Miracle-dz/UniFAR-FTUs huggingface dataset:
Tolerability, pharmacokinetics, and pharmacodynamics of mirogabalin in healthy subjects: Results from phase 1 studies

Three phase 1 pharmacokinetic (PK)/pharmacodynamics (PD) studies were conducted in healthy men and women to further characterize the safety, tolerability, and PK/PD of mirogabalin administration with or without food and to guide the dose selection and regimen for phase 2 and 3 clinical development. The 3 studies included 2 randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending‐dose studies, and 1 open‐label, crossover study to evaluate the PK of mirogabalin administered under fasting and fed (high‐fat meal) conditions. Forty‐eight and 47 healthy volunteers completed the single‐ and multiple‐dose studies, respectively. Thirty subjects were enrolled and completed the food effect study. Mirogabalin was well tolerated in the fed and fasted states. The most frequent treatment‐emergent adverse events (TEAEs)—dizziness and somnolence—were expected based on mirogabalin's mechanism of action. Subjects receiving the highest mirogabalin doses (50 and 75 mg single dose) showed greater dizziness and sedation and higher rates of TEAEs than subjects receiving 3‐30 mg. After oral administration, mirogabalin was rapidly absorbed (time to maximum concentration, ∼1 hour) and eliminated through urine unchanged (61%‐72% urinary excretion). Exposure increased in a dose‐proportional manner after single or multiple mirogabalin doses. No significant accumulation occurred with multiple doses over 14 days. After single doses of mirogabalin (15 mg), the bioavailability was considered equivalent in the fed and fasted states, indicating that mirogabalin can be taken without food restrictions. Based on these data, mirogabalin 15 mg twice daily was selected as the highest target dose for further clinical development.
Universal or selective ultrasound screening for developmental dysplasia of the hip? A discussion of the key issues

Purpose To summarize recent developments and provide recommendations as to whether universal or selective programmes are advisable. Methods A literature review was performed and preference given to studies with higher levels of evidence. All programmes reviewed included clinical screening. Results Recent studies underline the need for high quality screening programmes to promote the early detection of developmental dysplasia of the hip (DDH). A small number of cases may be missed clinically but with universal ultrasound screening programmes the late presentation rates appear to be virtually zero. Contemporary studies show treatment rates with universal screening programmes which are now lower than those with selective ultrasound. There is little agreement over the criteria used for selective programmes. Alternative outcome measures, such as the first operation rate or the percentage undergoing major (open) surgery are both lowest with universal ultrasound screening programmes. Furthermore, a significant reduction in the rate of surgery for DDH later in life was seen after the introduction of universal ultrasound screening, whereas the defined criteria for selective screening may not detect the majority of patients who require late surgery. Abduction bracing with modern orthoses is associated with a zero rate of avascular necrosis (AVN), whereas closed reduction techniques have an overall risk of 10%. Conclusion On clinical grounds, if future studies confirm that hip abduction in flexible orthoses is not associated with AVN, it may be time for a paradigm shift of screening for DDH towards a universal ultrasound protocol. The costs associated both with each type of screening programme and with the management of late presenting cases are also important but may be secondary to clinical benefit.
CausalTriad: Toward Pseudo Causal Relation Discovery and Hypotheses Generation from Medical Text Data

Deriving pseudo causal relations from medical text data lies at the heart of medical literature mining. Existing studies have utilized extraction models to find pseudo causal relation from single sentences, while the knowledge created by causation transitivity - often spanning multiple sentences - has not been considered. Furthermore, we observe that many pseudo causal relations follow the rule of causation transitivity, which makes it possible to discover unseen casual relations and generate new causal relation hypotheses. In this paper, we address these two issues by proposing a factor graph model to incorporate three clues to discover causation expressions in the text data. We propose four types of triad structures to represent the rules of causation transitivity among causal relations. Our proposed model, called CausalTriad, uses textual and structural knowledge to infer pseudo causal relations from the triad structures. Experimental results on two datasets demonstrate that (a) CausalTriad is effective for pseudo causal relation discovery within and across sentences; (b) CausalTriad is highly capable at recognizing implicit pseudo causal relations; (c) CausalTriad can infer missing/new pseudo causal relations from text data.
Incidence of Coexisting Talar and Tibial Osteochondral Lesions Correlates With Patient Age and Lesion Location

Background: The incidence of coexisting osteochondral lesions (OCLs) of the tibia and talus has been negatively correlated with successful clinical outcomes, yet these lesions have not been extensively characterized. Purpose: To determine the incidence of coexisting tibial and talar OCLs, assess the morphologic characteristics of these lesions, and evaluate whether these characteristics are predictive of outcome. Study Design: Case series; Level of evidence, 4. Methods: A total of 83 patients who underwent surgery for a talar OCL were evaluated for coexisting OCLs of the distal tibia with preoperative magnetic resonance images. Size, location, containment, International Cartilage Repair Society (ICRS) grade, patient age, and patient sex were analyzed for predictors of coexisting lesions or patient outcome. The talar and tibial surfaces were each divided into 9 zones, with 1 corresponding to the most anteromedial region and proceeding laterally and then posteriorly. The Foot and Ankle Outcome Score (FAOS) was evaluated pre- and postoperatively. Results: Twenty-six patients (31%) had coexisting tibial and talar OCLs, with 9 (35%) identified as kissing lesions. Age correlated with coexisting lesion incidence, as older patients were more likely to have a coexisting tibial OCL (P = .038). More than half of talar OCLs were found in zone 4 (61%), whereas the majority of tibial OCLs were located in zones 2, 4, and 5 (19% each). Patients with coexisting lesions were more likely to have a lateral talar OCL (P = .028), while those without a coexisting tibial lesion were more likely to have a talar OCL in zone 4 (P = .016). There was no difference in FAOS result or lesion size between patients with and without coexisting OCLs, but patients with coexisting lesions were more likely to have an ICRS grade 4 talar OCL (P = .034). For patients with coexisting lesions, kissing lesions were more likely to be located in zone 6 (P = .043). There was no difference in OCL size or containment between kissing and nonkissing coexisting OCLs. Conclusion: The incidence of coexisting talar and tibial OCLs may be more prevalent than what previous reports have suggested, with older patients being more likely to present with this pathology. The location of a talar OCL correlates with the incidence of a coexisting tibial OCL.
Hidden diversity in forest soils: Characterization and comparison of terrestrial flatworm’s communities in two national parks in Spain

Abstract Terrestrial flatworms (Platyhelminthes, Tricladida, and Geoplanidae) belong to what is known as cryptic soil fauna of humid forests and are animals not easily found or captured in traps. Nonetheless, they have been demonstrated to be good indicators of the conservation status of their habitat as well as a good model to reconstruct the recent and old events affecting biodiversity. This is mainly due to their delicate constitution, their dependence on the integrity of their habitat, and their very low dispersal capacity. At present, little is known about their communities, except for some studies performed in Brazil. In this work, we analyze for the first time in Europe terrestrial flatworm communities. We have selected two protected areas belonging to the Red Española de Parques Nacionales. Our aims include performing a first study of the species richness and community structure for European terrestrial planarian species at regional and local scale. We evaluate the effect of type of forests in the community composition and flatworms’ abundance, but also have into account the phylogenetic framework (never considered in previous studies) analyzed based on molecular data. We find differences in the species composition among parks, with an astonishingly high diversity of endemic species in the Parque Nacional de Picos de Europa and an extremely low diversity of species in the Parque Nacional de Ordesa y Monte Perdido. These divergent patterns cannot be attributed to differences in physical variables, and in addition, the analyses of their phylogenetic relationships and, for a few species, their genetic structure, point to a more probable historical explanation.
Barriers and enablers of COPD telerehabilitation – a frontline staff perspective

Background Telerehabilitation (TR) aimed at patients with COPD has shown promising effects on symptoms, physical function, and quality of life, but little research has been conducted to understand the impact of implementation on frontline health professionals. Therefore, the aim of this study was to examine the barriers and enablers of health professionals to online exercise-based TR in patients with COPD, to support a successful implementation process. Methods Semistructured individual and focus group interviews were conducted with 25 health professionals working with conventional COPD rehabilitation or TR. Interviews were audio-taped and transcribed verbatim. Investigator triangulation was applied during data generation. The Theoretical Domains Framework directed the interview guide and was used as a coding framework in the analysis. Results We identified six predominant domains essential in understanding the enablers and barriers of TR from a staff perspective: 1) skills, 2) professional role and identity, 3) beliefs about capabilities, 4) beliefs about consequences, 5) environmental context and resources, and 6) social influences. We found that health professionals held both enablers and barriers important for the implementation process of TR. TR introduces new work tasks and new ways for the health professionals to communicate and exercise with the patients, which influence their professional role and self-perceived capability. Conclusion Specific attention toward involvement of the health professionals in the decision process combined with sufficient education and skill training is highly essential to support a successful implementation of TR in clinical practice.
Specialty Board Certification Rate as an Outcome Metric for GME Training Institutions: A Relationship With Quality of Care

Educational outcome measures, known to be associated with the quality of care, are needed to support improvements in graduate medical education (GME). This retrospective observational study sought to determine whether there was a relationship between the specialty board certification rates of GME training institutions and the quality of care delivered by their graduates. It is based on 7 years of hospitalizations in Pennsylvania (N = 354,767) with diagnoses of acute myocardial infarction, congestive heart failure, gastrointestinal hemorrhage, or pneumonia. The 2,265 attending physicians were self-identified internists, and they completed their training in 59 institutions. The percentage of board-certified physicians from each training institution, excluding the physician herself or himself, was calculated and an indicator of whether it exceeded 80% was created. This was analyzed against inhospital mortality and length of stay, adjusted for patient/physician/hospital characteristics. There were significantly lower odds of mortality (adjusted Odd’s ratio [OR] = .92, 95% CI [0.86, 0.98]) and log length of stay (adjusted OR = .98, 95% CI [.94, .99]) when the attending physician trained in a residency program with an 80% or greater certification rate. The results suggest that specialty certification rates may be a useful educational outcome for residency training programs.
New concepts in opioid analgesia

ABSTRACT Introduction: Opioids are the oldest and most potent drugs for the treatment of severe pain, but they are burdened by detrimental side effects such as respiratory depression, addiction, sedation, nausea, and constipation. Their clinical application is undisputed in acute (e.g. perioperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny and has contributed to the current ‘opioid crisis. ’ Areas covered: This article reviews pharmacological principles and research strategies aiming at novel opioids with reduced side effects. Basic mechanisms underlying pain, opioid analgesia, and other opioid actions are outlined. To illustrate the clinical situation and medical needs, plasticity of opioid receptors, intracellular signaling pathways, endogenous and exogenous opioid receptor ligands, central and peripheral sites of analgesic, and side effects are discussed. Expert opinion: The epidemic of opioid misuse has taught us that there is a lack of fundamental knowledge about the characteristics and management of chronic pain, that conflicts of interest and validity of models must be considered in the context of drug development, and that novel analgesics with less abuse liability are badly needed. Currently, the most promising perspectives appear to be augmenting endogenous opioid actions and selectively targeting pathological conformations of peripheral opioid receptors.
Chinese foreign direct investment and economic growth in West Africa: evidence from pooled mean group model

Over the last decade, diverse efforts have been deploy in place by various governments of the developing economies to attract more inward China FDI and accelerate its economic growth remains one of the most important issues in the economic debates. Many empirical works support the impact of Chinese FDI flows on economic growth, but some do not. West Africa, high poverty, non-existing markets, low savings and terrorism-torn economy and political crisis, countries may find in FDI an important and potential source of finances. Therefore, this paper is attempts to evaluate the long-run and short-run relationships between China FDI and economic growth of West Africa by using Pooled Mean Group (PMG) models over the period of 2003--2015. The Pooled Mean Group results provide strong evidence on the significantly positive effects of China FDI on West Africa's economic growth (real GDP per capita). However; the causality results suggest that China FDI hasn't causal effects on West Africa 'economic growth. This can be concluded that an additional investment for Chinese investor and technology transfer is sufficiently supported in West Africa.
Therapeutic Immunization against Glioblastoma

Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient’s immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.
Deep Convolutional Neural Networks for Chest Diseases Detection

Chest diseases are very serious health problems in the life of people. These diseases include chronic obstructive pulmonary disease, pneumonia, asthma, tuberculosis, and lung diseases. The timely diagnosis of chest diseases is very important. Many methods have been developed for this purpose. In this paper, we demonstrate the feasibility of classifying the chest pathologies in chest X-rays using conventional and deep learning approaches. In the paper, convolutional neural networks (CNNs) are presented for the diagnosis of chest diseases. The architecture of CNN and its design principle are presented. For comparative purpose, backpropagation neural networks (BPNNs) with supervised learning, competitive neural networks (CpNNs) with unsupervised learning are also constructed for diagnosis chest diseases. All the considered networks CNN, BPNN, and CpNN are trained and tested on the same chest X-ray database, and the performance of each network is discussed. Comparative results in terms of accuracy, error rate, and training time between the networks are presented.
Obstructive Sleep Apnea in Children with Down Syndrome: Demographic, Clinical, and Polysomnographic Features

Objectives To evaluate demographic, clinical, and polysomnographic features of children with Down syndrome suspected of having obstructive sleep apnea. To identify factors that predict severe obstructive sleep apnea among children with Down syndrome. Study Design Case series with chart review. Setting Children’s Medical Center Dallas / University of Texas Southwestern Medical Center. Subject and Methods Demographic, clinical, and polysomnographic data were collected for children with Down syndrome aged 2 to 18 years. Simple and multivariable regression models were used to study predictors of severe obstructive sleep apnea (apnea-hypopnea index ≥10). P≤ . 05 was considered significant. Results A total of 106 children with Down syndrome were included, with 89 (84%) <12 years old, 56 (53%) male, 72 (68%) Hispanic, 15 (14%) African American, and 14 (13%) Caucasian. Ninety percent of children had ≥1 medical comorbidities; 95 (90%) patients had obstructive sleep apnea; and 46 (44%) had severe obstructive sleep apnea. The mean SaO2 nadir was lower among obese than nonobese children (80% vs 85%, P = .02). Obese versus nonobese patients had a higher prevalence of severe obstructive sleep apnea (56% vs 35%, P = .03). Severe OSA was associated with heavier weight (odds ratio = 1.0, 95% CI: 1.0-1.1, P = .002) and age ≥12 years (odds ratio = 1.2, 95% CI: 0.2-2.5, P = .02). The multivariable model showed that severe obstructive sleep apnea was associated only with weight (odds ratio = 1.1, 95% CI: 1.0-1.1, P = .02). Conclusion Obese children with DS are at a high risk for severe OSA, with weight as the sole risk factor. The results of this study show the importance of monitoring the weight of children with DS and counseling parents of children with DS about weight loss.
Deep Emotion: A Computational Model of Emotion Using Deep Neural Networks

Emotions are very important for human intelligence. For example, emotions are closely related to the appraisal of the internal bodily state and external stimuli. This helps us to respond quickly to the environment. Another important perspective in human intelligence is the role of emotions in decision-making. Moreover, the social aspect of emotions is also very important. Therefore, if the mechanism of emotions were elucidated, we could advance toward the essential understanding of our natural intelligence. In this study, a model of emotions is proposed to elucidate the mechanism of emotions through the computational model. Furthermore, from the viewpoint of partner robots, the model of emotions may help us to build robots that can have empathy for humans. To understand and sympathize with people's feelings, the robots need to have their own emotions. This may allow robots to be accepted in human society. The proposed model is implemented using deep neural networks consisting of three modules, which interact with each other. Simulation results reveal that the proposed model exhibits reasonable behavior as the basic mechanism of emotion.
So you're planning a baby?: a review of preconception care apps

Previous research shows couples favour online information sources when seeking support for preconception health and pregnancy planning, with mobile applications (apps) becoming increasingly popular. This study aimed to establish what smartphone apps currently exist to support couples when preparing for pregnancy. A functionality review was conducted to explore app content and an analysis of user reviews was undertaken to investigate user views towards existing apps. 25 apps were analysed, which provided information on diet, weight, alcohol, smoking and caffeine amongst others. Positive reviews mainly referred to the helpfulness of the app. Negative comments focused on the over simplification of information. Overall, user comments showed a positive response towards existing preconception care apps, but users reported concerns towards information accuracy and reliability. Further work will be undertaken to evaluate whether existing apps engage users to improve their preconception health care and whether these apps fulfils user requirements.