary Rehabilitation on Exercise Capacity, Dyspnea, and Quality of Life in COPD

The effects of intensive 3-week outpatient pulmonary rehabilitation (PR) on exercise capacity, dyspnea, and health-related quality of life (HRQL) were investigated in patients with COPD. Two hundred ten patients with COPD (mean FEV1 = 54%pred) underwent PR consisting of exercise training, patient and psychosocial education, breathing and relaxation therapy, nutrition counseling, and smoking cessation support. Before and after PR, exercise capacity was assessed with 6-min walking tests (6MWT) and constant cycle ergometer exercise (CEE). Dyspnea was measured after 6MWTs with a Borg scale and after PR with the Transition Dyspnoea Index (TDI). HRQL was examined with the Medical Outcomes Study Short Form 36 (SF-36). Results showed improvements in the 6MWT (+39 m, p < 0.001) and CEE (+241 W × min, p < 0.001) after PR, paralleled by decreased dyspnea during the 6MWT (−0.5, p < 0.001) and during activities (TDI score = 3.6). Increases in all SF-36 subscales reflected improved HRQL after PR (p < 0.001). No gender differences were found. Patients with milder versus more severe COPD improved similarly in most outcomes. Regression analyses revealed that TDI scores were the most important predictor of improvements in HRQL. The results suggest that intensive 3-week outpatient PR is associated with improvements in exercise capacity, dyspnea, and HRQL in male and female patients with COPD irrespective of COPD severity. Reduced dyspnea during activities contributed the most to improvements in HRQL.
Reduced NKX2.1 Expression Predicts Poor Prognosis of Gastric Carcinoma

Thyroid transcription factor-1 (NKX2.1/TITF-1) is a member of the thyroid tissue-specific transcription factor family that has been proven to be closely associated with many human diseases. Recently, it was reported that NKX2.1 expression is lost or reduced in some human cancers such as lung cancer and thyroid cancer. However, there was insufficient data to suggest that NKX2.1 functionality could be used as a prognostic factor. Therefore, this study aims to investigate NKX2.1 expression and its prognostic significance in primary gastric carcinoma. Then, we attempted to investigate if NKX2.1 expression was related to the clinicopathological characteristics and prognosis of gastric carcinoma (GC)patients. The expression levels of NKX2.1 were analyzed in tissue samples from 205 gastric carcinoma patients by real-time quantitative PCR (qRT-PCR), Western blotting, and immunohistochemical staining(IHC). Our qRT-PCR results showed that the expression of NKX2.1 mRNA was reduced in tumor tissue samples compared with that in matched adjacent non-tumor tissue samples (P < 0.001); this finding was confirmed by Western blot analysis (P < 0.001). Our immunohistochemical staining data indicated that NKX2.1 expression was significantly decreased in 87 of 205 (42.4%) gastric carcinoma cases. Kaplan-Meier survival curves revealed that the decreased expression of NKX2.1 was significantly associated with poor prognosis in gastric carcinoma patients (P < 0.001). Multivariate Cox analysis identified NKX2.1 expression as an independent prognostic factor for overall survival (P = 0.005). Furthermore, the functions of Nkx2.1 were analyzed with respect to the proliferation, migration, and invasion of GC cell lines. Our data suggest that NKX2.1 may function as a tumor suppressor in primary gastric carcinoma and that its reduced expression independently predicts an unsatisfactory prognosis in gastric carcinoma patients.
Effectiveness of a specific care plan in patients with Alzheimer’s disease: cluster randomised trial (PLASA study)

To test the effectiveness of a comprehensive specific care plan in decreasing the rate of functional decline in patients with mild to moderate Alzheimer's disease compared with usual care in memory clinics.



Cluster randomised trial.



50 memory clinics in France.



Patients with Alzheimer's disease (mini-mental state examination score 12-26). 1131 patients were included: 574 from 26 clinics in the intervention group, and 557 from 24 clinics in the usual care (control) group. Memory clinics were the unit of randomisation.



The intervention included a comprehensive standardised twice yearly consultation for patients and their caregivers, with standardised guidelines for the management of problems identified during the assessment.



The primary outcome measure was change on the Alzheimer's Disease Cooperative Study-activities of daily living scale assessed at 12 and 24 months. Secondary outcome measures were the rate of admission to institutional care and mortality.



At two years the assessment was completed by 58.4% (n=335) of patients in the intervention group and 61.6% (n=343) in the control group. The rate of functional decline at two years did not differ between the groups. The annual rate of change on the Alzheimer's Disease Cooperative Study-activities of daily living was estimated at -5.73 (95% confidence interval -6.89 to -4.57) in the intervention group and -5.96 (-7.05 to -4.86) in the control group (P=0.78).



A comprehensive specific care plan in memory clinics had no additional positive effect on functional decline in patients with mild to moderate Alzheimer's disease. Future research should aim to determine the effects of more direct involvement of general practitioners.
Surgical management and outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry.

Pulmonary endarterectomy is a curative surgical treatment option for the majority of patients with chronic thromboembolic pulmonary hypertension. The current surgical management and postoperative outcome of patients enrolled in an international registry on chronic thromboembolic pulmonary hypertension were investigated.



The registry included newly diagnosed (≤6 months) consecutive patients with chronic thromboembolic pulmonary hypertension from February 2007 to January 2009.



A total of 679 patients were registered from 1 Canadian and 26 European centers, of whom 386 (56.8%) underwent surgery. The median age of patients undergoing surgery was 60 years, and 54.1% were male. Previous pulmonary embolism was confirmed for 79.8% of patients. Perioperative complications occurred in 189 patients (49.2%): infection (18.8%), persistent pulmonary hypertension (16.7%), neurologic (11.2%) or bleeding (10.2%) complications, pulmonary reperfusion edema (9.6%), pericardial effusion (8.3%), need for extracorporeal membrane oxygenation (3.1%), and in-hospital mortality due to perioperative complications (4.7%). Documented 1-year mortality was 7%. Preoperative exercise capacity was predictive of 1-year mortality. Postoperative pulmonary vascular resistance predicted in-hospital and 1-year mortality. In patients evaluated within 1 year after surgery, the median pulmonary vascular resistance had decreased from 698 to 235 dyn x s x cm(-5) (95% confidence limit, 640-874 and 211-255, respectively, n = 70) and the median 6-minute walk distance had increased from 362 to 459 m (95% confidence limit, 340-399 and 440-473, respectively, n = 168). New York Heart Association functional class improved with most patients progressing from class III/IV to class I/II.



Pulmonary endarterectomy is associated with a low in-hospital mortality rate and improvements in hemodynamics and exercise capacity.
Effect of mifentidine on peptone meal-stimulated gastric acid secretion and plasma gastrin levels in duodenal ulcer patients

Mifentidine is a new H2-receptor antagonist with distinct characteristics of potency and long plasma half-life. The aim of this study was to evaluate the effects of mifentidine on peptone meal-stimulated gastric acid secretion. Nine duodenal ulcer patients in remission were enrolled in the study and given in double-blind and at random, on two different occasions, a single tablet of 10 or 20 mg mifentidine or placebo according to an incomplete balanced block design. Ninety min after ingestion of the drug, basal gastric secretion was collected for 30 min and volume, pH and acid output determined. Thereafter, the acid output following peptone meal-stimulation was measured for 2 h by a modified version of the intragastric titration method of Thompson and Swierczek. Plasma samples were collected for gastrin and mifentidine determinations. Basal acid output was strongly inhibited by both the low dose (−78%) and the high dose (−98%) (p<0.01). The peptone meal-stimulated acid output was reduced in a dose-dependent manner (−45% by 10 mg and −90% by 20 mg). The drug did not affect the fasting serum gastrin levels but increased, although not significantly, the gastrin response to food. The log of the area under the mifentidine plasma levels correlated linearly with total acid output (p<0.01). The results of this study indicate that mifentidine dose-dependently suppresses basal acid secretion and reduces peptone-stimulated gastric acid secretion in duodenal ulcer patients.
Multiple ADH genes are associated with upper aerodigestive cancers

Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10−10 and 10−9, respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.
Thin-film optical notch filter spectacle coatings for the treatment of migraine and photophobia

Previous evidence suggests optical treatments hold promise for treating migraine and photophobia. We designed an optical notch filter, centered at 480nm to reduce direct stimulation of intrinsically photosensitive retinal ganglion cells. We used thin-film technology to integrate the filter into spectacle lenses. Our objective was to determine if an optical notch filter, designed to attenuate activity of intrinsically photosensitive retinal ganglion cells, could reduce headache impact in chronic migraine subjects. For this randomized, double-masked study, our primary endpoint was the Headache Impact Test (HIT-6; GlaxoSmithKline, Brentford, Middlesex, UK). We developed two filters: the therapeutic filter blocked visible light at 480nm; a 620nm filter was designed as a sham. Participants were asked to wear lenses with one of the filters for 2weeks; after 2weeks when no lenses were worn, they wore lenses with the other filter for 2weeks. Of 48 subjects, 37 completed the study. Wearing either the 480 or 620nm lenses resulted in clinically and statistically significant HIT-6 reductions. However, there was no significant difference when comparing overall effect of the 480 and 620nm lenses. Although the 620nm filter was designed as a sham intervention, research published following the trial indicated that melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, is bi-stable. This molecular property may explain the unexpected efficacy of the 620nm filter. These preliminary findings indicate that lenses outfitted with a thin-film optical notch filter may be useful in treating chronic migraine.
Affective instability and the course of bipolar depression: results from the STEP-BD randomised controlled trial of psychosocial treatment.

Little is known about predictors of recovery from bipolar depression.



We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression.



A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n= 141) or a brief psychoeducational intervention (n= 111). All analyses were by intention-to-treat.



Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression.



Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression.
Management of calyceal diverticular calculi: a comparison of percutaneous nephrolithotomy and flexible ureterorenoscopy

To compare the outcomes in patients who have been treated with flexible ureterorenoscopy (f-URS) and percutaneous nephrolithotomy (PNL) in managing stone-bearing caliceal diverticula. Between April 2007 and October 2013, we performed a retrospective analysis of 54 evaluable patients (28 women and 26 men) with symptomatic stone-bearing caliceal diverticula, who underwent PNL (n = 29) or F-URS (n = 25) in four referral hospitals in Turkey. The groups were compared with respect to demographics, stone location/size, success rate, stone-free status, symptom-free status, complication rates, and hospital stay. The average stone burden preoperatively was significantly larger in patients who were treated with PNL, with the average size for f-URS being 154 ± 77 mm2 and that for PNL being 211 ± 97 mm2 (p = 0.023). Symptom-free rates, success rates, stone-free rates and clinically insignificant residual fragments were similar between the groups (p = 0.880 vs. p = 0.537 vs. p = 0.539, and p = 0.877, respectively). There was no statistical difference between the groups for minor complications (p = 0.521) but no major complication (Clavien III–V) occured in the f-URS group; although there were three major complications (10.3 %) (Clavien III) in the PNL group (p < 0.001). Hospitalization time per patient was 1.04 ± 0.20 days in the f-URS group, while it was 3.86 ± 1.94 days in the PNL group (p < 0.001). Even though this study clearly shows that both techniques have high overall success and symptom-free rates with similar complication rates for stone-bearing calyceal diverticulum, major complication rates may suggest consideration of the invasiveness of PNL. The f-URS procedure is advantageous with respect to a shorter hospital stay and absence of major complications. Therefore, it should be emphasized that the location of the stone and diverticula is an important factor for the selection of the procedure.