nils-herrmann/clean_scirepeval huggingface dataset:
Interfractional anatomic variation in patients treated with respiration‐gated radiotherapy

As quality assurance for respiration-gated treatments using the Varian RPM system, we monitor interfractional diaphragm variation throughout treatment using extra anterior-posterior (AP) portal images. We measure the superior-inferior (SI distance between one or more bony landmarks and the ipsilateral diaphragm dome in each such radiograph and calculate its difference, D, from the corresponding distance in a planning CT scan digitally reconstructed radiograph (DRR). For each patient, the mean of D represents the systematic diaphragm displacement, and the standard deviation of D represents random diaphragm variations and is a measure of interfractional gating reproducibility. We present results for 31 sequential patients (21 lung, 10 liver tumors), each with at least 8 such portal images. For all patients, the gate included end-exhale. The patient-specific duty cycle ranged from 30% to 60%. All patients received customized audio prompting for simulation and treatment, and 14 patients also received visual prompting. Respiration-synchronized fluoroscopic movies taken at a conventional simulator revealed patient-specific diaphragm excursions from 1.0 cm to 5.0 cm and diaphragm excursion within the gate from 0.5 cm to 1.0 cm, demonstrating a significant reduction of intra-fractional diaphragm (and by inference tumor) motion by respiratory gating. One standard deviation of the systematic displacement (the mean of D) was 0.63 cm and 0.48 cm for the lung and liver patient groups, respectively. The average +/-1 SD of the random displacements (i.e., the average of the standard deviations of D) was 0.42 +/- 0.11 cm and 0.50 +/- 0.19 for the two groups, respectively. The similar magnitude of the systematic and random displacements suggests that both derive from a common distribution of interfractional variations. Combining visual with audio prompting did not significantly improve performance, as judged by D. Guided by these portal images, field changes were made during the course of treatment for 6 patients (1 lung, 5 liver).
Adding Defibrillation Therapy to Cardiac Resynchronization on the Basis of the Myocardial Substrate.

Patients with nonischemic dilated cardiomyopathy (DCM) may be at lower risk for ventricular arrhythmias compared with those with ischemic cardiomyopathy (ICM). In addition, DCM has been identified as a predictor of positive response to cardiac resynchronization therapy (CRT).



The aim of this study was to investigate the impact of an additional implantable cardioverter-defibrillator over CRT, according to underlying heart disease, in a large study group of primary prevention patients with heart failure.



This was an observational, multicenter, European cohort study of 5,307 consecutive patients with DCM or ICM, no history of sustained ventricular arrhythmias, who underwent CRT implantation with (n = 4,037) or without (n = 1,270) a defibrillator. Propensity-score and cause-of-death analyses were used to compare outcomes.



After a mean follow-up period of 41.4 ± 29.0 months, patients with ICM had better survival when receiving CRT with a defibrillator compared with those who received CRT without a defibrillator (hazard ratio for mortality adjusted on propensity score and all mortality predictors: 0.76; 95% confidence interval [CI]: 0.62 to 0.92; p = 0.005), whereas in patients with DCM, no such difference was observed (hazard ratio: 0.92; 95% CI: 0.73 to 1.16; p = 0.49). Compared with recipients of defibrillators, the excess mortality in patients who did not receive defibrillators was related to sudden cardiac death in 8.0% among those with ICM but in only 0.4% of those with DCM.



Among patients with heart failure with indications for CRT, those with DCM may not benefit from additional primary prevention implantable cardioverter-defibrillator therapy, as opposed to those with ICM.
Population-based study of long-term functional outcomes after prostate cancer treatment.

To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median (interquartile range) follow-up of 12 (11-13) years.



In this nationwide, population-based study, we identified 6 003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate-specific antigen <20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 from the National Prostate Cancer Register, Sweden. The men were aged ≤70 years at diagnosis. A control group of 1 000 men without prostate cancer were also selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire.



Responses were obtained from 3 937/6 003 cases (66%) and 459/1 000 (46%) controls. At 12 years after diagnosis and at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction/sexual inactivity, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62, 6 and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction compared with the men in the control group. Radical prostatectomy was associated with an increased risk of urinary incontinence (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.36-2.62) and radiotherapy increased the risk of bowel dysfunction (OR 2.46, 95% CI 1.73-3.49) compared with men in the control group. Multi-modal treatment, in particular treatment including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance, radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 (95% CI 1.76-7.95) for erectile dysfunction and an OR of 3.22 (95% CI 1.93-5.37) for urinary incontinence.



The proportion of men who experienced a long-term impact on functional outcomes after prostate cancer treatment was substantial.
A phase II trial of CI-958 in patients with hormone-refractory prostate cancer

To assess the antitumor activity of the benzothiopyranoindazole CI-958 {5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H-[l]benzothi- opyrano[4,3,2-cd]-indazol-8-ol trihydrochloride} in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m2 every 3 weeks.  Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria.  All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1–23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions.  CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.
Exact and Asymptotic Solutions of a Divide-and-Conquer Recurrence Dividing at Half: Theory and Applications

Divide-and-conquer recurrences of the form <i>f</i>(<i>n</i>) = <i>f</i> (⌊ &fracn2;⌋ ) + <i>f</i> ( ⌈ &fracn2;⌉ ) + <i>g</i>(<i>n</i>) (<i>n</i>⩾ 2), with <i>g</i>(<i>n</i>) and <i>f</i>(1) given, appear very frequently in the analysis of computer algorithms and related areas. While most previous methods and results focus on simpler crude approximation to the solution, we show that the solution always satisfies the simple <i>identity</i> <i>f</i>(<i>n</i>) = <i>n</i> <i>P</i>(log<sub>2</sub><i>n</i>) − <i>Q</i>(<i>n</i>) under an optimum (iff) condition on <i>g</i>(<i>n</i>). This form is not only an identity but also an asymptotic expansion because <i>Q</i>(<i>n</i>) is of a smaller order than linearity. Explicit forms for the <i>continuous</i> periodic function <i>P</i> are provided. We show how our results can be easily applied to many dozens of concrete examples collected from the literature and how they can be extended in various directions. Our method of proof is surprisingly simple and elementary but leads to the strongest types of results for all examples to which our theory applies.
Phase III open-label randomized study of cytarabine in combination with amonafide L-malate or daunorubicin as induction therapy for patients with secondary acute myeloid leukemia.

Secondary acute myeloid leukemia (sAML), defined as AML arising after a prior myelodysplastic syndrome or after antineoplastic therapy, responds poorly to current therapies. It is often associated with adverse karyotypic abnormalities and overexpression of proteins that mediate drug resistance. We performed a phase III trial to determine whether induction therapy with cytarabine and amonafide L-malate, a DNA intercalator and non-ATP-dependent topoisomerase II inhibitor that evades drug resistance mechanisms, yielded a superior complete remission rate than standard therapy with cytarabine and daunorubicin in sAML.



Patients with previously untreated sAML were randomly assigned at a one-to-one ratio to cytarabine 200 mg/m(2) continuous intravenous (IV) infusion once per day on days 1 to 7 plus either amonafide 600 mg/m(2) IV over 4 hours on days 1 to 5 (A + C arm) or daunorubicin 45 mg/m(2) IV over 30 minutes once per day on days 1 to 3 (D + C arm).



The complete remission (CR) rate was 46% (99 of 216 patients) in A + C arm and 45% (97 of 217 patients) in D + C arm (P = .81). The 30- and 60-day mortality rates were 19% and 28% in A + C arm and 13% and 21% in D + C arm, respectively.



Induction treatment with A + C did not improve the CR rate compared with D + C in patients with sAML.
No evidence for genetically determined alteration in insulin secretion or sensitivity predisposing to type 1 diabetes: a study of identical twins.

To determine whether inherited changes in insulin secretion or sensitivity could predispose to type 1 diabetes, we studied identical twins of type 1 diabetic patients.



We studied prospectively a consecutive series of 27 identical twins of patients with type 1 diabetes who were initially nondiabetic, as well as 14 control subjects, over a period of 18 years. Of these 27 twins, 15 remain nondiabetic (now estimated at low disease risk) and 12 developed diabetes (pre-diabetic twins). Subjects were tested when not diabetic on at least two occasions with an intravenous glucose tolerance test (IVGTT), and we estimated insulin secretion as first-phase insulin response (FPIR), glucose clearance (K(g)), and insulin sensitivity both by homeostasis model assessment of insulin resistance (HOMA-IR) and relative to insulin response by the basal HOMA-IR-to-FPIR ratio.



Twins now at low risk and control subjects had similar fasting blood glucose and insulin levels, FPIR, K(g), HOMA-IR, and HOMA-IR-to-FPIR ratio. In contrast, pre-diabetic twins compared with control twins had higher fasting insulin levels (10.3 +/- 6.0 vs. 4.6 +/- 4.0 mIU/ml), lower FPIR (245 +/- 129 vs. 796 +/- 622 mIU . ml(-1) . 10 min(-1)), lower K(g) (1.5 +/- 0.6 vs. 2.6 +/- 0.8% per min), and higher HOMA-IR-to-FPIR ratio (0.007 +/- 0.005 vs. 0.001 +/- 0.0009) (all P < 0.01).



These observations in low-risk nondiabetic identical twins failed to identify a familial alteration in either insulin secretion or sensitivity predisposing to type 1 diabetes.
Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study.

This study defined long-term patency of saphenous vein grafts (SVG) and internal mammary artery (IMA) grafts.



This VA Cooperative Studies Trial defined 10-year SVG patency in 1,074 patients and left IMA patency in 457 patients undergoing coronary artery bypass grafting (CABG).



Patients underwent cardiac catheterizations at 1 week and 1, 3, 6, and 10 years after CABG.



Patency at 10 years was 61% for SVGs compared with 85% for IMA grafts (p < 0.001). If a SVG or IMA graft was patent at 1 week, that graft had a 68% and 88% chance, respectively, of being patent at 10 years. The SVG patency to the left anterior descending artery (LAD) (69%) was better (p < 0.001) than to the right coronary artery (56%), or circumflex (58%). Recipient vessel size was a significant predictor of graft patency, in vessels >2.0 mm in diameter SVG patency was 88% versus 55% in vessels </=2.0 mm (p < 0.001). Other positive significant predictors of graft patency were use of aspirin after bypass, older age, lower serum cholesterol, and lowest Canadian Functional Class (p < 0.001 to 0.058).



The 10-year patency of IMA grafts is better than SVGs. The 10-year patency for SVGs is better and the 10-year patency for IMA grafts is worse than expected. The 10-year patency of SVGs to the LAD is better than that to the right or circumflex. The best long-term predictors of SVG graft patency are grafting into the LAD and grafting into a vessel that is >2.0 mm in diameter.
Beta-blocker therapy for cardiac dysfunction in patients with muscular dystrophy.

In muscular dystrophy, cardiac function deteriorates with time and heart failure is one of the major causes of death. Although the combination of angiotensin-converting enzyme inhibitors (ACEI) and beta-blockers improves cardiac function in adults, little is known about the efficacy of those drugs in patients with muscular dystrophy.



The effect of the beta-blocker, carvedilol, and/or ACEI on ventricular function in patients with muscular dystrophy was studied. Carvedilol and an ACEI were given to 13 patients (ACEI group; mean age 18 years, range 7-27 years), and an ACEI only to 15 patients (carvedilol group; mean age 15 years, range 8-29 years). Diagnoses included Duchenne muscular dystrophy (n=25), Fukuyama muscular dystrophy (n=2), and Emery-Dreifuss muscular dystrophy (n=1). Echocardiographic parameters of the left ventricle were measured during the 2-3 years of follow-up. In the carvedilol group, combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS). In the ACEI group, there was no significant change in LVFS. Left ventricular end-diastolic dimension increased in the ACEI group, but not in the carvedilol group.



Carvedilol plus an ACEI improves left ventricular systolic function in patients with muscular dystrophy.
NMDA hypofunction in the posterior cingulate as a model for schizophrenia: an exploratory ketamine administration study in fMRI

Based on animal data, NMDA receptor hypofunction has been suggested as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction affects several corticolimbic brain regions, of which the posterior cingulate seems to be the most sensitive. However, empirical support for a crucial role of posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms is still missing in humans. We therefore conducted an fMRI study using the NMDA antagonist ketamine in healthy human subjects during episodic memory retrieval, which is supposed to activate the posterior cingulate.



We investigated 16 healthy subjects which were assigned to either placebo (n = 7; saline) or ketamine (n = 9; 0.6 mg/kg/h) group in a double-blind study design. All subjects received their infusion while performing an episodic memory retrieval task in the scanner. Immediately after the fMRI session, psychopathological effects of ketamine were measured using the Altered States of Consciousness Questionnaire.



The placebo group showed BOLD signal increases in the posterior and anterior cingulate during retrieval. Signal increases were significantly lower in the ketamine group. Lower signal increases in the posterior cingulate correlated significantly with positive (i.e. psychosis-like) symptoms induced by ketamine.



The present study for the first time demonstrates a relationship between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like) symptoms in humans. Confirming findings from animal studies, it supports the hypothesis of a pathophysiological role of NMDA receptor hypofunction in the posterior cingulate in schizophrenia.
Untangling attention bias modification from emotion: A double-blind randomized experiment with individuals with social anxiety disorder.

Uncertainty abounds regarding the putative mechanisms of attention bias modification (ABM). Although early studies showed that ABM reduced anxiety proneness more than control procedures lacking a contingency between cues and probes, recent work suggests that the latter performed just as well as the former did. In this experiment, we investigated a non-emotional mechanism that may play a role in ABM.



We randomly assigned 62 individuals with a DSM-IV diagnosis of social anxiety disorder to a single-session of a non-emotional contingency training, non-emotional no-contingency training, or control condition controlling for potential practice effects. Working memory capacity and anxiety reactivity to a speech challenge were assessed before and after training.



Consistent with the hypothesis of a practice effect, the three groups likewise reported indistinguishably significant improvement in self-report and behavioral measures of speech anxiety as well as in working memory. Repeating the speech task twice may have had anxiolytic benefits.



The temporal separation between baseline and post-training assessment as well as the scope of the training sessions could be extended.



The current findings are at odds with the hypothesis that the presence of visuospatial contingency between non-emotional cues and probes produces anxiolytic benefits. They also show the importance of including a credible additional condition controlling for practice effects.
Value of reserve pulse pressure in improving the risk stratification of patients with normal myocardial perfusion imaging.

To evaluate the incremental prognostic value of reserve-pulse pressure (reserve-PP: exercise-PP minus rest-PP) to standard risk factors among patients with suspected coronary artery disease (CAD) but normal exercise myocardial perfusion imaging (MPI).



We studied 4269 consecutive symptomatic patients without known CAD who were referred for exercise MPI but had normal MPI results (mean age 58 ± 12 years, 56% females, 84% referred for evaluation of chest pain or dyspnoea, 95% with intermediate pretest likelihood of CAD). There were 202 deaths over 5.1 ± 1.4 years of follow-up. Reserve-PP was abnormal (<44 mmHg increase in PP from rest) in 1894 patients (44%). Patients with an abnormal reserve-PP had a higher risk of death compared with patients with normal reserve-PP [hazard ratio (HR): 2.47, 95% CI, 1.8-3.3]. In multivariable models adjusting for age, sex, ejection fraction, medications, heart rate recovery, Duke treadmill score (DTS), and rest-PP, each 10 mmHg lower reserve-PP was associated with a 20.6% increase in risk-adjusted mortality (adjusted HR 0.83, 95% CI 0.76-0.91). Models incorporating reserve-PP significantly reclassified risk compared with models without these parameters (net reclassification index 14.3%, P = 0.0007; integrated discrimination index 0.69, P = 0.01).



In patients without a history of CAD and a normal MPI, an abnormal reserve-PP identified and reclassified those at higher risk of death independent of known risk factors and DTS.
Effect of running therapy on depression (EFFORT-D). Design of a randomised controlled trial in adult patients [ISRCTN 1894]

The societal and personal burden of depressive illness is considerable. Despite the developments in treatment strategies, the effectiveness of both medication and psychotherapy is not ideal. Physical activity, including exercise, is a relatively cheap and non-harmful lifestyle intervention which lacks the side-effects of medication and does not require the introspective ability necessary for most psychotherapies. Several cohort studies and randomised controlled trials (RCTs) have been performed to establish the effect of physical activity on prevention and remission of depressive illness. However, recent meta-analysis's of all RCTs in this area showed conflicting results. The objective of the present article is to describe the design of a RCT examining the effect of exercise on depressive patients.



The EFFect Of Running Therapy on Depression in adults (EFFORT-D) is a RCT, studying the effectiveness of exercise therapy (running therapy (RT) or Nordic walking (NW)) on depression in adults, in addition to usual care. The study population consists of patients with depressive disorder, Hamilton Rating Scale for Depression (HRSD) ≥ 14, recruited from specialised mental health care. The experimental group receives the exercise intervention besides treatment as usual, the control group receives treatment as usual. The intervention program is a group-based, 1 h session, two times a week for 6 months and of increasing intensity. The control group only performs low intensive non-aerobic exercises. Measurements are performed at inclusion and at 3,6 and 12 months.Primary outcome measure is reduction in depressive symptoms measured by the HRSD. Cardio-respiratory fitness is measured using a sub maximal cycling test, biometric information is gathered and blood samples are collected for metabolic parameters. Also, co-morbidity with pain, anxiety and personality traits is studied, as well as quality of life and cost-effectiveness.



Exercise in depression can be used as a standalone or as an add-on intervention. In specialised mental health care, chronic forms of depression, co-morbid anxiety or physical complaints and treatment resistance are common. An add-on strategy therefore seems the best choice. This is the first high quality large trial into the effectiveness of exercise as an add-on treatment for depression in adult patients in specialised mental health care.
The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures

More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P < 0.001), median total cholesterol was significantly increased (from 180 to 285 mg/dl, P < 0.001), median serum low-density lipoprotein (LDL) was significantly increased (from 91 to 175 mg/dl, P < 0.001), and median serum high-density lipoprotein (HDL) was significantly increased (from 51 to 58 mg/dl, P < 0.001). Results of this study indicate that a classic ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.