Miracle-dz/UniFAR-FTUs huggingface dataset:
The MOVEMENT Trial

Background Morphine administration is a strong predictor of delayed onset of action of orally administered ticagrelor in patients with ST‐segment–elevation myocardial infarction, likely because of impaired gastrointestinal motility. The aim of this study was to evaluate whether the peripheral opioid antagonist methylnaltrexone could improve pharmacodynamics and pharmacokinetics of orally administered ticagrelor in patients with ST‐segment–elevation myocardial infarction receiving morphine. Methods and Results The MOVEMENT (Methylnaltrexone to Improve Platelet Inhibition of Ticagrelor in Morphine‐Treated Patients With ST‐Segment Elevation Myocardial Infarction) trial was a multicenter, prospective, randomized, controlled trial in patients with ST‐segment–elevation myocardial infarction treated with morphine and ticagrelor. Upon arrival to the catheterization laboratory, patients were randomized to a blinded intravenous injection of either methylnaltrexone (8 or 12 mg according to weight) or 0.9% sodium chloride. The proportion of patients with high on‐treatment platelet reactivity and plasma concentrations of ticagrelor and AR‐C124910XX were assessed at baseline (arrival in the catheterization laboratory) and 1 and 2 hours later. A total of 82 patients received either methylnaltrexone (n=43) or placebo (n=39). Median (interquartile range) time from ticagrelor administration to randomization was 41 (31–50) versus 45.5 (37–60) minutes (P=0.16). Intravenous methylnaltrexone administration did not significantly affect prevalence of high on‐treatment platelet reactivity at 2 hours after inclusion, the primary end point, when compared with placebo (54% versus 51%, P=0.84). Plasma concentrations of ticagrelor and its active metabolite, the prespecified secondary end points, did not differ significantly between the groups over time. There was no significant difference in patient self‐estimated pain between the groups. Conclusions Methylnaltrexone did not significantly improve platelet reactivity or plasma concentrations of orally administered ticagrelor in patients with ST‐segment–elevation myocardial infarction receiving morphine. Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT02942550.
Sema3E/PlexinD1 signaling inhibits postischemic angiogenesis by regulating endothelial DLL4 and filopodia formation in a rat model of ischemic stroke

Angiogenesis is a crucial defense response to hypoxia that regulates the process of raising the promise of long‐term neurologic recovery during the management of stroke. A high expression of antiangiogenic factors leads to the loss of neovascularization capacity in pathologic conditions. We have previously documented an impairment of the cerebral vessel perfusion and neovascularization in the cortex neighboring the stroke‐induced lesion, which was accompanied by an activation of semaphorin 3E (Sema3E)/PlexinD1 after ischemic stroke. In this study, we employed micro‐optical sectioning tomography to fully investigate the details of the vascular pattern, including the capillaries. We found that after transient middle cerebral artery occlusion, inhibiting PlexinD1 signaling led to an organized recovery of the vascular network in the ischemic area. We then further explored the possible mechanisms. In vivo, Sema3E substantially decreased dynamic delta‐like 4 (DLL4) expression. In cultured brain microvascular endothelial cells, Sema3E down‐regulated DLL4 expression via inhibiting Ras‐related C3 botulinum toxin substrate 1–induced JNK phosphorylation. At the microcosmic level, Sema3E/PlexinD1 signaling promoted F‐actin disassembly and focal adhesion reduction by activating the small guanosine triphosphatase Ras homolog family member J by releasing RhoGEF Tuba from direct binding to PlexinD1, thus mediating endothelial cell motility and filopodia retraction. Our study reveals that Sema3E/PlexinD1 signaling, which suppressed endothelial DLL4 expression, cell motility, and filopodia formation, is expected to be a novel druggable target for angiogenesis during poststroke progression. — Zhou, Y. ‐F. , Chen, A. ‐Q. , Wu, J.‐H. , Mao, L. , Xia, Y. ‐P., Jin, H. ‐J., He, Q. ‐W. , Miao, Q. R. , Yue, Z. ‐Y. , Liu, X. ‐L. , Huang, M. , Li, Y. ‐N. , Hu, B. Sema3E/PlexinD1 signaling inhibits postischemic angiogenesis by regulating endothelial DLL4 and filopodia formation in a rat model of ischemic stroke. FASEB J. 33, 4947–4961 (2019). www.fasebj. org
A Comparison of Total and Plasma Membrane Abundance of Transporters in Suspended, Plated, Sandwich-Cultured Human Hepatocytes Versus Human Liver Tissue Using Quantitative Targeted Proteomics and Cell Surface Biotinylation

Suspended (SH), plated (PH), and sandwich-cultured hepatocytes (SCH) are commonly used models to predict in vivo transporter-mediated hepatic uptake (SH or PH) or biliary (SCH) clearance of drugs. When doing so, the total and the plasma membrane abundance (PMA) of transporter are assumed not to differ between hepatocytes and liver tissue (LT). This assumption has never been tested. In this study, we tested this assumption by measuring the total and PMA of the transporters in human hepatocyte models versus LT (total only) from which they were isolated. Total abundance of OATP1B1/2B1/1B3, OCT1, and OAT2 was not significantly different between the hepatocytes and LT. The same was true for the PMA of these transporters across the hepatocyte models. In contrast, total abundance of the sinusoidal efflux transporter, MRP3, and the canalicular efflux transporters, MRP2 and P-gp, was significantly greater (P < 0.05) in SCH versus LT. Of the transporters tested, only the percentage of PMA of OATP1B1, P-gp, and MRP3, in SCH (82.8% ± 7.3%, 57.5% ± 10.9%, 69.3% ± 5.7%) was significantly greater (P < 0.05) than in SH (73.3% ± 6.4%, 27.4% ± 6.4%, 53.6% ± 4.1%). If the transporters measured in the plasma membrane are functional and the PMA in SH is representative of that in LT, these data suggest that SH, PH, and SCH will result in equal prediction of hepatic uptake clearance of drugs mediated by the transporters tested above. However, SCH will predict higher sinusoidal efflux and biliary clearance of drugs if the change in PMA of these transporters is not taken into consideration.
Health economics methods for public health resource allocation: a qualitative interview study of decision makers from an English local authority

Abstract Local authorities in England have responsibility for public health, however, in recent years, budgets have been drastically reduced placing decision makers under unprecedented financial pressure. Although health economics can offer support for decision making, there is limited evidence of it being used in practice. The aim of this study was to undertake in-depth qualitative research within one local authority to better understand the context for public health decision making; what, and how economics evidence is being used; and invite suggestions for how methods could be improved to better support local public health decision making. The study included both observational methods and in-depth interviews. Key meetings were observed and semi-structured interviews conducted with participants who had a decision-making role to explore views on economics, to understand the barriers to using evidence and to invite suggestions for improvements to methods. Despite all informants valuing the use of health economics, many barriers were cited: including a perception of a narrow focus on the health sector; lack of consideration of population impact; and problems with translating long timescales to short term impact. Methodological suggestions included the broadening of frameworks; increased use of natural experiments; and capturing wider non-health outcomes that resonate with the priorities of multiple stakeholders.
Efficacy of Methotrexate in Real-world Management of Giant Cell Arteritis: A Case-control Study

Objective. To determine the effect of methotrexate (MTX) on relapse risk and glucocorticoid (GC) use in a large single-institution cohort of patients with giant cell arteritis (GCA). Methods. Patients diagnosed with GCA from 1998 to 2013 with confirmed evidence of temporal artery biopsy and/or radiographic evidence of large vessel vasculitis were identified. Each patient with GCA treated with adjunct MTX (case) was matched to a similar patient with GCA treated only with GC (control). GC requirements and relapse events before and after MTX initiation (or corresponding index date) were compared using rate ratios (RR). Results. Eighty-three cases and 83 controls were identified and compared. No significant differences in age, demographics, laboratory variables, baseline disease characteristics, or mean initial prednisone doses were observed. Median [interquartile range (IQR)] time from GCA diagnosis to MTX initiation in cases was 39 (13–80) weeks and the median (IQR) starting dose was 13.5 (10–15) mg/week. RR comparing relapse rates before and after MTX initiation/index date were significantly reduced in both cases (RR 0.32, 95% CI 0.24–0.41) and controls (RR 0.60, 95% CI 0.43–0.86). The decrease in relapse rate was significantly greater in patients taking MTX than in those taking GC alone (p = 0.004). Rates of GC discontinuation did not differ between groups. Conclusion. In this large single-institution cohort, the addition of MTX to GC decreased the rate of subsequent relapse by nearly 2-fold compared to patients taking GC alone. MTX may be considered as adjunct therapy in patients with GCA to decrease the risk of further relapse events.
Intimate Partner Violence and Health: The Roles of Social Support and Communal Mastery in Five American Indian Communities

Elevated rates of intimate partner violence (IPV) have been documented among American Indian (AI) populations and multiple negative health outcomes are associated with IPV among the general population. The aims of this study were to examine associations between IPV and health outcomes among AI women and men (N = 192) in five reservations in the upper Midwest and test for possible moderating roles of social support and communal mastery. Data were from quantitative survey results from the Gathering for Health study, a community-based participatory research project investigating the impact of stress on health among AI adults living with type 2 diabetes. Computer-assisted surveys measured IPV with current or most recent partner, depressive symptoms, adverse physical health conditions frequently co-occurring with type 2 diabetes, drug abuse, and self-reported levels of social support and communal mastery. Forty-eight percent of women and 43% of men reported IPV in their current or most recent relationship. Higher IPV scores were positively associated with depressive symptoms, physical health, and drug abuse and negatively associated with social support and communal mastery. Social support was negatively associated with depressive symptoms and drug abuse, and communal mastery and depressive symptoms were inversely correlated. Ordinary least squares regression analyses demonstrated positive relationships between IPV and all three adverse health outcomes, but communal mastery was not significantly related to any of the outcomes in multivariate models. Social support moderated the effects of IPV on depressive symptoms only and communal mastery demonstrated no moderating effect. Findings suggest that social support may be protective against negative health outcomes among this population and corroborate previous scientific literature on the negative health outcomes specifically related to IPV. Interventions seeking to increase social support may be an area in which to focus IPV preventive and treatment efforts.
A demonstration of a multi-method variable selection approach for treatment selection: Recommending cognitive–behavioral versus psychodynamic therapy for mild to moderate adult depression

ABSTRACT Objective: We use a new variable selection procedure for treatment selection which generates treatment recommendations based on pre-treatment characteristics for adults with mild-to-moderate depression deciding between cognitive behavioral (CBT) versus psychodynamic therapy (PDT). Method: Data are drawn from a randomized comparison of CBT versus PDT for depression (N = 167, 71% female, mean-age = 39.6). The approach combines four different statistical techniques to identify patient characteristics associated consistently with differential treatment response. Variables are combined to generate predictions indicating each individual’s optimal-treatment. The average outcomes for patients who received their indicated treatment versus those who did not were compared retrospectively to estimate model utility. Results: Of 49 predictors examined, depression severity, anxiety sensitivity, extraversion, and psychological treatment-needs were included in the final model. The average post-treatment Hamilton-Depression-Rating-Scale score was 1.6 points lower (95%CI = [0.5:2.8]; d = 0.21) for those who received their indicated-treatment compared to non-indicated. Among the 60% of patients with the strongest treatment recommendations, that advantage grew to 2.6 (95%CI = [1.4:3.7]; d = 0.37). Conclusions: Variable selection procedures differ in their characterization of the importance of predictive variables. Attending to consistently-indicated predictors may be sensible when constructing treatment selection models. The small N and lack of separate validation sample indicate a need for prospective tests before this model is used.
Experimental and Numerical Study of a Thermal Expansion Gyroscope for Different Gases †

A new single-axis gas thermal gyroscope without proof mass is presented in this paper. The device was designed, manufactured and experimentally characterized. The obtained results were compared to numerical simulation. The working principle of the gyroscope is based on the deflection of a laminar gas flow caused by the Coriolis effect. A bidirectional hot air flow is generated by alternating activation of two suspended resistive micro-heaters. The heated gas is encapsulated in a semi-open cavity and the gas expands primarily inside the cavity. The thermal expansion gyroscope has a simple structure. Indeed, the device is composed of a micromachined cavity on which three bridges are suspended. The central bridge is electrically separated into two segments enabling to set up two heaters which may be supplied independently from each other. The two other bridges, placed symmetrically on each side of the central bridge, are equipped with temperature detectors which measure variations in gas temperature. The differential temperature depends on the rotational velocity applied to the system. Various parameters such as the heating duty cycle, the type of the gas and the power injected into the heaters have been studied to define the optimal working conditions required to obtain the highest level of sensitivity over a measurement range of around 1000°/s. The robustness of the device has also been tested and validated for a shock resistance of 10,000 g for a duration of 400 µs.
Clinical Safety of PMR(Palatal Muscle Resection) In Which Performed OSAS Patients

Background and Objectives: The purpose of this study was to analyze clinical safety of PMR(Palatal Muscle Resection) in obstructive sleep apnea patients. Materials and Methods : Fourteen Patients underwent only PMR were reviewed retrospectively. ESS(Epworth Sleepiness Scale) was analyzed after PMR surgery to assess surgical results. Visual Analogue Scale were reviewed to evaluate postoperative pain. Eustachian tube function test, voice analysis, and measurement of forced expiration power were done after two months of surgery. Results : ESS were improved after PMR. There were little postoperative pain. There was no significant change is observed vowel sounds except /u/ nor postoperative nasalization in voice, Eustachian tube dysfunction and change of expiration power. Conclusion : PMR may be regarded clinically safe surgery in obstructive sleep apnea patient.
Pectus excavatum and congenital cystic lung lesion: simultaneous surgery advocated.

Background Severe pectus excavatum (PE) may be concomitant with congenital cystic lung lesions (CCLLs) that also require surgery. It is ideal to correct these two deformities concurrently, but the safety and efficacy of a simultaneous surgical technique remain unknown. Methods Between 2007 and 2017, 635 patients with severe PE were admitted at our medical center. Eight patients underwent minimally invasive repair of PE and lobectomy simultaneously. The patient characteristics and operative data were analyzed and compared with another group of patients who underwent lobectomy alone for contemporaneous CCLLs. Results The severity of PE (mean Haller index 5.70) and CCLLs were confirmed by computed tomography (CT). Simultaneous minimally invasive repair and lobectomy were performed successfully. There were no significant differences in the mean blood loss (14 mL/kg), the mean weaning time from mechanical ventilation (900 minutes) and the mean hospital stay (16 days) (P>0.05). The mean operative time (170 minutes) was extended, as expected (P=0.02). With a mean follow-up of 22 months, the overall cosmetic results were good. Conclusions Simultaneous minimally invasive repair and lobectomy appears to be a technically safe and reliable method for the treatment of concurrent PE and CCLLs, although further studies are needed in the long-term follow-up.
Ropivacaine for Intercostal Nerve Block Improves Early Postoperative Cognitive Dysfunction in Patients Following Thoracotomy for Esophageal Cancer

Background Ropivacaine is commonly used as an intercostal nerve block, but its effects on postoperative cognitive dysfunction (POCD) have not previously been investigated. This study aimed to examine the effects of the use of ropivacaine as an intercostal nerve block on early POCD, postoperative analgesia, and inflammation in patients following thoracotomy for esophageal cancer. Material/Methods One hundred patients with esophageal cancer undergoing thoracotomy were randomly divided into a group with intercostal nerve block (group A) (n=50) and a control group (group B) (n=50). The cognitive function score and visual analog scale (VAS) scores for pain were measured at one hour before surgery (T1), two hours after surgery (T2), 12 hours after surgery (T3), and 24 hours after surgery (T4). Blood samples were collected at each time point, and plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10, and S100-β were measured using an enzyme-linked immunosorbent assay (ELISA). Cognitive function was determined using the Mini-Mental State Examination (MMSE) scale. Results The VAS scores in group A were significantly lower compared with group B (p<0.05). In the T2, T3, and T4 time points, group A had significantly increased MMSE scores compared with group B (p<0.05). Compared with group B, the levels of IL-6 and TNF-α were significantly decreased in group A at T3 and T4 (p<0.05), while the levels of IL-10 were significantly increased (p<0.05) when compared with group A. Conclusions The use of the intercostal nerve block, ropivacaine, improved early PCOD in patients following thoracotomy for esophageal cancer.
Surgical aortic valve replacement and patient-prosthesis mismatch: a meta-analysis of 108 182 patients.

OBJECTIVES This study sought to evaluate the impact of patient-prosthesis mismatch (PPM) on the risk of perioperative, early-, mid- and long-term mortality rates after surgical aortic valve replacement. METHODS Databases were searched for studies published until March 2018. The main outcomes of interest were perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality. RESULTS The search yielded 3761 studies for inclusion. Of these, 70 articles were analysed, and their data were extracted. The total number of patients included was 108 182 who underwent surgical aortic valve replacement. The incidence of PPM after surgical aortic valve replacement was 53.7% (58 116 with PPM and 50 066 without PPM). Perioperative mortality [odds ratio (OR) 1.491, 95% confidence interval (CI) 1.302-1.707; P < 0.001], 1-year mortality (OR 1.465, 95% CI 1.277-1.681; P < 0.001), 5-year mortality (OR 1.358, 95% CI 1.218-1.515; P < 0.001) and 10-year mortality (OR 1.534, 95% CI 1.290-1.825; P < 0.001) were increased in patients with PPM. Both severe PPM and moderate PPM were associated with increased risk of perioperative mortality, 1-year mortality, 5-year mortality and 10-year mortality when analysed together and separately, although we observed a higher risk in the group with severe PPM. CONCLUSIONS Moderate/severe PPM increases perioperative, early-, mid- and long-term mortality rates proportionally to its severity. The findings of this study support the implementation of surgical strategies to prevent PPM in order to decrease mortality rates.
Design and commissioning of the non‐dedicated scanning proton beamline for ocular treatment at the synchrotron‐based CNAO facility

PURPOSE Only few centers worldwide treat intraocular tumors with proton therapy, all of them with a dedicated beamline, except in one case in the USA. The Italian National Center for Oncological Hadrontherapy (CNAO) is a synchrotron-based hadrontherapy facility equipped with fixed beamlines and pencil beam scanning modality. Recently, a general-purpose horizontal proton beamline was adapted to treat also ocular diseases. In this work, the conceptual design and main dosimetric properties of this new proton eyeline are presented. METHODS A 28 mm thick water-equivalent range shifter (RS) was placed along the proton beamline to shift the minimum beam penetration at shallower depths. FLUKA Monte Carlo (MC) simulations were performed to optimize the position of the RS and patient-specific collimator, in order to achieve sharp lateral dose gradients. Lateral dose profiles were then measured with radiochromic EBT3 films to evaluate the dose uniformity and lateral penumbra width at several depths. Different beam scanning patterns were tested. Discrete energy levels with 1 mm water-equivalent step within the whole ocular energy range (62.7-89.8 MeV) were used, while fine adjustment of beam range was achieved using thin polymethylmethacrylate additional sheets. Depth-dose distributions (DDDs) were measured with the Peakfinder system. Monoenergetic beam weights to achieve flat spread-out Bragg Peaks (SOBPs) were numerically determined. Absorbed dose to water under reference conditions was measured with an Advanced Markus chamber, following International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice. Neutron dose at the contralateral eye was evaluated with passive bubble dosimeters. RESULTS Monte Carlo simulations and experimental results confirmed that maximizing the air gap between RS and aperture reduces the lateral dose penumbra width of the collimated beam and increases the field transversal dose homogeneity. Therefore, RS and brass collimator were placed at about 98 cm (upstream of the beam monitors) and 7 cm from the isocenter, respectively. The lateral 80%-20% penumbra at middle-SOBP ranged between 1.4 and 1.7 mm depending on field size, while 90%-10% distal fall-off of the DDDs ranged between 1.0 and 1.5 mm, as a function of range. Such values are comparable to those reported for most existing eye-dedicated facilities. Measured SOBP doses were in very good agreement with MC simulations. Mean neutron dose at the contralateral eye was 68 μSv/Gy. Beam delivery time, for 60 Gy relative biological effectiveness (RBE) prescription dose in four fractions, was around 3 min per session. CONCLUSIONS Our adapted scanning proton beamline satisfied the requirements for intraocular tumor treatment. The first ocular treatment was delivered in August 2016 and more than 100 patients successfully completed their treatment in these 2 yr.