Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasticity of Dopaminergic Phenotype and Locomotion in Larval Zebrafish Induced by Brain Excitability Changes during the Embryonic Period

Visual Abstract During the embryonic period, neuronal communication starts before the establishment of the synapses with alternative forms of neuronal excitability, called here embryonic neural excitability (ENE). ENE has been shown to modulate the unfolding of development transcriptional programs, but the global consequences for developing organisms are not all understood. Here, we monitored calcium (Ca2+) transients in the telencephalon of zebrafish embryos as a proxy for ENE to assess the efficacy of transient pharmacological treatments to either increase or decrease ENE. Increasing or decreasing ENE at the end of the embryonic period promoted an increase or a decrease in the numbers of dopamine (DA) neurons, respectively. This plasticity of dopaminergic specification occurs in the subpallium (SP) of zebrafish larvae at 6 d postfertilization (dpf), within a relatively stable population of vMAT2-positive cells. Nondopaminergic vMAT2-positive cells hence constitute an unanticipated biological marker for a reserve pool of DA neurons that can be recruited by ENE. Modulating ENE also affected larval locomotion several days after the end of the treatments. In particular, the increase of ENE from 2 to 3 dpf promoted hyperlocomotion of larvae at 6 dpf, reminiscent of zebrafish endophenotypes reported for attention deficit hyperactivity disorders (ADHDs). These results provide a convenient framework for identifying environmental factors that could disturb ENE as well as to study the molecular mechanisms linking ENE to neurotransmitter specification.
Cardiac magnetic resonance haemodynamics in paediatric heart transplant patients: fick oximetry versus cardiac magnetic resonance phase contrast

Background: Lifetime radiation exposure for paediatric orthotopic heart transplant (OHT) patients is significant with cardiac catheterisation as the dominant source. Interventional cardiac magnetic resonance is utilised to obtain simultaneous, radiation-free haemodynamics and flow/function measurements. We sought to compare invasive haemodynamic measurements and radiation exposure in traditional cardiac catheterisation, to comprehensive interventional cardiac magnetic resonance. Methods: Twenty-eight OHT patients who underwent 67 interventional cardiac magnetic resonance procedures at Children’s National Hospital were identified. Both invasive oximetry with peripheral oxygen saturation (Fick) and cardiac magnetic resonance phase contrast measurements of pulmonary and systemic blood flow were performed. Systemic and pulmonary blood flow from the two modalities was compared using Bland–Altman, concordance analysis, and inter-reader correlation. A mixed model was implemented to account for confounding variables and repeat encounters. Radiation dosage data were collected for a contemporaneous cohort of orthotopic heart transplant patients undergoing standard, X-ray-guided catheterisation. Results: Simultaneous cardiac magnetic resonance and Fick have poor agreement in our study based on Lin’s correlation coefficient of 0.68 and 0.73 for pulmonary and systemic blood flow, respectively. Bland–Altman analysis demonstrated a consistent over estimation of cardiac magnetic resonance cardiac output by Fick. The average indexed dose area product for patients undergoing haemodynamics with endomyocardial biopsy was 0.73 (SD ±0.6) Gy*m2/kg. With coronary angiography added, the indexed dose area product was 14.6 (SD ± 7.8) Gy*m2/kg. Conclusions: Cardiac magnetic resonancemeasurements of cardiac output/index in paediatric orthotopic heart transplant patients have poor concordance with Fick estimates; however, cardiac magnetic resonance has good internal validity and inter-reader reliability. Radiation doses are small for haemodynamics with biopsy and increase exponentially with angiography, identifying a new target for cardiac magnetic resonance imaging.
Twelve tips for practical clinical skills coaching

Abstract Coaching is rapidly evolving in clinical medicine, including for clinical skills (CS) learning. Yet a schema is needed for how to coach students in the many CS that are pivotal to the practice of medicine. These twelve tips aim to provide practical strategies for teachers and educators to coach students for CS learning. The tips cover many important aspects of CS coaching, including establishing a safe space, ways to prepare to coach, setting goals, guiding a coaching relationship, fostering coaching conversations, and in-person or virtual approaches. Together, the tips align as seven key steps of an overall coaching process. The twelve tips apply equally to coaching struggling students and all students seeking to improve CS and offer a guide for coaching at an individual or program level.
Heat-driven molecule gatekeepers in MOF membrane for record-high H2 selectivity

Hydrogen/carbon dioxide (H2/CO2) separation for sustainable energy is in desperate need of reliable membranes at high temperatures. Molecular sieve membranes take their nanopores to differentiate sizes between H2 and CO2 but have compromised at a marked loss of selectivity at high temperatures owing to diffusion activation of CO2. We used molecule gatekeepers that were locked in the cavities of the metal-organic framework membrane to meet this challenge. Ab initio calculations and in situ characterizations demonstrate that the molecule gatekeepers make a notable move at high temperatures to dynamically reshape the sieving apertures as being extremely tight for CO2 and restitute with cool conditions. The H2/CO2 selectivity was improved by an order of magnitude at 513 kelvin (K) relative to that at the ambient temperature.
Subjective awareness of sleepiness while driving in younger and older adults

Understanding whether drivers can accurately assess sleepiness is essential for educational campaigns advising drivers to stop driving when feeling sleepy. However, few studies have examined this in real‐world driving environments, particularly among older drivers who comprise a large proportion of all road users. To examine the accuracy of subjective sleepiness ratings in predicting subsequent driving impairment and physiological drowsiness, 16 younger (21–33 years) and 17 older (50–65 years) adults drove an instrumented vehicle for 2 h on closed loop under two conditions: well‐rested and 29 h sleep deprivation. Sleepiness ratings (Karolinska Sleepiness Scale, Likelihood of Falling Asleep scale, Sleepiness Symptoms Questionnaire) were obtained every 15min, alongside lane deviations, near crash events, and ocular indices of drowsiness. All subjective sleepiness measures increased with sleep deprivation for both age groups (p < 0.013). While most subjective sleepiness ratings significantly predicted driving impairment and drowsiness in younger adults (OR: 1.7–15.6, p < 0.02), this was only apparent for KSS, likelihood of falling asleep, and “difficulty staying in the lane for the older adults” (OR: 2.76–2.86, p = 0.02). This may be due to an altered perception of sleepiness in older adults, or due to lowered objective signs of impairment in the older group. Our data suggest that (i) younger and older drivers are aware of sleepiness; (ii) the best subjective scale may differ across age groups; and (iii) future research should expand on the best subjective measures to inform of crash risk in older adults to inform tailored educational road safety campaigns on signs of sleepiness.
Caries Experience in Elderly People Consuming a Milk-Based Drink Nutritional Supplement: A Cross-Sectional Study

Nutritional supplements have been recommended to cope with malnutrition in elderly persons. In Chile, the Supplementary Nutrition Program for the Elderly (PACAM, for its Spanish acronym) consists in a monthly distribution of a low-fat-milk-based drink that contains 8% sucrose. The aim of this study was to determine whether older persons consuming the milk-based drink have a higher caries experience when compared to those not receiving the supplement. A cross-sectional study was conducted in the Maule Region in Chile. The representative sample comprised two groups: (a) PACAM consumers (CS) (n = 60) and (b) nonconsumers (NCS) (n = 60). Participants received intraoral examination and coronal (DMFT/DMFS) and root caries (RCI index) experience were recorded. Additionally, questionnaires regarding acceptability and consumption habits of PACAM and a 24-h diet recall were applied. The influence of predictors was calculated using binary logistic regression for a dichotomized DMFS and Poisson Regression for root caries lesions. A p value <0.05 was considered significant. No differences were detected in food consumption patterns between study groups (p > 0.05). CS participants had increased dairy product consumption. Higher DMFS mean value was observed in the CS (85.35 ± 39.0) compared with NCS (77.28 ± 28.9) (p = 0.043). The multivariate analysis showed nonconsumers of the milk-based product (β = −0.41, p = 0.02) are less likely to have root surfaces affected by caries. Additionally, CS show higher RCI, compared to nonconsumers (β = −0.17, p = 0.02). Daily consumption of a PACAM’s milk-based drink supplement seems to increase coronal and root caries risk. Based on these results, composition modification of milk-based drinks with added sucrose appears mandatory.
New Results On Sequencing With Rate Modification

Abstract In many production systems a time period is scheduled for machine maintenance, during which the machine is idle. After the maintenance activity is completed the production rate may be affected. The decisions under consideration are (i) when to schedule this rate-modifying activity, and (ii) how to sequence the jobs. We study three single machine scheduling problems with a rate-modifying activity: minimum makespan with precedence constraints, minimum makespan with a learning effect and minimum number of tardy jobs. We introduce a polynomial time solution for each of the three problems.
“We All Want to Be Able to Tell You Something Hopeful”: Clinicians’ Experiences Providing Maternal-Fetal Surgery Counseling

Introduction: Prenatal counseling about maternal-fetal surgery can be traumatic and confusing for pregnant people. It can also be technically and emotionally complex for clinicians. As maternal-fetal surgery rapidly advances and becomes more common, more evidence is needed to inform counseling practices. The objective of this study was to develop a deeper understanding of the methods clinicians currently use to train for and provide counseling, as well as their needs and recommendations for future education and training. Methods: We used interpretive description methods and interviewed interprofessional clinicians who regularly counsel pregnant people about maternal-fetal surgery. Results: We conducted 20 interviews with participants from 17 different sites who were maternal-fetal medicine specialists (30%), pediatric surgeons (30%), nurses (15%), social workers (10%), a genetic counselor (5%), a neonatologist (5%), and a pediatric subspecialist (5%). Most were female (70%), non-Hispanic white (90%), and practiced in the Midwest (50%). We identified four overarching themes: (1) contextualizing maternal-fetal surgery counseling; (2) establishing shared understanding; (3) supporting decision-making; and (4) training for maternal-fetal surgery counseling. Within these themes, we identified key practice differences among professions, specialties, institutions, and regions. Conclusion: Participants are committed to practicing informative and supportive counseling to empower pregnant people to make autonomous decisions about maternal-fetal surgery. Nevertheless, our findings indicate a dearth of evidence-based communication practices and guidance. Participants identified significant systemic limitations affecting pregnant people’s decision-making options related to maternal-fetal surgery.
Diagnostic difficulties in non‐tuberculous mycobacterial infection in lung transplant recipients

Despite antimicrobial prophylaxis, 34% to 59% of lung transplant recipients experience severe life–threatening opportunistic infections, sometimes caused by Nontuberculous Mycobacteria (NTM) and Nocardia. Although differentiating these infections is of utmost importance for effective treatment, it can be challenging as they share morphological and growth characteristics. Therefore, culture remains the gold standard for laboratory confirmation. With the aid of novel molecular methods performed on the cultured organisms, diagnosis may be accomplished rapidly and precisely. We present a case of a lung transplant recipient with a pulmonary infection where long, thin, beaded, branching filamentous organisms were seen with Acid‐Fast Bacilli (AFB) and Modified Gomori's Methenamine Silver (GMS) stains in bronchoalveolar lavage sample. Cytological characteristics led to the suspicion of a Nocardia species infection. However, culture and the PCR‐restriction fragment length polymorphism analysis (PRA) identified M. fortuitum. Additionally, antibiotic resistance was detected, which aided in choosing the appropriate treatment. Therefore, to overcome such diagnostic difficulties to differentiate NTM and Nocardia, a multidisciplinary approach including culture, molecular methods, and cytology is needed to enhance clinical outcomes.
Racial Disparities in MiT Family Translocation Renal Cell Carcinoma

Abstract Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian (2 of 14 [14.3%] vs 10 of 525 [1.9%]; P = .036) and Black (8 of 113 [7.1%] vs 1.9%; P = .007) patients with RCC showed significantly higher prevalence of TRCC compared with White patients with RCC. The overall mortality rate of TRCC was slightly higher in Asian and Black patients compared with White patients (HR: 6.05, P = .069). OrigiMed2020 Chinese patients with RCC had a significantly higher proportion of TRCC with TFE3 fusions than TCGA White patients with RCC (13 of 250 [5.2%] vs 7 of 525 [1.3%]; P = .003). Black patients with TRCC were more likely to exhibit the proliferative subtype than White patients (6 of 8 [75%] vs 2 of 9 [22.2%]; P = .057) for those who had RNA-seq profiles. We present evidence of higher prevalence of TRCC in Asian and Black patients with RCC compared with White patients and show that these tumors in Asian and Black patients have distinct transcriptional signatures and are associated with poor outcomes.
Bringing the Walk with Ease Programme to the UK: a mixed-methods study to assess the relevance, acceptability, and feasibility of implementation for people with arthritis and musculoskeletal conditions

Abstract Developed in the United States (US), Walk With Ease (WWE) is a popular evidence-based, 6-week community walking programme for adults with arthritis, delivered in either an instructor-led or self-directed format. While WWE has expanded into communities across the USA, it is relatively unknown in other countries across the globe. This study, in collaboration with community and patient partners, aimed to examine the relevance, acceptability and feasibility of introducing WWE into a UK context. After initial cultural adaptation, participants were recruited into the study. Eligible (≥18 years, doctor diagnosed arthritis (confirmed or self-report), self-reported joint symptoms in last 30 days, BMI ≥25 kg/m2, and <150 min/week of moderate/vigorous PA) and consented participants were randomized into two groups: WWE programme or usual care. A mixed-methods analysis approach integrated quantitative data (physical performance assessment; baseline and post-six week programme questionnaire) and qualitative data (narrative interviews exploring participants’ pre- and post-WWE experiences and stakeholders’ perceptions). Of 149 participants, the majority were women (70%) aged ≥60 years (76%). Among the 97 receiving the programme, 52 chose instructor-led; 45 chose self-directed. Participants found WWE relevant and acceptable—99% indicating they would recommend WWE to family/friends. Within both WWE formats, mixed differences representing improvement were observed at 6 weeks from baseline for physical performance and arthritis symptoms. Emergent themes included improved motivation, health, and social well-being. WWE is a relevant and acceptable walking programme with scope for wider implementation to support UK health and well-being policy strategies.
Interoceptive Awareness of the Breath Preserves Attention and Language Networks amidst Widespread Cortical Deactivation: A Within-Participant Neuroimaging Study

Abstract Interoception, the representation of the body’s internal state, serves as a foundation for emotion, motivation, and wellbeing. Yet despite its centrality in human experience, the neural mechanisms of interoceptive attention are poorly understood. The Interoceptive/Exteroceptive Attention Task (IEAT) is a novel neuroimaging paradigm that compares behavioral tracking of the respiratory cycle (Active Interoception) to tracking of a visual stimulus (Active Exteroception). Twenty-two healthy participants completed the IEAT during two separate scanning sessions (N = 44) as part of a randomized control trial of mindful awareness in body-oriented therapy (MABT). Compared with Active Exteroception, Active Interoception deactivated somatomotor and prefrontal regions. Greater self-reported interoceptive sensibility (MAIA scale) predicted sparing from deactivation within the anterior cingulate cortex (ACC) and left-lateralized language regions. The right insula, typically described as a primary interoceptive cortex, was only specifically implicated by its deactivation during an exogenously paced respiration condition (Active Matching) relative to self-paced Active Interoception. Psychophysiological interaction (PPI) analysis characterized Active Interoception as promoting greater ACC connectivity with lateral prefrontal and parietal regions commonly referred to as the dorsal attention network (DAN). In contrast to evidence relating accurate detection of liminal interoceptive signals such as the heartbeat to anterior insula activity, interoceptive attention toward salient signals such as the respiratory cycle may involve reduced cortical activity but greater ACC-DAN connectivity, with greater sensibility linked to reduced deactivation within the ACC and language-processing regions.
Ultrasound-Assisted Continence Care Support in an Inpatient Care Setting: Protocol for a Pilot Implementation Study

Background This nonrandomized exploratory intervention and feasibility study examines how digital assistive technology (DAT), comprising a DFree ultrasound sensor, affects nursing care for continence support and evaluates nurses’ willingness to incorporate DAT into the planning and practical implementation of care processes. Objective The relief provided by DFree in the clinical care setting and the extent to which it supports nursing care for activities of daily living pertaining to “micturition” is unclear. DAT DFree is expected to reduce nurses’ workload in clinical continence-care settings and was designed as a human-technology interaction that ensures a high level of usability for the subjects (ie, the nurses) and increases user acceptance by at least one level (eg, from average to slightly above average) during the study. Methods Approximately 45 nurses from neurology, neurosurgery, and geriatric medicine clinics and polyclinics at the University Medicine Halle will be included in the 90-day (3-month) intervention on-site in the respective wards. After the wards are equipped with digital technologies, the participating nurses will be trained to use DFree and will be able to select DFree as a possible patient-care resource if the anamnesis includes bladder dysfunction among only patients who are willing to participate. The willingness of nurse participants to use DFree in planning their care process will be assessed using the Technology Usage Inventory at 3 measurement points. The primary target values include the results of the multidimensional Technology Usage Inventory assessment that will be processed using descriptive statistics. Ten participating nurses will be invited to conduct extensive guided interviews that are intended to provide information about the device’s usefulness and feasibility in the specific field of continence care and possible improvements. Results It is expected that the intention to use will be confirmed by nurses, and the number of nursing problems, such as bladder dysfunction-induced bedwetting, will be reduced with a high rating of DAT usability. Conclusions First, this study aims to produce multilevel innovative impacts, including practical, scientific, and societal effects. The results will provide practical solutions for workload reduction in the field of nursing support for continence care, where digital assistive technologies are becoming increasingly important. The DFree ultrasonic sensor is a new technical tool for the treatment of bladder dysfunction. Generating feedback to improve technical applications can increase the user-friendliness and usefulness of the device. Trial Registration Deutsches Register Klinischer Studien DRKS00031483; https://drks.de/search/en/trial/DRKS00031483 International Registered Report Identifier (IRRID) PRR1-10.2196/47025
Health care registers can be instrumental for endpoint capture in clinical diabetes trials: example of microvascular complications in Swedish patients with type 2 diabetes

Aims SMARTEST is a register-based randomized clinical trial (RRCT) that compares dapagliflozin to metformin in early-stage type 2 diabetes. The primary outcome includes progression of microvascular complications based on data from the Swedish National Diabetes Register (NDR). In this sub-study, the aim was to validate microvascular complication variables in the NDR against electronic health records (EHRs). Methods Data were extracted from EHRs of 276 SMARTEST participants with a median observation period of 3 years in the Uppsala, Örebro and Sörmland counties and compared with NDR data. Agreement was determined for all corresponding data entries as well as for progression of microvascular complications after randomization. Results The agreement for all corresponding data entries was 98.9% (Intraclass Correlation Coefficient 0.999) for creatinine and eGFR, 95.1% for albuminuria, 91.6% for foot-at-risk and 98.2% for retinopathy status (Kappa 0.67-0.91). The agreement for progression of microvascular complications was 98.0% for CKD stage, 98.9% for albuminuria grade, 96.3% for foot-at-risk grade and 99.6% for retinopathy grade progression (Gwet’s AC1 0.96-1.00). Conclusion Microvascular complication variables in the NDR show good agreement with EHR data. The use of a well-established national health care registry, exemplified by the NDR, for endpoint collection in RRCTs such as SMARTEST is supported by this study.
Comparing the Fried frailty phenotype versus the Veterans Affairs frailty index among dialysis dependent patients

Frailty in dialysis patients is a modifiable disease state which can increase mortality if left untreated but remains underdiagnosed as frailty evaluations can be arduous or time consuming. We evaluate the agreement between a clinical frailty construct (Fried frailty phenotype, FFP) against and an electronic health record‐based Veterans Affairs Frailty Index (VAFI) and their association with mortality.