Miracle-dz/UniFAR-FTUs huggingface dataset:
Coupling of Human Rhodopsin to a Yeast Signaling Pathway Enables Characterization of Mutations Associated with Retinal Disease

G protein-coupled receptors (GPCRs) are crucial sensors of extracellular signals in eukaryotes, and direct measurement of GPCR-mediated signaling is useful for high-throughput mutational studies. However, this is particularly difficult for the light-activated GPCR rhodopsin. G protein-coupled receptors (GPCRs) are crucial sensors of extracellular signals in eukaryotes, with multiple GPCR mutations linked to human diseases. With the growing number of sequenced human genomes, determining the pathogenicity of a mutation is challenging, but can be aided by a direct measurement of GPCR-mediated signaling. This is particularly difficult for the visual pigment rhodopsin—a GPCR activated by light—for which hundreds of mutations have been linked to inherited degenerative retinal diseases such as retinitis pigmentosa. In this study, we successfully engineered, for the first time, activation by human rhodopsin of the yeast mating pathway, resulting in signaling via a fluorescent reporter. We combine this novel assay for rhodopsin light-dependent activation with studies of subcellular localization, and the upregulation of the unfolded protein response in response to misfolded rhodopsin protein. We use these assays to characterize a panel of rhodopsin mutations with known molecular phenotypes, finding that rhodopsin maintains a similar molecular phenotype in yeast, with some interesting differences. Furthermore, we compare our assays in yeast with clinical phenotypes from patients with novel disease-linked mutations. We demonstrate that our engineered yeast strain can be useful in rhodopsin mutant classification, and in helping to determine the molecular mechanisms underlying their pathogenicity. This approach may also be applied to better understand the clinical relevance of other human GPCR mutations, furthering the use of yeast as a tool for investigating molecular mechanisms relevant to human disease.
Impact of nurse champion on quality of care and outcomes in type 2 diabetes patients

ABSTRACT Over 29 million people in the United States have diabetes, with an additional 86 million living with prediabetes. On inpatient hospital units it is estimated that 50% of admitted patients have diabetes as a primary or secondary diagnosis. Nurse champions have improved outcomes and quality of life for patients across different clinical settings. The purposes of this evidence literature review are to evaluate and synthesize evidence regarding the impact of a nurse champion model on nurses’ performances and diabetic patient health outcomes. Nurse champions in this review also refer to clinical nurse specialists, certified diabetes educators, and clinical mentors. Search of evidence-based literature was conducted using PubMed, CINAHL, Ovid, Cochrane Library, and Google Scholar databases. Keywords included Nurse Champion and Diabetes, Clinical Mentor and Diabetes, and Diabetes Educator. Search limits included date of publication within last 15 years, English language, and peer-reviewed journals. A total of 14 articles were included in the synthesis of literature with level of evidence ranging from I to V. The study designs of selected evidence fluctuate from randomized controlled trials (3), case studies (6), qualitative studies (2), systematic review (1), and quasi-experimental study (1). The synthesis of evidence indicated that implementation of a nurse champion model did not only significantly improve nurses’ diabetic knowledge and skills, but also improved the health outcomes of diabetic patients including reduction in hemoglobin A1c levels, reduction in perceived Diabetes Distress Scale, quality of life improvement, reduction of number of near misses, decreased readmission rates, improved hypoglycemic outcomes, and greater weight loss in patients with type 2 diabetes. Improving diabetic patient outcomes could save the hospital a significant amount of money and create a higher standard of care across the healthcare field. Bettering patient outcomes are good not only for the patient but also the hospital and nurses. Implementation of nurse champion models into nursing practice could significantly improve patient outcomes and quality of life as well as nursing performance. Nurse champion models also can create new leadership roles in nursing.
The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function

Research has suggested a number of beneficial effects arising from the consumption of dietary flavonoids, found in foods such as cocoa, apples, tea, citrus fruits and berries on cardiovascular risk factors such as high blood pressure and endothelial dysfunction. These effects are thought to have a significant impact upon both vascular and cerebrovascular health, ultimately with the potential to prevent cardiovascular and potentially neurodegenerative disease with a vascular component, for example vascular dementia. This review explores the current evidence for the effects of flavonoid supplementation on human endothelial function and both peripheral and cerebral blood flow (CBF). Evidence presented includes their potential to reduce blood pressure in hypertensive individuals, as well as increasing peripheral blood perfusion and promoting CBF in both healthy and at-risk populations. However, there is great variation in the literature due to the heterogeneous nature of the randomised controlled trials conducted. As such, there is a clear need for further research and understanding within this area in order to maximise potential health benefits.
Cyclin C directly stimulates Drp1 GTP affinity to mediate stress-induced mitochondrial hyperfission

Mitochondria exist in an equilibrium between fragmented and fused states that shifts heavily toward fission in response to cellular damage. Nuclear-to-cytoplasmic cyclin C relocalization is essential for dynamin-related protein 1 (Drp1)–dependent mitochondrial fission in response to oxidative stress. This study finds that cyclin C directly interacts with the Drp1 GTPase domain, increases its affinity to GTP, and stimulates GTPase activity in vitro. In addition, the cyclin C domain that binds Drp1 is contained within the non–Cdk binding second cyclin box domain common to all cyclin family members. This interaction is important, as this domain is sufficient to induce mitochondrial fission when expressed in mouse embryonic fibroblasts in the absence of additional stress signals. Using gel filtration chromatography and negative stain electron microscopy, we found that cyclin C interaction changes the geometry of Drp1 oligomers in vitro. High–molecular weight low–GTPase activity oligomers in the form of short filaments and rings were diminished, while dimers and elongated filaments were observed. Our results support a model in which cyclin C binding stimulates the reduction of low–GTPase activity Drp1 oligomers into dimers capable of producing high–GTPase activity filaments.
Neuromodulation - Science and Practice in Epilepsy: Vagus Nerve Stimulation, Thalamic Deep Brain Stimulation, and Responsive NeuroStimulation

ABSTRACT Introduction: Neuromodulation devices can be safe and effective for the treatment of drug-resistant epilepsy. A body of scientific work supports peripheral, subcortical and cortical targets, each with different fundamental methods of action. Areas covered: High-quality evidence is available for vagal nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Mechanistic research in animals and human studies are reviewed, along with key data from VNS, DBS, and RNS clinical trials. Specifically, the authors review some of the science behind the most frequently used medical devices for neuromodulation, the evidence that lead to their adoption, a delineation of the populations that often benefit from these devices, and perspectives on clinical practice to optimize benefit in treatment of seizures. Expert Commentary: Neuromodulation is increasingly used to complement medical management of refractory epilepsy. Device preference will be made on the basis of patient preference, physician familiarity and other individualized factors. Right now, the field is very new and decision-making will improve with experience.
Epigenetic Programming Effects of Early Life Stress: A Dual-Activation Hypothesis

Epigenetic processes during early brain development can function as ‘developmental switches’ that contribute to the stability of long-term effects of early environmental influences by programming central feedback mechanisms of the HPA axis and other neural networks. In this thematic review, we summarize accumulated evidence for a dual-activation of stress-related and sensory networks underlying the epigenetic programming effects of early life stress. We discuss findings indicating epigenetic programming of stress-related genes with impact on HPA axis function, the interaction of epigenetic mechanisms with neural activity in stress-related neural networks, epigenetic effects of glucocorticoid exposure, and the impact of stress on sensory development. Based on these findings, we propose that the combined activation of stress-related neural networks and stressor-specific sensory networks leads to both neural and hormonal priming of the epigenetic machinery, which sensitizes these networks for developmental programming effects. This allows stressor-specific adaptations later in life, but may also lead to functional mal-adaptations, depending on timing and intensity of the stressor. Finally, we discuss methodological and clinical implications of the dual-activation hypothesis. We emphasize that, in addition to modifications in stress-related networks, we need to account for functional modifications in sensory networks and their epigenetic underpinnings to elucidate the long-term effects of early life stress.
Providing very preterm infants with donor human milk led to faster breastfeeding rates but worse biometric gains

AIM To evaluate the immediate clinical impact of donor human milk availability in a NICU about nutritional, clinical and biometric parameters. METHODS This retrospective-cohort study included 28-32 weeks gestational age born at our hospital in a three-year period before and after the donor human milk implementation. Data about starting, advance and discharge enteral nutrition, clinical outcomes, hospital stay and biometrics, was collected. RESULTS Infants in period with donor human milk started enteral nutrition 16 hours earlier (p<0.001) and achieved minimum, complete and 150 mL/kg/day enteral nutrition 26, 15 and 94 hours earlier respectively (p<0.001). Breastfeeding at discharge and own mother's milk intakes showed no differences except for a greater volume in first day in the second group (p=0.016). Patients in period with donor human milk also showed slower growth in weight, length and head circumference. CONCLUSIONS The donor human milk implementation at our NICU allowed an earlier starting and faster progression of enteral nutrition, maintaining own mother's milk intakes and breastfeeding rates at discharge. Biometric gain parameters were lower in the donor human milk group. This article is protected by copyright. All rights reserved.
Advance care planning for patients with cancer in the palliative phase in Dutch general practices.

Background Advance care planning (ACP) is a crucial element of palliative care. It improves the quality of end-of-life care and reduces aggressive and needless life-prolonging medical interventions. However, little is known about its application in daily practice. This study aims to examine the application of ACP for patients with cancer in general practice. Methods We performed a retrospective cohort study in 11 general practices in the Netherlands. Electronic patient records (EPRs) of deceased patients with colorectal or lung cancer were analysed. Data on ACP documentation, correspondence between medical specialist and GP, and health care use in the last year of life were extracted. Results Records of 163 deceased patients were analysed. In 74% of the records, one or more ACP items were registered. GPs especially documented patients' preferences for euthanasia (58%), palliative sedation (46%) and preferred place of death (26%). Per patient, GPs received on average six letters from medical specialists. These letters mainly contained information regarding medical treatment and rarely ACP items. In the last year of life, patients contacted the GP over 30 times, and 51% visited the emergency department at least once, of whom 54% in the last month. Conclusions Registration of ACP items in GPs' EPRs appeared to be limited. ACP elements were rarely subject of communication between primary and secondary care, which may impact the continuity of patient care during the last year of life. More emphasis on registration of ACP items and better exchange of information regarding patients' preferences are needed.
Intergenerational Transmission of DNA Methylation Signatures Associated with Early Life Stress

Early life stress in humans (i.e. maltreatment, violence exposure, loss of a loved one) and in rodents (i.e. disrupted attachment or nesting, electric shock, restraint, predator odor) occurs during critical steps of neural circuit formation. ELS in humans is associated with increased risk for developmental psychopathology, including anxious and depressive phenotypes. The biological mechanisms underlying these potentially persistent maladaptive changes involve long-term epigenetic modifications, which have been suggested to be potentially transmissible to subsequent generations. DNA methylation is an epigenetic mechanism that modifies gene expression patterns in response to environmental challenges and influences mutation rates. It remains to be seen whether a functionally relevant fraction of DNA methylation marks can escape genome-wide erasures that occur in primordial germ cells and after fertilization within the zygote. Early life-stress-triggered changes in epigenetic mediated transmission of acquired behavioral traits among humans have been assessed mainly by targeting genes involved in the hypothalamic-pituitary-adrenal (HPA) axis, such as NR3C1 and FKBP5. Recently, researchers examining epigenetic transmission have begun to apply genome-wide approaches. In humans, reduced representation bisulfite sequencing (RRBS) was performed on peripheral samples that were obtained from individuals who were prenatally exposed to the “Dutch Hunger Winter”, resulting in two Differentially Methylated Regions (DMRs) in INSR and CPTIA genes that were functionally, biologically and technically validated, and significantly associated with birth weights and LDL cholesterol levels in offspring. In rodents, non-genomic intergenerational transmission of anxiety which was associated with differentially methylated enhancers that were putatively involved in lipid signaling and synaptic/neurotransmission in hippocampal granule cells, was discovered also using RRBS. Finally, transgenerational transmission of altered behaviors was associated with sperm-derived microRNAs produced by ELS male mice. The field of epigenetic transmission is just beginning to enter the epigenomic era by using genome-wide analyses. Such approaches remain of strong interest to human studies, first in order to help to assess the relevance of the previous targeted studies, and second to discover new important epigenetic modifications of potential clinical importance. New discoveries may help to assess how transmittable the negative impact of stress may be to offspring. The latter may open doors for future treatments and resilience-promoting interventions, as well as new approaches to treat the effects of childhood trauma before the onset of psychiatric disorder.
Musculoskeletal Screening to Identify Female Collegiate Rowers at Risk for Low Back Pain.

CONTEXT Rowers are at risk for overuse injuries, including low back pain (LBP). Defining the utility of screening tests for identifying those at risk for LBP can aid in the development of guidelines for injury prevention. OBJECTIVE To determine if the Functional Movement Screen (FMS) and impairments can identify rowers at risk for developing LBP. DESIGN Prospective cohort study. SETTING Athletic training room. PATIENTS OR OTHER PARTICIPANTS A total of 31 National Collegiate Athletic Association Division I, female, open-weight rowers (age = 19.9 ± 1.4 years, height = 163.6 ± 30.8 cm, mass = 84.1 ± 37.63 kg); coxswains were excluded. MAIN OUTCOME MEASURE(S) We assessed the FMS and 5 impairment measures of the Star Excursion Balance Test, closed kinetic chain dorsiflexion range of motion, and the plank, Sorensen, and sit-and-reach tests before the fall season. Low back pain injuries were tracked by the sports medicine staff. Impairment measures were compared between the injured and uninjured athletes. The FMS cutoff score that discriminated injured from uninjured rowers was determined using a receiver operating characteristic curve analysis. Impairments were compared between those at a higher versus lower risk of LBP. RESULTS Eighteen rowers sustained an LBP injury. No differences in FMS or impairments between groups were demonstrated. The FMS receiver operating characteristic curve analysis cutoff score was 16 points (area under the curve = 0.60, specificity = 0.67, risk ratio = 1.4 [95% confidence interval = 0.91, 2.11]). Rowers with an FMS score ≤16 had a shorter plank-test time (109.5 ± 60.2 seconds) than those with less risk (175.3 ± 98.6 seconds, mean difference = 65.9 seconds, 95% confidence interval = -129.4, -2.3; P = .043). CONCLUSIONS Those with an FMS score ≤16 had a shorter plank-test hold time, indicating that a lack of core endurance may contribute to the increased risk of LBP in female rowers. An FMS score ≤16 indicated a small increased risk (1.4) of developing LBP compared with rowers who had scores >16; however, the FMS is not recommended for widespread screening of female rowers because the risk ratio was relatively small and had a wide 95% confidence interval.
Evaluating sociotechnical dynamics in a simulated remotely-piloted aircraft system: a layered dynamics approach

Abstract As coordination mechanisms change and technology failures occur, a sociotechnical system must reorganise itself across human and technological layers to maintain effectiveness. We present a study examining reorganisation across communication, controls and vehicle layers of a remotely-piloted aircraft system (RPAS) using a layered dynamics approach. Team members (pilot; navigator; photographer) performed 5 simulated RPAS missions using different operator configurations, including all-human and human-autonomy teams. Reorganization (operationally defined using entropy) time series measured the changing system reorganisation profiles under different operator configurations and following autonomy failures. Correlations between these reorganisation profiles and team effectiveness scores describe the manner in which the system had to be coordinated to maintain effectiveness under these changing conditions. Four unplanned autonomy failures were analysed to visualise system reorganisation following a technology failure. With its objective and real-time modelling and measurement capabilities, layered dynamics complements existing systems thinking tools for understanding sociotechnical complexity and enhancing system effectiveness. Practitioner summary: A layered dynamics approach for understanding how a sociotechnical system dynamically reorganises itself is presented. The layered dynamics of RPAS were analysed under different operator configurations and following autonomy failures. Layered dynamics complements existing system-thinking tools for modelling sociotechnical system complexity and effectiveness. Abbreviation: RPAS: remotely-piloted aircraft system; HIS: human-systems integration; EAST: event analysis of systemic teamwork; H1: hypothesis 1; H2: hypothesis 2; H3: hypothesis 3; CERTT-STE: cognitive engineering research on team tasks--synthetic task environment; AVO: air vehicle operator; PLO: payload operator; DEMPC: data exploitation, mission planning, and communications; ACT-R: adaptive control of thought-rational; sec: seconds; ANOVA: analysis of variance
Management Recommendations on Sleep Disturbance of Patients with Parkinson's Disease

iNtroDuCtioN Sleep disturbance is one of the most common nonmotor symptoms in Parkinson’s disease (PD). Sleep disturbance affects 40–98% of PD patients in the world. [1‐3] In China, the prevalence of PD patients with sleep disturbance ranges from 47.66% to 89.10%. [4‐9] Sleep disturbance usually has adverse impact on the quality of life of PD patients. A possible pathogenesis of PD with sleep disturbance include thalamocortical pathway degeneration and changes of neurotransmitter systems. [3] The etiology of sleep disturbance is multifactorial, involving degeneration of areas regulating sleep, sleep structure affected by drugs, sleep disturbance induced by drug, and sleep fragmentation by multiple factors. [3] Although three reviews on the sleep disturbances of PD have recently been published, there is no consensus of recommendations on the management of PD patients with sleep disturbance. [1,3,10]
Determination of car seat contact area for personalised thermal sensation modelling

A lot of daily activities are conducted in a sedentary posture. This includes a thermal interaction between the human and the seat that has implications on thermal perception and comfort. These interactions are investigated by simulating heat and mass transfer, thus, reducing a need for costly and time demanding subject studies. However, it is not clear, from the available literature, what portion of the body surface area is actually affected by the seat with respect to human anthropometry. The aim of this study was to develop a predicting function of the seat contact area based on anthropometric parameters. The results showed strong linear correlation between the contact area obtained by printing a body silhouette on paper placed at the seat and body weight, height, body surface area, and body mass index. The body surface area and the body weight were identified as the best predictors for the contact area.