Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and Progressive Glioblastoma

Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. Experimental Design: We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood–brain barrier penetration of the indicated therapies, drug–drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Conclusions: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system–penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma. Clin Cancer Res; 24(2); 295–305. ©2017 AACR. See related commentary by Wick and Kessler, p. 256
Active Cycles of Breathing Technique (ACBT) versus conventional chest physical therapy on airway clearance in bronchiectasis – A crossover trial

Bronchiectasis is associated with impairment of the mucociliary escalator and retention of secretions within the bronchial tree, making airway clearance a primary concern in the management of bronchiectasis. The objective of the study was to compare the efficacy of Active Cycles of Breathing Techniques (ACBT) with conventional chest physical therapy as a method of airway clearance in adults with productive bronchiectasis. The study design was a crossover trial carried out in Kasturba Hospital, Manipal, and PKTB & CD Hospital, Mysore, India. Thirty-five adult patients of both genders with productive bronchiectasis were recruited. Patients underwent conventional chest physical therapy or ACBT following postural drainage as airway clearance techniques in a random order on successive days. All patients were compared pre- and post-intervention for the outcome measures. Pulmonary function, wet weight and volume of sputum expectorated and visual analogue score (VAS) for comfort of either technique were measured. Wet sputum weight and volume measured after conventional and ACBT therapies showed no statistically significant difference. The measured value differences of the Pulmonary Function Test suggest no statistically significant difference between the two therapies. VAS score comparison for comfort showed a statistically significant difference with the majority of patients reporting comfort in performing ACBT. ACBT in postural drainage positions is found to be equally effective as conventional chest physical therapy in airway clearance of bronchiectasis and patients have rated ACBT to be more comfortable.
The management of adult growth hormone deficiency syndrome

Background: In patients with hypopituitarism, growth hormone deficiency (GHD) is almost inevitably present. Lack of other pituitary hormones may require prompt replacement, but lack of growth hormone (GH) is also associated with several abnormalities. Growth hormone treatment safely improves or normalizes many of these deviations. Results: The aberrations include low bone mass and increased risk of fractures, abnormal body composition in terms of increased fat mass, and reduced lean body mass resulting in reduced muscle mass and strength. The decreased exercise capacity in GHD may be influenced by impaired cardiac performance and heat intolerance. Increased abdominal fat results in metabolic disturbancies such as reduced insulin sensitivity and hyperlipidemia, leading to an increased risk of cardiovascular diseases. Patients with hypopituitarism who have had relevant hormones replaced except GH have increased mortality due to, for example, cardiovascular diseases. Conclusions: Thus, it is important to diagnose GHD, which requires precise diagnostic criteria and methods. Dynamic testing of GH secretion with insulin tolerance test or arginine + GH releasing hormone can be used. Patients with childhood onset GHD should be re-evaluated if GH therapy is maintained into adulthood. Although GH replacement therapy improves the patophysiological manifestations of GHD and quality of life, it is unclear whether mortality is reduced.
Olive oil consumption and risk of type 2 diabetes in US women.

BACKGROUND Olive oil has been shown to improve various cardiometabolic risk factors. However, to our knowledge, the association between olive oil intake and type 2 diabetes (T2D) has never been evaluated in the US population. OBJECTIVE We aimed to examine the association between olive oil intake and incident T2D. DESIGN We followed 59,930 women aged 37-65 y from the Nurses' Health Study (NHS) and 85,157 women aged 26-45 y from the NHS II who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by validated food-frequency questionnaires, and data were updated every 4 y. Incident cases of T2D were identified through self-report and confirmed by supplementary questionnaires. RESULTS After 22 y of follow-up, we documented 5738 and 3914 incident cases of T2D in the NHS and NHS II, respectively. With the use of Cox regression models with repeated measurements of diet and multivariate adjustment for major lifestyle and dietary factors, the pooled HR (95% CI) of T2D in those who consumed >1 tablespoon (>8 g) of total olive oil per day compared with those who never consumed olive oil was 0.90 (0.82, 0.99). The corresponding HRs (95% CIs) were 0.95 (0.87, 1.04) for salad dressing olive oil and 0.85 (0.74, 0.98) for olive oil added to food or bread. We estimated that substituting olive oil (8 g/d) for stick margarine, butter, or mayonnaise was associated with 5%, 8%, and 15% lower risk of T2D, respectively, in the pooled analysis of both cohorts. CONCLUSIONS Our results suggest that higher olive oil intake is associated with modestly lower risk of T2D in women and that hypothetically substituting other types of fats and salad dressings (stick margarine, butter, and mayonnaise) with olive oil is inversely associated with T2D.
Genetic Depletion or Hyperresponsiveness of Natural Killer Cells Do Not Affect Atherosclerosis Development

Rationale: Chronic inflammation is central in the development of atherosclerosis. Both innate and adaptive immunities are involved. Although several studies have evaluated the functions of natural killer (NK) cells in experimental animal models of atherosclerosis, it is not yet clear whether NK cells behave as protective or proatherogenic effectors. One of the main caveats of previous studies was the lack of specificity in targeting loss or gain of function of NK cells. Objectives: We used 2 selective genetic approaches to investigate the role of NK cells in atherosclerosis: (1) Ncr1iCre/+R26lsl−DTA/+ mice in which NK cells were depleted and (2) Noé mice in which NK cells are hyperresponsive. Methods and Results: No difference in atherosclerotic lesion size was found in Ldlr−/− (low-density lipoprotein receptor null) mice transplanted with bone marrow (BM) cells from Ncr1iCreR26Rlsl−DTA, Noé, or wild-type mice. Also, no difference was observed in plaque composition in terms of collagen content, macrophage infiltration, or the immune profile, although Noé chimera had more IFN (interferon)-&ggr;–producing NK cells, compared with wild-type mice. Then, we investigated the NK-cell selectivity of anti–asialoganglioside M1 antiserum, which was previously used to conclude the proatherogenicity of NK cells. Anti–asialoganglioside M1 treatment decreased atherosclerosis in both Ldlr−/− mice transplanted with Ncr1iCreR26Rlsl−DTA or wild-type bone marrow, indicating that its antiatherogenic effects are unrelated to NK-cell depletion, but to CD8+ T and NKT cells. Finally, to determine whether NK cells could contribute to the disease in conditions of pathological NK-cell overactivation, we treated irradiated Ldlr−/− mice reconstituted with either wild-type or Ncr1iCreR26Rlsl−DTA bone marrow with the viral mimic polyinosinic:polycytidylic acid and found a significant reduction of plaque size in NK-cell–deficient chimeric mice. Conclusions: Our findings, using state-of-the-art mouse models, demonstrate that NK cells have no direct effect on the natural development of hypercholesterolemia-induced atherosclerosis, but may play a role when an additional systemic NK-cell overactivation occurs.
Competition between cytotypes changes across a longitudinal gradient in Centaurea stoebe (Asteraceae).

PREMISE OF THE STUDY Polyploidy resulting from whole genome duplication has contributed to the adaptive evolution of many plant species. However, the conditions necessary for successful polyploid evolution and subsequent establishment and persistence in sympatry with diploid progenitors are often quite limited. One condition thought to be necessary for establishment is a substantial competitive superiority of the polyploid. METHODS We conducted a pairwise competition experiment using diploid and tetraploid cytotypes of Centaurea stoebe L. to determine whether (1) tetraploids have greater competitive ability than diploids, (2) cytotypes from mixed-cytotype populations have more balanced competitive abilities than single-cytotype populations, and (3) competitive abilities change along a longitudinal gradient. KEY RESULTS Across sampling localities, tetraploids did not produce greater aboveground biomass than diploids but suffered from greater intracytotypic competition. Tetraploids allocated greater biomass belowground than diploids, regardless of competition treatment, and had greater performance for traits associated with long-term persistence (bolted more frequently and produced more accessory rosettes). Competitive ability of tetraploids did not differ between single- and mixed-cytotype populations but varied along a longitudinal gradient. Tetraploids were stronger intercytotypic competitors in Western Europe (Switzerland and Germany) than in Eastern Europe (Hungary and Slovakia), which indicates that cytotype coexistence may be more likely in Eastern Europe, the proposed origin of tetraploids, than in Western Europe. CONCLUSIONS Our study addresses the importance of examining competitive interactions between cytotypes across their distributional range, as competitive interactions were not consistent across sampling localities.
Assessment of Risk

Risk assessment during the perinatal period is an important tool in the identification and management of high-risk infants. Assessment of risk is examined from three perspectives: perinatal risk from preconception through pregnancy and, after birth, family, and environmental in order to orient the developmental therapist to the scope of potential biologic, psychosocial and environmental factors affecting the neonatal population.
N-arachidonylethanolamide-induced increase in aqueous humor outflow facility.

PURPOSE To study the effects of N-arachidonylethanolamide (anandamide [AEA]) on aqueous humor outflow and to investigate the existence and activity of fatty acid amide hydrolase (FAAH), an AEA metabolic enzyme in trabecular meshwork (TM) tissue. METHODS The effects of AEA on aqueous humor outflow were measured using a porcine anterior segment-perfused organ culture model. Western blot analysis was used to study the expression of FAAH, and a thin-layer chromatography-based approach was used to measure the enzymatic activity of FAAH in TM tissue. RESULTS Administration of AEA caused a transient enhancement of aqueous humor outflow facility. In the presence of 100 nM URB597, an FAAH inhibitor, the effect of 10 nM AEA on outflow facility was prolonged by at least 4 hours. The AEA-induced enhancement of outflow facility was blocked by SR141716A, a CB1 antagonist, and was partially blocked by SR144528, a CB2 antagonist. In Western blot studies, positive signals were detected on TM tissues with an anti-FAAH antibody. In the enzyme activity studies, the enzymatic activity of AEA hydrolysis was detected in TM tissues, and this activity was reduced with the addition of 100 nM URB597. CONCLUSIONS Results from this study demonstrate that the administration of AEA increases aqueous humor outflow facility and that this effect of AEA involves CB1 and CB2 cannabinoid receptors. In addition, this study reveals the existence and the activity of FAAH, an AEA-metabolizing enzyme, in the TM tissues.
Gender Differences in Management and Outcome of Acute Myocardial Infarctions Treated in 2006–2007

Objectives: Women with acute myocardial infarction (AMI) previously received less invasive evaluation and experienced higher mortality than men. After improvements in AMI care it is unclear whether gender differences still exist in management and outcome of AMI. Methods: All patients admitted to Ullevål University Hospital for AMI during 2006 and 2007 were included in this cohort study. Predefined data were recorded during the hospital stay, and the survival status of the patients was ascertained on June 30, 2008. Results: A total of 931 women and 2,174 men were included. No gender differences were observed in treatment delay or age-adjusted odds ratio (OR) of invasive evaluation in ST-elevation myocardial infarction (STEMI). In non-ST-elevation myocardial infarction (NSTEMI), women were less likely than men to undergo coronary angiography (adjusted OR 0.72, 95% CI 0.53–0.99, p = 0.044) and percutaneous coronary intervention (adjusted OR 0.60, 95% CI 0.47–0.76, p = 0.0001). Age-adjusted in-hospital mortality and long-term survival were similar between men and women. Conclusions: Women with STEMI experienced similar treatment delays and odds of invasive evaluation as men. However, gender differences in invasive evaluation were still observed in NSTEMI patients. No sex differences were observed in age-adjusted early and long-term mortality.
HBV infection decreases risk of liver metastasis in patients with colorectal cancer: A cohort study.

AIM To evaluate the effect of hepatitis B virus (HBV) infection on liver metastasis of colorectal cancer. METHODS A total of 1298 colorectal cancer patients were recruited from January 2001 to March 2005 in this study. Enzyme-linked immunosorbent assay was used to test serum HBV markers for colorectal cancer. Patients were divided into study (infection) group and control (non-infection) group. Clinical features of patients in two groups were compared. RESULTS Liver metastasis was found in 319 out of the 1298 colorectal cancer patients. The incidence of liver metastasis was significantly lower in study group than in control group (14.2% vs 28.2%, P < 0.01). HBV infection significantly decreased the risk of liver metastasis [hazard ratio (HR): 0.50, 95% confidence interval (95% CI): 0.38-0.66], but the incidence of extrahepatic metastasis was significantly higher in study group than in control group (31.9% vs 17.0%, P < 0.01). The HR was the lowest in chronic hepatitis B group (HR: 0.29, 95% CI: 0.12-0.72). The number of liver metastatic lesions was significantly less in study group than in control group with a higher surgical resection rate. However, no significant difference was found in survival rate between the two groups (P = 0.95). CONCLUSION HBV infection decreases the risk of liver metastasis in patients with colorectal cancer and elevates the surgical resection rate of liver metastatic lesions.
Production , Manufacturing and Logistics An effective heuristic for the review period in an inventory model with staggered deliveries and normal demands

Consider a single-item, periodic review, infinite-horizon, undiscounted, inventory model with stochastic demands, proportional holding and shortage costs, and full backlogging. Orders can arrive in every period, and the cost of receiving them is negligible (as in JIT). Every T periods, one audits the stocks and chooses a delivery schedule for each of the next T periods, thus incurring a fixed audit cost and—when one schedules actual deliveries—a fixed order cost. The problem is to find a review period T and an ordering policy minimizing the average cost. An earlier article developed an algorithm for computing an optimal T, and undertook a numerical study to evaluate various approximations. Assuming normal demands, we characterize the asymptotic behavior (for large l/r) of the optimal T and establish the asymptotic optimality of a heuristic, calculable on a spreadsheet. A numerical study indicates that patterns established here for large l/r hold for r/l above 2. 2007 Elsevier B.V. All rights reserved.
Maternal and Perinatal Outcome in Severe Pre-eclampsia and Eclampsia

Background: Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Present study was planned to find the maternal and perinatal outcome in patients of severe pre-eclampsia and eclampsia.Methodology:It is a prospective study, carried out on 100 pregnant women admitted with severe pre-eclampsia and eclampsia at a tertiary care referral unit. Detailed history and examination was carried out. Investigations like complete hemogram, liver function tests, renal function tests, coagulation profile, fundus and 24 hours urine for protein were done. Obstetric management was done as per existing protocol in the department, magnesium sulphate was the drug of choice for controlling convulsions, and blood pressure was controlled either by oral nefidipene or methyl dopa. Maternal and perinatal complications were noted down.Results:M The majority of the patients was unbooked (82%), belonged to lower socioeconomic status (84%) and had rural background (84%). Headache was the most common antecedent symptom (44%) followed by epigastric pain (20%), oliguria (9%), blurring of vision (8%) and ascitis (5%). There was high incidence of maternal complications like PPH (31%), abruption placentae (11%), renal dysfunction (8%), pulmonary edema (8%), pulmonary embolism (4%), HELLP syndrome (2%) and DIC (2%). Maternal mortality was 8% and the causes were pulmonary embolism in four women, DIC in two, HELLP and pulmonary edema in one each. Perinatal complications were also high 71.43% were low birth weight, 66% had preterm delivery, 52.4% babies had birth asphyxia and 28.57% were still born. Maternal and perinatal outcome was much poorer in eclampsia as compared to severe pre-eclampsia.Conclusion: There is a very high maternal and perinatal morbidity and mortality and 82% patients had no antenatal care. Good antenatal care could have been prevented severe pre-eclampsia and eclampsia to some extent. Thus it is suggested that developing countries have to go a long way to create awareness about importance of antenatal check ups and take measures for implementation.
Bone Mass and Somatic Development in Young Female Gymnasts: A Longitudinal Study

The aim of this study was to assess the effects of vigorous activity on the somatic and skeletal growths in young females reaching puberty. From a group of 41 prepubertal girls, 24 remained in this study: 10 gymnasts training 15 to 22 hr a week and 14 non-exercising controls. At the start and during the study period, bone age, height, weight, fat and lean mass were significantly lower in the gymnasts vs. the controls (p < .05). These variables had increased in the same way for both groups. At each investigation, the gymnasts had significantly higher BMC, BMD, and BMAD at all the sites (p < .01) except the whole body. The strong correlation between somatic measurements at the start and at the end of the study indicated that physical exercise does not disrupt the normal growth in these children.
Elevated Psychosocial Stress at Work in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis

Objective. Psychosocial stress at work not only affects the healthy working population, but also workers with chronic diseases. We aimed to investigate the psychosocial work stress levels in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods. A cross-sectional study applied the Effort-Reward Imbalance (ERI) questionnaire — an internationally established instrument that measures work stress — to patients with SLE and RA who were capable of work and to a group of controls without these diseases. Participants were recruited through rheumatologists in private practices, hospitals, and from self-help groups by personal communication, paper-based flyers, and online advertisements. Because very few studies tested the ERI’s applicability in patient groups, with a lack of evidence in patients with inflammatory rheumatic diseases, internal consistency and construct validity of the ERI measure were evaluated. Results. Data came from 270 patients with RA and 247 with SLE, and 178 controls. Patients showed elevated psychosocial stress at work compared to controls. Across the total sample and all groups, satisfactory internal consistencies of the scales effort, reward, and overcommitment were obtained (Cronbach’s alpha coefficients > 0.70), and confirmatory factor analysis replicated the theoretical structure of the ERI model (goodness-of-fit index > 0.80). Conclusion. We found elevated psychosocial stress at work in patients with SLE and RA compared to controls by applying the ERI model. Despite some heterogeneity in the sample, we achieved satisfactory psychometric properties of the ERI questionnaire. Our results suggest that the ERI questionnaire is a psychometrically useful tool to be implemented in epidemiological studies of employed patients with SLE and RA.
Parsing Argumentation Structures in Persuasive Essays

In this article, we present a novel approach for parsing argumentation structures. We identify argument components using sequence labeling at the token level and apply a new joint model for detecting argumentation structures. The proposed model globally optimizes argument component types and argumentative relations using Integer Linear Programming. We show that our model significantly outperforms challenging heuristic baselines on two different types of discourse. Moreover, we introduce a novel corpus of persuasive essays annotated with argumentation structures. We show that our annotation scheme and annotation guidelines successfully guide human annotators to substantial agreement.