Miracle-dz/UniFAR-FTUs huggingface dataset:
The experiences of nurses and midwives who provide surgical abortion care: A qualitative systematic review.

AIM To synthesize qualitative evidence on nurses' and midwives' experiences in the provision of surgical abortion care. We address three specific questions: (a) what are the experiences of nurses and midwives in surgical abortion care? (b) what are their responses and coping strategies? (c) what are the deficiencies in surgical abortion care? DESIGN Qualitative studies were synthesized using Thomas and Harden's qualitative thematic synthesis method. DATA SOURCES Electronic databases, including PubMed, Embase, CINAHL, PsycINFO, Scopus and Web of Science were searched. Grey literature using ProQuest was searched. The databases were searched from inception to 5 August 2020. REVIEW METHODS The SPIDER (Sample, Phenomenon of Interest, Design, Evaluation and Research type) search tool was used in the literature search. Data synthesis was conducted using the three-stage thematic synthesis method described by Thomas and Harden. RESULTS 966 studies were identified in the initial search and 18 studies were included. Four analytical themes were generated: 'Providing abortion care requires high emotional labour'; 'Professionalism of abortion care providers'; 'Initiatives in professional development' and 'Improving directions for high-quality abortion care'. CONCLUSION Nurses and midwives indicated that they require support to enhance psychological health and improve professional skills. Hospital managers should organize regular debriefing or structured group workshops for exchange of practical experiences and strengthening emotional support. More research is required to establish comprehensive training related to abortion care for nurses and midwives. The findings demonstrate that optimization of abortion services should start from hospital management models, pain management and bereavement care. IMPACT Understanding the experiences of nurses and midwives in abortion provision will inform future clinical practice in surgical abortion care, which would be helpful in improving the professionalism and confidence of abortion providers. Our findings have implications for the training, development of policies and standards for surgical abortion care for nurses and midwives.
Impact of the SARS-CoV-2 (COVID-19) crisis on surgical training: global survey and a proposed framework for recovery

Abstract Background The SARS-CoV-2 pandemic had a profound impact on surgical services, potentially having a detrimental impact on training opportunities. The aim of this global survey was to assess the impact of the COVID-19 crisis on surgical training and to develop a framework for recovery. Methods A cross-sectional, web-based survey was conducted. This was designed by a steering committee of medical educationalists and validated by a group of trainees before dissemination. Results A total of 608 responses were obtained from 34 countries and 15 specialties. The results demonstrated major disruption in all aspects of training. The impact was greatest for conferences (525 of 608) and hands-on courses (517 of 608), but less for inpatient care-related training (268 of 608). European trainees were significantly more likely to experience direct training disruption than trainees in Asia (odds ratio 0.15) or Australia (OR 0.10) (χ2 = 87.162, P < 0.001). Alternative training resources (webinars, 359 of 608; educational videos, 234 of 608) have emerged, although trainees expressed some dissatisfaction with them. The collective responses generated a four-pillar framework for training recovery that involved: guidance from training stakeholders with the involvement of trainees; prioritization of training, especially the roles of senior surgeons/trainers; provision of access to alternative/new teaching methods; and measures to address trainee anxiety. Conclusion Training has been greatly affected by the COVID-19 pandemic. The introduction of new teaching methods and a focus on training after the pandemic are imperative.
Snord116 Post-transcriptionally Increases Nhlh2 mRNA Stability: Implications for Human Prader-Willi Syndrome.

The smallest genomic region causing Prader-Willi Syndrome (PWS) deletes the non-coding RNA SNORD116 cluster; however, the function of SNORD116 remains a mystery. Previous work in the field revealed the tantalizing possibility that expression of NHLH2, a gene previously implicated in both obesity and hypogonadism, was downregulated in PWS patients and differentiated stem cells. In silico RNA: RNA modeling identified several potential interaction domains between SNORD116 and NHLH2 mRNA. One of these interaction domains was highly conserved in most vertebrate NHLH2 mRNAs examined. A construct containing the Nhlh2 mRNA, including its 3'-UTR, linked to a c-myc tag was transfected into a hypothalamic neuron cell line in the presence and absence of exogenously-expressed Snord116. Nhlh2 mRNA expression was upregulated in the presence of Snord116 dependent on the length and type of 3'UTR used on the construct. Furthermore, use of actinomycin D to stop new transcription in N29/2 cells demonstrated that the upregulation occurred through increased stability of the Nhlh2 mRNA in the 45 minutes immediately following transcription. In silico modeling also revealed that a single nucleotide variant (SNV) in the NHLH2 mRNA could reduce the predicted interaction strength of the NHLH2:SNORD116 diad. Indeed, use of an Nhlh2 mRNA construct containing this SNV significantly reduces the ability of Snord116 to increase Nhlh2 mRNA levels. For the first time, these data identify a motif and mechanism for SNORD116-mediated regulation of NHLH2, clarifying the mechanism by which deletion of the SNORD116 snoRNAs locus leads to PWS phenotypes.
O‐GlcNAcylation of TDP‐43 suppresses proteinopathies and promotes TDP‐43’s mRNA splicing activity

Pathological TDP‐43 aggregation is characteristic of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD‐TDP); however, how TDP‐43 aggregation and function are regulated remain poorly understood. Here, we show that O‐GlcNAc transferase OGT‐mediated O‐GlcNAcylation of TDP‐43 suppresses ALS‐associated proteinopathies and promotes TDP‐43's splicing function. Biochemical and cell‐based assays indicate that OGT's catalytic activity suppresses TDP‐43 aggregation and hyperphosphorylation, whereas abolishment of TDP‐43 O‐GlcNAcylation impairs its RNA splicing activity. We further show that TDP‐43 mutations in the O‐GlcNAcylation sites improve locomotion defects of larvae and adult flies and extend adult life spans, following TDP‐43 overexpression in Drosophila motor neurons. We finally demonstrate that O‐GlcNAcylation of TDP‐43 promotes proper splicing of many mRNAs, including STMN2, which is required for normal axonal outgrowth and regeneration. Our findings suggest that O‐GlcNAcylation might be a target for the treatment of TDP‐43‐linked pathogenesis.
Human antigen R promotes lung fibroblast differentiation to myofibroblasts and increases extracellular matrix production

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring caused by excessive extracellular matrix (ECM) deposition and activation of α‐SMA‐expressing myofibroblasts. Human antigen R (HuR) is an RNA binding protein that promotes protein translation. Upon translocation from the nucleus to the cytoplasm, HuR functions to stabilize messenger RNA (mRNA) to increase protein levels. However, the role of HuR in promoting ECM production, myofibroblast differentiation, and lung fibrosis is unknown. Human lung fibroblasts (HLFs) treated with transforming growth factor β1 (TGF‐β1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF‐β‐treated HLFs that were transfected with HuR small interfering RNA had a significant reduction in α‐SMA protein as well as the ECM proteins COL1A1, COL3A, and FN1. HuR was also bound to mRNA for ACTA2, COL1A1, COL3A1, and FN. HuR knockdown affected the mRNA stability of ACTA2 but not that of the ECM genes COL1A1, COL3A1, or FN. In mouse models of pulmonary fibrosis, there was higher cytoplasmic HuR in lung structural cells compared to control mice. In human IPF lungs, there was also more cytoplasmic HuR. This study is the first to show that HuR in lung fibroblasts controls their differentiation to myofibroblasts and consequent ECM production. Further research on HuR could assist in establishing the basis for the development of new target therapy for fibrotic diseases, such as IPF.
Correlation between the burden of family caregivers and health status of people with diabetes mellitus

Background: Family caregivers play an important role in providing long-term care for people with diabetes mellitus because it is a chronic disease that requires critical attention. This increases the burden of family caregivers which affects the health status of people with this disease. Therefore, the aim of this study is to determine the correlation between the burden of family caregivers and the health status of people with diabetes mellitus. Design and methods: This is an analytic observational study which was carried out in the work area of public health centers in Malang City using a cross-sectional design approach. The subjects used were 327 people with diabetes mellitus and their families were selected using the cluster sampling technique. Data collection was carried out using demographic data instruments, Zarit Burden Interview (ZBI) questionnaire to measure the burden of family caregivers and the SF 12 questionnaire to measure the health status of people with diabetes mellitus. Results: The results of the Spermank-Rank statistical test showed that there was a negative relationship between the burden of family caregivers and the health status of people with diabetes mellitus (p-value 0.000 and coefficient value of -0.333). Conclusions: It was concluded that the lesser the burden on family caregivers, the better the health status of people with diabetes mellitus. Therefore, interventions are needed to reduce the burden of family caregiver and improve the health status of patients with diabetes mellitus. Significance for public health Families are regarded as the smallest unit of the society consisting of the head and several other people that live together and are dependent on each other. Family members with diabetes mellitus require long-term care and therefore require the assistance of a family caregiver at home. The burden of family caregivers and the health status of people with this diabetes diseases have an impact on morbidity, mortality and the degree of public health. This study contains the basic data of policy made for public health services to improve public health status, especially for people with diabetes mellitus and their family.
Distribution of High-Sensitivity Troponin Taken Without Conventional Clinical Indications in Critical Care Patients and Its Association With Mortality*

Supplemental Digital Content is available in the text. OBJECTIVES: To describe the distribution of high-sensitivity troponin in a consecutive cohort of patients in critical care units, regardless of clinical indication, and its association with clinical outcomes. DESIGN: Prospective observational study. SETTING: Single-center teaching hospital. PATIENTS: Consecutive patients admitted to two adult critical care units (general critical care unit and neuroscience critical care unit) over a 6-month period. INTERVENTIONS: All patients had high-sensitivity troponin tests performed at admission and tracked throughout their critical care stay, regardless of whether the supervising team felt there was a clinical indication. The results were not revealed to patients or clinicians unless clinically requested. MEASUREMENTS AND MAIN RESULTS: There were 1,033 patients in the study cohort (general critical care unit 750 and neuroscience critical care unit 283). The median high-sensitivity troponin was 21 ng/L (interquartile range, 7–86 ng/L), with 560 patients (54.2%) above the upper limit of normal as defined by the manufacturer. Admission high-sensitivity troponin concentrations above the upper limit of normal in general critical care unit and neuroscience critical care unit were associated with increasing age, comorbidity, markers of illness severity, and the need for organ support. On adjusted analysis, the high-sensitivity troponin concentration remained an independent predictor of critical care mortality in general critical care unit and neuroscience critical care unit. CONCLUSIONS: High-sensitivity troponin elevation, taken outside the context of conventional clinical indications, was common in the critically ill. Such elevations were associated with increasing age, comorbidity, illness severity, and the need for organ support. Admission high-sensitivity troponin concentration is an independent predictor of critical care mortality and as such may represent a novel prognostic biomarker at admission.
Carotenoid composition and antioxidant activities of Chinese orange-colored tomato cultivars and the effects of thermal processing on the bioactive components.

To facilitate the production of tomato products with high bioactivity and improve the utilization of orange-colored tomatoes, the carotenoids of 11 tomato cultivars were analyzed using high-performance liquid chromatography with photodiode array detection. Moreover, antioxidant activities were evaluated by four chemical-based assays, and the influences of thermal treatment on the carotenoids in orange-colored tomatoes rich in tetra-cis (7Z, 9Z, 7'Z, and 9'Z)-lycopene, phytofluene, and phytoene were studied. The nine orange-colored tomatoes (OT) were divided into two categories: OT-B, containing five cultivars rich in β-carotene, and OT-L, containing the other four cultivars that were abundant in tetra-cis-lycopene, phytofluene, and phytoene. The antioxidant activities of OT-L were higher than those of OT-B and the SD-2 cultivar in OT-L showed similar antioxidant activity to the red tomatoes. During thermal processing, tetra-cis-lycopene in SD-2 decreased about 38% after being exposed to heat for 2 hr at 80 °C, while its content was still higher than other lycopene isomers. Other-Z-lycopenes and all-trans (E)-lycopene increased from 2.36 ± 0.19 to 14.73 ± 1.16 µg/g fresh weight (FW) and 0.75 ± 0.10 to 5.91 ± 1.02 µg/g FW, respectively. Thus, thermal treatments at lower temperature, such as cold break and pasteurization, were more suitable for processing OT-L. The results demonstrated that OT-L could be an excellent raw material to produce tomato products with high bioavailability and bioactivity. The results of this research could provide helpful information for the research and development of tomato products using orange tomatoes and benefit planters and consumers. PRACTICAL APPLICATION: Some orange tomato cultivars are promising raw materials for tomato products because of their high contents of bioactive tetra-cis-lycopene, phytofluene, and phytoene. This study demonstrated the carotenoid components and antioxidant activities of the widely planted orange-colored tomatoes in China. The obtained knowledge, including the thermal processing effects on the isomerization and degradation of carotenoids in the cultivars, will offer useful information to food processors and benefit the consumers.
A Prescription for Resilience

Objective: Globally, leaders require strategies to sustain the performance and well-being of themselves and their teams while managing and adapting to uncertainty, workplace turbulence, and high job demands. This study evaluates the Resilience at Work Leader 180 Scale assessing leader behaviors that either promote or detract from resilience in others. Method: Study participants comprised Australian pharmacy employees (N = 80) in two groups made up of the senior leadership team (n = 10) and their direct report employees (n = 70). A mixed-methods design was employed using a directed content analysis. Results: Results indicate that the Resilience at Work Leader 180 Scale provides insight into leader behaviors that foster or detract from employee resilience. Conclusion: This scale is of value to researchers and organizations interested in a measure of leader resilience.
Acute toxicity from the synthetic cathinone N-ethylpentylone (ephylone) in the United Kingdom

Abstract Introduction Acute toxicity caused by New Psychoactive Substances (NPS) has created a significant burden for Emergency Departments (EDs). Here we report characteristics of people presenting with toxicity after exposure to the synthetic cathinone N-ethylpentylone (NEP). Methods Adults presenting to hospital with severe acute toxicity after suspected NPS use were recruited between March 2015 and October 2020. Clinical features were recorded using consistent methodology and biological samples analysed using liquid chromatography-tandem mass-spectrometry. Results NEP was detected in at least one sample from 9 of 893 patients recruited during the period of study, all presenting between 2016 and 2019 and 8 presenting in southern England. Commonly reported clinical features included tachycardia (6), agitation (6), confusion (6), mydriasis (5), hallucinations (4), acidosis (3) and elevated creatine kinase (3). Co-used drugs, detected in 6 patients, may have contributed to these features, but agitation and hallucinations were also reported in all 3 patients without analytical evidence of co-use. Conclusions NEP was detected infrequently in episodes of drug toxicity in the UK between 2016 and 2019, especially in southern England. Clinical characteristics of toxicity are similar to those of other cathinones, although co-use of other drugs is common and may contribute to the features observed.
Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree Relatives at Risk of Developing MEN1: A Prospective Study

Abstract Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as ‘MEN1-like’. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3′ and 5′ untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3′ and 5′ UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.
Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma

Significance Primary Open Angle Glaucoma (POAG) is the most common form of glaucoma that leads to irreversible vision loss and blindness worldwide. POAG is often associated with elevated intraocular pressure (IOP). The trabecular meshwork (TM), a molecular sieve-like structure, tightly controls IOP by constantly adjusting the resistance to aqueous humor (AH) outflow. In POAG, there is increased resistance to AH outflow, elevating IOP. Here, we show that mechanically activated TRPV4 channels in TM play a critical role in IOP regulation via calcium-mediated activation of eNOS signaling and production of nitric oxide (NO). Importantly, we show that impaired TRPV4 channel activity results in reduced NO bioavailability and elevated IOP in glaucoma. Our findings support impaired TRPV4-eNOS signaling to the pathogenesis of POAG. Primary Open Angle Glaucoma (POAG) is the most common form of glaucoma that leads to irreversible vision loss. Dysfunction of trabecular meshwork (TM) tissue, a major regulator of aqueous humor (AH) outflow resistance, is associated with intraocular pressure (IOP) elevation in POAG. However, the underlying pathological mechanisms of TM dysfunction in POAG remain elusive. In this regard, transient receptor potential vanilloid 4 (TRPV4) cation channels are known to be important Ca2+ entry pathways in multiple cell types. Here, we provide direct evidence supporting Ca2+ entry through TRPV4 channels in human TM cells and show that TRPV4 channels in TM cells can be activated by increased fluid flow/shear stress. TM-specific TRPV4 channel knockout in mice elevated IOP, supporting a crucial role for TRPV4 channels in IOP regulation. Pharmacological activation of TRPV4 channels in mouse eyes also improved AH outflow facility and lowered IOP. Importantly, TRPV4 channels activated endothelial nitric oxide synthase (eNOS) in TM cells, and loss of eNOS abrogated TRPV4-induced lowering of IOP. Remarkably, TRPV4-eNOS signaling was significantly more pronounced in TM cells compared to Schlemm’s canal cells. Furthermore, glaucomatous human TM cells show impaired activity of TRPV4 channels and disrupted TRPV4-eNOS signaling. Flow/shear stress activation of TRPV4 channels and subsequent NO release were also impaired in glaucomatous primary human TM cells. Together, our studies demonstrate a central role for TRPV4-eNOS signaling in IOP regulation. Our results also provide evidence that impaired TRPV4 channel activity in TM cells contributes to TM dysfunction and elevated IOP in glaucoma.
Structural insights into the cause of human RSPH4A primary ciliary dyskinesia

Cilia and flagella are evolutionarily conserved eukaryotic organelles involved in cell motility and signaling. In humans, mutations in Radial Spoke Head Component 4A (RSPH4A) can lead to primary ciliary dyskinesia (PCD), a life-shortening disease characterized by chronic respiratory tract infections, abnormal organ positioning, and infertility. Despite its importance for human health, the location of RSPH4A in human cilia has not been resolved, and the structural basis of RSPH4A–/– PCD remains elusive. Here, we present the native three-dimensional structure of RSPH4A–/– human respiratory cilia using samples collected noninvasively from a PCD patient. Using cryo–electron tomography (cryo-ET) and subtomogram averaging, we compared the structures of control and RSPH4A–/– cilia, revealing primary defects in two of the three radial spokes (RSs) within the axonemal repeat and secondary (heterogeneous) defects in the central pair complex. Similar to RSPH1–/– cilia, the radial spoke heads of RS1 and RS2, but not RS3, were missing in RSPH4A–/– cilia. However, RSPH4A–/– cilia also exhibited defects within the arch domains adjacent to the RS1 and RS2 heads, which were not observed with RSPH1 loss. Our results provide insight into the underlying structural basis for RSPH4A–/– PCD and highlight the benefits of applying cryo-ET directly to patient samples for molecular structure determination.