Miracle-dz/UniFAR-FTUs huggingface dataset:
Design and Function of a New Conical Positive Expiratory Pressure Device to Be Used During Exercise

BACKGROUND: A flow-dependent conical positive expiratory pressure (PEP) resistor incorporated into a oronasal mask was developed, which might reduce dyspnea and dynamic hyperinflation and increase exercise endurance for patients with COPD. We reported here the flow-pressure relationships and the safety and suitability of the device when used by healthy young and older subjects. METHODS: The flow-pressure relationships were determined for a range of resistors with different orifice diameters and cone lengths. A 1-cm conical-PEP device with a 6- or 7-mm orifice was used during a cycle exercise test (60% heart rate reserve) in 15 young (mean ± SD, 24.3 ± 3.9 y) and 12 older (mean ± SD, 64.4 ± 3.5 y) adults. Cardiopulmonary function and dyspnea were monitored for up to 10 min of exercise. RESULTS: For a given flow, pressure decreased as the cone length and orifice size increased. A 1-cm cone with a 6 mm orifice generated pressures of 5.24 ± 0.17 cm H2O and 18.29 ± 0.34 cm H2O at flows of 0.5 and 0.9 L/s, while for a 7 mm orifice, pressures were 4.88 ± 0.13 cm H2O and 19.14 ± 0.10 cm H2O at flows of 0.5 and 1.1 L/s, such as might occur during exercise. The choice of orifice size for a subject depended on his or her estimated expiratory flow; larger flows required the larger orifice to generate an expiratory pressure of between 5 and 20 cm H2O. Breathing with the conical-PEP device did not affect exercise time, dyspnea, minute ventilation, heart rate, or blood pressure. The SpO2 was slightly lower and PETCO2 was somewhat higher than during control exercise, but the differences were not significant. There were no adverse physiological consequences. CONCLUSIONS: A conical-PEP device of 1-cm length with an orifice of 6 or 7 mm generates effective expiratory pressure for most subjects during exercise. There were no adverse effects in healthy young and older subjects, and the device is suitable for trials with patients with COPD. (ClinicalTrials.gov registration NCT 02788370.)
Enhanced skeletal muscle formation on microfluidic spun gelatin methacryloyl (GelMA) fibres using surface patterning and agrin treatment

Bioengineered functional muscle tissues are beneficial for regenerative medicine due to their treatment potential for various debilitating disorders, including myopathy and traumatic injuries. However, the contractile properties of engineered muscle constructs are lacking compared with their native counterparts. Here, we used microfluidic spinning to fabricate photocrosslinkable gelatin methacryloyl (GelMA) hydrogel fibres with well‐defined surface morphologies for engineering muscle tissues. We examined whether the combination of topographical cues from surface micropatterning and biochemical stimulation with recombinant agrin can improve the generation of bioengineered muscle tissue. Topographical cues on micropatterned fibres promoted alignment of C2C12 myoblasts and augmented myotube formation during differentiation, as assessed by increased myotube length, aspect ratio, and the elevated mRNA expression of myogenic genes. Moreover, agrin treatment significantly increased acetylcholine receptor expression/clustering and myotube formation and upregulated dystrophin expression in differentiated C2C12 myotubes. Interestingly, the combination of topographical cues with agrin treatment further enhanced myotube maturation and functionality as shown by improved contractility under electrical stimulation. Thus, combining topographical cues and agrin treatment improved functions of engineered muscle tissue, which has potential in biorobotics, drug screening, tissue engineering, and regenerative medicine.
Knockout of tnni1b in zebrafish causes defects in atrioventricular valve development via the inhibition of the myocardial wnt signaling pathway

The proper development of atrioventricular (AV) valves is critical for heart morphogenesis and for the formation of the cardiac conduction system. Defects in AV valve development are the most common type of congenital heart defect. Cardiac troponin I (ctnni), a structural and regulatory protein involved in cardiac muscle contraction, is a subunit of the troponin complex, but the functions and molecular mechanisms of ctnni during early heart development remain unclear. We created a knockout zebrafish model in which troponin I type 1b (tnnilb) (Tnni‐HC, heart and craniofacial) was deleted using the clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat‐associated protein system. In the homozygous mutant, the embryos showed severe pericardial edema, malformation of the heart tube, reduction of heart rate without contraction and with almost no blood flow, heart cavity congestion, and lack of an endocardial ring or valve leaflet, resulting in 88.8 ± 6.0% lethality at 7 d postfertilization. Deletion of tnni1b caused the abnormal expression of several markers involved in AV valve development, including bmp4, cspg2, has2, notch1b, spp1, and Alcam. Myocardial re‐expression of tnni1b in mutants partially rescued the pericardial edema phenotype and AV canal (AVC) developmental defects. We further showed that tnni1b knockout in zebrafish and ctnni knockdown in rat h9c2 myocardial cells inhibited cardiac wnt signaling and that myocardial reactivation of wnt signaling partially rescued the abnormal expression of AVC markers caused by the tnnilb deletion. Taken together, our data suggest that tnni1b plays a vital role in zebrafish AV valve development by regulating the myocardial wnt signaling pathway. —Cai, C. , Sang, C. , Du, J., Jia, H. , Tu, J., Wan, Q. , Bao, B. , Xie, S. , Huang, Y. , Li, A. , Li, J., Yang, K. , Wang, S. , Lu, Q. Knockout of tnnilb in zebrafish causes defects in atrioventricular valve development via the inhibition of myocardial wnt signaling pathway. FASEB J. 33, 696–710 (2019). www.fasebj. org
Distinguishing reference intervals and clinical decision limits – A review by the IFCC Committee on Reference Intervals and Decision Limits

Abstract Reference Intervals (RIs) and clinical decision limits (CDLs) are a vital part of the information supplied by laboratories to support the interpretation of numerical clinical pathology results. RIs describe the typical distribution of results seen in a healthy reference population while CDLs are associated with a significantly higher risk of adverse clinical outcomes or are diagnostic for the presence of a specific disease. However, as the two concepts are sometimes confused, there is a need to clarify the differences between these terms and to ensure they are easily distinguished, especially because CDLs have a clinical association with specific diseases and risks, thereby implying that effective clinical interventions are available. It is important to note that, because population-based RIs are derived from the range of values expected in a typical community population, laboratory results that fall outside a RI do not necessarily indicate a disease but rather that additional medical follow-up and/or treatment may be warranted. In contrast, CDLs are associated with a risk of specific adverse outcomes, and are commonly used to interpret laboratory test results, including lipid parameters, glucose, hemoglobin A1c (HbA1c), and tumor markers, to determine risk of disease, to diagnose or to treat. In recent years, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) has focused primarily on RIs and has performed multicenter studies to obtain common RIs. However, the broader responsibility of the Committee, from its name, includes “decision limits”. C-RIDL now aims to emphasize the importance of the correct use of both RIs and CDLs and to encourage laboratories to specify the appropriate information to clinicians as needed. This review discusses RIs and CDLs in detail, describes the similarities and the differences between these two important tools in laboratory medicine, and clearly explains the processes used to define them. C-RIDL encourages the involvement of laboratory professionals in the establishment of both RIs and CDLs.
Exploring the transition into practice of general paediatricians from a Canadian residency program.

Background Paediatric training programs are committed to graduating paediatricians able to function independently in professional practice. The focus of this study was to gain understanding of a training program's strengths and deficiencies, while also exploring new methods to aid in transitioning trainees into practice. Method Using the CanMEDS framework, semi-structured focus groups were conducted with recently graduated paediatricians. Data were analyzed using qualitative content analysis. Results Three focus groups were completed, including a total of nine participants. Key themes were identified pertaining to CanMEDS roles. Particular strengths were found in medical expert for managing acute illnesses, communicator for engaging in difficult conversations, and health advocate in responding to diverse patient populations. Relative deficits were recognized in collaborator for connecting patients with community services, leader related to practice development and management, and scholar for cultivating critical appraisal. Opportunities for training program growth included ensuring community exposures were timely and varied, engaging additional community preceptors in training and giving appropriate expectations and mentoring to trainees to develop as scholars. Conclusions Educators need to be mindful of the exposures that trainees receive in residency. New graduates may also ultimately benefit from mentorship in the community or ongoing contact with their past training program.
Fortacin™ Spray for the Treatment of Premature Ejaculation

Premature ejaculation (PE) is a common complaint of male sexual dysfunction affecting men and their partners and consequently causing significant personal and interpersonal distress. Increased sensitivity of the glans penis and abnormalities of the afferent-efferent reflex pathway within the ejaculatory process are involved in the occurrence of PE. Drugs that either selectively reduce penile sensitization or modify the afferent-efferent reflex are well established therapeutic options for PE. Fortacin™ is the first topical treatment to be officially approved for the treatment of primary PE in adult men, and is mentioned as an experimental aerosol (as TEMPE) in the current European Association of Urology guidelines. It was approved for use in the European Union and launched in the United Kingdom in November 2016. Fortacin™ is a eutectic-like mixture of lidocaine 150 mg/mL and prilocaine 50 mg/mL that meets the requirements of an ideal treatment for PE because it is fast acting (within 5 minutes), has durable effects, can be easily used “on-demand”, and shows minimal side-effects. The metered-dose spray delivery system allows the desensitizing agents to be deposited in a dose-controlled, concentrated film onto the glans penis consequently reducing its sensitivity. This is translated into a delaying of the ejaculatory latency time without adversely affecting the sensation of ejaculation and orgasmic pleasure. The efficacy and safety of Fortacin™ have been proven by means of increased ejaculatory latency, control, and sexual satisfaction in large scale studies demonstrating the significant benefits for both patients and their partners.
Deciphering the binding of carbendazim (fungicide) with human serum albumin: A multi-spectroscopic and molecular modelling studies

Abstract Carbendazim is a benzimidazole fungicide used to control the fungal invasion. However, its exposure might lead to potential health problems. The present study evaluates the interaction of carbendazim (CAR) with human serum albumin (HSA) which is an important drug carrier protein and plays a very crucial role in the transportation of small molecules. A number of biophysical techniques were employed to investigate the binding of CAR with HSA. The increased UV-absorption of HSA on titrating with CAR suggests the formation of HSA–CAR complex and it could be due to the exposure of aromatic residues. The fluorescence study confirmed that CAR quenches the fluorescence of HSA and showed the static mode of quenching. CAR (50 µM) quenches around 56.14% of the HSA fluorescence. The quenching constant, binding constant, number of binding site and free energy change was calculated by fluorescence quenching experiment. Competitive displacement assay showed Sudlow’s site I as the primary binding site of CAR on HSA. The synchronous fluorescence study revealed the perturbation in the microenvironment around tyrosine and tryptophan residues upon binding of CAR to HSA. The circular dichroism results suggested that the binding of CAR to HSA altered its secondary structure. Molecular docking experiment demonstrated the binding of CAR to Sudlow’s site I of HSA. Docking studies suggested that the hydrogen bonding, van der Waals and pi-alkyl are playing role in the interaction of CAR with HSA. The study confirmed the conformational changes within HSA upon binding of CAR.
Turbulucid: A Python Package for Post-Processing of Fluid Flow Simulations

A Python package for post-processing of plane two-dimensional data from computational fluid dynamics simulations is presented. The package, called turbulucid, provides means for scripted, reproducible analysis of large simulation campaigns and includes routines for both data extraction and visualization. For the former, the Visualization Toolkit (VTK) is used, allowing for post-processing of simulations performed on unstructured meshes. For visualization, several matplotlib-based functions for creating highly customizable, publication-quality plots are provided. To demonstrate turbulucid's functionality it is here applied to post-processing a simulation of a flow over a backward-facing step. The implementation and architecture of the package are also discussed, as well as its reuse potential.
Solidarity or dissonance? A systematic review of pharmacist and GP views on community pharmacy services in the UK

There has been a strong policy emphasis over the past decade on optimising patient-centred care and reducing general practitioners' (GPs') workload by extending community pharmacy services and collaboration between pharmacists and GPs. Our aim was to review current evidence of pharmacists' and GPs' views of extended community pharmacy services and pharmacists' roles in the United Kingdom (UK). A systematic review was undertaken looking at UK studies investigating pharmacists' and/or GPs' views of community pharmacy services or roles from 2005 to 2017. A range of databases were searched including EMBASE, PubMed, Scopus, Web of Science, International Pharmaceutical Abstracts (IPA), PsycINFO, Science Direct and The Cumulative Index to Nursing and Allied Health Literature (CINAHL). In addition, reference lists of included studies were screened and grey literature was searched. Following the application of inclusion/exclusion criteria, the quality of papers was critically analysed, findings were extracted into a grid and subjected to narrative synthesis following thematic analysis. The search strategy yielded a total of 4,066 unique papers from which 60 were included. Forty-seven papers covered pharmacists' views, nine combined both pharmacists' and GPs' views and four covered GPs' views. Study designs included interviews (n = 31, 52%), questionnaire surveys (n = 17, 28%) and focus groups (n = 7, 12%). Three main themes emerged from the data: "attitudes towards services/roles", "community pharmacy organisations" and "external influences". Pharmacists and GPs perceived a number of barriers to successful implementation and integration of pharmacy services. Moreover, collaboration between pharmacists and GPs remains poor despite the introduction of extended services. Overall, extending community pharmacy services require quality-driven incentives and joint working between community pharmacists and GPs to achieve better integration within the patient's primary care pathway.
Alcohol and pharmacologically similar sedatives impair encoding and facilitate consolidation of both recollection and familiarity in episodic memory

ABSTRACT Alcohol and other pharmacologically similar sedatives (i.e., GABAA positive allosteric modulators or PAMs) impair the encoding of new episodic memories but retroactively facilitate the consolidation of recently encoded memories. These effects are consistent for recollection (i.e., the retrieval of details) but some mixed results have been reported for familiarity (i.e., a feeling of knowing a stimulus was presented). Here, with dual-process models, we reanalyzed prior work testing the effects of GABAA PAMs at encoding or consolidation. Contrary to previous conclusions, we show that GABAA PAMs at encoding consistently impair both recollection and familiarity when an independence correction is applied to familiarity-based responses. These findings were further confirmed and extended in a dual-process signal detection analysis of a recent study on the effects of alcohol during encoding or consolidation: Alcohol at encoding impaired both recollection and familiarity, whereas alcohol at consolidation enhanced both recollection and familiarity. These findings speak to the ability of alcohol and other GABAA PAMs to induce ‘blackouts,’ highlighting the importance of dual-process approaches when analyzing drug manipulations at different phases of episodic memory.
Osteogenic impact of football training in 55‐ to 70‐year‐old women and men with prediabetes

The effects of football training on bone health were examined in 55‐ to 70‐year‐old sedentary women and men with prediabetes. Patients (n = 50) with prediabetes (age; 61 ± 9 years, BMI 29.7 ± 0.6 kg/m2, body fat content; 37 ± 1%, VO2max; 22.7 ± 0.8 mL/min/kg and mean arterial pressure; 104 ± 3 mm Hg) were randomized into a football training group (FTG; n = 27, 14 women) and a control group (CON; n = 23, 11 women). At baseline, 73% and 24% were diagnosed with femur osteopenia and osteoporosis, respectively. FTG performed football training twice weekly 30‐60‐minute sessions in 16 weeks, and both FTG and CON received professional dietary advice. Pre‐ and post‐intervention whole‐body and regional bone mineral content (BMC) and density (BMD) were determined with DXA‐scans, and venous blood samples were drawn and analyzed for plasma bone turnover markers. Change scores were greater (P < 0.05) in FTG compared to CON in leg BMD (0.023 ± 0.005 vs −0.004 ± 0.001 g/cm2) and in leg BMC (32 ± 8 vs −4 ± 6 g). Between‐group changes in favor of FTG (P < 0.05) also occurred in the femur neck BMD (3.2%) and femur shaft BMD (2.5%). Whole‐body BMC and BMD were unchanged in both groups during the intervention. In FTG, resting plasma osteocalcin, P1NP, and CTX‐1 rose (P < 0.05) by 23 ± 8, 52 ± 9 and 38 ± 7%, with greater change scores (P < 0.05) than in CON. Finally, P1NP (formation)/CTX‐1 (resorption) ratio increased (P < 0.05) in FTG (127 ± 15 vs 150 ± 11) from pre‐ to post‐intervention, with no change in CON (124 ± 12 and 123 ± 12). In conclusion, football training provides a powerful osteogenic stimulus and improves bone health in 55‐ to 70‐year‐old women and men diagnosed with prediabetes.
Obstetric anesthesia/analgesia does not affect disease course in multiple sclerosis: 10‐year retrospective cohort study

Multiple sclerosis (MS) often occurs in young women and the effect of obstetric anesthesia/analgesia on the disease is poorly understood. No previous study has investigated the course of the disease in women in labor in the Czech Republic. The aim of this study was to evaluate the occurrence or absence of relapses in the 6‐month postpartum period in MS parturients with and without obstetric anesthesia/analgesia.
The HIV Integrase Inhibitor Raltegravir Inhibits Felid Alphaherpesvirus 1 Replication by Targeting both DNA Replication and Late Gene Expression

The rise of drug-resistant herpesviruses is a longstanding concern, particularly among immunocompromised patients. Therefore, therapies targeting viral proteins other than the DNA polymerase that may be less likely to lead to drug-resistant viruses are urgently needed. Using FeHV-1, an alphaherpesvirus closely related to HHV-1 that similarly causes ocular herpes in its natural host, we found that the HIV integrase inhibitor raltegravir targets different stages of the virus life cycle beyond DNA replication and that it does so without developing drug resistance under the conditions tested. This shows that the drug could provide a viable strategy for the treatment of herpesvirus infections. ABSTRACT Alphaherpesvirus-associated ocular infections in humans caused by human alphaherpesvirus 1 (HHV-1) remain challenging to treat due to the frequency of drug application required and the potential for the selection of drug-resistant viruses. Repurposing on-the-market drugs is a viable strategy to accelerate the pace of drug development. It has been reported that the human immunodeficiency virus (HIV) integrase inhibitor raltegravir inhibits HHV-1 replication by targeting the DNA polymerase accessory factor and limits terminase-mediated genome cleavage of human betaherpesvirus 5 (HHV-5). We have previously shown, both in vitro and in vivo, that raltegravir can also inhibit the replication of felid alphaherpesvirus 1 (FeHV-1), a common ocular pathogen of cats with a pathogenesis similar to that of HHV-1 ocular disease. In contrast to what was reported for HHV-1, we were unable to select for a raltegravir-resistant FeHV-1 strain in order to define any basis for drug action. A candidate-based approach to explore the mode of action of raltegravir against FeHV-1 showed that raltegravir did not impact FeHV-1 terminase function, as described for HHV-5. Instead, raltegravir inhibited DNA replication, similarly to HHV-1, but by targeting the initiation of viral DNA replication rather than elongation. In addition, we found that raltegravir specifically repressed late gene expression independently of DNA replication, and both activities are consistent with inhibition of ICP8. Taken together, these results suggest that raltegravir could be a valuable therapeutic agent against herpesviruses. IMPORTANCE The rise of drug-resistant herpesviruses is a longstanding concern, particularly among immunocompromised patients. Therefore, therapies targeting viral proteins other than the DNA polymerase that may be less likely to lead to drug-resistant viruses are urgently needed. Using FeHV-1, an alphaherpesvirus closely related to HHV-1 that similarly causes ocular herpes in its natural host, we found that the HIV integrase inhibitor raltegravir targets different stages of the virus life cycle beyond DNA replication and that it does so without developing drug resistance under the conditions tested. This shows that the drug could provide a viable strategy for the treatment of herpesvirus infections.
Conceptual design of planar endfire circularly polarized antenna with enhanced directivity

Conceptual design of a novel non-turnstile, planar endfire circularly polarized (CP) antenna with enhanced directivity is presented. The V-shape, one and one-half wavelength dipole is employed to enhance the directivity of planar endfire CP antennas, while a simple configuration is maintained. Design considerations and preliminary simulated results on key design parameters of the proposed antenna are presented and discussed.