Miracle-dz/UniFAR-FTUs huggingface dataset:
Decreased airway epithelial ion transport was associated with the severity of the respiratory syncytial virus infection and complications in infants

The respiratory syncytial virus (RSV) primarily infects airway epithelial cells. It also decreases airway epithelial sodium transport, especially through the epithelial sodium channel (ENaC) (1), which is crucial for osmosis-based fluid absorption across respiratory epithelium. Meanwhile, the electrochemical balance is maintained by secretion of chloride ions through apical chloride channels, including the cystic fibrosis transmembrane conductance regulator (CFTR) (1). In animals, ENaC inhibition has caused middle ear fluid collection in acute otitis media (AOM) (2).
Territory acquisition mediates the influence of predators and climate on juvenile red squirrel survival

1) Juvenile survival to first breeding is a key life history stage. Survival through this period can be particularly challenging when it coincides with harsh environmental conditions like winter climate or food scarcity, and so cohort survival can be highly variable. However, the small size and dispersive nature of juveniles makes studying their survival difficult. 2) In territorial species, a key life history event is the acquisition of a territory. A territory is expected to enhance survival, but how it does so, possibly through mediating mortality, is not often identified. We tested how the timing of territory acquisition influenced the survival of juvenile North American red squirrels Tamiasciurus hudsonicus, hereafter red squirrels, and how the timing of this event mediated sources of mortality. We hypothesized that securing a territory prior to the caching season would reduce juvenile susceptibility to predation or climatic factors over winter. 3) Using 27 years of data on the survival of individually-marked juvenile red squirrels, we tested how the timing of territory acquisition influenced survival, whether the population density of red squirrel predators and mean temperature over winter were related to individual survival probability, and if territory ownership mediated these effects. 4) Juvenile survival was lower in years of high predator abundance and in colder winters. Autumn territory owners were less susceptible to lynx Lynx canadensis, and possibly mustelid Mustela and Martes spp. , predation. Autumn territory owners had lower survival in colder winters, while non-owners had higher survival in cold winters. 5) Our results show how the timing of a life history event like territory acquisition can directly affect survival and also mediate the effects of biotic and abiotic factors later in life. This engenders a better understanding of the fitness consequences of the timing of key life history events.
HMCES safeguards replication from oxidative stress and ensures error‐free repair

Replication across oxidative DNA lesions can give rise to mutations that pose a threat to genome integrity. How such lesions, which escape base excision repair, get removed without error during replication remains unknown. Our PCNA‐based screen to uncover changes in replisome composition under different replication stress conditions had revealed a previously unknown PCNA‐interacting protein, HMCES/C3orf37. Here, we show that HMCES is a critical component of the replication stress response, mainly upon base misincorporation. We further demonstrate that the absence of HMCES imparts resistance to pemetrexed treatment due to error‐prone bypass of oxidative damage. Furthermore, based on genetic screening, we show that homologous recombination repair proteins, such as CtIP, BRCA2, BRCA1, and PALB2, are indispensable for the survival of HMCES KO cells. Hence, HMCES, which is the sole member of the SRAP superfamily in higher eukaryotes known so far, acts as a proofreader on replication forks, facilitates resolution of oxidative base damage, and therefore ensures faithful DNA replication.
Patients’ Perspective on Mental Health Specialist Video Consultations in Primary Care: Qualitative Preimplementation Study of Anticipated Benefits and Barriers

Background Due to limited access to specialist services, most patients with common mental disorders (depression or anxiety, or both) usually receive treatment in primary care. More recently, innovative technology-based care models (eg, video consultations) have been proposed to facilitate access to specialist services. Against this background, the PROVIDE (Improving Cross-Sectoral Collaboration Between Primary and Psychosocial Care: An Implementation Study on Video Consultations) project aims to improve the provision of psychosocial care through implementing video consultations integrated into routine primary care. Objective From the patients’ perspective, this qualitative preimplementation study explored (1) anticipated benefits from and (2) barriers to implementing mental health specialist video consultations embedded in primary care services and (3) prerequisites for interacting with therapists via video consultations. Methods Using a purposive (ie, stratified) sampling strategy, we recruited 13 patients from primary care practices and a tertiary care hospital (psychosomatic outpatient clinic) for one-off semistructured interviews. In a computer-assisted thematic analysis, we inductively (bottom-up) derived key themes concerning the practicability of mental health specialist video consultations. To validate our results, we discussed our findings with the interviewees as part of a systematic member checking. Results Overall, we derived 3 key themes and 10 subthemes. Participants identified specific benefits in 2 areas: the accessibility of mental health specialist care (shorter waiting times: 11/13, 85%; lower threshold for seeking specialist mental health care: 6/13, 46%; shorter travel distances: 3/13, 23%); and the environment in primary care (familiar travel modalities, premises, and employees: 5/13, 38%). The main barriers to the implementation of mental health video consultations from the patients’ perspective were the lack of face-to-face contact (13/13, 100%) and technical challenges (12/13, 92%). Notably, participants’ prerequisites for interacting with therapists (12/13, 92%) did not seem to differ much from those concerning face-to-face contacts. Conclusions Mental health service users mostly welcomed mental health specialist video consultations in primary care. Taking a pragmatic stance, service users, who are often frustrated about uncoordinated care, particularly valued the embedment of the consultations in the familiar environment of the primary care practice. With respect to interventional studies and implementation, our findings underscore the need to minimize technical disruptions during video consultations and to ensure optimal resemblance to face-to-face settings (eg, by training therapists in consistently reacting to nonverbal cues). Trial Registration German Clinical Trials Register DRKS00012487; https://tinyurl.com/uhg2one
Improving Grasp Function After Spinal Cord Injury With a Soft Robotic Glove

People with tetraplegia resulting from spinal cord injury experience debilitating hand impairments that may lead to lifelong dependence on others to perform activities of daily living. Wearable robotic devices that actively support hand function during daily living tasks could bring great benefits to this population. In this work, the performance of a textile-based soft robotic glove controlled by the user with a button was evaluated in thirteen participants with tetraplegia. Performance outcomes included activities of daily living using the Jebsen Taylor Hand Function Test, active range of motion of the fingers, and grasp strength for power and pinch grasps. In the Jebsen Test, participants showed significant improvements in performance of activities of daily living with glove assistance, completing a median of 50% more tasks than in their baseline attempt without the glove. Significant improvements were also found for power and pinch grasp forces and active range of motion of the fingers with the glove assistance. Participants with lower baseline motor function received greater benefits from glove assistance. This work demonstrates the effectiveness of a user-controlled textile-based soft robotic glove to improve activity of daily living abilities in individuals with hand impairments resulting from spinal cord injury.
The evolving epidemic of breast cancer in sub‐Saharan Africa: Results from the African Cancer Registry Network

Breast cancer (BC) is the leading cause of cancer in sub‐Saharan Africa (SSA) with rapidly increasing incidence rates reported in Uganda and Zimbabwe. However, the magnitude of these rising trends in premenopausal and postmenopausal women is unknown in most African countries. We used data from the African Cancer Registry Network on incident breast cancers in women from 11 population‐based cancer registries in 10 countries representing each of the four SSA regions. We explored incidence changes among women before and after age 50 by calendar period and, where possible, generational effects in this unique sub‐Saharan African cohort. Temporal trends revealed increasing incidence rates in all registries during the study period, except in Nairobi where rates stabilised during 2010 to 2014 after rapidly increasing from 2003 to 2010 (APC = 8.5 95%, CI: 3.0‐14.2). The cumulative risk varied between and within regions, with the highest risks observed in Nairobi‐Kenya, Mauritius and the Seychelles. There were similar or more rapidly increasing incidence rates in women aged 50+ compared to women <50 years in all registries except The Gambia. Birth cohort analyses revealed increases in the incidence rates in successive generations of women aged 45 and over in Harare‐Zimbabwe and Kampala‐Uganda. In conclusion, the incidence of BC is increasing rapidly in many parts of Africa; however, the magnitude of these changes differs. These results highlight the need for urgent actions across the cancer continuum from in‐depth risk factor studies to provision of adequate therapy as well as the necessity of supporting the maintenance of good quality population‐based cancer registration in Africa.
Multidisciplinary Heart Team Approach for Complex Coronary Artery Disease: Single Center Clinical Presentation

Background The Heart Team approach is ascribed a Class I recommendation in contemporary guidelines for revascularization of complex coronary artery disease. However, limited data are available regarding the decision‐making and outcomes of patients based on this strategy. Methods and Results One hundred sixty‐six high‐risk coronary artery disease patients underwent Heart Team evaluation at a single institution between January 2015 and November 2018. We prospectively collected data on demographics, symptoms, Society of Thoracic Surgeons Predicted Risk of Mortality/Synergy Between PCI with Taxus and Cardiac Surgery (STS‐PROM/SYNTAX) scores, mode of revascularization, and outcomes. Mean age was 70.0 years; 122 (73.5%) patients were male. Prevalent comorbidities included diabetes mellitus (51.8%), peripheral artery disease (38.6%), atrial fibrillation (27.1%), end‐stage renal disease on dialysis (13.3%), and chronic obstructive pulmonary disease (21.7%). Eighty‐seven (52.4%) patients had New York Heart Association III‐IV and 112 (67.5%) had Canadian Cardiovascular Society III‐IV symptomatology. Sixty‐seven (40.4%) patients had left main and 118 (71.1%) had 3‐vessel coronary artery disease. The median STS‐PROM was 3.6% (interquartile range 1.9, 8.0) and SYNTAX score was 26 (interquartile range 20, 34). The median number of physicians per Heart Team meeting was 6 (interquartile range 5, 8). Seventy‐nine (47.6%) and 49 (29.5%) patients underwent percutaneous coronary intervention and coronary artery bypass grafting, respectively. With increasing STS‐PROM (low, intermediate, high operative risk), coronary artery bypass graft was performed less often (47.9%, 18.5%, 15.2%) and optimal medical therapy was recommended more often (11.3%, 18.5%, 30.3%). There were no trends in recommendation for coronary artery bypass graft, percutaneous coronary intervention, or optimal medical therapy by SYNTAX score tertiles. In‐hospital and 30‐day mortality was 3.9% and 4.8%, respectively. Conclusions Integrating a multidisciplinary Heart Team into institutional practice is feasible and provides a formalized approach to evaluating complex coronary artery disease patients. The comprehensive assessment of surgical, anatomical, and other risk scores using a decision aid may guide appropriate, evidence‐based management within this team‐based construct.
A new congenital multicore titinopathy associated with fast myosin heavy chain deficiency

Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin‐myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament loss. Immunohistochemistry and Western blotting revealed a marked reduction of fast myosin heavy chain isoforms. This is the first observation of a titinopathy suggesting that titin defect leads to secondary loss of fast myosin heavy chain isoforms.
GDF15: A Hormone Conveying Somatic Distress to the Brain

Abstract GDF15 has recently gained scientific and translational prominence with the discovery that its receptor is a GFRAL-RET heterodimer of which GFRAL is expressed solely in the hindbrain. Activation of this receptor results in reduced food intake and loss of body weight and is perceived and recalled by animals as aversive. This information encourages a revised interpretation of the large body of previous research on the protein. GDF15 can be secreted by a wide variety of cell types in response to a broad range of stressors. We propose that central sensing of GDF15 via GFRAL-RET activation results in behaviors that facilitate the reduction of exposure to a noxious stimulus. The human trophoblast appears to have hijacked this signal, producing large amounts of GDF15 from early pregnancy. We speculate that this encourages avoidance of potential teratogens in pregnancy. Circulating GDF15 levels are elevated in a range of human disease states, including various forms of cachexia, and GDF15-GFRAL antagonism is emerging as a therapeutic strategy for anorexia/cachexia syndromes. Metformin elevates circulating GDF15 chronically in humans and the weight loss caused by this drug appears to be dependent on the rise in GDF15. This supports the concept that chronic activation of the GDF15-GFRAL axis has efficacy as an antiobesity agent. In this review, we examine the science of GDF15 since its identification in 1997 with our interpretation of this body of work now being assisted by a clear understanding of its highly selective central site of action.
The effectiveness of mHealth interventions on postpartum depression: A systematic review and meta-analysis

Introduction Postpartum depression (PPD) is a common psychiatric condition during the postnatal period that negatively impacts the well-being of both the mother and her infant. This study describes a systematic review and preliminary meta-analysis to assess the efficacy of mobile health (mHealth) interventions, which is defined as the use of portable electronic devices to support public health and medical practice, in addressing depressive symptoms among postpartum women. Methods Databases including PubMed, PsycINFO, the Cochrane Library, Embase and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) assessing the effectiveness of mHealth interventions on PPD from database inception to December 2019. Results The initial search identified 754 studies, of which, 11 studies fulfilled the inclusion criteria. These studies evaluated four types of distinct mHealth interventions and involved 2424 participants across six countries. Pooled results demonstrated that compared to the controls, the Edinburgh Postnatal Depression Scale score decreased in the mHealth intervention group (mean difference: –1.09, 95% confidence interval: –1.39 to –0.79). Discussion Our study suggested that mHealth interventions may be a promising tool to complement routine clinical care in the prevention and treatment of PPD, but the clinical effectiveness of mHealth interventions needs to be better established. While most studies focused on telephone-based interventions, recent researches have also suggested the superiority and effectiveness of short messaging service (SMS) and smartphone applications, but the exact efficacy needs further evaluation. Therefore, more high-quality RCTs on app-based and SMS-based interventions are needed before the large-scale roll-out of these interventions in clinical practice.
Sex Steroids as Regulators of Gestural Communication

Abstract Gestural communication is ubiquitous throughout the animal kingdom, occurring in species that range from humans to arthropods. Individuals produce gestural signals when their nervous system triggers the production of limb and body movement, which in turn functions to help mediate communication between or among individuals. Like many stereotyped motor patterns, the probability of a gestural display in a given social context can be modulated by sex steroid hormones. Here, we review how steroid hormones mediate the neural mechanisms that underly gestural communication in humans and nonhumans alike. This is a growing area of research, and thus we explore how sex steroids mediate brain areas involved in language production, social behavior, and motor performance. We also examine the way that sex steroids can regulate behavioral output by acting in the periphery via skeletal muscle. Altogether, we outline a new avenue of behavioral endocrinology research that aims to uncover the hormonal basis for one of the most common modes of communication among animals on Earth.
Curcumin effect on cancer cells' multidrug resistance: An update

Chemotherapy is one of the main methods for cancer treatment. However, despite many advances in the design of anticancer drugs, their efficiency is limited due to their high toxicity and resistance of cells to chemotherapeutic drugs. In order to improve the cancer therapy, it is essential to use the compounds that can overcome drug resistance and increase treatment efficiency. Researchers have studied the effects of natural compounds for the controlling various drug resistance mechanisms. Curcumin is a natural phenolic compound which shows potent anticancer activities in different tumors, alone or as an adjuvant with other antitumor drugs to prevent or inhibit the survival and cancer progression by various mechanisms. The role of curcumin in overcoming drug resistance was followed by reviewing different applications of curcumin in cancer therapy. Afterward, the clinical impacts of curcumin, role of curcumin in decreasing drug resistance in different cancer cells and its mechanisms were discussed. It has been demonstrated that curcumin regulates signaling pathways in cancer cells, reduces the expression of proteins related to drug resistance, and increases the performance of antitumor drugs at various levels. Curcumin reverses multidrug resistance mechanisms and increases sensitivity of resistance cells to chemotherapy. This review mainly focuses on different mechanisms of drug resistance and curcumin as a nontoxic natural substance to eliminate the effects of drug resistance through modulation and controlling cell resistance pathways and eventually suggests curcumin as a potent chemosensitizer in cancers.
Analysis of electrocardiographic intervals before and after transcatheter aortic valve implantation to predict the need for permanent pacing

Abstract Transcatheter aortic valve implantation (TAVI) is growing in utilization in the USA, and atrioventricular heart block is a common complication of the procedure. In patients with conduction system changes following TAVI, there are no clear guidelines for permanent pacing, leading to difficult clinical decisions on how long to leave temporary transvenous pacemakers in place. The aim of our study was to determine whether changes in electrocardiogram characteristics could predict the need for permanent pacing. A retrospective analysis was conducted of 209 consecutive TAVI patients seen from January 2012 to December 2015 at Baylor Heart and Vascular Hospital, Dallas. The baseline characteristics were similar between those who received a permanent pacemaker (PPM) within 7 days of the procedure (21.1%) and those who did not (78.9%); of those who did receive a PPM, 79.5% were implanted for complete heart block. The median (range) percentage change in the sum of QRS and PR was significantly higher in those who received a PPM (20.2%) than those who did not (7.1%) (P = 0.004). Using the percentage change in the sum of QRS and PR to predict PPM, the area under the curve was found to be 0.69. The optimal cutpoint was found to be 18.9% (sensitivity = 0.63, specificity = 0.73). Our study suggests that delay in the conduction system immediately following TAVI predicts the need for permanent pacing.
The beginnings of tuberculosis pharmacological treatment

The appearance of new anti-tuberculosis drugs such as bedaquiline and delamanid makes it impossible not to remember that the first strictly controlled medical trials of tuberculosis treatment were published in two rigorously researched outstanding articles that can be qualified as historical. In 1948, streptomycin was formally studied as an efficacious anti-tuberculosis drug. In 1952, another trial compared streptomycin-paramino salicylic acid with isoniazid, by means of which the first bases of pharmacological tuberculosis treatment were established.
Anatomy, Head and Neck, Eye Cornea

The cornea is the outermost, clear layer of the eye, immediately anterior to the anterior chamber, iris, and pupil. The cornea borders the sclera at the corneal limbus and is involved in the refraction of light entering the human eye. Five distinct layers make up the cornea, including the epithelium, Bowman's membrane, the stroma, Descemet's membrane, and the endothelium (from the exterior to interior). Albumin is the most abundant soluble protein in the human cornea.