Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase II randomized clinical trial of samarium-153 EDTMP (Sm-153) with or without PSA-TRICOM vaccine in metastatic castration-resistant prostate cancer (mCRPC) after docetaxel.

102 Background: A prior randomized, placebo-controlled, multi-center phase 2 trial of PSA-TRICOM demonstrated survival benefit. Sm-153 is a radiopharmaceutical that targets osteoblastic lesions. Preclinical data indicated that Sm-153 could alter tumor phenotype, causing upregulation of Fas, MHC Class I, and tumor-associated antigens, making tumor cells more amenable to immune-mediated killing. This trial was intended to examine the safety and efficacy of the Sm-153 with PSA-TRICOM vs. Sm-153 alone. METHODS This phase 2 multi-center trial was designed to randomize 68 pts to Sm-153 with or without PSA-TRICOM. Eligibility included mCRPC, bone metastases, no visceral disease, prior docetaxel, ECOG ≤2, and normal organ function. Sm-153 was given at 1mCi/kg IV on day 8 and then every 12 weeks. PSA-TRICOM was given on days 1, 15, 29, then every 4 weeks. The 1° endpoint was comparison of progression-free survival at 4 months (mo) utilizing PCCWG, but not PSA criteria. A Fisher's exact test, assuming a one-tailed alpha = 0.10, was used to compare these fractions. 2° endpoints were OS, ORR, PSA changes, immunologic, and toxicity. RESULTS 44 pts were enrolled, 5 were not evaluable for the 1° endpoint due to withdrawal prior to 4 mos (4 on Arm A, 1 on Arm B). PFS and PSA findings are provided below. Hematologic toxicities were most common, and were well matched. CONCLUSIONS This final analysis suggests the combination of PSA-TRICOM and Sm-153 has a similar toxicity profile to Sm-153 alone. Despite early closure of this trial due to poor accrual, which may be related to recent approval of multiple agents for mCRPC, this analysis appears to demonstrate improvement in PFS with the combination. This may indicate synergy between PSA-TRICOM and bone-seeking radiopharmaceuticals. Based on the data presented here, we are exploring the potential to combine PSA-TRICOM with alpharadin (radium-223), a next generation bone-seeking radiopharmaceutical. CLINICAL TRIAL INFORMATION NCT00450619. [Table: see text].
Long-term survival after aortic valve replacement in octogenarians and high-risk subgroups.

OBJECTIVES The increasing age in the population and improvements in the treatment options for aortic valvular disease have resulted in a considerable rise in the number of elderly patients being admitted for conventional aortic valve surgery. Recently, transcatheter aortic valve implantation (TAVI) has been developed as a less invasive treatment option. However, both open heart surgery and transcatheter treatment have serious complications. Thus, the knowledge of contemporary results of conventional surgery is important in guiding treatment allocation. METHODS From the database at Feiring Heart Clinic, 1525 patients were identified who had undergone aortic valve replacement from 1999 to 2010; of these, 361 patients were more than 80 years of age. The population was followed for all-cause mortality until March 2011, with special reference to the age group older than 80 years and other high-risk subsets. RESULTS The short-term mortality was 2.2% in the whole population and 3.9% in octogenarians. Five-year survival was 83.1 and 68.1%, respectively. In the high-risk subgroup of patients with a logistic EuroSCORE above 20%, the equivalent figures were 4.2 and 72.7%. CONCLUSIONS Contemporary results after conventional aortic valve surgery are excellent in both short- and long-term survival and should not be withheld in the elderly or otherwise high-risk populations. The logistic EuroSCORE grossly overestimates the operative risk and should be used with caution in allocating patients to TAVI instead of conventional surgery.
Existence of Solutions for -Generalized Vector Variational-Like Inequalities

We introduce and study a class of -generalized vector variational-like inequalities and a class of -generalized strong vector variational-like inequalities in the setting of Hausdorff topological vector spaces. An equivalence result concerned with two classes of -generalized vector variational-like inequalities is proved under suitable conditions. By using FKKM theorem, some new existence results of solutions for the -generalized vector variational-like inequalities and -generalized strong vector variational-like inequalities are obtained under some suitable conditions.
Long‐Term Impact of Young Age at Diagnosis on Treatment Outcome and Patterns of Failure in Patients with Ductal Carcinoma In Situ Treated with Breast‐Conserving Therapy

We reviewed our institution's long‐term experience treating patients diagnosed with ductal carcinoma in situ (DCIS) of the breast with breast‐conserving therapy (BCT) to determine the impact of patient age on outcome over time. All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics (including age <45) and pathologic factors were analyzed for effect on outcomes including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included limited surgery (excisional biopsy or lumpectomy) followed by radiotherapy to the whole breast (median whole‐breast dose: 50 Gy, median tumor bed dose: 60.4 Gy). One hundred and forty‐five cases were evaluated; the median follow‐up was 19.3 years. Twenty‐five patients developed an IBTR, for 5‐, 10‐, 15‐, and 20‐year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. The 10‐year ipsilateral rate of recurrence was 23.3% (<45 years) versus 9.1% (≥45 years) (p = 0.05). Younger patients more frequently developed invasive recurrences (20‐year actuarial rates: 20.4% versus 12.8%, p = 0.22) and true recurrences/marginal misses of the index lesion (23.3% versus 9.7%, p = 0.04) with lower rates of contralateral breast cancer (0.0% and 0.0% versus 12.0% and 20.5%, p = < 0.01, at 10 and 20 years, respectively). Young women under the age of 45 diagnosed with DCIS have a greater risk of local recurrence with different patterns of failure following BCT, which is most notable within 10 years of diagnosis.
Cardiopulmonary Bypass-induced Complement Activation. Evidence for C5a Participation

Plasma activity inducing polymorphonuclear neutrophils (PMN) aggregation, augmenting PMN adherence, plasma chemotatic activity as well as peripheral PMN count were estimated in patients during cardiopulmonary bypass. In the course of the surgical procedure the chemotactic activity and the activity inducing PMN aggregation were detected in plasma. The top of these two activities was always followed by the significant fall of the peripheral PMN count. The increase of the activity augmenting PMN adherence was observed in a part of cases, but when noticed, always preceded the maximum of the remaining evaluated activities.
PECTIN METHYLESTERASE 48 Is Involved in Arabidopsis Pollen Grain Germination 1 [ OPEN ]

Laboratoire Glycobiologie et Matrice Extracellulaire, Normandie Université, Institute for Research and Innovation in Biomedicine, Végétal, Agronomie, Sol, et Innovation, 76821 Mont-Saint-Aignan, France (C.L., M.-C.K.-M., A.M., A.D., P.L., A.L., J.-C.M.); Unité Biologie des Plantes et Innovation (S.B., S.G., F.F., J.P.) and Centre de Ressources Régionales en Biologie Moléculaire (S.G.), Université de Picardie Jules Verne, 80039 Amiens, France; and Institute of Plant Biology, University of Zürich, 8008 Zurich, Switzerland (T.N.F., C.R.)
Cardiovascular Outcomes Improved by Bariatric Surgery Independent of Baseline BMI

Setting and participants. The Swedish Obese Subjects (SOS) trial is one of the largest and longest-running prospective trials of bariatric surgery in the world. Participants were enrolled between 1987 and 2001 from 480 Swedish primary health care centers. Individuals were eligible to participate if they were between 37 and 60 years of age and obese (minimum BMI of 34 for men and 38 for women) but had not had previous bariatric or gastric/duodenal ulcer surgery, recent gastric ulcer, ongoing or recent (within 5 years) malignancy, recent (within 6 months) myocardial infarction (MI), drug or alcohol abuse, or other behavioral and psychological problems. Of 5335 eligible patients, 2010 elected to undergo surgery. They were matched with 2037 control participants based on 18 baseline variables. Intervention patients underwent 1 of 3 surgeries: 376 (18.7%) had gastric banding, 1369 (68.1%) had vertical banded gastroplasty (VBG, or “stomach stapling”), and 265 (13.2%) underwent gastric bypass. The decision about type of surgical procedure was presumably made by providers at the clinical site of the patient’s surgery, though this is not made explicitly clear in the article. Patients in the control group received “the customary treatments for obesity at their centers of registration. ” The investigators describe that in some cases this meant lifestyle advice, while in others it meant no treatment whatsoever. Patients were followed for up to 20 years after enrollment.
Clinical Significance and Mechanism of Gas Formation of Pyogenic Liver Abscess Due to Klebsiella pneumoniae

ABSTRACT We enrolled 22 patients with gas-forming pyogenic liver abscess in a study to assess the mechanism of gas formation. Klebsiella pneumoniae was cultured from specimens from all patients. Gas and pus samples from abscesses revealed four major components: nitrogen, oxygen, carbon dioxide, and hydrogen; this implicates mixed acid fermentation of glucose as the mechanism of gas formation.
Crossing the ethic – non ethic border: A cognitive dissonance theory approach

The main purpose of this study is to identify the importance of several variables in the ethical decision making process, propose a model that incorporates the Festinger (1957) Cognitive Dissonance Theory and the Jones (1991) model. With that in mind a measurement instrument was developed using the Personal Ethical Threshold (Comer and Vega, 2008). The results provide valuable data worth considering in the design of business curriculums.
Gender-related differences in muscle injury, oxidative stress, and apoptosis.

UNLABELLED Due to its alleged antioxidant properties, 17beta-estradiol (E2) may protect against muscle injury, oxidative stress, and apoptosis. PURPOSE This study sought to determine whether such mechanisms existed between genders for muscle injury, oxidative stress, and apoptosis after eccentric exercise. METHODS Eight men and eight women (no oral contraceptive use; midluteal phase of menstrual cycle) performed 7 x 10 eccentric repetitions of the knee extensors at 150% 1RM. Strength, soreness, and blood samples were taken before exercise and 6, 24, 48, and 72 h after exercise while muscle samples were collected before and 6 and 24 h after exercise. Blood samples were assayed for free E2, lactate dehydrogenase (LDH), superoxide dismutase (SOD), and 8-isoprostane (8-iso). Muscle samples were assayed for mitochondrial apoptosis (e.g., bax, bcl-2, cytochrome c, and cell death), total DNA content, and myofibrillar protein content. RESULTS Men reported greater soreness levels at 24, 48, and 72 h after exercise, whereas strength changes were similar among genders. At baseline and independent of exercise, females had higher E2 (P < 0.001) and SOD in conjunction with lower 8-iso levels when compared with men. Bax increased in both genders, whereas bcl-2 increased only in women with no cytochrome c changes for either gender after exercise. The bax/bcl-2 ratio in women significantly decreased after 6 h (P = 0.03) and returned to baseline levels after 24 h. Men exhibited greater cell death at all time points (P < 0.05), whereas myofibrillar protein content and total DNA content decreased in both genders at 24 h after exercise. No changes in LDH were found (P > 0.05). CONCLUSIONS Although more research is needed, differences between gender may provide greater endogenous protection against oxidative stress and apoptosis.
The Valsalva DCR Bubble Test: A New Method of Assessing Lacrimal Patency After DCR Surgery

Objective confirmation of nasolacrimal patency following dacryocystorhinostomy is a desirable postoperative goal for both the surgeon and the patient. The authors describe a simple method to demonstrate dacryocystorhinostomy patency and present a study comparing the effectiveness of this novel test with Jones fluorescein testing in 32 cases seen consecutively at postoperative follow-up. The test consists of demonstrating reflux of air through the dacryocystorhinostomy as the patient performs the Valsalva maneuver. This reflux is most easily seen as bubbles rising through a drop of saline placed in the medial canthus. A high correlation was found between this test and Jones testing. The Valsalva dacryocystorhinostomy bubble test (VBT) appears to be a fast, safe, and accurate method of confirming dacryocystorhinostomy patency.
Two Isoforms of the Human Cyclin C Gene are Expressed Differentially Suggesting that they May Have Distinct Functions

Cyclin C is a highly conserved protein that is involved in divergent cellular processes. The exact roles of its isoforms are presently not very well defined and it is possible that there is a functional divergence amongst them. We therefore sought to assess the expression pattern of cyclin C1 and C2 isoforms in various human tissues and in cell cycle by using real-time PCR experiments. Our findings strongly suggest that the C2 isoform may play a presently unexplored and important role in mammalian testis and probably this isoform is the one that is mainly implicated in cell cycle regulation.
Protection from Cardiac Arrhythmia Through Ryanodine Receptor-Stabilizing Protein Calstabin2

Ventricular arrhythmias can cause sudden cardiac death (SCD) in patients with normal hearts and in those with underlying disease such as heart failure. In animals with heart failure and in patients with inherited forms of exercise-induced SCD, depletion of the channel-stabilizing protein calstabin2 (FKBP12.6) from the ryanodine receptor–calcium release channel (RyR2) complex causes an intracellular Ca2+ leak that can trigger fatal cardiac arrhythmias. A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak that triggers arrhythmias. Thus, enhancing the binding of calstabin2 to RyR2 may be a therapeutic strategy for common ventricular arrhythmias.
Rapid Identification of Cryptococcus neoformans and Cryptococcus gattii by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry

ABSTRACT Compared to DNA sequence analysis, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) correctly identified 100% of Cryptococcus species, distinguishing the notable pathogens Cryptococcus neoformans and C. gattii. Identification was greatly enhanced by supplementing a commercial spectral library with additional entries to account for subspecies variability.
Prevalence and characteristics of patients with advanced chronic conditions in need of palliative care in the general population: A cross-sectional study

Background: Of deaths in high-income countries, 75% are caused by progressive advanced chronic conditions. Palliative care needs to be extended from terminal cancer to these patients. However, direct measurement of the prevalence of people in need of palliative care in the population has not been attempted. Aim: Determine, by direct measurement, the prevalence of people in need of palliative care among advanced chronically ill patients in a whole geographic population. Design: Cross-sectional, population-based study. Main outcome measure: prevalence of advanced chronically ill patients in need of palliative care according to the NECPAL CCOMS-ICO© tool. NECPAL+ patients were considered as in need of palliative care. Setting/participants: County of Osona, Catalonia, Spain (156,807 inhabitants, 21.4% > 65 years). Three randomly selected primary care centres (51,595 inhabitants, 32.9% of County’s population) and one district general hospital, one social-health centre and four nursing homes serving the patients. Subjects were all patients attending participating settings between November 2010 and October 2011. Results: A total of 785 patients (1.5% of study population) were NECPAL+: mean age = 81.4 years; 61.4% female. Main disease/condition: 31.3% advanced frailty, 23.4% dementia, 12.9% cancer (ratio of cancer/non-cancer = 1/7), 66.8% living at home and 19.7% in nursing home; only 15.5% previously identified as requiring palliative care; general clinical indicators of severity and progression present in 94% of cases. Conclusions: Direct measurement of prevalence of palliative care needs on a population basis is feasible. Early identification and prevalence determination of these patients is likely to be the cornerstone of palliative care public health policies.
Nonadditive Effects of Genes in Human Metabolomics

Genome-wide association studies (GWAS) are widely applied to analyze the genetic effects on phenotypes. With the availability of high-throughput technologies for metabolite measurements, GWAS successfully identified loci that affect metabolite concentrations and underlying pathways. In most GWAS, the effect of each SNP on the phenotype is assumed to be additive. Other genetic models such as recessive, dominant, or overdominant were considered only by very few studies. In contrast to this, there are theories that emphasize the relevance of nonadditive effects as a consequence of physiologic mechanisms. This might be especially important for metabolites because these intermediate phenotypes are closer to the underlying pathways than other traits or diseases. In this study we analyzed systematically nonadditive effects on a large panel of serum metabolites and all possible ratios (22,801 total) in a population-based study [Cooperative Health Research in the Region of Augsburg (KORA) F4, N = 1,785]. We applied four different 1-degree-of-freedom (1-df) tests corresponding to an additive, dominant, recessive, and overdominant trait model as well as a genotypic model with two degree-of-freedom (2-df) that allows a more general consideration of genetic effects. Twenty-three loci were found to be genome-wide significantly associated (Bonferroni corrected P ≤ 2.19 × 10−12) with at least one metabolite or ratio. For five of them, we show the evidence of nonadditive effects. We replicated 17 loci, including 3 loci with nonadditive effects, in an independent study (TwinsUK, N = 846). In conclusion, we found that most genetic effects on metabolite concentrations and ratios were indeed additive, which verifies the practice of using the additive model for analyzing SNP effects on metabolites.
Detoxification of cassava products and effects of residual toxins on consuming animals by

The use of cassava in livestock feeding has been limited. Reasons include the presence of toxic cyanogenic glucosides, deficiency in nutrients other than energy, dustiness of the dried products, mouldiness during processing and the high fibre and ash content of the peel, which limits the selection of other ingredients which are high in these components. Nevertheless, the development of cassava products which meet minimum requirements for incorporation into commercial livestock feed production, in cassava producing areas, would certainly relieve the pressure on demand for available cereal grains. Additionally it would help guarantee the supply of energy for livestock feeding, in these regions, that are perennially acutely short of animal feed ingredients and due to unfavourable trade balances are unable to make up deficiencies with imports.
The stigmatisation of pregnancy: societal influences on pregnant women’s physical activity Behaviour

Abstract Many women going through the major life transition of pregnancy experience decreases in physical activity behaviour, which may compromise maternal and infant health and wellbeing. Although research suggests that the social environment plays a large role in influencing women’s physical activity behaviour, little is known about the association between societal attitudes and physical activity behaviour during the course of pregnancy. Through a qualitative longitudinal study, we explored women’s physical activity experiences throughout pregnancy and how these were formed, supported and/or opposed by their social environment. This research included telephone interviews with 30 pregnant participants, recruited via a regional public hospital. Using a feminist standpoint analysis incorporating modern dialectics, three major tensions were identified, reflecting dominant societal discourses around physical activity and pregnancy: (1) engaging in physical activity and keeping the baby safe, (2) engaging in physical activity and obtaining social approval and (3) listening to oneself and to others. These findings present previously unrecognised opportunities for developing tailored and effective physical activity interventions among pregnant women.
Quadriceps muscle blood flow and oxygen availability during repetitive bouts of isometric exercise in simulated sailing

Abstract In this study, we wished to determine whether the observed reduction in quadriceps muscle oxygen availability, reported during repetitive bouts of isometric exercise in simulated sailing efforts (i.e. hiking), is because of restricted muscle blood flow. Six national-squad Laser sailors initially performed three successive 3-min hiking bouts followed by three successive 3-min cycling tests sustained at constant intensities reproducing the cardiac output recorded during each of the three hiking bouts. The blood flow index (BFI) was determined from assessment of the vastus lateralis using near-infrared spectroscopy in association with the light-absorbing tracer indocyanine green dye, while cardiac output was determined from impedance cardiography. At equivalent cardiac outputs (ranging from 10.3±0.5 to 14.8±0.86 L · min−1), the increase from baseline in vastus lateralis BFI across the three hiking bouts (from 1.1±0.2 to 3.1±0.6 nM · s−1) was lower (P = 0.036) than that seen during the three cycling bouts (from 1.1±0.2 to 7.2±1.4 nM · s−1) (Cohen's d: 3.80 nM · s−1), whereas the increase from baseline in deoxygenated haemoglobin (by ∼17.0±2.9 μM) (an index of tissue oxygen extraction) was greater (P = 0.006) during hiking than cycling (by ∼5.3±2.7 μM) (Cohen's d: 4.17 μM). The results suggest that reduced vastus lateralis muscle oxygen availability during hiking arises from restricted muscle blood flow in the isometrically acting quadriceps muscles.