Miracle-dz/UniFAR-FTUs huggingface dataset:
Sample size determination for GEE analyses of stepped wedge cluster randomized trials

In stepped wedge cluster randomized trials, intact clusters of individuals switch from control to intervention from a randomly assigned period onwards. Such trials are becoming increasingly popular in health services research. When a closed cohort is recruited from each cluster for longitudinal follow‐up, proper sample size calculation should account for three distinct types of intraclass correlations: the within‐period, the inter‐period, and the within‐individual correlations. Setting the latter two correlation parameters to be equal accommodates cross‐sectional designs. We propose sample size procedures for continuous and binary responses within the framework of generalized estimating equations that employ a block exchangeable within‐cluster correlation structure defined from the distinct correlation types. For continuous responses, we show that the intraclass correlations affect power only through two eigenvalues of the correlation matrix. We demonstrate that analytical power agrees well with simulated power for as few as eight clusters, when data are analyzed using bias‐corrected estimating equations for the correlation parameters concurrently with a bias‐corrected sandwich variance estimator.
Integrative literature review: access to primary healthcare services.

OBJECTIVE Analyze the scientific production that describes the type of access to primary healthcare services and identify specific populations that have differentiated access to health services. METHOD An integrative review. For study selection, the following databases were used: PubMed, Scopus, Bireme, and Cinahl. The sample included 22 national and international articles. RESULTS The results describe the access of specific populations to health services, the access to primary care through health plans and proposed improvements to the access to primary care. CONCLUSION The access to services is a challenge in many countries and some strategies and policies are implemented to solve and improve primary health care.
Patient considerations in the treatment of COPD: focus on the new combination inhaler fluticasone furoate/umeclidinium/vilanterol

The pharmacological treatment for stable COPD is based on the use of inhaled bronchodilators (long-acting muscarinic receptor antagonists and long-acting beta-2 adrenoceptor agonists) and inhaled corticosteroids. The use of triple inhaled therapy is recommended to selected patients with COPD. Among the various inhaler combinations in triple therapy, a new combination by fluticasone furoate, umeclidinium, and vilanterol is available for COPD patients. Recently, a large clinical trial using this combination has been published, resulting in a reduction in exacerbation rate in COPD patients. Furthermore, this combination has demonstrated efficacy and safety, with a single administration a day, through a dry powder inhalator device, which has shown a good adherence and is a preference of the patient. This review focuses on the main characteristics of this inhaler combination evaluating the main clinical effects, the patients’ adherence, and the safety.
Effects of tebuconazole on cytochrome P450 enzymes, oxidative stress, and endocrine disruption in male rats

The major objective of the present study was to determine the ability of a triazole fungicide tebuconazole to induce cytochrome P450‐dependent monooxygenases, oxidative stress, and endocrine‐disrupting activity using male rats treated with tebuconazole at 10, 25, and 50 mg/kg p.o. once daily for 28 days. In liver, tebuconazole dose‐dependently increased microsomal contents of cytochrome P450 and cytochrome b5 and the activities of NADPH‐cytochrome P450 reductase, 7‐ethoxyresorufin O‐deethylase, methoxyresorufin O‐demethylase, pentoxyresorufin O‐dealkylase, 7‐ethoxycoumarin O‐deethylase, aniline hydroxylase, and erythromycin N‐demethylase. In kidney, tebuconazole increased 7‐ethoxycoumarin O‐deethylase activity without affecting other monooxygenase activities. In marked contrast to liver and kidney, tebuconazole decreased testicular 7‐ethoxyresorufin O‐deethylase, methoxyresorufin O‐demethylase, 7‐ethoxycoumarin O‐deethylase, aniline hydroxylase, and erythromycin N‐demethylase activities. The results of immunoblot analysis of liver microsomes of controls and tebuconazole‐treated rats revealed that tebuconazole induced CYP1A1/2, CYP2B1/2, CYP2E1, and CYP3A proteins in liver. Additions of tebuconazole to liver microsomes inhibited microsomal 7‐ethoxycoumarin O‐deethylase activity in vitro (IC50 = 1.50–1.69 µM). Treatment of rats with tebuconazole decreased glutathione content and increased glutathione S‐transferase, superoxide dismutase, catalase, and glutathione peroxidase activities in liver; increased superoxide dismutase activities in kidney and testis; but decreased glutathione S‐transferase activity in testis. Treatments with tebuconazole decreased serum testosterone concentration and cauda epididymal sperm count. The present study demonstrates that tebuconazole induces a multiplicity of CYPs and oxidative stress in liver; inhibits testicular P450 and glutathione S‐transferase activities; and produces anti‐androgenic effects in male rats.
A Review of Tertiary Referrals for Management of Pediatric Esophageal Eosinophilia

Background: Eosinophilic esophagitis is a chronic, immune-mediated disease characterized by symptoms of esophageal dysfunction and ≥15 eosinophils/high-powered field (eos/hpf). Proton pump inhibitor responsive esophageal eosinophilia (1) is an entity of esophageal eosinophilia that responds to PPI therapy and is thought to be clinically and histologically similar to EoE. Current guidelines suggest therapy with PPI prior to endoscopy and use of PPI as first line for esophageal eosinophilia. In order to gain a better understanding of community practice patterns and to try differentiate between these two entities, we sought to evaluate the clinical presentations, treatment and final diagnoses of patients presenting to our institution for second opinions of esophageal eosinophilia. Methods: A search of our electronic medical record yielded a list of patients presenting for a second opinion of esophageal eosinophilia. Charts were reviewed for clinical information. Results: A total of 187 charts were included. Patients ranged from 1-19 years old with 75% being male and 74% being Caucasian. Of the patients who had documentation of their medications at the time of initial endoscopy, 70% were not on any PPI prior to their endoscopy, and 94% were on <2 mg/kg/day. Of the 19 patients who had full response to PPI therapy and were diagnosed with PPI-REE, close to half had previously been treated with diet, steroids, or both. Patients with final diagnosis of EoE had significantly higher eos/hpf on initial endoscopy compared to those with diagnosis of PPI-REE (51.9 ± 30.6 v. 35.8 ± 16.4. p = 0.027), as well as higher likelihood of having IgE-mediated food allergy (79 v. 47%, p = 0.003). Conclusions: Diagnostic and therapeutic algorithms are needed for esophageal eosinophilia to prevent misdiagnosis and unnecessary procedures and therapies.
α2δ-1 Is Essential for Sympathetic Output and NMDA Receptor Activity Potentiated by Angiotensin II in the Hypothalamus

Both the sympathetic nervous system and the renin-angiotensin system are critically involved in hypertension development. Although angiotensin II (Ang II) stimulates hypothalamic paraventricular nucleus (PVN) neurons to increase sympathetic vasomotor tone, the molecular mechanism mediating this action remains unclear. The glutamate NMDAR in the PVN controls sympathetic outflow in hypertension. In this study, we determined the interaction between α2δ-1 (encoded by Cacna2d1), commonly known as a Ca2+ channel subunit, and NMDARs in the hypothalamus and its role in Ang II-induced synaptic NMDAR activity in PVN presympathetic neurons. Coimmunoprecipitation assays showed that α2δ-1 interacted with the NMDAR in the hypothalamus of male rats and humans (both sexes). Ang II increased the prevalence of synaptic α2δ-1–NMDAR complexes in the hypothalamus. Also, Ang II increased presynaptic and postsynaptic NMDAR activity via AT1 receptors, and such effects were abolished either by treatment with pregabalin, an inhibitory α2δ-1 ligand, or by interrupting the α2δ-1–NMDAR interaction with an α2δ-1 C terminus-interfering peptide. In Cacna2d1 knock-out mice (both sexes), Ang II failed to affect the presynaptic and postsynaptic NMDAR activity of PVN neurons. In addition, the α2δ-1 C terminus-interfering peptide blocked the sympathoexcitatory response to microinjection of Ang II into the PVN. Our findings indicate that Ang II augments sympathetic vasomotor tone and excitatory glutamatergic input to PVN presympathetic neurons by stimulating α2δ-1-bound NMDARs at synapses. This information extends our understanding of the molecular basis for the interaction between the sympathetic nervous and renin-angiotensin systems and suggests new strategies for treating neurogenic hypertension. SIGNIFICANCE STATEMENT Although both the sympathetic nervous system and renin-angiotensin system are closely involved in hypertension development, the molecular mechanisms mediating this involvement remain unclear. We showed that α2δ-1, previously known as a calcium channel subunit, interacts with NMDARs in the hypothalamus of rodents and humans. Angiotensin II (Ang II) increases the synaptic expression level of α2δ-1–NMDAR complexes. Furthermore, inhibiting α2δ-1, interrupting the α2δ-1–NMDAR interaction, or deleting α2δ-1 abolishes the potentiating effects of Ang II on presynaptic and postsynaptic NMDAR activity in the hypothalamus. In addition, the sympathoexcitatory response to Ang II depends on α2δ-1-bound NMDARs. Thus, α2δ-1–NMDAR complexes in the hypothalamus serve as an important molecular substrate for the interaction between the sympathetic nervous system and the renin-angiotensin system. This evidence suggests that α2δ-1 may be a useful target for the treatment neurogenic hypertension.
Sublethal metabolic responses to contaminant mixture toxicity in Daphnia magna

Anthropogenic activity is increasing the presence of contaminants that enter waterways through wastewater effluent and urban and/or agricultural runoff, generally in complex mixtures. Depending on the mode of action of the individual contaminant within the mixture, toxicity can occur due to contaminants having similar or dissimilar modes of action. However, it is unknown how the metabolome responds to sublethal contaminant mixtures in the keystone genus Daphnia. In the present study we examined D. magna metabolic responses to acute sublethal exposure of propranolol, carbamazepine, and perfluorooctanesulfonic acid (PFOS) as well as in binary (propranolol–carbamazepine, propranolol–PFOS, carbamazepine–PFOS) and tertiary mixtures (carbamazepine–propranolol–PFOS), all at 10% of the median lethal concentration of the population (LC50). The metabolome was measured using 1H nuclear magnetic resonance (NMR) and characterized using principal component analysis, regression analysis, and fold changes in metabolite relative to the unexposed (control) group. The averaged principal component analysis scores plots revealed that carbamazepine–PFOS and carbamazepine–propranolol–PFOS exposures were significantly different from the control treatment. After normalizing the toxicity of each contaminant, we found that some metabolites responded monotonically, whereas others displayed a nonmonotonic response with increasing toxicity units. The single contaminant exposures and 2 binary mixtures (propranolol–carbamazepine, and propranolol–PFOS) resulted in minimal changes in the identified metabolites, whereas the carbamazepine–PFOS and carbamazepine–propranolol–PFOS displayed increases in several amino acid metabolites and decreases in glucose. Overall, our results highlight the sensitivity of the metabolome to distinguish the composition of the contaminant mixtures, with some mixtures displaying heightened responses versus others. Environ Toxicol Chem 2018;37:2448–2457. © 2018 SETAC
Harnessing T Follicular Helper Cell Responses for HIV Vaccine Development

Passive administration of broadly neutralizing antibodies (bNAbs) capable of recognizing a broad range of viral strains to non-human primates has led to protection from infection with chimeric SIV/HIV virus (SHIV). This data suggests that generating protective antibody responses could be an effective strategy for an HIV vaccine. However, classic vaccine approaches have failed so far to induce such protective antibodies in HIV vaccine trials. HIV-specific bNAbs identified in natural infection show high levels of somatic hypermutations, demonstrating that they underwent extensive affinity maturation. It is likely that to gain ability to recognize diverse viral strains, vaccine-induced humoral responses will also require complex, iterative maturation. T follicular helper cells (Tfh) are a specialized CD4+ T cell subset that provides help to B cells in the germinal center for the generation of high-affinity and long-lasting humoral responses. It is therefore probable that the quality and quantity of Tfh responses upon vaccination will impact development of bNAbs. Here, we review studies that advanced our understanding of Tfh differentiation, function and regulation. We discuss correlates of Tfh responses and bNAb development in natural HIV infection. Finally, we highlight recent strategies to optimize Tfh responses upon vaccination and their impact on prophylactic HIV vaccine research.
Mitochondria-Targeting Small Molecules Effectively Prevent Cardiotoxicity Induced by Doxorubicin

Doxorubicin (Dox) is a chemotherapeutic agent widely used for the treatment of numerous cancers. However, the clinical use of Dox is limited by its unwanted cardiotoxicity. Mitochondrial dysfunction has been associated with Dox-induced cardiotoxicity. To mitigate Dox-related cardiotoxicity, considerable successful examples of a variety of small molecules that target mitochondria to modulate Dox-induced cardiotoxicity have appeared in recent years. Here, we review the related literatures and discuss the evidence showing that mitochondria-targeting small molecules are promising cardioprotective agents against Dox-induced cardiac events.
Ultrasound-Guided Infraclavicular Brachial Plexus Block: Prospective Randomized Comparison of the Lateral Sagittal and Costoclavicular Approach

Background and Objectives It has recently been proposed that an infraclavicular brachial plexus block (BPB) at the costoclavicular (CC) space may overcome some of the limitations of the lateral sagittal (LS) approach. In this study, we hypothesized that the CC approach will produce faster onset of sensory blockade of the 4 major terminal nerves of the brachial plexus than the LS approach. Methods Forty patients undergoing elective upper extremity surgery under a BPB were randomized to receive either the LS (Gp-LS, n = 20) or CC approach (Gp-CC, n = 20) for infraclavicular BPB. Twenty-five milliliters of 0.5% ropivacaine was used for the BPB in both study groups. Sensory-motor blockade of the ipsilateral median, radial, ulnar, and musculocutaneous nerves was assessed by a blinded observer at regular intervals for 45 minutes after the block. Sensory block was assessed using a verbal rating scale (0–100) and motor block using a 3-point qualitative scale (0–2). Onset of sensory (primary outcome variable) and motor blockade was defined as the time it took to achieve a sensory verbal rating scale of 30 or less and motor grade of 1 or less, respectively. Time to readiness for surgery was defined as the time it took to achieve a sensory score of 30 or less and motor grade of 1 or less in all the 4 nerves tested. Results The overall sensory onset time (median [interquartile range]) was significantly faster (P = 0.004) in Gp-CC (10 [10–26.25] minutes) than in Gp-LS (20 [15–30] minutes). The overall sensory score was significantly lower in Gp-CC than in Gp-LS at 5 (P < 0.001), 10 (P = 001), 15 (P = 0.001), and 20 (P = 0.04) minutes after the BPB. The overall motor score was significantly lower (P = 0.009) in Gp-CC than in Gp-LS at 10 minutes after the BPB. There were more (P = 0.04) patients with complete sensory-motor blockade at 20 minutes after the BPB in Gp-CC (25%) than in Gp-LS (0%). Time to readiness for surgery was also significantly faster (P = 0.002) in Gp-CC (10 [10–26.5] minutes) than in Gp-LS (20 [15–30] minutes). Conclusions The CC approach for infraclavicular BPB produces faster onset of sensory blockade and earlier readiness for surgery than the LS approach. Clinical Trial Registration This study was registered at the Centre for Clinical Trials of The Chinese University of Hong Kong, identifier CUHK_CCT00389.
Type Vector Representations from Text: An Empirical Analysis

Knowledge Graphs (KGs) are abstractions used to represent knowledge in which real-world entities are organized using a type system where types are organized using a sub-type relation: the ontology. A key factor in many applications is to evaluate the similarity between the types of the ontology. Classical measures to evaluate the semantic similarity between types are often based on the structured organization of the sub-type system. In this work, we show that it is possible to use methods coming from Natural Language Processing to embed types in a vector space starting from textual documents. We show that in this representation some of the properties of the hierarchy are still present and that the similarity in this space captures also characteristics that are close to human behavior.
The alteration of first trimester screening markers in fresh and frozen-thawed blastocyst transfers

Objective: The aim of this study was to investigate whether first trimester combined screening for major fetal trisomies is influenced by assisted reproduction techniques (ART) from blastocyst transfer, with or without cryopreservation. Methods: This study is a retrospective analysis involving 115 singleton pregnancies with euploid fetuses recruited between January 2017 and December 2017. Sixty-five women conceived with fresh blastocysts from in vitro fertilization (IVF) cycles (fresh-blasto), 50 with frozen-thawed blastocysts. All cases underwent ultrasound assessment at 11+0 - 13+6 weeks with measurements of crown rump length, nuchal translucency (NT) , free beta-human chorionic gonadotrophin (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) concentrations. Results: Baseline characteristics and pregnancy outcomes did not differ substantially among the study groups. The NT was not significantly different in the frozen-thawed -blasto compared to the fresh-blasto group ( p = 0.741). The free β-hCG levels was not significantly different in frozen-thawed-blasto group compared to fresh-blasto group ( p = 0.495). The two groups showed no significant difference in the PAPP-A levels ( p = 0.139). The median delta crown rump length was also not significantly different among the two groups ( p = 0.758). Conclusions: In ART pregnancies from blastocyst transfer, with or without cryopreservation, the NT measurement, free β-hCG concentration and PAPP-A levels did not show any significant difference. These features are apparently unrelated to the outcome of pregnancy and may be due to alterations or delays in embryogenesis or placentation with potential relevance for the screening test performance.
The impact of loading, unloading, ageing and injury on the human tendon

A tendon transfers force from the contracting muscle to the skeletal system to produce movement and is therefore a crucial component of the entire muscle‐tendon complex and its function. However, tendon research has for some time focused on mechanical properties without any major appreciation of potential cellular and molecular changes. At the same time, methodological developments have permitted determination of the mechanical properties of human tendons in vivo, which was previously not possible. Here we review the current understanding of how tendons respond to loading, unloading, ageing and injury from cellular, molecular and mechanical points of view. A mechanistic understanding of tendon tissue adaptation will be vital for development of adequate guidelines in physical training and rehabilitation, as well as for optimal injury treatment.
Discriminatory Power of Women’s Handball Game-Related Statistics at the Olympic Games (2004-2016)

Abstract Sports performance analysis has been a growing field of study in the last decade. However, the number of studies in handball is small. The aims of this present study were (i) to compare handball game-related statistics by the match outcome (winning and losing teams) and (ii) to identify characteristics that discriminated performance in elite women’s handball. The game-related statistics of the 236 matches played in the last four Olympic Games (Athens, Greece, 2004; Beijing, China, 2008; London, United Kingdom, 2012; and Rio de Janeiro, Brazil, 2016) were analysed. Differences between match outcomes (winning or losing teams) were determined using the chi-squared statistic, also calculating the effect sizes of the differences. A discriminant analysis was then performed applying the sample-splitting method according to match outcomes. The results showed the differences between winning and losing teams were red cards and assists. Also, the discriminant analysis selected five variables (shots, goalkeeper-blocked shots, technical fouls, steals, and goalkeeper-blocked fast-break shots) that classified correctly 83% of matches. The selected variables included offensive and defensive predictors. Coaches and players can use these results as a reference against which to assess their performance and plan training.
Environmental Determinants of Malaria Transmission Around the Koka Reservoir in Ethiopia

New dam construction is known to exacerbate malaria transmission in Africa as the vectors of malaria—Anopheles mosquitoes—use bodies of water as breeding sites. Precise environmental mechanisms of how reservoirs exacerbate malaria transmission are yet to be identified. Understanding of these mechanisms should lead to a better assessment of the impacts of dam construction and to new prevention strategies. Combining extensive multiyear field surveys around the Koka Reservoir in Ethiopia and rigorous model development and simulation studies, environmental mechanisms of malaria transmission around the reservoir were examined. Most comprehensive and detailed malaria transmission model, Hydrology, Entomology, and Malaria Transmission Simulator, was applied to a village adjacent to the reservoir. Significant contributions to the dynamics of malaria transmission are shaped by wind profile, marginal pools, temperature, and shoreline locations. Wind speed and wind direction influence Anopheles populations and malaria transmission during the major and secondary mosquito seasons. During the secondary mosquito season, a noticeable influence was also attributed to marginal pools. Temperature was found to play an important role, not so much in Anopheles population dynamics, but in malaria transmission dynamics. Change in shoreline locations drives malaria transmission dynamics, with closer shoreline locations to the village making malaria transmission more likely. Identified environmental mechanisms help in predicting malaria transmission seasons and in developing village relocation strategies upon dam construction to minimize the risk of malaria.