Miracle-dz/UniFAR-FTUs huggingface dataset:
Biopsy rate and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD)

Abstract Background: Licensed therapies for nonalcoholic fatty liver disease (NAFLD) do not yet exist, but clinical trials are testing treatment options. Inclusion criteria often require liver biopsy showing fibrosis (F2/3) or cirrhosis (F4) and nonalcoholic steatohepatitis (NASH). However, histological criteria pose a serious obstacle for recruitment. Aims: Characterize the relevance of liver biopsies in the selection of patients with NAFLD. Methods: Patients between 2013 and 2018 with the ICD-10 code K76.0 were analyzed. Fibrosis was defined by the NASH clinical research network (CRN) fibrosis staging system, NASH by a NAFLD activity score (NAS) ≥4. Predictive factors were determined by logistic regression. Results: Liver biopsy was performed in 87/638 (13.6%) patients (49% female, age 52.5 ± 14.0, BMI 30.4 ± 5.9 kg/m2). Fibrosis stage F0/F1/F2/F3/F4 was observed in N = 7/47/7/17/9, an NAS ≥4 in N = 27. Fibrosis stage F2/F3 and F4 along with NAS ≥4 was found in 1.7% and 0.5% of cases. Liver stiffness measurement, LSM (OR 2.3 per doubling of value; CI 1.3–4.4, p = .005) and FIB-4 (OR 2.3 per doubling of value; CI 1.2–4.4, p = .012) were significant predictors for fibrosis ≥ F2. Predictive factors for NASH were not identified. Conclusion: The biopsy rate in NAFLD patients is low and fibrosis ≥ F2 along with NAS ≥4 only present in a few cases. Transient elastography and FIB-4 are useful to select patients at risk for fibrosis for liver biopsy.
Plastid biogenesis in malaria parasites requires the interactions and catalytic activity of the Clp proteolytic system

Significance The deadly malaria parasite, Plasmodium falciparum, has developed resistance to all currently available drugs, making the discovery of new drug targets a top priority. This eukaryotic pathogen has a unique organelle called the apicoplast that produces essential metabolites. Although the apicoplast carries its own genome, most of its proteins are encoded by the cell nucleus and it is unclear how the organelle regulates its own proteome. Here, we show that a protease complex functions as a master regulator of apicoplast biogenesis. We have shown that the essential function of the complex is determined by its proteolytic activity, regulation by a chaperone, and substrate selection. This study demonstrates the potential of the apicoplast caseinolytic-protease system as an excellent drug target. The human malaria parasite, Plasmodium falciparum, contains an essential plastid called the apicoplast. Most apicoplast proteins are encoded by the nuclear genome and it is unclear how the plastid proteome is regulated. Here, we study an apicoplast-localized caseinolytic-protease (Clp) system and how it regulates organelle proteostasis. Using null and conditional mutants, we demonstrate that the P. falciparum Clp protease (PfClpP) has robust enzymatic activity that is essential for apicoplast biogenesis. We developed a CRISPR/Cas9-based system to express catalytically dead PfClpP, which showed that PfClpP oligomerizes as a zymogen and is matured via transautocatalysis. The expression of both wild-type and mutant Clp chaperone (PfClpC) variants revealed a functional chaperone–protease interaction. Conditional mutants of the substrate-adaptor (PfClpS) demonstrated its essential function in plastid biogenesis. A combination of multiple affinity purification screens identified the Clp complex composition as well as putative Clp substrates. This comprehensive study reveals the molecular composition and interactions influencing the proteolytic function of the apicoplast Clp system and demonstrates its central role in the biogenesis of the plastid in malaria parasites.
An Innovative Online Knowledge Translation Curriculum in Graduate Education.

BACKGROUND There is increased acknowledgment of the importance of knowledge translation (KT) in the role of graduate-prepared healthcare practitioners, such as nurses, as change agents in the mobilization of evidence-based knowledge. The offering of flexible educational programming online and hybrid course delivery in higher education is a response to insufficient didactic methods for providing graduate students with the competencies to facilitate KT. AIMS To describe the development, implementation, and evaluation of a cohort-based, online, innovative KT curriculum using a theoretical approach to KT called the Knowledge-As-Action Framework, which focuses on the knower, knowledge, and context as being inseparable. This process strategically engages with stakeholders to link practice concerns with existing realities, thus providing the best available knowledge to inform KT action in complex healthcare contexts. METHODS The Model of Evidence-Informed, Context-Relevant, Unified Curriculum Development in Nursing Education guided the cohort-based online KT course process. The development, implementation, and evaluation involved (a) an environmental scan, (b) a literature review, (c) faculty development, (d) curriculum design of two 10-week courses, and (e) a summation of the concurrent participatory evaluation of the two courses, including faculty and student responses. The Knowledge-As-Action Framework is comprised of six interrelated dimensions as part of a "kite" metaphor, with the underlying premise that if any one of the dimensions results in an imbalance, the KT process may be grounded. RESULTS Evaluation revealed (a) intentionality of the core processes of curriculum work; (b) effectiveness of indicators for evaluating the KT courses; (c) leadership should be added as a learning domain for KT; (d) the Knowledge-As-Action Framework provided an integrated, philosophical, and evidence-based approach to KT; (e) cohort model facilitated a community of inquiry; and (f) the formalized structured approach of the courses with ongoing supervision and mentoring allowed for timely completion. LINKING EVIDENCE TO ACTION Teaching and learning in an online cohort model created a community of inquiry and facilitated experiential learning. The active engagement of students with their practice-based stakeholders promoted change in clinical settings and enhanced students' professional development to lead change.
Elevated circulating luteinizing hormone levels are associated with diabetic macroalbuminuria in Chinese men and postmenopausal women: A cross‐sectional study

Associations between sex hormones and diabetic vascular complications have recently been studied, but the role luteinizing hormone (LH) plays in diabetic kidney disease (DKD) remains uncertain. We aimed to investigate the relationship of LH and DKD in Chinese men and postmenopausal women with type 2 diabetes mellitus (T2DM).
Effects of Home Particulate Air Filtration on Blood Pressure

Supplemental Digital Content is available in the text. Air pollution is a major contributor to cardiovascular morbidity and mortality. Fine particulate matter <2.5 µm in diameter may be a modifiable risk factor for hypertension. The benefits of in-home air filtration on systolic blood pressure (BP) and diastolic BP are unclear. To examine the effects of in-home personal air cleaner use on fine particulate exposure and BP, we queried PubMed, Web of Science, Cochrane Central Register, Inspec, and EBSCO GreenFILE databases for relevant clinical trials. Included studies were limited to nonsmoking participants in smoke-free homes with active or sham filtration on indoor fine particulate concentrations and changes in systolic and diastolic BP. Of 330 articles identified, 10 trials enrolling 604 participants who met inclusion criteria were considered. Over a median 13.5 days, there was a significant reduction of mean systolic BP by ≈4 mm Hg (−3.94 mm Hg [95% CI, −7.00 to −0.89]; P=0.01) but a nonsignificant difference in mean diastolic BP (−0.95 mm Hg [95% CI, −2.81 to 0.91]; P=0.32). Subgroup analyses indicated no heterogeneity of effect by age, level of particulate exposure, or study duration. Given the variation in study design, additional study is warranted to confirm and better quantify the observed benefits in systolic BP found with personal air cleaner use.
Assessing the risks of intervention: immobilization, radio-collaring and vaccination of African wild dogs

Abstract Controversy has surrounded the role of intervention in studies of African wild dogs Lycaon pictus. Following the death or disappearance of all wild dogs under study in the Serengeti ecosystem, it was suggested that immobilization, radio-collaring or administration of rabies vaccines might have caused high mortality by compromising wild dogs′ immune response to rabies virus. Planning future management and research on wild dogs and other species demands an assessment of the risks associated with such intervention. This paper critically reviews the available evidence and concludes that it is extremely unlikely that intervention contributed to the extinction of wild dogs in the Serengeti ecosystem. A more likely scenario is that vaccination failed to protect wild dogs exposed to rabies virus. Radio-collaring is an important component of wild dog research; hence, the benefits of immobilization appear to outweigh the risks, as long as (i) research is orientated towards wild dog conservation, (ii) radiocollaring is followed up by efficient monitoring, (iii) the number of animals immobilized is kept to the minimum necessary to maintain scientific rigour, and (iv) full data on disease and genetics are collected from all immobilized animals. By contrast, rabies vaccination currently seems to confer few benefits, at least when a single dose of vaccine is given. Further research, on captive animals, is in progress to establish more effective protocols, and to assess the role that vaccination might play in future management of wild dog populations.
The diagnostic value of miRNA-141 in prostate cancer

Abstract Background: miR-141 has gradually demonstrated its value in the diagnosis of prostate cancer. However, the diagnostic parameters in previous studies differ. A systematic review was conducted to explore the diagnostic value of miR-141 in prostate cancer. Methods: A comprehensive search of the literature in the PubMed, Medline, Cochrane Library, and Embase databases was performed. The included 7 studies assessed the diagnostic value of miR-141 in patients with prostate cancer up to October 31, 2019. We used meta-disc version 1.4 and STATA software version 12.0 to analyze the data. Results: The pooled sensitivity and specificity were 0.70 (95% confidence interval [CI] 0.64–0.75) and 0.73 (95% CI 0.64–0.80), respectively. The positive likelihood ratio was 2.88 (95% CI 1.40–5.93), and the negative likelihood ratio was 0.38 (95% CI 0.20–0.71). Further, we note that the pooled diagnostic odds ratio of miR-141 for prostate cancer was 9.94 (95% CI: 2.55–38.80). The summary area under the receiver operating characteristic curve was 0.83 (95% CI: 0.79–0.86). The results of meta-regression suggested that heterogeneity was mainly derived from patient age. The results of the Fagan nomogram showed that it was increased significantly by testing miR-141 for diagnosing prostate cancer. Conclusion: This meta-analysis suggests that miR-141 has a high diagnostic value for prostate cancer. In the future, large-scale prospective studies are needed to verify and evaluate this result.
Management of cognitive decline in Alzheimer's disease using a non-pharmacological intervention program

Abstract Introduction: In China, the over 60 population is estimated to grow from 12% in 2010 to 33% of the overall population by 2050. The escalation in the aging population is projected to result in an Alzheimer's disease prevalence of 27.7 million people in China by 2050 causing substantial health and economic burden. While there are some published studies on multicomponent, non-pharmacological interventions for people with dementia, we have found no published community-based approach to care that encompasses personalized selection of non-pharmacological interventions, active social participation, and dementia education. Patient concerns: An elderly female living at home alone in urban Beijing presented with significant short-term memory impairment, episodes of confusion, difficulty with language skills, and episodes of wandering. She had become reclusive and disengaged from her previous social networks, and no longer attended any community activities or events. The patient had no significant past medical or psychiatric history. Diagnosis: The patient was diagnosed with Alzheimer's disease by a local physician based on clinical features of impaired communication, disorientation, confusion, poor judgement, behavioral changes, and difficulty speaking. Depression was considered a differential diagnosis but is also both a risk factor and symptom of dementia. Interventions: A novel, community-based, multicomponent social care program for dementia was used to facilitate implementation of non-pharmacological interventions, gradual socialization and provide supportive carer and community education. Non-pharmacological interventions included a combination of validation therapy, music therapy, art therapy, reminiscence therapy, talking therapy, reality orientation, cognitive training, smell therapy, food therapy, sensory stimulation, garden therapy, and physiotherapy. Outcomes: Improvements in the patient's Geriatric Depression Scale and Mini Mental State Examination scores were noted in association with increased social participation in the community. Conclusion: The community-based, multicomponent dementia social care program described in this case report has enabled a socially isolated patient with Alzheimer's disease to reduce her social isolation with an associated improvement in her mood and prevention of cognitive decline. Educating the community was an essential part of re-integrating the patient into the social setting. Reducing social isolation and increasing community engagement were essential to maintaining the patient's independence in her own home.
What students and new graduates perceive supports them to think, feel and act as a health professional in a rural setting.

OBJECTIVE Clinical placements in rural locations are perceived by students to provide positive learning experiences to support their transition to practice. This study explores how clinical placements in a rural health setting might influence students and new graduates to think, feel and act as a health professional. DESIGN A qualitative study comprising focus group discussions was conducted. SETTING The study was conducted in a rural health service in Queensland, Australia. PARTICIPANTS Allied health students (n = 12) on placement and new graduates (n = 11) working in a regional health service. MAIN OUTCOME MEASURES This study identified allied health student and new graduate perspectives on clinical placement factors which support them to think, feel and act as a health professional. RESULTS Thematic analysis was used to understand student and new graduate perceptions of how rural placements support thinking, feeling and acting as a health professional. Suggestions for supporting learning included the following: Development of learning partnerships between students and clinical educators with inbuilt expectations and opportunities for reflection and supervision. Creating a culture where students are welcomed, valued and encouraged to take meal breaks with the team supported connectedness. The importance of balancing student autonomy with educating and grading support to increase independence. CONCLUSIONS Findings show clinical placement experiences identified by allied health students and new graduates which support them to begin to think, feel and act as a health professional. Suggestions provided by students and new graduates can be used to inform implementation of clinical placement experiences.
3D Crumpled Ultrathin 1T MoS2 for Inkjet Printing of Mg-Ion Asymmetric Micro-supercapacitors

Metallic molybdenum disulfide (MoS2), e.g., 1T phase, is touted as a highly promising material for energy storage that already displays a great capacitive performance. However, due to its tendency to aggregate and restack, it remains a formidable challenge to assemble a high-performance electrode without scrambling the intrinsic structure. Here, we report an electrohydrodynamic-assisted fabrication of 3D crumpled MoS2 (c-MoS2) and its formation of an additive-free stable ink for scalable inkjet printing. The 3D c-MoS2 powders exhibited a high concentration of metallic 1T phase and an ultrathin structure. The aggregation-resistant properties of the 3D crumpled particles endow the electrodes with open space for electrolyte ion transport. Importantly, we experimentally discovered and theoretically validated that 3D 1T c-MoS2 enables an extended electrochemical stable working potential range and enhanced capacitive performance in a bivalent magnesium-ion aqueous electrolyte. With reduced graphene oxide (rGO) as the positive electrode material, we inkjet-printed 96 rigid asymmetric micro-supercapacitors (AMSCs) on a 4-in. Si/SiO2 wafer and 100 flexible AMSCs on photo paper. These AMSCs exhibited a wide stable working voltage of 1.75 V and excellent capacitance retention of 96% over 20 000 cycles for a single device. Our work highlights the promise of 3D layered materials as well-dispersed functional materials for large-scale printed flexible energy storage devices.
Safety considerations for forward falls

Objective: Forward falls are among the most frequent causes of upper extremity fractures. This study investigated the safety considerations to prevent wrist injuries during bimanual forward falls. Methods: A biomechanical model was developed with two separated arms to facilitate investigation of asymmetrical contact and predict the impact force applied to each hand separately. To validate the developed model, a series of fall experiments were conducted in which one hand collided with a hard surface, while the other collided with a soft surface. Results: The results show that the impact force applied to each hand is independent of the other. Using these results and our model, the safety aspects of human forward falls were analyzed with a view to preventing injuries. Specifically, we sought to determine the safe range of surface stiffness and damping to ensure that the occurrence of forward falls does not lead to trauma. Conclusion: The results of this study can be applied in the design of compliant flooring to ensure the safety of people in environments with potential fall hazards. From a robotics viewpoint, the results are applicable in the design of compliant flooring for shared workplaces, where robots collaborate with people and collisions between humans and robots may cause falls.
Efficacy of Guanfacine Extended Release in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder.

OBJECTIVE To assess the efficacy of the non-stimulant guanfacine extended release (GXR) on attention-deficit/hyperactivity disorder (ADHD) symptoms in children and adolescents, with and without comorbid oppositional defiant disorder (ODD). METHODS Data were derived from 4 phase 3, randomized, placebo-controlled trials of dose-optimized GXR monotherapy, in which at least 10% of participants had a diagnosis of comorbid ODD. SPD503-312 and SPD503-316 were 10- to 13-week studies of GXR (1-7 mg/d). SPD503-314 and SPD503-307 were 8-week studies of GXR (1-4 mg/d). Efficacy was assessed using the ADHD Rating Scale IV (ADHD-RS-IV) total scores. RESULTS In total, 1,084 participants were included (SPD503-312 and SPD503-316, n = 537; SPD503-314, n = 333; and SPD503-307, n = 214). GXR was associated with significant improvements in ADHD core symptoms at endpoint in participants with and without ODD (p < 0.01 in all studies). Placebo-adjusted least-squares mean (95% confidence interval) changes from baseline to endpoint in the ADHD-RS-IV total scores in participants with and without ODD were -8.6 (-14.4, -2.8) and -7.3 (-9.5, -5.0) in the pooled data from SPD503-312 and SPD503-316, -12.6 (-19.6, -5.7) and -8.7 (-11.8, -5.5) in SPD503-314, and -12.7 (-17.3, -8.1) and -11.8 (-19.3, -4.4) in SPD503-307, respectively. The corresponding effect sizes were 0.688 and 0.598 in SPD503-312 and SPD503-316, 0.876 and 0.729 in SPD503-314, and 0.962 and 0.842 in SPD503-307. CONCLUSION The findings demonstrate the efficacy of GXR for treating ADHD in children and adolescents with comorbid ODD.
Are legume-based recipes an appropriate source of nutrients for healthy ageing? A prospective cohort study

Abstract Although legumes are rich in protein and fibre, and low in saturated fat and Na, traditional legume-based recipes include substantial amounts of processed meat, salt and potatoes, which could counteract the potential benefits of legumes. This prospective study aimed to assess the longitudinal association of consumption of different types of legumes, and traditional legume-based recipes, with unhealthy ageing in older adults. Data were taken from 2505 individuals aged ≥60 years from the Seniors-ENRICA cohort. Habitual legume consumption was assessed in 2008–2010 with a validated diet history. Unhealthy ageing was measured in the 2013, 2015 and 2017 follow-up waves, with a fifty-two-item multidimensional health deficit accumulation index (DAI) which ranges from 0 (best) to 100 (worst health). The mean age was 68·7 years, with 53·1 % of women. Among study participants, 78·4 % reported consumption of legumes, with a mean intake of 57·9 g/d. Multivariable-adjusted linear regression models did not show an association between total legume consumption and the DAI over a 7-year follow-up (non-standardised coefficient for the second and highest v. the lowest tertile of consumption: 0·94 (95 % CI −0·30, 2·17) and 0·18 (95 % CI −1·07, 1·43), respectively; Ptrend = 0·35). Similar results were observed for the 3-year and 5-year follow-ups and, separately, for lentils, beans, chickpeas and traditional legume-based recipes. According to the results obtained, consumption of legumes and traditional legume-based recipes is not associated with unhealthy ageing and can be part of a healthy diet in old age.