Miracle-dz/UniFAR-FTUs huggingface dataset:
Citalopram Enhances B Cell Numbers in a Murine Model of Morphine‐Induced Immunosuppression

Patients with chronic pain are often challenged with depression stemming from the long‐term psychophysiological effects of their condition. Consequently, patients with chronic pain are often treated with morphine, which can induce immunosuppression, along with an antidepressant. The antidepressant citalopram (CTP; Sigma‐Aldrich Chemical, St. Louis, MO, U.S.A.) is a serotonin reuptake inhibitor that is reported to have immunomodulatory effects. Thus, we investigated whether CTP administration impacted immunity in morphine‐treated animals. Adult mice were pretreated for 7 days with either saline or CTP (10 or 30 mg/kg intraperitoneal injections twice daily), followed by subcutaneous implantation of a 25 mg morphine pellet for 48 hours. Spleen, thymus, and lymph nodes were harvested to analyze total cell numbers, relative lymphocyte populations, and lymphocyte function. In this study, CTP had no effect on either total cell counts or lymphocyte populations in the thymus. However, in the spleen, total splenocyte numbers in all CTP‐treated animals displayed an increasing trend over saline‐treated animals. Interestingly, although more cells were found in the spleen, distribution of splenic lymphocyte populations did not differ between treatments. Despite no increase in total cell number, a high dose of CTP (30 mg/kg) resulted in a significantly higher B cell population in the lymph nodes, while T cell and NK cell numbers were not different. CTP did not significantly reverse morphine‐induced weight loss or splenic B cell antibody secretion in vitro. Additionally, CTP treatment demonstrated a slight but not significant increase in both splenic B and T cell mitogen‐induced proliferation in vitro. In summary, CTP may have a specific potential in the attenuation of morphine's immunosuppressive effect by enhancing splenocyte numbers and lymph node B cell populations.
Effects of an 18-Week Strength Training Program on Low-Handicap Golfers' Performance

Abstract Álvarez, M, Sedano, S, Cuadrado, G, and Redondo, JC. Effects of an 18- week strength training program on low-handicap golfers' performance. J Strength Cond Res 26(4): 1110–1121, 2012—The purpose of this study was to determine the effects of an 18-week strength training program on variables related to low-handicap golfers' performance. Ten right-handed male golfers, reporting a handicap of 5 or less, were randomly divided into two groups: the control group (CG) (N = 5, age: 23.9 ± 6.7 years) and the treatment group (TG) (N = 5, age: 24.2 ± 5.4 years). CG players followed the standard physical conditioning program for golf, which was partially modified for the TG. The TG participated in an 18-week strength training program divided into three parts: maximal strength training including weightlifting exercises (2 days a week for 6 weeks), explosive strength training with combined weights and plyometric exercises (2 days a week for 6 weeks), and golf-specific strength training, including swings with a weighted club and accelerated swings with an acceleration tubing system (3 days a week for 6 weeks). Body mass, body fat, muscle mass, jumping ability, isometric grip strength, maximal strength (RM), ball speed, and golf club mean acceleration were measured on five separate occasions. The TG demonstrated significant increases (p < 0.05) in maximal and explosive strength after 6 weeks of training and in driving performance after 12 weeks. These improvements remained unaltered during the 6-week golf-specific training period and even during a 5-week detraining period. It may be concluded that an 18-week strength training program can improve maximal and explosive strength and these increases can be transferred to driving performance; however, golfers need time to transfer the gains.
Imaging of the Right Heart—CT and CMR

Right ventricular (RV) structure and function is of substantial importance in a broad variety of clinical conditions. Cardiac magnetic resonance (CMR) and computed tomography (CT) each provide three‐dimensional RV imaging, high‐resolution evaluation of RV structure/anatomy, and accurate functional assessment without geometric assumptions. This is of particular significance for the RV, where complex geometry compromises reliance on indices derived from two‐dimensional (2D) imaging planes. CMR flow‐based imaging can be applied to right‐sided heart valves, enabling evaluation of hemodynamic and valvular dysfunction that may contribute to or result from RV dysfunction. Tissue characterization imaging by both CMR and CT provides valuable complementary assessment of the RV. Changes in myocardial tissue composition provide a mechanistic substrate for RV dysfunction and cardiac arrhythmias. This review provides an overview of RV imaging by both CMR and CT, with focus on assessment of RV structure/function, flow, and tissue characterization. Emerging evidence and established guidelines are discussed in the context of imaging contributions to diagnosis, prognostic risk stratification and disease management of clinical conditions that impact the right ventricle.
Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders

The limbic localization of the arginine vasopressin V1b receptor has prompted speculation as to a potential role of this receptor in the control of emotional processes. To investigate this possibility, we have studied the behavioral effects of SSR149415, the first selective and orally active non-peptide antagonist of vasopressin V1b receptors, in a variety of classical (punished drinking, elevated plus-maze, and light/dark tests) and atypical (fear/anxiety defense test battery and social defeat-induced anxiety) rodent models of anxiety, and in two models of depression [forced swimming and chronic mild stress (CMS)]. When tested in classical tests of anxiety, SSR149415 produced anxiolytic-like activity at doses that ranged from 1 to 30 mg/kg (i.p. or p.o.), but the magnitude of these effects was overall less than that of the benzodiazepine anxiolytic diazepam, which was used as a positive control. In contrast, SSR149415 produced clear-cut anxiolytic-like activity in models involving traumatic stress exposure, such as the social defeat paradigm and the defense test battery (1–30 mg/kg, p.o.). In the forced swimming test, SSR149415 (10–30 mg/kg, p.o.) produced antidepressant-like effects in both normal and hypophysectomized rats. Moreover, in the CMS model in mice, repeated administration of SSR149415 (10 and 30 mg/kg, i.p.) for 39 days improved the degradation of the physical state, anxiety, despair, and the loss of coping behavior produced by stress. These findings point to a role for vasopressin in the modulation of emotional processes via the V1b receptor, and suggest that its blockade may represent a novel avenue for the treatment of affective disorders.
Identification of Multiple Forms of RNA Transcripts Associated with Human-Specific Retrotransposed Gene Copies

The human genome contains thousands of retrocopies, mostly as processed pseudogenes, which were recently shown to be prevalently transcribed. In particular, those specifically acquired in the human lineage are able to modulate gene expression in a manner that contributed to the evolution of human-specific traits. Therefore, knowledge of the human-specific retrocopies that are transcribed or their full-length transcript structure contributes to better understand human genome evolution. In this study, we identified 16 human-specific retrocopies that harbor 5′ CpG islands by in silico analysis and showed that 12 were transcribed in normal tissues and cancer cell lines with a variety of expression patterns, including cancer-specific expression. Determination of the structure of the transcripts associated with the retrocopies revealed that none were transcribed from their 5′ CpG islands, but rather, from inside the 3′ UTR and the nearby 5′ flanking region of the retrocopies as well as the promoter of neighboring genes. The multiple forms of the transcripts, such as chimeric and individual transcripts in both the sense and antisense orientation, might have introduced novel post-transcriptional regulation into the genome during human evolution. These results shed light on the potential role of human-specific retrocopies in the evolution of gene regulation and genomic disorders.
Protein determinants of phage T4 lysis inhibition

Genetic studies have established that lysis inhibition in bacteriophage T4 infections occurs when the RI antiholin inhibits the lethal hole‐forming function of the T holin. The T‐holin is composed of a single N‐terminal transmembrane domain and a ∼20 kDa periplasmic domain. It accumulates harmlessly throughout the bacteriophage infection cycle until suddenly causing permeabilization of the inner membrane, thereby initiating lysis. The RI antiholin has a SAR domain that directs its secretion to the periplasm, where it can either be inactivated and degraded or be activated as a specific inhibitor of T. Previously, it was shown that the interaction of the soluble domains of these two proteins within the periplasm was necessary for lysis inhibition. We have purified and characterized the periplasmic domains of both T and RI. Both proteins were purified in a modified host that allows disulfide bond formation in the cytoplasm, due to the functional requirement of conserved disulfide bonds. Analytical centrifugation and circular dichroism spectroscopy showed that RI was monomeric and exhibited ∼80% alpha‐helical content. In contrast, T exhibited a propensity to oligomerize and precipitate at high concentrations. Incubation of RI with T inhibits this aggregation and results in a complex of equimolar T and RI content. Although gel filtration analysis indicated a complex mass of 45 kDa, intermediate between the predicted 30 kDa heterodimer and 60 kDa heterotetramer, sedimentation velocity analysis indicated that the predominant species is the former. These results suggest that RI binding to T is necessary and sufficient for lysis inhibition.
The association between human resource investment by audit firms and their audit quality*

Abstract Utilizing unique data available only in Korea, we examine the association between investment in human resources and audit quality provided by audit firms. While human resources investment is important in improving audit quality, few studies have examined this association mainly because public data about human resources investment and financial statements of audit firms are unavailable. Using two proxies for audit quality (i.e. discretionary accruals and accounting conservatism), we provide evidence that higher compensation in audit firms improves audit quality. In addition, we find higher audit quality in audit firms with higher education expenses, when audit quality is measured by the level of conservatism of clients’ financial statements. These results support regulators’ stance that quality control through human resources investment in audit firms can effectively improve audit quality and therefore the quality of clients’ financial reporting. However, we find no association between education expenses and the average absolute value of discretionary accruals of audit clients. These results generally suggest that direct investment in human capital (i.e. compensation) is more effective in improving audit quality than indirect investment in human capital (i.e. education expenses).
Evaluation of the pharmacokinetic profile and analgesic efficacy of oral morphine after total hip arthroplasty

Background and objective: Oral morphine may be useful for postoperative pain relief, but few studies have tested its use after in‐hospital surgery. Methods: We evaluated clinical efficacy and the pharmacokinetic parameters of oral morphine after total hip arthroplasty. We recruited 60 patients who had total hip arthroplasty under general anaesthesia. The patients were randomized to receive placebo, 10 mg morphine sulphate or 20 mg morphine sulphate orally every 4 h for 24 h. The oral administration was started 3 h after the morphine‐loading dose in the Post Anaesthesia Care Unit and then patients used intravenous morphine patient‐controlled analgesia for 24 h. Pain score at rest (scored by patients on a visual analogue scale), sedation, nausea, vomiting and urinary retention were monitored. In 11 additional total hip arthroplasty patients, we determined the pharmacokinetics of morphine and its metabolites after oral administration of 20 mg morphine sulphate every 4 h for 16 h. Results: The amount of morphine administered via patient‐controlled analgesia over 24 h was reduced in the 20‐mg group compared with that in the placebo group (19.0 ± 2.7 mg vs. 33.0 ± 5.5 mg; P = 0.03). No significant morphine‐sparing effect was observed in the 10‐mg group. Pain scores and side‐effects were similar in all groups. The pharmacokinetic study revealed a limited and slow absorption of morphine. Conclusion: Despite a limited absorption of oral morphine postoperatively, high doses of oral morphine have a significant analgesic effect after total hip arthroplasty.
Lipid peroxidation and biochemical parameters in maternal pre-delivery and post-delivery plasma

Lipid peroxidation (LPX) can play an important role in development of functional and pathological changes of maternal tissues in the course of pregnancy and delivery. LPX products were measured as thiobarbituric acid reacting substances (TBARS), using malondialdehyde as the standard solution. Actual TBARS determined in maternal post-delivery plasma (2.71 ± 0.602 nmol/mL) were not statistically different from those determined in pre-delivery plasma (3.45 ± 0.530 nmol/mL). TBARS production was measured in vitro in the both incubated plasma (30 min, 37°C) with and without the added LPX activator (125 μM L-ascorbate plus 5 μM FeSO4). A difference in the TBARS formation was found only in the post-delivery plasma, as a result of approximately twice higher (marginally significant) TBARS formation in the incubated plasma without the added LPX activator comparing with the actual TBARS levels in this plasma. These results suggest that changes in maternal tissues in the process of labour could create suitable conditions for activation of LPX in maternal plasma. On the other hand, all other analysed biochemical parameters (iron, total iron-binding capacity, uric acid, proteins, magnesium, calcium, phosphate, glucose, potassium, sodium, chlorides, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, creatine kinase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, α-amylase, alkaline phosphatase, acid phosphatase in the post-delivery plasma were not different from those analysed in the pre-delivery plasma.
Use of Medications and Resources for Treatment of Nausea, Vomiting, or Constipation in Hospitalized Patients Treated With Analgesics

ObjectivesHospitalized patients often experience adverse events of the gastrointestinal tract due to analgesic treatment. The objectives of this study were to estimate use of medications for treatment of nausea, vomiting, or constipation (NVC medications) after initiation of analgesic treatment, and to compare differences in length of stay and treatment costs between patients who received NVC medications and those who did not. MethodsThis retrospective cohort study used the Premier Perspective data from January 1, 2005 to December 31, 2007 and stratified inpatients into 4 groups based on the first analgesic agent they were given. Patients were observed for 14 days after the first analgesic use until a regimen change, first use of NVC medication, or hospital discharge, whichever occurred first. Data were analyzed using a Cox proportional hazards model and a generalized linear model. ResultsThis study found that 239,183 (55.1%) of 434,304 patients received NVC medications after analgesic administration. Compared with oral nonopioid analgesics, the risk of using NVC medication was 4.8 times higher for injectable opioid analgesics after controlling for confounders. Patients who received NVC medications were hospitalized 0.26 days longer (P<0.0001) at an additional cost of $756 per patient compared with patients who did not receive NVC medications (P<0.0001). DiscussionUse of an analgesic with improved gastrointestinal tolerability may potentially reduce use of NVC medications and hospital resources.
Stable Control of Physiological Parameters, But Not Infection, in Preterm Lambs Maintained on Ex Vivo Uterine Environment Therapy

Ex vivo uterine environment (EVE) therapy is an experimental neonatal intensive care strategy wherein gas exchange is performed by membranous oxygenators attached to the umbilical vessels. Our aim was to assess the ability of a newly refined EVE system to maintain key physiological parameters in preterm lambs within optimal ranges for 48 h. EVE group; n = 6: Preterm lambs were delivered under general anesthesia at 115 ± 2 days of gestational age. Animals were submerged in a bath of artificial amniotic fluid on EVE therapy for 48 h. Physiological parameters were monitored in real-time over the length of the experiment. Control group; n = 11: Ewes carrying a single fetus (115 ± 2 days of gestational age) underwent recovery surgery to allow placement of a fetal carotid artery catheter. Fetuses received an infusion of sterile saline only. After euthanasia, EVE and Control group fetuses underwent necroscopy to perform static pressure-volume curves and for sampling of lung and cord blood plasma for molecular analyses. Five out of six fetuses in the EVE group completed the study period with key physiological variables remaining within their respective reference ranges for the duration of the 48 h study. Bacteremia was identified in four out of five EVE fetuses, and was associated with a systemic inflammatory response. Using our refined EVE therapy platform, preterm lambs were maintained in a stable physiological condition for 48 h. These findings represent a significant advance over earlier work with this system; however, the identification of bacteremia and a fetal inflammatory response suggests that further refinement to the EVE therapy platform is required.
Functionally heterogeneous synaptic vesicle pools support diverse synaptic signalling

Synaptic communication between neurons is a highly dynamic process involving specialized structures. At the level of the presynaptic terminal, neurotransmission is ensured by fusion of vesicles to the membrane, which releases neurotransmitter in the synaptic cleft. Depending on the level of activity experienced by the terminal, the spatiotemporal properties of calcium invasion will dictate the timing and the number of vesicles that need to be released. Diverse presynaptic firing patterns are translated to neurotransmitter release with a distinct temporal feature. Complex patterns of neurotransmitter release can be achieved when different vesicles respond to distinct calcium dynamics in the presynaptic terminal. Specific vesicles from different pools are recruited during various modes of release as the particular molecular composition of their membrane proteins define their functional properties. Such diversity endows the presynaptic terminal with the ability to respond to distinct physiological signals via the mobilization of specific subpopulation of vesicles. There are several mechanisms by which a diverse vesicle population could be generated in single presynaptic terminals, including distinct recycling pathways that utilize various adaptor proteins. Several additional factors could potentially contribute to the development of a heterogeneous vesicle pool such as specialized release sites, spatial segregation within the terminal and specialized delivery pathways. Among these factors molecular heterogeneity plays a central role in defining the functional properties of different subpopulations of vesicles.
Joint User-Entity Representation Learning for Event Recommendation in Social Network

User-managed-events is a popular feature on social networks. Take Facebook Events as an example: over 135 million events were created in 2015 and over 550 million people use events each month. In this work, we consider the heavy sparseness in both user and event feedback history caused by short lifespans (transiency) of events and user participation patterns in a production event system. We propose to solve the resulting cold-start problems by introducing a joint representation model to project users and events into the same latent space. Our model based on parallel Convolutional Neural Networks captures semantic meaning in event text and also utilizes heterogeneous user knowledge available in the social network. By feeding the model output as user and event representation into a combiner prediction model, we show that our representation model improves the prediction accuracy over existing techniques (+6% AUC lift). Our method provides a generic way to match heterogeneous information from different domains and applies to a wide range of applications in social networks.
RORγt inhibitors as potential back-ups for the phase II candidate VTP-43742 from Vitae Pharmaceuticals: patent evaluation of WO2016061160 and US20160122345

ABSTRACT Retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt or RORc2) is a key transcription factor for the differentiation of naïve proinflammatory CD4+ T cells and the production of T helper-17 (TH17) cells. Inhibiting RORγt activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders. Recently Vitae Pharmaceuticals (to be acquired by Allergan) reported positive top-line results from a Phase 2a clinical trial of RORγt inhibitor VTP-43742 in psoriatic patients. The compound was reported to demonstrate a clear signal of efficacy over a short four-week period and no drug-related cardiac abnormalities were observed; however, in the 700 mg dose group reversible transaminase elevations were observed in four patients, which prompted the company to cancel testing VTP-43742 at a initially planned third, higher dose. In Vitae Pharmaceuticals latest patent applications, WO2016061160 and US20160122345, potential dihydropyrrolopyridine back-up compounds of clinical candidate VTP-43742 (covered in WO2015116904) are disclosed. In light of the recently announced RORγt back-up molecule VTP-45489, the improvements of the new compounds are discussed and their potential impact is elucidated.