Miracle-dz/UniFAR-FTUs huggingface dataset:
Running economy and effort after cycling: Effect of methodological choices

ABSTRACT Prior exercise can negatively affect movement economy of a subsequent task. However, the impact of cycling exercise on the energy cost of subsequent running is difficult to ascertain, possibly because of the use of different methods of calculating economy. We examined the influence of a simulated cycling bout on running physiological cost (running economy, heart rate and ventilation rates) and perceptual responses (ratings of perceived exertion and effort) by comparing two running bouts, performed before and after cycling using different running economy calculation methods. Seventeen competitive male triathletes ran at race pace before and after a simulated Olympic-distance cycling bout. Running economy was calculated as V̇O2 (mL∙kg−1∙min−1), oxygen cost (EO2, mL∙kg−1∙m−1) and aerobic energy cost (Eaer, J∙kg−1∙m−1). All measures of running economy and perceptual responses indicated significant alterations imposed by prior cycling. Despite a good level of agreement with minimal bias between calculation methods, differences (p < 0.05) were observed between Eaer and both V̇O2 and EO2. The results confirmed that prior cycling increased physiological cost and perceptual responses in a subsequent running bout. It is recommended that Eaer be calculated as a more valid measure of running economy alongside perceptual responses to assist in the identification of individual responses in running economy following cycling.
A model for focal seizure onset, propagation, evolution, and progression

We developed a neural network model that can account for major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus, and postulates a role for synaptic plasticity in the emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this model can provide a roadmap and potentially an in silico testbed for future explorations of seizure mechanisms and clinical therapies.
A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs

In vitro reconstitutions reveal the essential components of a mammalian, cytoplasmic mRNA transport system and their functions. Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3′UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.
Truncating mutations in SHANK3 associated with global developmental delay interfere with nuclear β‐catenin signaling

Mutations in SHANK3, coding for a large scaffold protein of excitatory synapses in the CNS, are associated with neurodevelopmental disorders including autism spectrum disorders and intellectual disability (ID). Several cases have been identified in which the mutation leads to truncation of the protein, eliminating C‐terminal sequences required for post‐synaptic targeting of the protein. We identify here a patient with a truncating mutation in SHANK3, affected by severe global developmental delay and intellectual disability. By analyzing the subcellular distribution of this truncated form of Shank3, we identified a nuclear localization signal (NLS) in the N‐terminal part of the protein which is responsible for targeting Shank3 fragments to the nucleus. To determine the relevance of Shank3 for nuclear signaling, we analyze how it affects signaling by β‐catenin, a component of the Wnt pathway. We show that full length as well as truncated variants of Shank3 interact with β‐catenin via the PDZ domain of Shank3, and the armadillo repeats of β‐catenin. As a result of this interaction, truncated forms of Shank3 and β‐catenin strictly co‐localize in small intra‐nuclear bodies both in 293T cells and in rat hippocampal neurons. On a functional level, the sequestration of both proteins in these nuclear bodies is associated with a strongly repressed transcriptional activation by β‐catenin owing to interaction with the truncated Shank3 fragment found in patients. Our data suggest that truncating mutations in SHANK3 may not only lead to a reduction in Shank3 protein available at postsynaptic sites but also negatively affect the Wnt signaling pathway.
The application of ‘omics’ to pulmonary arterial hypertension

Recent genome‐wide analyses of rare and common sequence variations have brought greater clarity to the genetic architecture of pulmonary arterial hypertension and implicated novel genes in disease development. Transcriptional signatures have been reported in whole lung tissue, pulmonary vascular cells and peripheral circulating cells. High‐throughput platforms for plasma proteomics and metabolomics have identified novel biomarkers associated with clinical outcomes and provided molecular instruments for risk assessment. There are methodological challenges to integrating these datasets, coupled to statistical power limitations inherent to the study of a rare disease, but the expectation is that this approach will reveal novel druggable targets and biomarkers that will open the way to personalized medicine. Here, we review the current state‐of‐the‐art and future promise of ‘omics’ in the field of translational medicine in pulmonary arterial hypertension.
Ethical problems experienced by nurses who work in psychiatry clinics in Turkey

Conclusion: Based on study results, serious ethical problems were observed in psychiatric treatment and care, but these problems were not identified as being ethical problems or even taken into consideration sufficiently by nurses. Therefore, beginning ethical discussion with nurses who work in psychiatry clinics about ethical problems in psychiatry, establishing ethical codes and guidelines for practice, and sharing these codes and guidelines with psychiatric team members will help to prevent ethical dilemmas.
Distinct functions of megalin and cubilin receptors in recovery of normal and nephrotic levels of filtered albumin.

Proximal tubule (PT) cells express a single saturable albumin binding site whose affinity matches the estimated tubular concentration of albumin, however albumin uptake capacity is greatly increased under nephrotic conditions. Deciphering the individual contributions of megalin and cubilin to the uptake of normal and nephrotic levels of albumin is impossible in vivo, as knockout of megalin in mice globally disrupts PT endocytic uptake. We quantified concentration-dependent albumin uptake in an optimized opossum kidney (OK) cell culture model and fit the kinetic profiles to identify albumin binding affinities and uptake capacities. Mathematical deconvolution fit best to a three component model that included saturable high- and low-affinity uptake sites for albumin and underlying non-saturable uptake consistent with passive uptake of albumin in the fluid-phase. Knockdown of cubilin or its chaperone amnionless selectively reduced the binding capacity of the high-affinity site, whereas knockdown of megalin impacted the low-affinity site. Knockdown of disabled-2 (Dab2) decreased the capacities of both binding sites. Additionally, knockdown of megalin or Dab2 profoundly inhibited the uptake of a fluid phase marker, with cubilin knockdown having a more modest effect. We propose a novel model for albumin retrieval along the PT in which cubilin and megalin receptors have different functions in recovering filtered albumin in proximal tubule cells. Cubilin binding to albumin is tuned to capture normally-filtered levels of the protein. By contrast, megalin binding to albumin is of lower affinity, and its expression is also essential for enabling the recovery of high concentrations of albumin in the fluid phase.
Influence of Purposeful Activities on Upper Extremity Motor Performance: A Systematic Review

Following upper extremity injury, exercise-approaches are commonly used to address motor impairments. Occupation-based approaches are also used but less widely promoted and their mechanisms of action not well-understood. Movement performed during purposeful activities and occupations may yield better motor performance than during nonpurposeful tasks. This review investigated the influence of engagement in purposeful activities and occupations on upper extremity motor performance in healthy and musculoskeletal populations. Databases were searched for studies in healthy or upper extremity musculoskeletal–injured adults that compared motor performance during purposeful activities against nonpurposeful movements. Twenty-one studies of moderate quality, conducted predominantly in healthy populations, were included. Upper extremity movement quantity and quality were enhanced when performed during purposeful conditions. Purposeful activities have potential to be used following injury to enhance movement and address motor impairments to a greater extent than is currently promoted. Research in musculoskeletal populations is required.
Neuropsychological performance across symptom dimensions of obsessive-compulsive disorder: a comment on the state and critical review of the literature

ABSTRACT Introduction: Obsessive-compulsive disorder (OCD) is a heterogeneous disorder, with multiple symptom presentations. Delineating the neuropsychological characteristics associated with previously identified symptom clusters may therefore be useful in assisting to better define symptom subtypes of OCD. Areas covered: This review summarizes the existing literature on the assessment of neuropsychological performance in symptom-based dimensions of OCD. Results of 23 studies are described and the methodological issues and challenges present in this body of literature are discussed. Expert opinion: The current state of the literature precludes a meaningful meta-analysis of cognitive dysfunction across the breadth of symptom dimensions of OCD. This is due primarily to significant methodological differences observed between studies, both in terms of neuropsychological measures and symptom subtyping methods employed, and any resulting meta-analytic results would be biased by varying quality of evidence. Future studies addressing these limitations should include more consistent neuropsychology measures and methods of classifying OCD symptoms with the aim of reproducing the results of previous research to identify more concrete patterns of neuropsychological performance across dimensions; best practices and alternative approaches are discussed.
Intervention targets for people living with HIV and depressive symptoms in Botswana

Background: The prevalence of HIV in Botswana is high. Many people living with HIV (PLWH) suffer from depressive symptoms and have inadequate coping skills. Most PLWH do not receive adequate psychological treatment. Empirically based interventions for PLWH with depressive symptoms in Botswana should be developed, with a focus on improving coping skills. The present study was a first step towards this goal, by trying to identify targets for intervention. The study aimed to provide prevalence rates of depression among PLWH in Botswana, to assess their mental health treatment needs and wishes as expressed by themselves, and to study the relationships between cognitive and behavioural coping strategies and depressive symptoms. Method: A cross-sectional study was conducted. The sample consisted of 291 participants (73% female) from 8 HIV treatment centres from Botswana. Participants completed standardized questionnaires on depressive symptoms (CES-D) and coping skills (CERQ, BERQ). They also answered questions regarding their mental health care needs and wishes. Results: In total 43.4% of participants reported clinically significant depressive symptoms. The majority of participants indicated that they needed help with the following topics: feelings of depression, physical tension, finding new goals and coping with HIV. In addition, they indicated preferring a self-help programme in booklet format. Multiple regression analyses showed that the following coping strategies had significant relationships with depressive symptoms: rumination, catastrophising, withdrawal, positive refocusing and refocus on planning (the latter two negatively). Conclusion: Almost half of the PLWH reported depressive symptoms that were clinically significant. The findings suggested that an intervention for PLWH with depressive symptoms in Botswana should preferably be a self-help programme presented in booklet format. With regard to content, the results confirmed that the intervention should focus on specific coping skills. In addition, elements like goal finding and strategies to reduce physical tension should be added.
Genital Secretion HIV RNA Shedding in HIV-Positive Patients on Ritonavir-Boosted Protease Inhibitor Monotherapy or Standard Combination ART: A Cross-Sectional Sub-Study from the PIVOT Trial

Background Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PI-mono). Methods We measured HIV RNA and PI drug concentrations in samples of semen, cervicovaginal and rectal mucosa secretions, and plasma in patients after 48–96 weeks on PI-mono or standard triple therapy. Results A total of 85 participants were recruited. Of the 43 participants on PI-mono (70% on darunavir [DRV]/ ritonavir [r]), 3 had detectable virus in semen or vaginal secretions (all below quantification limit), and none in rectal mucosa or plasma. Among those taking triple therapy, five had detectable virus in semen or vaginal secretions (HIV RNA >50 copies/ml in one), none in rectal mucosa and one in plasma. The median (IQR) concentration of DRV and atazanavir in semen (659.7 [339–1,089] and 128.8 [63–368] ng/ml, respectively) and cervico-vaginal samples (2,768 [312–7,879] and 1,836 [359–3,314] ng/ml, respectively) exceeded their protein adjusted median inhibition concentration (MIC50). DRV concentration in rectal secretions showed higher variability compared with concentration in the other sites, with particularly high rectal secretion/blood ratios (median 8.4, IQR 2.6–68.7:1). Conclusions We found no substantive evidence of HIV shedding in patients taking PI-mono, suggesting that PIs provide adequate control of virus in the genital compartment and are unlikely to lead to ongoing sexual transmission.
HUBUNGAN PENGETAHUAN PASIEN TUBERCULOSIS PARU DENGAN KEPATUHAN PASIEN DALAM KONSUMSI OBAT

Tubercolusis (TBC) merupakan penyakit infeksi kronik yang dapat disembuhkan bila mengkonsumsi obat secara teratur. Penyakit tubercolusis adalah penyakit yang dapat menyebabkan kematian bila tidak mengkonsumsi obat secara teratur dan teratur sampai 6 bulan. Terbukti dengan peningkatan jumlah kematian di dunia maupun indonesia. Untuk mengatasi hal tersebut perlu pengatuhan dan kepatuhan pasien tubercolusis untuk minum obat secara teratur. Penelitian ini bertujuan untuk mengidentifikasi pengetahuan pasien Tubercolosis Paru tentang kepatuhan makan obat OATdi Puskesmas Kedundung Kota Mojokerto. Desain penelitian ini menggunakan analitik korelasi dengan pendekan cross sectional. Metode sampling yang digunakan adalah Simple Random Sampling yang diambil sebanyak 40 responden yaitu pasien tubercolusis yang masuk pengobatan di Pukesmas Kedundung Mojokerto tahun 2010. Data penelitian diambil dengan menggunkan lembar kuesioner dan lembar observasi. Setelah ditabulasi data yang ada dianalisis dengan menggunakan uji statistic pearson korelasi dengan (= 0,05). Hasil penelitian menunjukkan pengetahuan pasien tubercolusis sebagai besar yaitu 4 orang (10%) berpengetahuan kurang, dan sebagian besar yaitu 23 orang (57.5%) berpengetahuan baik. Dan pada kepatuhan pasien tubercolusis hampir setengahnya yaitu 15 orang (37.5%) mempunyai kepatuhan lemah, dan sebagian besar 25 (62.5%) mempunyai kepatuhan kuat. Sedangkan dari hasil uji statistik diperoleh hasil ada hubungan pengetahuan pasien tubercolusis dengan kepatuhan pasien dalam mengkonsumsi obat di Puskesmas Kedundung Mojokerto. ( = 0,002 0,05 ). Melihat hasil penelitian ini dapat di adakan penyuluhan tentang penyakit dan pengobatan tubercolusis, agar pasien tubercolusis lebih mengetahui penyakit tubercolosis dan dampak bila tidak mengkonsumsi obat secara teratur sesuai dengan pentunjuk
‘I’d say I’m fat, I’m not obese’: obesity normalisation in urban-poor South Africa

Abstract Objective: In the past decade, South Africa’s obesity epidemic has increased in both children and adults, and being overweight is becoming the norm. Several contributing factors lead to the normalisation of obesity. One of these is the culturally entrenched likeness of larger body sizes or shapes within a milieu of easily accessible unhealthy food and beverages. This qualitative study advances knowledge about the influence of socio-cultural norms and obesogenic environments on weight under estimation and ‘obesity normalisation’ amongst black South Africans living in an urban setting. Design: A theory-based qualitative study used focus group discussions (FGDs) with a semi-structured interview guide. FGDs were transcribed verbatim and analysed thematically using a constant comparison method. Setting: Soweto, Johannesburg, South Africa, is a setting which has undergone rapid urbanisation and nutrition transition with ubiquitous availability of processed and fast-foods. Participants: Adults older than 18 years living in Soweto (n 57). Results: There is a wide misperception about obesity amongst black Africans living in an urban setting in Soweto. Participants who admitted to being fat or overweight did not view themselves as such. This could be attributed to unchanging socio-cultural factors that reinforce the acceptability of bigger bodies and living in obesogenic environment. Conclusions: Without addressing socio-cultural norms that attribute bigger bodies to beauty and wealth, motivating individuals to address weight gain will prove difficult especially for populations living in obesogenic environments. A multi-faceted strategy is required to address obesity in urban South African settings.
COVID-19 and Cardiovascular Disease

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.
Tracheostomy at a tertiary level hospital in Bangladesh: any change in pattern?

Objective: This study was conducted on tracheostomy to find out the different indications and complications occured at the tertiary level hospital in Bangladesh. Study design: Cross-sectional observational study. Place and Duration: This study was conducted at the department of Otolaryngology & Head Neck surgery and department of ICU, Sir Salimullah Medical College Mitford Hospital, Dhaka & DMCH over one year from January 2014 to December 2014. Methodology: 55 tracheostomy operation were performed in both genders and all age groups either in emergency situations or within an elective environment. All the patients were registered with a definite protocol by filling a pre designed proforma equipped with demographic data, details of present illness mirroring the indication for the procedure, relevant physical examination & investigations, details of the surgical procedure of tracheostomy and postoperative follow up with note of any attendant complications described as immediate, early and late postoperative. Results: Mean age of this study was 40.09 years and male female ratio iwas 3.2: 1. 30(54.54%) patients underwent emergency tracheostomy and 25(45.46%) underwent tracheostomy electively. The commonest indications were laryngeal & hypopharyngeal malignancies which affected 28(50.9%) patients. The overall rate of complications was 25.45%. These were 4(28.57%) immediate post operative, 8(57.14%) early post operative and 2(3.63%) late post operative. Out of overall 14 complications, 11(36.66%) complications occurred in 40 patients who underwent tracheostomy in emergency and 3(12%) complications occurred in 25 patients who underwent tracheostomy electively. Conclusion: Upper airway obstruction due to laryngeal and hypopharyngal carcinoma still remains the most common indication for tracheostomy in our centre but prolonged intubation as an indication for tracheostomy is evolving based on recent improvement in the facilities available
Photocatalytic activity and water purification performance of in situ and ex situ synthesized bacterial cellulose‐CuO nanohybrids

The aim of this research was synthesizing of bacterial cellulose (BC) nanohybrids by incorporation of CuO‐NPs and evaluation of their ability in the removing of microbial, heavy metals, and dyes pollutants from water. CuO‐BC nanohybrids were synthesized by two in situ (sonochemical and precipitation) methods and compared with ex situ synthesized nanohybrid. FE‐SEM images revealed that the growth of CuO‐NPs in the sonochemically synthesized in situ substrate is better. The ex situ nanohybrid had the highest loading capacity (27.17 μg/cm2) but the migration of CuO‐NPs from this substrate was higher than in situ ones. According to antimicrobial tests, 80% and 90% of initial population of E. coli and S. aureus, respectively, were removed after 6 hr contact of substrates with water. The potential of the substrates in the adsorption of lead and arsenic was about 60% after 24 hr. About 75% of methylene blue and methyl orange dyes were adsorbed into substrates after 6 hr. CuO doped substrates had the photocatalytic activity and caused to decrease the oxygen content about 4%–7% during 6 hr. In general, the reusability of ex situ synthesized substrate was lower than in situ nanohybrids. Sonochemically synthesized substrate was suggested as the best nanohybrid for water purification applications in terms of morphological properties and reusability.