Sexual and gender minority content in undergraduate medical education in the United States and Canada: current state and changes since 2011.

PURPOSE: To characterize current lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI +) health-related undergraduate medical education (UME) curricular content and associated changes since a 2011 study and to determine the frequency and extent of institutional instruction in 17 LGBTQI + health-related topics, strategies for increasing LGBTQI + health-related content, and faculty development opportunities. METHOD: Deans of medical education (or equivalent) at 214 allopathic or osteopathic medical schools in Canada and the United States were invited to complete a 36-question, Web-based questionnaire between June 2021 and September 2022. The main outcome measured was reported hours of LGBTQI + health-related curricular content. RESULTS: Of 214 schools, 100 (46.7%) responded, of which 85 (85.0%) fully completed the questionnaire. Compared to 5 median hours dedicated to LGBTQI + health-related in a 2011 study, the 2022 median reported time was 11 h (interquartile range [IQR], 6-16 h, p < 0.0001). Two UME institutions (2.4%; 95% CI, 0.0%-5.8%) reported 0 h during the pre-clerkship phase; 21 institutions (24.7%; CI, 15.5%-33.9%) reported 0 h during the clerkship phase; and 1 institution (1.2%; CI, 0%-3.5%) reported 0 h across the curriculum. Median US allopathic clerkship hours were significantly different from US osteopathic clerkship hours (4 h [IQR, 1-6 h] versus 0 h [IQR, 0-0 h]; p = 0.01). Suggested strategies to increase content included more curricular material focusing on LGBTQI + health and health disparities at 55 schools (64.7%; CI, 54.6%-74.9%), more faculty willing and able to teach LGBTQI + -related content at 49 schools (57.7%; CI, 47.1%-68.2%), and more evidence-based research on LGBTQI + health and health disparities at 24 schools (28.2%; CI, 18.7%-37.8%). CONCLUSION: Compared to a 2011 study, the median reported time dedicated to LGBTQI + health-related topics in 2022 increased across US and Canadian UME institutions, but the breadth, efficacy, or quality of instruction continued to vary substantially. Despite the increased hours, this still falls short of the number of hours based on recommended LGBTQI + health competencies from the Association of American Medical Colleges. While most deans of medical education reported their institutions' coverage of LGBTQI + health as 'fair,' 'good,' or 'very good,' there continues to be a call from UME leadership to increase curricular content. This requires dedicated training for faculty and students.

Mutations in the dwarf3 gene confer height stability in sorghum.

Dwarfism is a useful trait in many crop plants because it contributes to improved lodging resistance and harvest index. The mutant allele dw3-ref (dwarf3-reference) of sorghum [Sorghum bicolor (L.) Moench] is characterized by an 882 bp tandem duplication in the fifth exon of the gene that is unstable and reverts to wild-type at a frequency greater than 0.001 in many genetic backgrounds. The goal of this research was to identify stable alleles of dw3 (dwarf3) that could be backcrossed into elite parent lines to improve height stability of the crop. To discover new alleles of dw3, a panel consisting mostly of sorghum conversion lines (SC-lines) was screened by polymerase chain reaction for the 882 bp tandem duplication in the fifth exon of dw3-ref. Sanger sequencing was used to characterize the DNA sequence of this fragment in genotypes that did not contain the 882 bp tandem duplication. Sequence analysis identified three indel mutations, including an 82 bp deletion, a 6 bp duplication, and a 15 bp deletion in this region of the gene. Field trials of the donor genotypes with these new alleles indicated no wild-type revertants of dw3-sd3 (dwarf3-stable dwarf), dw3-sd4, and dw3-sd5. These alleles were backcrossed into Tx430. Field trials of backcross progeny (BC2F4) with the dw3-sd3, dw3-sd4, and dw3-sd5 alleles indicated no revertants. The plant height and flowering time characteristics of the backcross progeny were similar or slightly shorter and earlier than the recurrent parent. These findings demonstrate that dw3-sd3, dw3-sd4, and dw3-sd5 alleles will be useful in breeding for the stable dwarf trait.

STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179.

Thyrotropin (TSH) is the master regulator of thyroid gland growth and function. Resistance to TSH (RTSH) describes conditions with reduced sensitivity to TSH. Dominantly inherited RTSH has been linked to a locus on chromosome 15q, but its genetic basis has remained elusive. Here we show that non-coding mutations in a (TTTG)4 short tandem repeat (STR) underlie dominantly inherited RTSH in all 82 affected participants from 12 unrelated families. The STR is contained in a primate-specific Alu retrotransposon with thyroid-specific cis-regulatory chromatin features. Fiber-seq and RNA-seq studies revealed that the mutant STR activates a thyroid-specific enhancer cluster, leading to haplotype-specific upregulation of the bicistronic MIR7-2/MIR1179 locus 35 kb downstream and overexpression of its microRNA products in the participants' thyrocytes. An imbalance in signaling pathways targeted by these micro-RNAs provides a working model for this cause of RTSH. This finding broadens our current knowledge of genetic defects altering pituitary-thyroid feedback regulation.

The Impact of Deprescribing Interventions on the Drug Burden Index and Other Outcomes: A Systematic Review.

OBJECTIVES: The Drug Burden Index (DBI) calculates a person's exposure to anticholinergic and sedative medications. We aimed to review randomized controlled trials (RCTs) of deprescribing interventions that reported the DBI as an outcome, their characteristics, effectiveness in reducing the DBI, and impact on other outcomes. DESIGN: Systematic review with meta-analysis. SETTING AND PARTICIPANTS: RCTs of deprescribing interventions where the DBI was measured as a primary or secondary outcome in humans within any setting were included. METHODS: Electronic databases, citation indexes, and gray literature were searched from January 4, 2007, to January 9, 2023. Quality was assessed using the Cochrane risk-of-bias tool. RESULTS: Of 1721 records identified, 9 met the inclusion criteria. Six interventions were delivered by pharmacists and 3 were delivered by pharmacists/nurses or pharmacists/geriatricians. All interventions required at least intermediate-level skills and involved multiple components and target groups. Studies were conducted in the community (n = 5), nursing homes (n = 2), and hospitals (n = 2). The mean or median age was ≥75 years and most participants were women in all studies. Most (n = 6) studies were underpowered. The follow-up period ranged from 3 to 12 months. Three studies reported a lower DBI in the intervention group compared with control: 1 pharmacist independent prescriber-delivered in nursing homes (adjusted rate ratio, 0.83; 95% CI, 0.74-0.92), 1 pharmacist/nurse practitioner-delivered in hospital (adjusted mean difference (MD), -0.28; 95% CI, -0.51 to -0.04), and 1 geriatrician/pharmacist-delivered in hospital (MD, -0.28; 95% CI, -0.52 to -0.04). Meta-analysis showed no difference in the change in DBI between control and intervention groups in the community including nursing homes (MD, -0.03; 95% CI, -0.08 to 0.01) or hospital setting (MD, -0.19; 95% CI, -0.45 to 0.06). Interventions had inconsistent effects on cognition and no effect on other reported outcomes. CONCLUSIONS AND IMPLICATIONS: RCTs of deprescribing interventions had no significant impact on reducing DBI or improving outcomes. Further suitably powered studies are required.

Natural Products That Protect Against Acetaminophen Hepatotoxicity: A Call for Increased Rigor in Preclinical Studies of Dietary Supplements.

Acetaminophen (APAP) overdose is one of the most common causes of acute liver injury. The current standard-of-care treatment for APAP hepatotoxicity, N-acetyl-l-cysteine, is highly effective when administered early after overdose, but loses efficacy in later-presenting patients. As a result, there is interest in the identification of new treatments for APAP overdose patients. Natural products are a promising source of new treatments because many are purported to have hepatoprotective effects. In fact, a great deal of research has been done to identify natural products that can protect against APAP-induced liver injury. However, serious concerns have been raised about the rigor and human relevance of these studies. Here, we systematically reviewed the APAP-natural product literature from 2013 to 2023 to determine the veracity of these concerns and the scope of the potential problem. The results substantiate the concerns that have been previously raised and point to concrete steps that can be taken to improve APAP-natural product research.

Impact of comorbidities in severely injured patients with blunt chest injury: A population-based retrospective cohort study.

INTRODUCTION: Blunt chest injuries result in up to 10 % of major trauma admissions. Comorbidities can complicate recovery and increase the mortality rate in this patient cohort. A better understanding of the association between comorbidities and patient outcomes will facilitate enhanced models of care for particularly vulnerable groups of patients, such as older adults. AIMS: i) compare the characteristics of severely injured patients with blunt chest injury with and without comorbidities and ii) examine the relationship between comorbidities and key patient outcomes: prolonged length of stay, re-admission within 28 days, and mortality within 30 days in a cohort of patients with blunt chest injury admitted after severe trauma. METHODS: A retrospective cohort study using linked data from the NSW Trauma Registry and NSW mortality and hospitalisation records between 1st of January 2012 and 31st of December 2019. RESULTS: After adjusting for potential confounding factors, patients with severe injuries, chest injuries, and comorbidities were found to have a 34 % increased likelihood of having a prolonged length of stay (OR = 1.34, 95 %I = 1.17-1.53) compared to patients with no comorbidities. There was no difference in 30-day mortality for patients with a severe chest injury who did or did not have comorbidities (OR = 1.05, 95 %CI = 0.80-1.39). No significant association was found between comorbidities and re-admission within 28 days. CONCLUSION: Severely injured patients with blunt chest injury and comorbidities are at risk of prolonged length of stay.

Epigenetic Aging Associations With Psychoneurological Symptoms and Social Functioning in Adults With Sickle Cell Disease.

Objective: Sickle cell disease (SCD), the most common inherited blood disorder in the United States, is associated with severe psychoneurological symptoms. While epigenetic age acceleration has been linked to psychoneurological symptom burden in other diseases, this connection is unexplored in SCD. This study aimed to assess the association between epigenetic age acceleration and psychoneurological symptom burden in SCD. Methods: In this cross-sectional study, emotional impact, pain impact, sleep impact, social functioning, and cognitive function were assessed in 87 adults living with SCD. DNA methylation data were generated from blood specimens and used to calculate epigenetic age using five clocks (Horvath, Hannum, PhenoAge, GrimAge, & DunedinPACE). Associations between epigenetic age acceleration and symptoms were assessed. Results: The sample (N = 87) had a mean (SD) chronologic age was 30.6 (8.1) years. Epigenetic age acceleration was associated with several symptom outcomes. GrimAge age acceleration (ß = -0.49, p = .03) and increased DunedinPACE (ß = -2.23, p = .004) were associated with worse emotional impact scores. PhenoAge (ß = -0.32, p = .04) and the GrimAge (ß = -0.48, p = .05) age acceleration were associated with worse pain impact scores. Increased DunedinPACE (ß = -2.07 p = .04) were associated with worse sleep impact scores. Increased DunedinPACE (ß = -2.87, p = .005) was associated with worse social functioning scores. We did not find associations between epigenetic age acceleration and cognitive function in this sample. Conclusion: Epigenetic age acceleration was associated with worse symptom experiences, suggesting the potential for epigenetic age acceleration as a biomarker to aid in risk stratification or targets for intervention to mitigate symptom burden in SCD.

Lenalidomide, rituximab (R2), and ixazomib for frontline treatment of high risk follicular and indolent non-Hodgkin lymphoma.

Lenalidomide and rituximab (R2) is an effective frontline treatment for patients with indolent B-cell non-Hodgkin lymphoma (iNHL). We investigated the safety and efficacy of addition of the proteasome inhibitor ixazomib to R2 for treatment of iNHL through a phase I/II clinical trial for high-risk patients. Twenty patients were enrolled, 18 were treated. The target dose of ixazomib 4 mg weekly was achieved during dose escalation. The most common treatment-related adverse events (AEs) were low grade gastrointestinal, rash, neuropathy, and myalgia/arthralgia. There were 33% grade 2 and 17% grade 3 infections. With median follow-up of 5.2 years, four patients discontinued treatment due to lymphoma progression. Best overall response rate (ORR) was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. Kaplan-Meier estimates of progression free and overall survival (OS) were 73% and 87% at 36 months, respectively. R2 can safely be combined with ixazomib for treatment-naïve iNHL patients.

HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.

OBJECTIVES: HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort. DESIGN: Prospective cohort study. SETTING: 22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010). PARTICIPANTS: 451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data. MAIN OUTCOME MEASURES: Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years. RESULTS: 12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes. CONCLUSIONS: Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.

Neighborhood Environment and Poor Maternal Glycemic Control-Associated Complications of Gestational Diabetes Mellitus.

Introduction: Risk of complications due to gestational diabetes mellitus is increasing in the U.S., particularly among individuals from racial minorities. Research has focused largely on clinical interventions to prevent complications, rarely on individuals' residential environments. This retrospective cohort study aims to examine the association between individuals' neighborhoods and complications of gestational diabetes mellitus. Methods: Demographic and clinical data were extracted from electronic health records and linked to American Community Survey data from the U.S. Census Bureau for 2,047 individuals who had 2,164 deliveries in 2014-2018. Data were analyzed in 2021-2022 using Wilcoxon rank sum test and chi-square test for bivariate analyses and logistic regression for analysis of independent effects. All census tract-based variables used in the model were dichotomized at the median. Results: Bivariate analysis showed that the average percentage of adults earning <$35,000 was higher in neighborhoods where individuals with complications were living than in neighborhoods where individuals without complications were living (30.40%±12.05 vs 28.94%±11.71, p=0.0145). Individuals who lived in areas with ≥8.9% of residents aged >25 years with less than high school diploma had a higher likelihood of complications than those who lived in areas with <8.9% of such residents (33.43% vs 29.02%, p=0.0272). Individuals who lived in neighborhoods that had ≥1.8% of households receiving public assistance were more likely to have complications than those who lived in areas where <1.8% of households received public assistance (33.33% vs 28.97%, p=0.0287). Logistic regression revealed that the odds of deliveries with complications were 44% higher for individuals with obesity (OR=1.44; 95% CI=1.17, 1.77), 35% greater for individuals residing in neighborhoods with higher percentages of households living below the poverty level (OR=1.35; 95% CI=1.09, 1.66), and 28% lower for individuals from neighborhoods where a higher percentage of households had no vehicles available for transportation to work (OR=0.72; 95% CI=0.59, 0.89). Conclusions: Clinical interventions in concert with environmental changes could contribute to preventing maternal and neonatal complications of gestational diabetes mellitus.

Access to Care and Health Care Utilization Among Patients With Nephrolithiasis.

OBJECTIVE: To characterize the impact of nephrolithiasis diagnosis and treatment on health care utilization and identify predictors of barriers to care in the patient population. METHODS: We conducted a retrospective cohort study using the All of Us Database, a National Institutes of Health database targeting recruitment of underrepresented populations. Patients with a diagnosis of kidney stones were included and matched to a control group. Primary outcomes were patients' self-reported health care access and utilization. Univariable and multivariable regression analyses were performed. RESULTS: 9173 patients with a diagnosis of nephrolithiasis were included and matched to 9173 controls without a diagnosis of nephrolithiasis. Patients with kidney stones were less likely to have had >1 year since last provider visit (1.7% vs 3.8%, P <.001), but did not report increased delays obtaining care (31%), inability to afford care (11.4%), or higher likelihood of skipping medications (12.9%). Among patients with stones, 1208 (13.2%) had been treated surgically. On multivariable analysis, younger age, female sex, lower income, lower education, non-insured status, and lower physical and mental health were all associated with delays obtaining care, difficulty affording care, skipping medications, and/or prolonged time since seeing a provider. CONCLUSION: A diagnosis of nephrolithiasis and subsequent surgical intervention were not associated with an increase in patient-reported barriers to care. However, among patients with nephrolithiasis, younger, comorbid, female patients from lower socioeconomic status are at significant risk of being unable to access and utilize treatment.

The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation.

BACKGROUND: Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchronized forms may be superior. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) delivers NIV synchronized to the neural signal for breathing, which is detected with a specialized catheter. The DIVA (Diaphragmatic Initiated Ventilatory Assist) trial aims to determine in infants born 240/7-276/7 weeks' gestation undergoing extubation whether NIV-NAVA compared to non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) reduces the incidence of extubation failure within 5 days of extubation. METHODS: This is a prospective, unblinded, pragmatic, multicenter phase III randomized clinical trial. Inclusion criteria are preterm infants 24-276/7 weeks gestational age who were intubated within the first 7 days of life for at least 12 h and are undergoing extubation in the first 28 postnatal days. All sites will enter an initial run-in phase, where all infants are allocated to NIV-NAVA, and an independent technical committee assesses site performance. Subsequently, all enrolled infants are randomized to NIV-NAVA or NS-NIPPV at extubation. The primary outcome is extubation failure within 5 days of extubation, defined as any of the following: (1) rise in FiO2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO2 ≥ 70 mmHg; (3) > 1 apnea requiring positive pressure ventilation (PPV) or ≥ 6 apneas requiring stimulation within 6 h; (4) emergent intubation for cardiovascular instability or surgery. Our sample size of 478 provides 90% power to detect a 15% absolute reduction in the primary outcome. Enrolled infants will be followed for safety and secondary outcomes through 36 weeks' postmenstrual age, discharge, death, or transfer. DISCUSSION: The DIVA trial is the first large multicenter trial designed to assess the impact of NIV-NAVA on relevant clinical outcomes for preterm infants. The DIVA trial design incorporates input from clinical NAVA experts and includes innovative features, such as a run-in phase, to ensure consistent technical performance across sites. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , trial identifier NCT05446272 , registered July 6, 2022.

Inequities in Conversion Practice Exposure at the Intersection of Ethnoracial and Gender Identities.

Objectives. To examine inequities in conversion practice exposure across intersections of ethnoracial groups and gender identity in the United States. Methods. Data were obtained from The Population Research in Identity and Disparities for Equality Study of sexual and gender minority people from 2019 to 2021 (n = 9274). We considered 3 outcomes: lifetime exposure, age of first exposure, and period between first and last exposure among those exposed to conversion practices. We used log-binomial, Cox proportional hazards, and negative binomial models to examine inequities by ethnoracial groups and gender identity adjusting for confounders. We considered additive interaction. Results. Conversion practice prevalence was highest among minoritized ethnoracial transgender and nonbinary participants (TNB; 8.6%). Compared with White cisgender participants, minoritized ethnoracial TNB participants had twice the prevalence (prevalence ratio = 2.16; 95% confidence interval [CI] = 1.62, 2.86) and risk (hazard ratio = 2.04; 95% CI = 1.51, 2.69) of conversion practice exposure. Furthermore, there was evidence of a positive additive interaction for age of first exposure. Conclusions. Minoritized ethnoracial TNB participants were most likely to recall experiencing conversion practices. Public Health Implications. Policies banning conversion practices may reduce the disproportionate burden experienced by minoritized ethnoracial TNB participants. (Am J Public Health. 2024;114(4):424-434. https://doi.org/10.2105/AJPH.2024.307580).

The Impact of Standard vs Early Apical Release Holmium Laser Enucleation of the Prostate Technique on Postoperative Incontinence and Quality of Life.

OBJECTIVE: To investigate the difference in postoperative incontinence and quality of life comparing standard vs early apical release (EAR) Holmium Laser Enucleation of the Prostate (HoLEP). METHODS: A retrospective review was performed to identify patients who underwent HoLEP from December 2021 to December 2022 at a single tertiary referral center with two participating consultant urologists. Patients were assessed with questionnaires and evaluated clinically. We performed propensity score matching with a logistic regression and a 1:1 matching method. A propensity score-adjusted logistic regression (PSRM) was performed to compare the pads per day between surgical techniques controlling for age, prostate size, preoperative survey data, uroflow, and postvoid residual. RESULTS: One hundred fourteen patients underwent HoLEP, of which 60 patients were treated with EAR and 54 patients with standard technique. EAR technique demonstrated shorter operative times (P = .046). The EAR cohort demonstrated improved AUASS (P = .034, P = .001), QOL (P = .001, P <.001), and continence rates (P <.001, P <.001) at 6 and 12weeks postoperatively. PSRM showed that the standard HoLEP increased the risk of requiring ≥2 pads per day 4.2x (P = .031, HR 95%, CI=1.16, 15.35) and 8.3x (P <.001, HR 95% CI 3.17, 21.6) at 6 and 12weeks postoperatively. CONCLUSION: EAR technique promoted earlier return of continence and improved quality of life within 6weeks of surgery.

Are adverse events during surgery for benign prostatic hyperplasia device related? A review of the MAUDE database.

PURPOSE: The Manufacturer and User Facility Device Experience database contains anonymous, voluntary medical device reports. A review of device-related adverse events associated with Benign Prostatic Hyperplasia surgeries was completed. The objective was to evaluate the occurrence and contributing factors to clinically significant complications in a cohort of patients electing to undergo surgical intervention for Benign Prostatic Hyperplasia. METHODS: The Manufacturer and User Facility Device Experience database was queried for "Aquablation, Greenlight Laser, Holmium Laser, Morcellator, Water Vapor Thermal Therapy, Loop Resection, and Prostatic Urethral Lift" from 2018 through 2021. A complication classification system (Level I-IV) based on the Clavien-Dindo system was used to categorize events. These events were then correlated with procedural technology malfunctions and classified as "device related" and "non-device related." Chi squared analysis was performed to identify associations between procedural technology and complication classification distribution. RESULTS: A total of 873 adverse events were identified. The adverse events were classified into level I (minimal harm) versus levels II-IV (clinically significant). Aquablation (p < 0.017) and Water Vapor Thermal Therapy (p < 0.012) were associated with a higher proportion of reports with Level II-IV complications compared with other procedure types. Level II-IV complications were not associated with a reported device related malfunction. CONCLUSIONS: Aquablation and water vapor thermal therapy demonstrated noteworthy clinically significant complications which were not driven by device-related malfunctions.

Advancing in vivo reprogramming with synthetic biology.

Reprogramming cells will play a fundamental role in shaping the future of cell therapies by developing new strategies to engineer cells for improved performance and higher-order physiological functions. Approaches in synthetic biology harness cells' natural ability to sense diverse signals, integrate environmental inputs to make decisions, and execute complex behaviors based on the health of the organism or tissue. In this review, we highlight strategies in synthetic biology to reprogram cells, and discuss how recent approaches in the delivery of modified mRNA have created new opportunities to alter cell function in vivo. Finally, we discuss how combining concepts from synthetic biology and the delivery of mRNA in vivo could provide a platform for innovation to advance in vivo cellular reprogramming.

Understanding the role of gaze behaviour and coaching experience in the assessment of youth soccer teams.

This study aimed to explore the perceptual-cognitive characteristics of coaches as they assessed team performance in youth soccer. The primary focus was to investigate the alignment between coaches' subjective analyses of team behaviour and objective analyses, while also examining the relationship between coaches' gaze behaviour and their levels of coaching experience, particularly considering the potential differences that may exist among coaches with varying levels of experience. Sixty-five male and female adults with various soccer coaching experience (experienced, novice, other team sport experience, and non-team sport experience) watched five 4-minute videos and assessed team behaviour. These subjective evaluations were compared to objective data obtained from video analysis and GPS, which included measures of completed skills, spatiotemporal characteristics, and passing networks. The participants' fixation duration and frequency were measured for each video clip, and the area around the ball specifically. The study found no significant differences between groups regarding the number of times participants' subjective analysis aligned with the objective data (p = 0.059, ɳ2 = 0.07). However, coaches with soccer coaching experience demonstrated a higher fixation frequency and more revisits to the ball area when compared to participants without soccer experience (p = <.001, ɳ2 = 0.09). The current study offers a unique approach to uncovering soccer coaching expertise by combining objective and subjective evaluations of team performance. In summary, the study reveals that coaching experience did not impact how often coaches subjective analyses matched objective data. However, soccer coaches had distinctive gaze behaviour patterns where they revisited the area around the ball more often.

Coaches' perceptions of collective behaviour in soccer teams do not align with objective data, regardless of their level of coaching experience.Gaze behaviour differs between coaches with varying expertise levels.Both experienced and novice coaches visually revisit the area around the ball more often than non-coaches when assessing team performance.Quantitative data may provide an additional level of team analysis than subjective coach assessment alone.