PROPEL: a scalable model for postbaccalaureate training to promote diversity in the biomedical workforce.

Promoting diversity in the scientific workforce is crucial for harnessing the potential of available talent and ensuring equitable access to Science, Technology, Engineering, Mathematics, and Medicine (STEM-M) careers. We have developed an innovative program called Postbaccalaureate Research Opportunity to Promote Equity in Learning (PROPEL) that provides scientific and career development training for postbaccalaureate scholars from historically excluded backgrounds in STEM-M fields with an interest in pursuing a PhD or MD/PhD degree. Our program is distinct from other postbaccalaureate programs in that scholars are hired by individual labs rather than funded centrally by the program. This funding mechanism removes the idea that central funding is necessary to encourage faculty to train diverse scholars and allows the program to scale dynamically according to the needs of the scientific community. The PROPEL program started in 2020 with six scholars and has since grown to an enrollment of over 100, making it the largest postbaccalaureate program for biomedical research in the country. Here, we describe the program structure and curriculum, our strategy for recruitment, the enrollment trends, the program demographics, metrics of scholar engagement, and outcomes for scholars who completed the program in 2023. Our experience demonstrates the strong demand from both scholars and faculty for programming of this type and describes the feasibility of implementation.

The Relationship Between Sexual Minority Stress and Sexual Satisfaction: A Meta-Analytic Review.

Despite increased scholarly attention being paid to minority stress and sexual satisfaction among sexual minorities, to our knowledge, no researchers have attempted to systematically synthesize this literature. To address this omission, we conducted a meta-analytic review of the association between sexual minority stress (i.e. sexual identity stigma, internalized sexual identity stigma, and sexual identity concealment) and sexual satisfaction. Suitable studies were recruited through electronic databases, with article screening adhering to PRISMA guidelines. Twenty-eight articles containing 61 effect sizes were analyzed (N = 183,832). Findings indicated a small, inverse relationship between these constructs, indicating that minority stress may lead to diminished sexual satisfaction among gay/lesbian and bisexual individuals. Further, the overall effect size varied as a function of minority stress type, such that the effect for internalized stigma was significantly larger than the effects for sexual identity stigma or concealment. Age was also a significant moderator; specifically, older age was associated with a smaller effect, suggesting that older adults may be better than younger adults at coping with minority stress. Limitations and directions for future research are discussed. We also articulate the implications of these findings vis-à-vis the health and wellbeing of sexual minorities and suggest that clinicians should target internalized stigma in their treatment of sexual concerns among members of this population.

Expression-environment associations in transcriptomic heat stress responses for a global plant lineage.

The increasing frequency and severity of heatwaves will intensify stress on plants. Given regional variation in heatwave exposure and expected differences in thermal tolerance between species it is unlikely that all plant species will be affected equally by climate change. However, little is currently known about variation in the responses of plants to heat stress, or how those responses differ among closely related species adapted to different environments. Here we quantify the response of 17 Acacia species (175 RNA-seq libraries), from across Australia's diverse biomes, to a multi-day experimental heatwave treatment to identify variation in transcriptomic and physiological responses to heat stress. Genes with known heat response functions showed consistent responses across Acacia species. Up to 10% of all genes and over 100 gene families showed significant clinal variation in the magnitude of their expression plasticity across species. Specifically, gene families linked to the temperature stress response were overrepresented among significant relationships with home range temperature conditions. Gene expression responses seen on the first day of the heatwave were more frequently associated with home range climates, while expression responses by day four were more commonly related to photosystem II acclimation. Comparative transcriptomics on non-model species has the potential to provide key information on stress response plasticity, especially when linked with our understanding of model species. Our study indicates that the pressing challenge to identifying potentially vulnerable species to climate change could be benefited by the further exploration of clinal variation in transcriptome plasticity.

Effect of estrogen receptor α on cardiopulmonary adaptation to chronic developmental hypoxia in a rat model.

Humans living at high-altitude (HA) have adapted to this environment by increasing pulmonary vascular and alveolar growth. RNA sequencing data from a novel murine model that mimics this phenotypical response to HA suggested estrogen signaling via estrogen receptor alpha (ERα) may be involved in this adaptation. We hypothesized ERα was a key mediator in the cardiopulmonary adaptation to chronic hypoxia and sought to delineate the mechanistic role ERα contributes to this process by exposing novel loss-of-function ERα mutant (ERαMut) rats to simulated HA. ERα mutant or wild-type (wt) rats were exposed to normoxia or hypoxia starting at conception and continued postnatally until 6 wk of age. Both wt and ERαMut animals born and raised in hypoxia exhibited lower body mass and higher hematocrits, total alveolar volumes (Va), diffusion capacities of carbon monoxide (DLCO), pulmonary arteriole (PA) wall thickness, and Fulton indices than normoxia animals. Right ventricle adaptation was maintained in the setting of hypoxia. Although no major physiologic differences were seen between wt and ERαMut animals at either exposure, ERαMut animals exhibited smaller mean linear intercepts (MLI) and increased PA total and lumen areas. Hypoxia exposure or ERα loss-of-function did not affect lung mRNA abundance of vascular endothelial growth factor, angiopoietin 2, or apelin. Sexual dimorphisms were noted in PA wall thickness and PA lumen area in ERαMut rats. In summary, in room air-exposed rats and rats with peri- and postnatal hypoxia exposure, ERα loss-of-function was associated with decreased alveolar size (primarily driven by hypoxic animals) and increased PA remodeling.NEW & NOTEWORTHY By exposing novel loss-of-function estrogen receptor alpha (Erα) mutant rats to a novel model of human high-altitude exposure, we demonstrate that ERα has subtle but inconsistent effects on endpoints relevant to cardiopulmonary adaptation to chronic hypoxia. Given that we observed some histologic, sex, and genotype differences, further research into cell-specific effects of ERα during hypoxia-induced cardiopulmonary adaptation is warranted.

A high-throughput method for quantifying Drosophila fecundity.

Measurements of Drosophila fecundity are used in a wide variety of studies, such as investigations of stem cell biology, nutrition, behavior, and toxicology. In addition, because fecundity assays are performed on live flies, they are suitable for longitudinal studies such as investigations of aging or prolonged chemical exposure. However, standard Drosophila fecundity assays have been difficult to perform in a high-throughput manner because experimental factors such as the physiological state of the flies and environmental cues must be carefully controlled to achieve consistent results. In addition, exposing flies to a large number of different experimental conditions (such as chemical additives in the diet) and manually counting the number of eggs laid to determine the impact on fecundity is time-consuming. We have overcome these challenges by combining a new multiwell fly culture strategy with a novel 3D-printed fly transfer device to rapidly and accurately transfer flies from one plate to another; the RoboCam, a low-cost, custom built robotic camera to capture images of the wells automatically; and an image segmentation pipeline to automatically identify and quantify eggs. We show that this method is compatible with robust and consistent egg laying throughout the assay period; and demonstrate that the automated pipeline for quantifying fecundity is very accurate (r2 = 0.98 for the correlation between the automated egg counts and the ground truth) In addition, we show that this method can be used to efficiently detect the effects on fecundity induced by dietary exposure to chemicals. Taken together, this strategy substantially increases the efficiency and reproducibility of high throughput egg laying assays that require exposing flies to multiple different media conditions.

Prevalence of Renal Neoplasia in Autosomal Dominant Polycystic Kidney Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition; however, its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients. METHODS: A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed. RESULTS: Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1-5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1,147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7-7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9-56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7-95.1, I2 = 66.9%]). CONCLUSION: ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however, may become apparent as outcomes and life expectancy amongst APDKD patients improve.

Evolving brain and behaviour changes in rats following repetitive subconcussive head impacts.

There is growing concern that repetitive subconcussive head impacts, independent of concussion, alter brain structure and function, and may disproportionately affect the developing brain. Animal studies of repetitive subconcussive head impacts are needed to begin to characterize the pathological basis and mechanisms underlying imaging and functional effects of repetitive subconcussive head impacts seen in humans. Since repetitive subconcussive head impacts have been largely unexplored in animals, we aimed to characterize the evolution of imaging, behavioural and pathological effects of repetitive subconcussive head impacts in awake adolescent rodents. Awake male and female Sprague Dawley rats (postnatal Day 35) received 140 closed-head impacts over the course of a week. Impacted and sham-impacted animals were restrained in a plastic cone, and unrestrained control animals were included to account for effects of restraint and normal development. Animals (n = 43) underwent repeated diffusion tensor imaging prior to and over 1 month following the final impact. A separate cohort (n = 53) was assessed behaviourally for fine motor control, emotional-affective behaviour and memory at acute and chronic time points. Histological and immunohistochemical analyses, which were exploratory in nature due to smaller sample sizes, were completed at 1 month following the final impact. All animals tolerated the protocol with no overt changes in behaviour or stigmata of traumatic brain injury, such as alteration of consciousness, intracranial haemorrhage or skull fracture. We detected longitudinal, sex-dependent diffusion tensor imaging changes (fractional anisotropy and axial diffusivity decline) in corpus callosum and external capsule of repetitive subconcussive head impact animals, which diverged from both sham and control. Compared to sham animals, repetitive subconcussive head impact animals exhibited acute but transient mild motor deficits. Repetitive subconcussive head impact animals also exhibited chronic anxiety and spatial memory impairment that differed from the control animals, but these effects were not different from those seen in the sham condition. We observed trends in the data for thinning of the corpus callosum as well as regions with elevated Iba-1 in the corpus callosum and cerebral white matter among repetitive subconcussive head impact animals. While replication with larger study samples is needed, our findings suggest that subconcussive head impacts cause microstructural tissue changes in the developing rat brain, which are detectable with diffusion tensor imaging, with suggestion of correlates in tissue pathology and behaviour. The results point to potential mechanisms underpinning consequences of subconcussive head impacts that have been described in humans. The congruence of our imaging findings with human subconcussive head impacts suggests that neuroimaging could serve as a translational bridge to advance study of injury mechanisms and development of interventions.

Stress and headaches in university students during the COVID-19 pandemic.

With regards to the relationship between mental and physical health conditions, some studies predict increased headache frequency as a result of exposure to stressful situations. Thus, the purpose of our study was to investigate whether headache characteristics among a sample of university students (N = 234) correlated with fear of COVID-19, stress and quality of life vis-à-vis the pandemic. We found statistically significant positive correlations between headache frequency and both general stress and quality of life. Further, results from a multiple regression analysis suggested that fear of COVID-19 did not account for incremental variance in headache intensity. Explanations for our key findings, limitations of our study, and future directions for post pandemic studies on headache experience are outlined.

Development of the nonbinary gender microaggressions (NBGM) scale.

Background: While research pertaining to nonbinary microaggressions has become increasingly comprehensive in recent years, a measure specifically assessing this construct does not yet exist.Aims: The purpose of the present research was to develop and validate the Nonbinary Gender Microaggressions (NBGM) scale, which will allow future researchers to quantitatively examine nonbinary individuals' experiences of microaggressions. Methods and Results: In Study 1 (n = 5), interviews with nonbinary individuals were conducted to explore their microaggressive experiences. The results of this study, as well as findings from previous qualitative research, were used to generate an initial pool of 92 items. In Study 2 (n = 158), a principal component analysis, which was used for item reduction, resulted in the retention of 41 items. In Studies 3 (n = 151) and 4 (n = 266), an exploratory factor analysis yielded a 23-item 5-factor solution (i.e., Negation of Identity [6 items], Inauthenticity [6 items], Deadnaming [4 items], Trans Exclusion [3 items], and Misuse of Gendered Terminology [4 items]), and a confirmatory factor analysis found that this solution demonstrates adequate model fit. Evidence of the measure's scale score reliability, convergent validity, and incremental validity also were provided. Discussion: These findings indicate that, overall, the NBGM scale is a psychometrically sound measure of nonbinary individuals' experiences of microaggressions. As such, this measure can be utilized by future researchers and clinicians to better understand nonbinary individuals' microaggressive experiences.

Tecovirimat Resistance in Mpox Patients, United States, 2022-2023.

During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat.

Single-cell RNA sequencing identifies eggplant as a regulator of germ cell development in Drosophila.

Drosophila ovarian germline stem cells (GSCs) are a powerful model for stem cell research. In this study, we use single-cell RNA sequencing (scRNA-seq), an RNAi screen and bioinformatic analysis, to identify genes involved in germ cell differentiation, including 34 genes with upregulated expression during early germ cell development and 19 genes that may regulate germ cell differentiation. Among these, a gene we have named eggplant (eggpl) is highly expressed in GSCs and downregulated in early daughter cells. RNAi knockdown of eggpl causes germ cell proliferation and differentiation defects. In flies fed a rich yeast diet, the expression of eggpl is significantly lower and knockdown or knockout of eggpl phenocopies a rich diet. In addition, eggpl knockdown suppresses the reduction in germ cell proliferation caused by inhibition of the insulin effector PI3K. These findings suggest that downregulation of eggpl links nutritional status to germ cell proliferation and differentiation. Collectively, this study provides new insights into the signaling networks that regulate early germ cell development and identifies eggpl as a key player in this process.

Phylogenomics reveals extreme gene tree discordance in a lineage of dominant trees: hybridization, introgression, and incomplete lineage sorting blur deep evolutionary relationships despite clear species groupings in Eucalyptus subgenus Eudesmia.

Eucalypts are a large and ecologically important group of plants on the Australian continent, and understanding their evolution is important in understanding evolution of the unique Australian flora. Previous phylogenies using plastome DNA, nuclear-ribosomal DNA, or random genome-wide SNPs, have been confounded by limited genetic sampling or by idiosyncratic biological features of the eucalypts, including widespread plastome introgression. Here we present phylogenetic analyses of Eucalyptus subgenus Eudesmia (22 species from western, northern, central and eastern Australia), in the first study to apply a target-capture sequencing approach using custom, eucalypt-specific baits (of 568 genes) to a lineage of Eucalyptus. Multiple accessions of all species were included, and target-capture data were supplemented by separate analyses of plastome genes (average of 63 genes per sample). Analyses revealed a complex evolutionary history likely shaped by incomplete lineage sorting and hybridization. Gene tree discordance generally increased with phylogenetic depth. Species, or groups of species, toward the tips of the tree are mostly supported, and three major clades are identified, but the branching order of these clades cannot be confirmed with confidence. Multiple approaches to filtering the nuclear dataset, by removing genes or samples, could not reduce gene tree conflict or resolve these relationships. Despite inherent complexities in eucalypt evolution, the custom bait kit devised for this research will be a powerful tool for investigating the evolutionary history of eucalypts more broadly.

Politically related stress and low-birth-weight infants among Arab, Asian, Hispanic, non-Hispanic Black, and non-Hispanic White women in Michigan.

BACKGROUND: Despite the high cost of low birth weight and the persistent challenge of racial inequities affecting the Arab American community, there has been limited research to identify and examine risk factors for these inequities with validated data on Arab American ethnicity and recent population stressors. OBJECTIVES: This study examined whether the 2016 presidential election is associated with low birth weight among non-Hispanic White, Arab American, Hispanic, and non-Hispanic Black women. DESIGN: This population-based study of singleton births in Michigan (2008-2017) used an algorithm to identify mothers who were of Arab descent. METHODS: We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between race/ethnicity and the odds of low birth weight. We examined whether these associations differed before and after the 2016 presidential election and according to maternal education. RESULTS: There were 1,019,738 births, including 66,272 (6.5%) classified as low birth weight. The odds of having a low-birth-weight infant were higher among all minority women compared to non-Hispanic White women. The association was similar before and after the 2016 presidential election and stronger among women with higher levels of education. CONCLUSION: This is the first study to estimate low birth weight among Arab American women in the context of political events. There are opportunities for future studies to discuss this issue in depth.

Integrated halide perovskite photoelectrochemical cells with solar-driven water-splitting efficiency of 20.8.

Achieving high solar-to-hydrogen (STH) efficiency concomitant with long-term durability using low-cost, scalable photo-absorbers is a long-standing challenge. Here we report the design and fabrication of a conductive adhesive-barrier (CAB) that translates >99% of photoelectric power to chemical reactions. The CAB enables halide perovskite-based photoelectrochemical cells with two different architectures that exhibit record STH efficiencies. The first, a co-planar photocathode-photoanode architecture, achieved an STH efficiency of 13.4% and 16.3 h to t60, solely limited by the hygroscopic hole transport layer in the n-i-p device. The second was formed using a monolithic stacked silicon-perovskite tandem, with a peak STH efficiency of 20.8% and 102 h of continuous operation before t60 under AM 1.5G illumination. These advances will lead to efficient, durable, and low-cost solar-driven water-splitting technology with multifunctional barriers.

Evolving radon diffusion through earthen barriers at uranium waste disposal sites.

Field measurements of Rn-222 fluxes from the tops and bottoms of compacted clay radon barriers were used to calculate effective Rn diffusion coefficients (DRn) at four uranium waste disposal sites in the western United States to assess cover performance after more than 20 years of service. Values of DRn ranged from 7.4 × 10-7 to 6.0 × 10-9 m2/s, averaging 1.42 × 10-7. Water saturation (SW) from soil cores indicated that there was relatively little control of DRn by SW, especially at higher moisture levels, in contrast to estimates from most steady-state diffusion models. This is attributed to preferential pathways intrinsic to construction of the barriers or to natural process that have developed over time including desiccation cracks, root channels, and insect burrows in the engineered earthen barriers. A modification to some models in which fast and slow pathway DRn values are partitioned appears to give a good representation of the data; 4% of the fast pathway was needed to fit the data regression. For locations with high Sw and highest DRn (and fluxes) at each site, the proportion of fast pathway ranged from 1.7% to 34%, but for many locations with lower fluxes, little if any fast pathway was needed.

Pharmaceutical innovation and access to financial markets.

While prior research shows that pharmaceutical innovation generates measurable benefits for society, over the last 70 years, the innovative activities of pharmaceutical firms have dramatically declined. In this study, we develop and test the hypothesis that to innovate, pharmaceutical firms must have access to capital through well-developed financial markets. Using a broad cross-country sample from 1989 to 2016, we document that financial market development is associated with greater levels of pharmaceutical innovation. To draw stronger causal inferences, and to overcome potential endogeneity issues, we use both instrumental variable and difference-in-difference analysis. Our results suggest that access to capital markets plays a vital role in pharmaceutical innovation.

In situ Soil Moisture Sensors in Undisturbed Soils.

Soil moisture directly affects operational hydrology, food security, ecosystem services, and the climate system. However, the adoption of soil moisture data has been slow due to inconsistent data collection, poor standardization, and typically short record duration. Soil moisture, or quantitatively volumetric soil water content (SWC), is measured using buried, in situ sensors that infer SWC from an electromagnetic response. This signal can vary considerably with local site conditions such as clay content and mineralogy, soil salinity or bulk electrical conductivity, and soil temperature; each of these can have varying impacts depending on the sensor technology. Furthermore, poor soil contact and sensor degradation can affect the quality of these readings over time. Unlike more traditional environmental sensors, there are no accepted standards, maintenance practices, or quality controls for SWC data. As such, SWC is a challenging measurement for many environmental monitoring networks to implement. Here, we attempt to establish a community-based standard of practice for in situ SWC sensors so that future research and applications have consistent guidance on site selection, sensor installation, data interpretation, and long-term maintenance of monitoring stations. The videography focuses on a multi-agency consensus of best-practices and recommendations for the installation of in situ SWC sensors. This paper presents an overview of this protocol along with the various steps essential for high-quality and long-term SWC data collection. This protocol will be of use to scientists and engineers hoping to deploy a single station or an entire network.

Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo.

The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.