nils-herrmann/clean_scirepeval huggingface dataset:
Cortisol reactivity to experimentally manipulated psychosocial stress in young adults at varied risk for depression.

This study examined cortisol and affective reactivity to a psychosocial stress task in 102 young adults who varied in risk for depression (56 remitted depressed, 46 never depressed). Participants were randomly assigned to either a stress (i.e., social-evaluative threat) or control (i.e., no social-evaluative threat) condition. For never-depressed individuals, cortisol responses were significantly greater in the stress compared to the control condition. Moreover, cortisol responses were significantly greater for never-depressed than remitted-depressed individuals in the stress condition. For individuals with a history of depression, cortisol responses did not differ significantly between the stress and control conditions. Negative affective reactivity also was higher for never depressed, but not remitted depressed, individuals in the stress compared to the control condition. Moreover, cortisol responses were inversely related to negative affect during the recovery phase in both stress and control conditions. Findings indicate the lack of a robust cortisol response to social evaluation stress among remitted-depressed individuals as compared to that of never-depressed controls. Future studies should investigate unique and interactive links between these hypothalamic-pituitary-adrenal and affective reactivity alterations and risk for subsequent depressive episodes.
Trajectories of depressive symptoms following breast cancer diagnosis.

This longitudinal study sought to identify groups of breast cancer survivors exhibiting distinct trajectories of depressive symptoms up to 24 months following diagnosis, and to describe characteristics associated with these trajectories.



A total of 653 women completed baseline questionnaires within 8 months of breast cancer diagnosis on patient characteristics, symptoms, and psychosocial variables. Depressive symptoms were assessed at baseline and 6, 12, and 18 months after baseline. Chart reviews provided cancer and treatment-related data. Finite mixture modeling identified trajectories of depressive symptoms measured with the Beck Depression Inventory (BDI).



Six distinct trajectories were identified. Just over half of the sample had consistently very low (3.8%) or low (47.3%) BDI scores well below the traditional BDI cutoff point of 10 thought to be indicative of clinically significant depression; 29.2% had consistently borderline scores; 11.3% had initially high scores that declined over time, but remained above the cutoff point; 7.2% showed increased BDI over time; and a small but unique group (1.1%) reported chronically high scores above 25. Women in groups with lower depressive symptom levels were older, had less rigorous chemotherapy, fewer physical symptoms (fatigue and pain), and lower levels of illness intrusiveness.



Approximately 20% of women had levels of depressive symptoms indicative of clinical depression that were maintained 2 years postdiagnosis. Factors related to trajectory membership such as illness intrusiveness, social support, fatigue, pain, and vasomotor symptoms suggest targets for possible intervention.



Results demonstrate the heterogeneity of depressive symptoms following breast cancer and the need for continued screening posttreatment.
Adenocarcinoma of the third and fourth portions of the duodenum: results of surgical treatment.

To verify the adequacy of duodenal segmentectomy after intestinal derotation in the treatment of primary adenocarcinoma of the third and fourth portions of the duodenum.



A retrospective review of the surgical management of patients who underwent derotation of the third and fourth portions of the duodenum was undertaken to determine long-term outcome.



Departments of surgery in 3 university hospitals.



Between January 1, 1980, and December 31, 2000, 47 patients with primary adenocarcinoma of the third and fourth portions of the duodenum were surgically treated at 3 different institutions.



Details of primary surgery were abstracted from clinical records of the original hospital referral. Postoperative clinical course and long-term outcome were evaluated by a review of the hospital records and follow-up.



The results of a barium swallow test series was positive in 38 cases (80.8%) and esophagogastroduodenoscopy was primarily diagnostic in 30 patients (63.8%). In all cases duodenal segmentectomy was attempted. Twenty-two patients underwent palliative gastrojejunal bypass and in 9 patients pancreaticoduodenectomy was performed. In 16 cases duodenal segmentectomy was performed after intestinal derotation. Anastomoses were performed manually in all cases. Fifteen of the resected patients died of recurrent disease. A median (SD) disease-free survival of 36 (23.6) months (range, 6-85 months) was observed. The median (SD) overall survival was 37.5 (23.9) months (range, 11-85 months), the overall 5-year survival rate was 23% (11 patients), and the actuarial 5-year survival rate was 51% (24 patients).



Duodenal segmentectomy associated with intestinal derotation was shown to be a straightforward, safe procedure for the treatment of the primary adenocarcinoma of the third and fourth portions of the duodenum. This surgical procedure should be preferred to pancreaticoduodenectomy because it is associated with negligible rates of morbidity and mortality, while allowing for satisfactory margin clearance and adequate lymphadenectomy.
Effect of baseline breast density on breast cancer incidence, stage, mortality, and screening parameters: 25-year follow-up of a Swedish mammographic screening.

We aimed to quantitatively assess the effect of baseline breast density on the incidence, stage, and mortality, and also the natural course of the disease, considering the sensitivity of mammography to clarify its causal or masking effect.



In total, 15,658 women ages 45 to 59 years from the Kopparberg randomized controlled trial in Sweden were prospectively followed from 1977 until 2004 to ascertain breast cancer incidence and death. Dense breast tissue collected at the beginning of the study was defined as pattern IV or V by the Tabár classification. Conventional risk factors were also collected at baseline. The three-state Markov model was used to estimate the preclinical incidence rate and the mean sojourn time given the fixed sensitivity.



Dense breast tissue was significantly associated with breast cancer incidence [relative risk (RR)=1.57 (1.18-1.67)] and with breast cancer mortality [RR=1.91 (1.26-2.91)] after adjusting for other risk factors. Cumulative incidence rates irrespective of nonadvanced and advanced breast cancer were higher in dense breast tissue compared with nondense tissue but no difference in survival was detected between dense and nondense breast tissue. Dense breast tissue had a higher preclinical incidence rate (causal effect) and shorter mean sojourn time (masking effect) compared with nondense breast tissue by controlling the sensitivity of mammography.



We corroborated the effect of baseline breast density with a higher incidence and mortality and also showed its contribution to a masking effect with long-term follow-up data.



Results suggest that the screening policy with a predominantly shorter screening interval and with alternative imaging techniques might be indicated in women with dense breast tissue.
Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma

Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80-100 mg/m² i.v.) on day 1. The original 21-day schedule was early amended for extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1.3 mg/m² i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty-four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m². The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression-free survival (PFS) was 19.1 months. B-MuD resulted effective in patients previous exposed to bortezomib without difference of response (P = 0.25) and PFS (P = 0.87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase.
Alterations in Sagittal Plane Knee Kinetics in Knee Osteoarthritis Using a Biomechanical Therapy Device

Knee frontal (adduction/abduction) and sagittal (flexion/extension) moments have been implicated in the pathomechanics of knee osteoarthritis (OA). The aim of this study was to evaluate the change in the knee sagittal moment in a cohort of patients with knee OA undergoing a biomechanical training program. Twenty-five female patients with symptomatic medial compartment knee OA were enrolled in a customized biomechanical intervention program. All patients underwent consecutive gait analyses prior to treatment initiation, and after 3 months and 9 months of therapy. Self-evaluative questionnaires, spatiotemporal gait parameters, peak knee sagittal moments, knee sagittal impulses, and duration of knee moments were compared throughout the duration of therapy. Differences between baseline and follow-up values were examined using nonparametric tests. Peak knee flexion moment (KFM) at loading response decreased significantly with therapy (p = 0.001). Duration of KFM and impulse of knee flexion also decreased significantly (p = 0.024 and p = 0.029, respectively). These changes were accompanied by increased walking velocity, significant pain reduction, and increased functional activity. Post-training kinetic evaluation demonstrated profound alterations of knee sagittal moments at the loading response KFM. We speculate that knee sagittal moments can potentially be improved in patients with knee OA over time with a biomechanical training program.
Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort.

We examined whether persistence of epigenetic DNA methylation (DNA-me) alterations at specific loci over two different time points in people with diabetes are associated with metabolic memory, the prolonged beneficial effects of intensive vs. conventional therapy during the Diabetes Control and Complications Trial (DCCT) on the progression of microvascular outcomes in the long-term follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We compared DNA-me profiles in genomic DNA of whole blood (WB) isolated at EDIC Study baseline from 32 cases (DCCT conventional therapy group subjects showing retinopathy or albuminuria progression by EDIC Study year 10) vs. 31 controls (DCCT intensive therapy group subjects without complication progression by EDIC year 10). DNA-me was also profiled in blood monocytes (Monos) of the same patients obtained during EDIC Study years 16-17. In WB, 153 loci depicted hypomethylation, and 225 depicted hypermethylation, whereas in Monos, 155 hypomethylated loci and 247 hypermethylated loci were found (fold change ≥1.3; P < 0.005; cases vs. controls). Twelve annotated differentially methylated loci were common in both WB and Monos, including thioredoxin-interacting protein (TXNIP), known to be associated with hyperglycemia and related complications. A set of differentially methylated loci depicted similar trends of associations with prior HbA1c in both WB and Monos. In vitro, high glucose induced similar persistent hypomethylation at TXNIP in cultured THP1 Monos. These results show that DNA-me differences during the DCCT persist at certain loci associated with glycemia for several years during the EDIC Study and support an epigenetic explanation for metabolic memory.
The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study

We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD.



A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample.



Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families.



Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men.
ComposingWeb Services with Nondeterministic Behavior

The promise of Web services is to enable the composition of new distributed applications/solutions: when no available service can satisfy a client request, (parts of) available services can be composed and orchestrated in order to satisfy such a request. Service composition involves two different issues: the synthesis, in order to synthesize, either manually or automatically, a specification of how coordinating the component services to fulfill the client request, and the orchestration, i.e., how executing the previous obtained specification by suitably supervising and monitoring both the control flow and the data flow among the involved services. In this work, we address the automatic composition synthesis when the behavior of the available services is non-deterministic, and hence is not fully controllable by the orchestrator. The service behavior is modeled by the possible conversations the service can have with its clients. The presence of nondeterministic conversations stems naturally when modeling services in which the result of each interaction with its client on the state of the service can not be foreseen
Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis: a prospective study.

Most patients with cerebral sinus thrombosis (CST) recover after treatment with heparin, but a subgroup has a poor prognosis. Those patients may benefit from endovascular thrombolysis.



Prospective case series. Patients with sinus thrombosis were selected for thrombolysis if they had an altered mental status, coma, straight sinus thrombosis, or large space-occupying lesions. Urokinase was infused into the sinuses (bolus 120 to 600 x 10(3) U; then 100 x 10(3) U/h) via a jugular catheter, in 15 cases combined with mechanical thrombus disruption or removal.



We treated 20 patients (16 women), mean age 32 years. Twelve patients were comatose and 14 had hemorrhagic infarcts before thrombolysis. Twelve patients recovered (Rankin score 0 to 2), 2 survived with handicaps, and 6 died. Factors associated with a fatal outcome were leukemia (3/6 versus 0/14, P=0.02) and large hemorrhagic infarcts (4/6 versus 2/14, P=0.04). Seizures were less frequent in the fatal cases (P=0.05). Patients who died had a larger mean lesion surface than survivors (30.5 versus 13.6 cm(2); P=0.03), larger midline shift (5.2 versus 1.7 mm; P=0.02), and a more rapid course (2.7 versus 8.2 days; P=0.01). Five patients who died had large hemispheric infarcts and edema before thrombolysis, causing herniation. Five patients had increased cerebral hemorrhage (3 minor, 2 major) after thrombolysis.



Thrombolysis can be effective for severe sinus thrombosis, but patients may deteriorate because of increased cerebral hemorrhage. Patients with large infarcts and impending herniation did not benefit.
Research Paper: The Risks of Multimedia Methods: Effects of Actor's Race and Gender on Preferences for Health States

While the use of multimedia methods in medical education and decision support can facilitate learning, it also has certain hazards. One potential hazard is the inadvertent triggering of racial and gender bias by the appearance of actors or patients in presentations. The authors hypothesized that race and gender affect preferences. To explore this issue they studied the effects of actors' race and gender on preference ratings for health states that include symptoms of schizophrenia.



A convenience sample of patients with schizophrenia, family members of patients, and health professionals was used. Participants were randomly assigned to rate two health states, one portrayed by either a man of mixed race (Hispanic-black) or a white man and the second portrayed by either a white woman or a white man.



Visual analog scale (VAS) and standard gamble ratings of health state preferences for health states that include symptoms of mild and moderate schizophrenia.



Studies of the effects of the race of the actor (n = 114) revealed that racial mismatch between the actor and the participant affected the participant's preferences for health states. Ratings were lower when racial groups differed (mean difference, 0.098 for visual analog scale ratings and 0.053 lower in standard gamble, P = 0.006 for interactions between the race of the subject and the actor). In studies of the effects of a female actress on ratings (n = 117), we found no evidence of a corresponding interaction between the gender of the actor and the study participant. Rather, an interaction between actor's gender and method of assessment was observed. Standard gamble ratings (difference between means, 0.151), but not visual analog scale ratings (difference, 0.005), were markedly higher when the state was portrayed by the actress (P = 0.003 for interactions between actor's gender and method of preference assessment). Differential effects on standard gamble ratings suggest that an actor's gender may influence the willingness of viewers to gamble to gain health benefits (or risk attitude).



Educators and researchers considering the use of multimedia methods for decision support need to be aware of the potential for the race and gender of patients or actors to influence preferences for health states and thus, potentially, medical decisions.
Week 144 resistance analysis of elvitegravir/cobicistat/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir DF in antiretroviral-naive patients.

Here, the baseline and emergent resistance to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) versus efavirenz (EFV)/FTC/TDF in HIV-1-infected antiretroviral-naive adults through 144 weeks from the randomized, ongoing, Phase III study GS-US-236-0102 is described.



HIV-1 protease (PR) and reverse transcriptase (RT) were sequenced at screening; patients with HIV-1 resistant to EFV, FTC or TDF were excluded. Genotypic/phenotypic analyses were performed at virological failure confirmation and baseline for PR, RT and integrase (IN) for patients with virological failure and for patients with HIV-1 RNA≥400 copies/ml at weeks 48, 96, 144 or early study drug discontinuation. Retrospective, baseline, IN genotyping was conducted for EVG/COBI/FTC/TDF patients.



In the EVG/COBI/FTC/TDF group through week 144, HIV-1 from 10 patients (2.9%; 10/348 treated patients) developed primary IN strand transfer inhibitor (n=9) and/or nucleoside RT inhibitor resistance substitutions (n=10). The emergence of resistance decreased over time with 8, 2 and 0 patients developing HIV-1 resistance through week 48, post-week 48-96 and post-week 96-144, respectively. Emergent substitutions were E92Q (n=7), N155H (n=3), Q148R (n=1) and T66I (n=1) in IN, and M184V/I (n=10) and K65R (n=4) in RT. All 10 isolates had reduced susceptibility to EVG, FTC or TDF. Virus with EVG phenotypic resistance had cross-resistance to raltegravir. In the EFV/FTC/TDF group, virus from 14 patients (4.0%; 14/352 treated patients; 4 during weeks 96-144) developed a resistance substitution to EFV (n=14; K103N: n=13), FTC (M184V/I: n=4) or TDF (K65R: n=3).



Resistance development to EVG/COBI/FTC/TDF was infrequent through 144 weeks of therapy and decreased over time, consistent with durable efficacy.
Living with prostate cancer: randomised controlled trial of a multimodal supportive care intervention for men with prostate cancer

Prostate cancer is the most common male cancer in developed countries and diagnosis and treatment carries with it substantial morbidity and related unmet supportive care needs. These difficulties may be amplified by physical inactivity and obesity. We propose to apply a multimodal intervention approach that targets both unmet supportive care needs and physical activity. A two arm randomised controlled trial will compare usual care to a multimodal supportive care intervention "Living with Prostate Cancer" that will combine self-management with tele-based group peer support. A series of previously validated and reliable self-report measures will be administered to men at four time points: baseline/recruitment (when men are approximately 3-6 months post-diagnosis) and at 3, 6, and 12 months after recruitment and intervention commencement. Social constraints, social support, self-efficacy, group cohesion and therapeutic alliance will be included as potential moderators/mediators of intervention effect. Primary outcomes are unmet supportive care needs and physical activity levels. Secondary outcomes are domain-specific and health-related quality of life (QoL); psychological distress; benefit finding; body mass index and waist circumference. Disease variables (e.g. cancer grade, stage) will be assessed through medical and cancer registry records. An economic evaluation will be conducted alongside the randomised trial. This study will address a critical but as yet unanswered research question: to identify a population-based way to reduce unmet supportive care needs; promote regular physical activity; and improve disease-specific and health-related QoL for prostate cancer survivors. The study will also determine the cost-effectiveness of the intervention.