nils-herrmann/clean_scirepeval huggingface dataset:
A Head and Neck Cancer Tumor Response-Specific Gene Signature for Cisplatin, 5-Fluorouracil Induction Chemotherapy Fails with Added Taxanes

It is a major clinical challenge to predict which patients, with advanced stage head and neck squamous cell carcinoma, will not exhibit a reduction in tumor size following induction chemotherapy in order to avoid toxic effects of ineffective chemotherapy and delays for instituting other therapeutic options. Further, it is of interest to know to what extent a gene signature, which identifies patients with tumors that will not respond to a particular induction chemotherapy, is applicable when additional chemotherapeutic agents are added to the regimen.



To identify genes that predict tumor resistance to induction with cisplatin/5-fluorouracil (PF) or PF and a taxane, we analyzed patient tumor biopsies with whole genome microarrays and quantitative reverse transcriptase-PCR (TLDA) cards. A leave one out cross-validation procedure allowed evaluation of the prediction tool. A ten-gene microarray signature correctly classified 12/13 responders and 7/10 non-responders to PF (92% specificity, 82.6% accuracy). TLDA analysis (using the same classifier) of the patients correctly classified 12/12 responders and 8/10 non-responders (100% specificity, 90.9% accuracy). Further, TLDA analysis correctly predicted the response of 5 new patients and, overall, 12/12 responders and 13/15 non-responders (100% specificity, 92.6% accuracy). The protein products of the genes constituting the signature physically associate with 27 other proteins, involved in regulating gene expression, constituting an interaction network. In contrast, TLDA-based prediction (with the same gene signature) of responses to induction with PF and either of two taxanes was poor (0% specificity, 25% accuracy and 33.3% specificity, 25% accuracy).



Successful transfer of the microarray-based gene signature to an independent, PCR-based technology suggests that TLDA-based signatures could be a useful hospital-based technology for determining therapeutic options. Although highly specific for tumor responses to PF induction, the gene signature is unsuccessful when taxanes are added. The results illustrate the subtlety in developing "personalized medicine".
Assessment of the value of therapeutic monitoring of tacrine in Alzheimer's disease

The purpose of this study was to validate the lower end of the putative therapeutic range of serum tacrine concentrations of 7–20 ng · ml−1 in the treatment of Alzheimer's disease.  The relationship between dose, steady-state serum tacrine concentrations and change in MMSE score (a measure of cognitive function) was examined in 106 Alzheimer's disease patients who had been treated with the drug for 12 weeks.  In all, 72% of patients showed some response, but there was no relationship between dose and the chance of a favourable outcome. The proportion of patients with serum concentrations above 7 ng · ml−1 who improved (79%) was significantly greater than that of those with serum concentrations below this level (47%) (P < 0.02). Also, a significantly greater proportion of patients with serum concentrations above both 5 ng · ml−1 and 9 ng · ml−1 showed improvement in comparison to those with concentrations below these levels.  This study indicates that therapeutic monitoring of serum tacrine concentrations might increase the possibility of responding to tacrine by some 68%. This represents an important contribution to the management of Alzheimer's disease patients with this drug, and may also be relevant to the use of the newer generation of cholinesterase inhibitors.
Alcoholic marriage: later start, sooner end.

Although associations between drinking behavior and marital status are well documented, timing of marital transitions as a function of alcohol use or disorder has received limited empirical attention.



We examine the relationship between lifetime history of alcohol dependence (AD) and timing and survival of first marriages in a sample of 3,575 female and 1,845 male adult Australian twins born mostly between 1940 and 1964. Survival analyses were conducted using Cox proportional hazards regression models.



Results indicate moderate delays in marriage associated with AD for both women and men. Among ever-married respondents, AD was strongly predictive of early separation, with similar effects observed for women and men. Heritable sources of covariation were also documented. For women, genetic influences shared between early-onset AD and marital timing were found. Genetic influences shared between AD and marital survival were observed for women without regard to onset and for men with later-onset AD.



Results confirm the importance of AD as a predictor of both timing and survival of first marriages, with genetic influences contributing to observed associations.
Novel genetic markers improve measures of atrial fibrillation risk prediction

Atrial fibrillation (AF) is associated with adverse outcome. Whether recently discovered genetic risk markers improve AF risk prediction is unknown.



We derived and validated a novel AF risk prediction model from 32 possible predictors in the Women's Health Study (WHS), a cohort of 20 822 women without cardiovascular disease (CVD) at baseline followed prospectively for incident AF (median: 14.5 years). We then created a genetic risk score (GRS) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS. The newly derived WHS AF risk algorithm included terms for age, weight, height, systolic blood pressure, alcohol use, and smoking (current and past). In the validation cohort, this model was well calibrated with good discrimination [C-index (95% CI) = 0.718 (0.684-0.753)] and improved all reclassification indices when compared with age alone. The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [0.741 (0.709-0.774); P = 0.001], the category-less net reclassification [0.490 (0.301-0.670); P < 0.0001], and the integrated discrimination improvement [0.00526 (0.0033-0.0076); P < 0.0001]. However, there was no improvement in net reclassification into 10-year risk categories of <1, 1-5, and 5+% [0.041 (-0.044-0.12); P = 0.33].



Among women without CVD, a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF. The addition of genetic information resulted in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categories.
The working alliance in a randomized controlled trial comparing online with face-to-face cognitive-behavioral therapy for depression

Although numerous efficacy studies in recent years have found internet-based interventions for depression to be effective, there has been scant consideration of therapeutic process factors in the online setting. In face-to face therapy, the quality of the working alliance explains variance in treatment outcome. However, little is yet known about the impact of the working alliance in internet-based interventions, particularly as compared with face-to-face therapy.



This study explored the working alliance between client and therapist in the middle and at the end of a cognitive-behavioral intervention for depression. The participants were randomized to an internet-based treatment group (n = 25) or face-to-face group (n = 28). Both groups received the same cognitive behavioral therapy over an 8-week timeframe. Participants completed the Beck Depression Inventory (BDI) post-treatment and the Working Alliance Inventory at mid- and post- treatment. Therapists completed the therapist version of the Working Alliance Inventory at post-treatment.



With the exception of therapists' ratings of the tasks subscale, which were significantly higher in the online group, the two groups' ratings of the working alliance did not differ significantly. Further, significant correlations were found between clients' ratings of the working alliance and therapy outcome at post-treatment in the online group and at both mid- and post-treatment in the face-to-face group. Correlation analysis revealed that the working alliance ratings did not significantly predict the BDI residual gain score in either group.



Contrary to what might have been expected, the working alliance in the online group was comparable to that in the face-to-face group. However, the results showed no significant relations between the BDI residual gain score and the working alliance ratings in either group.
Plant sterol-enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects

To compare effects on plasma total-, LDL-, and HDL-cholesterol concentrations of margarines enriched with different vegetable oil sterols or sitostanol-ester. A randomized double-blind placebo-controlled balanced incomplete Latin square design with five treatments and four periods of 3.5 weeks. Margarines enriched with sterols from soybean, sheanut or ricebran oil or with sitostanol-ester were compared to a non-enriched control margarine. Sterol intake was between 1.5–3.3 g/d. Two thirds of the soybean oil sterols were esterified to fatty acids. Unilever Research Laboratory, Vlaardingen, The Netherlands. One hundred healthy non-obese normocholesterolaemic and mildly hypercholesterolaemic volunteers aged 45±12.8 y, with plasma total cholesterol levels below 8 mmol/L at entry. Plasma lipid, carotenoid and sterol concentrations, blood clinical chemistry and haematology, fatty acid composition of plasma cholesterylesters and food intake. Ninety-five volunteers completed the study. None of the margarines induced adverse changes in blood clinical chemistry, serum total bile acids or haematology. Plasma total- and LDL-cholesterol concentrations were significantly reduced by 8–13% (0.37–0.44 mmol/L) compared to control for margarines enriched in soybean oil sterol-esters or sitostanol-ester. No effect on HDL-cholesterol concentrations occurred. The LDL- to HDL-cholesterol ratio was reduced by 0.37 and 0.33 units for these margarines, respectively. Effects on blood lipids did not differ between normocholesterolaemic and mildly hypercholesterolaemic subjects. Plasma sitosterol and campesterol levels were significantly higher for the soybean oil sterol margarine and significantly lower for the sitostanol-ester margarine compared to control. Dietary intake was very similar across treatments. The fatty acid composition of plasma cholesterylesters confirmed the good compliance to the treatment. All sterol enriched margarines reduced lipid-standardized plasma α- plus β-carotene levels. Plasma lycopene levels were also reduced but this effect was not significant for all products. A margarine with sterol-esters from soybean oil, mainly esters from sitosterol, campesterol and stigmasterol, is as effective as a margarine with sitostanol-ester in lowering blood total- and LDL-cholesterol levels without affecting HDL-cholesterol concentrations. Incorporation in edible fat containing products of such substances may substantially reduce the risk of cardiovascular disease in the population.
Up-front allogeneic hematopoietic cell transplantation in acute myeloid leukemia arising from the myelodysplastic syndrome.

In patients with secondary acute myeloid leukemia (s-AML) arising from the myelodysplastic syndrome (MDS), treatment outcome is unsatisfactory. We compared up-front allogeneic hematopoietic cell transplantation (HCT) to induction chemotherapy (IC) as an initial treatment in patients with s-AML arising from MDS. This retrospective study included 85 patients who were diagnosed with s-AML arising from MDS; 11 patients proceeded to up-front HCT without IC (HCT group) and 74 received IC (IC group) as an initial treatment for s-AML, 28 of whom subsequently underwent HCT. In the IC group, 41.9% achieved complete remission (CR) compared to 81.8% in the HCT group (p = 0.013). The HCT group showed a significantly longer event-free survival (EFS) than the IC group (median 29.2 vs. 5.2 months, p = 0.042). Overall survival of the HCT group was higher than that of the IC group, but the difference was not statistically significant (median 34.6 vs. 7.6 months, p = 0.149). After adjustment for other clinical factors, outcome in the HCT group was significantly better than in the IC group in terms of CR rate (hazard ratio, HR, 11.195; p = 0.007) and EFS (HR, 0.384; p = 0.029). Up-front HCT is a viable option in s-AML arising from MDS if an appropriate donor is available.
Can chronic disease management programs for patients with type 2 diabetes reduce productivity-related indirect costs of the disease? Evidence from a randomized controlled trial.

The objective was to assess the impacts of diabetes self-management programs on productivity-related indirect costs of the disease. Using an employer's perspective, this study estimated the productivity losses associated with: (1) employee absence on the job, (2) diabetes-related disability, (3) employee presence on the job, and (4) early mortality. Data were obtained from electronic medical records and survey responses of 376 adults aged ≥18 years who were enrolled in a randomized controlled trial of type 2 diabetes self-management programs. All study participants had uncontrolled diabetes and were randomized into one of 4 study arms: personal digital assistant (PDA), chronic disease self-management program (CDSMP), combined PDA and CDSMP, and usual care (UC). The human-capital approach was used to estimate lost productivity resulting from 1, 2, 3, and 4 above, which are summed to obtain total productivity loss. Using robust regression, total productivity loss was modeled as a function of the diabetes self-management programs and other identified demographic and clinical characteristics. Compared to subjects in the UC arm, there were no statistically significant differences in productivity losses among persons undergoing any of the 3 diabetes management interventions. Males were associated with higher productivity losses (+$708/year; P<0.001) and persons with greater than high school education were associated with additional productivity losses (+$758/year; P<0.001). Persons with more than 1 comorbid condition were marginally associated with lower productivity losses (-$326/year; P=0.055). No evidence was found that the chronic disease management programs examined in this trial affect indirect productivity losses.
Screening for diabetic retinopathy using digital colour photography and oral fluorescein angiography

To evaluate digital colour photography and oral fluorescein angiography (OFA) for diabetic retinopathy screening.  Thirty-seven patients were selected from either a diabetic retinopathy screening or a medical retina clinic. Three 45° colour digital images and a single macula 45° OFA image were taken from each eye. Standard seven- field stereo photography with ETDRS grading was used as a gold standard for data comparison. The images were assessed by two graders and the results of each method compared using the McNemar test.  Five eyes had no diabetic retinopathy, 50 had background diabetic retinopathy, 3 had pre-proliferative diabetic retinopathy, 11 had proliferative disease and 3 had quiescent post- treatment disease. Clinically significant macular oedema was present in 25 eyes and absent in 48. For grading diabetic retinopathy digital colour photography produced a sensitivity of 0.87 (specificity 0.83); OFA produced a sensitivity of 0.87 (specificity 0.80) (p = 0.1). For the detection of diabetic maculopathy, the sensitivity of digital colour photography was 0.48 (specificity of 0.95) and for OFA was 0.87 (specificity 0.87) (p < 0.01).  This pilot study has shown that both digital colour photography and OFA compare well with conventional methods for diabetic retinopathy screening. The results encourage the further evaluation of OFA in the screening for diabetic maculopathy.
Correlates of adjudicative competence among psychiatrically impaired juveniles.

This study examines the competence-related abilities of 120 psychiatrically hospitalized male juveniles age 10 to 17 years, using the MacArthur Competence Assessment Tool-Criminal Adjudication (MacCAT-CA), the Brief Psychiatric Rating Scale-Anchored (BPRS-A), the Massachusetts Youth Screening Instrument (MAYSI), the Kaufman Brief Intelligence Test (K-BIT), and discharge diagnoses derived from file review. The findings indicate significant age-related differences across adolescence with a relatively strong performance for most of the youths on the competence measure. While intellectual and psychiatric factors were found to contribute substantially to deficits in legal decisional ability, they were modulated by age and the developmental factors associated with it. These findings, replete with caveats concerning both the dimensional structure of competence as measured by the MacCAT-CA and the interplay with the mental status and developmental factors affecting it, underscore the multifarious nature of legal decisional capacity in youths of varying ages. The relevance of these findings to the structuring of restoration services and the application of legal theory to the competence standard in juvenile court are discussed.
Biatrial lesion sets

The Cox-Maze procedure was developed more than 20 years ago at our institution. This traditional cut-and-sew operation had high success rates but was very invasive. To simplify this procedure, our group developed an operation, the Cox-Maze IV procedure, that replaces most of the incisions with linear lines of ablation while preserving the traditional biatrial lesion set. The technical aspects of the procedure are discussed in detail. Initial operative results with this new procedure have been good, with a freedom from atrial fibrillation of 90% at 1 year. The success rate is not significantly different from the traditional cut-and-sew procedure.
A prospective, randomized trial comparing 25-gauge and 22-gauge needles for endoscopic ultrasound-guided fine needle aspiration of pancreatic masses.

Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is widely performed for pancreatic masses. The 25-gauge needle (25G) might be easier to be manipulated and expected to be associated with fewer complications since it is thinner and more flexible than the 22-gauge needle (22G) although obtaining adequate specimens is questioned. In this randomized trial, the authors tried to compare prospectively 25G and 22G in diagnostic accuracy, manipulability from the operator's viewpoint and procedure-related complications.



A total of 188 consecutive patients undergoing EUS-FNA for solid or cystic pancreatic masses were consecutively enrolled and 94 patients were randomized to either 25G or 22G group, respectively.



Baseline characteristics were similar except that more masses of 25G group were located in the head or uncinate process of pancreas than those from 22G group. Although there was no difference in diagnostic accuracy (89.4% vs. 88.3% with p = 0.82), 25G was easier to be manipulated (p = 0.004) and related with fewer procedure-related complications (10.6% vs. 3.2% with p = 0.004).



25G can be chosen in preference to 22G when performing pancreatic EUS-FNA because 25G was significantly superior to 22G in terms of manipulability and complications although both were effective for accurate diagnosis.
Phase I study of safety and tolerability of sunitinib in combination with sirolimus in patients with refractory solid malignancies and determination of VEGF (VEGF-A) and soluble VEGF-R2 (sVEGFR2) in plasma

Sirolimus, an oral mTOR inhibitor, may complement the anti-angiogenic and anti-tumor activity of sunitinib, an oral small molecule inhibitor of multiple receptor tyrosine kinases, by vertical disruption of vascular epithelial growth factor receptor (VEGFR) signaling, by reducing the compensatory production of VEGF in sunitinib-treated patients and also by directly inhibiting tumor cell proliferation. We conducted this phase 1 study to investigate the maximum tolerated dose (MTD) for this combination of sunitinib and sirolimus in humans. Sunitinib was given at 50 mg daily × 28 every 6 weeks. The first cohort received sunitinib alone for cycle 1 (50 mg daily for 2 weeks followed by 2 weeks off) and received sunitinib at standard dose 50 mg daily for 4 weeks followed by 2 weeks off in combination with sirolimus 4 mg weekly; this dose and schedule were further investigated in second cohort. The third cohort received decreased dose of sunitinib at 37.5 mg daily for 4 weeks followed by 2 weeks off in combination with sirolimus at 4 mg weekly. Sirolimus dose was escalated to 8 mg weekly in fourth cohort. Eighteen patients with ECOG PS of 0 or 1 were enrolled, median age 57 years (range 24–76), M:F ratio: 11:7. Median number of prior treatments is 2 (range 0–5); six patients had no prior systemic therapy. Half of patients from the first two cohorts required dose reduction or early discontinuation of treatment; therefore, sunitinib dose was decreased to 37.5 mg daily in third and fourth cohort. In third and fourth cohort, one-third of patients required dose modification during cycle 1 or cycle 2. Multiple patients had significant toxicities including fatigue and hand–foot syndrome. One patient developed interstitial pneumonitis, and one patient died suddenly on day 8 due to progressive disease. There were six patients who tolerated four or more cycles. Among these six patients, two patients with renal cell carcinoma (RCC) achieved partial response; one subsequently underwent surgical resection of residual renal mass and lymph node dissection and achieved complete response afterward. One with metastatic melanoma also achieved complete response after metastatectomy. There was no apparent pharmacokinetic interaction between sunitinib and sirolimus. 4 mg weekly sirolimus did not reduce the sunitinib-induced circulating VEGF production but stimulated more VEGF production through some unknown compensatory mechanism. Toxicity precluded dose escalation of weekly sirolimus in combination with a standard sunitinib dose/schedule. These results suggest caution when combining targeted agents lacking specificity for tumor signaling or vasculature.