A New Era in Perforator Flap Surgery for Breast Reconstruction: A Comparative Study of Robotic versus Standard Harvest of Bilateral Deep Inferior Epigastric Artery Perforator Flaps.

BACKGROUND: Traditional deep inferior epigastric artery perforator (DIEP) flap harvest splits the anterior sheath, weakening the abdominal wall and predisposing patients to bulge or hernia. Abdominal wall morbidity may be decreased using minimally invasive techniques. We refined a transabdominal approach to the robotic harvest of bilateral DIEP flaps. METHODS: A retrospective medical record study involving all patients who underwent bilateral or bipedicled robotic DIEP (rDIEP) or standard DIEP (sDIEP) flap harvest between July 2021 and September 2022. Outcomes included abdominal wall morbidity, total operative time, length of stay (LOS), and complications. RESULTS: Forty-seven patients were included (48 sDIEP flaps, 46 rDIEP flaps) with no significant difference in patient characteristics. Fascial incision length in the rDIEP group was shorter (4.1 vs. 11.7 cm, p < 0.001). Mesh reinforcement of the abdominal wall was used in 13/24 sDIEP and none in rDIEP patients (p < 0.001). Operative time was longer in the rDIEP cohort (739 vs. 630 minutes, p = 0.013), although subanalysis showed no difference in the second half of the cohort. The average robotic dissection time was 135 minutes, which decreased significantly with the surgeon's experience. There were no intraoperative complications from using the robot. LOS was shorter with rDIEP but not statistically significant (3.9 vs. 4.3 days, p = 0.157). CONCLUSION: This study represents the most extensive cohort analysis of bilateral rDIEP flap harvest, offering a comprehensive comparison to traditional sDIEP. The initial results underscore the viability of robotic techniques for flap harvesting, highlighting potential advantages including reduced fascial incision length and decreased abdominal disruption. Furthermore, using robotics may obviate the necessity for fascial reinforcement with mesh.

Sex difference in mitral valve prolapse regurgitant volume is resolved by normalization of regurgitant volume to left ventricular end-diastolic volume.

Women with primary mitral insufficiency have a smaller regurgitant volume at the same regurgitant fraction than men. We hypothesized that normalizing regurgitant volume with left ventricular end-diastolic volume or allometric scaling would eliminate the difference in regurgitant volume between women and men. The study cohort consisted of 101 patients with mitral valve prolapse undergoing cardiac MRI. Descriptive statistics and linear regression were performed to assess differences between sexes. Of the 101 patients, 46 (46%) were women. Women had a significantly smaller left and right ventricular end-diastolic volume, end-systolic volume, and stroke volume. While there was no difference in regurgitant fraction between women and men (34 ± 13% vs. 35 ± 14%; p = 0.71), women had a significantly smaller regurgitant volume (36 ± 18 ml vs. 49 ± 26 ml; p = 0.005). The slope-intercept relationship between regurgitant fraction and regurgitant volume revealed unique slopes and y-intercept values for men and women (p-value < 0.0001). Normalizing regurgitant volume to left ventricular end-diastolic volume (RVol/LVEDV), body surface area1.5 (RVol/BSA1.5) and height2.7 (RVol/height2.7) all had essentially identical slope-intercept relationships with regurgitant fraction for men and women, but RVol/LVEDV had the smallest effect size. In mitral insufficiency secondary to mitral valve prolapse women have a significantly smaller regurgitant volume than men despite no difference in regurgitant fraction. The significant difference in regurgitant volume between women and men is secondary to women having a smaller left ventricular end-diastolic volume.

Disparities in Cancer Stage Outcomes by Catchment Areas for a Comprehensive Cancer Center.

Importance: The National Cancer Institute comprehensive cancer centers (CCCs) lack spatial and temporal evaluation of their self-designated catchment areas. Objective: To identify disparities in cancer stage at diagnosis within and outside a CCC's catchment area across a 10-year period using spatial and statistical analyses. Design, Setting, and Participants: This cross-sectional, population-based study conducted between 2010 and 2019 utilized cancer registry data for the Johns Hopkins Sidney Kimmel CCC (SKCCC). Eligible participants included patients with cancer in the contiguous US who received treatment for cancer, a diagnosis of cancer, or both at SKCCC. Patients were geocoded to zip code tabulation areas (ZCTAs). Individual-level variables included sociodemographic characteristics, smoking and alcohol use, treatment type, cancer site, and insurance type. Data analysis was performed between March and July 2023. Exposures: Distance between SKCCC and ZCTAs were computed to generate a catchment area of the closest 75% of patients and outer zones in 5% increments for comparison. Main Outcomes and Measures: The primary outcome was cancer stage at diagnosis, defined as early-stage, late-stage, or unknown stage. Multinomial logistic regression was used to determine associations of catchment area with stage at diagnosis. Results: This study had a total of 94 007 participants (46 009 male [48.94%] and 47 998 female [51.06%]; 30 195 aged 22-45 years [32.12%]; 4209 Asian [4.48%]; 2408 Hispanic [2.56%]; 16 004 non-Hispanic Black [17.02%]; 69 052 non-Hispanic White [73.45%]; and 2334 with other or unknown race or ethnicity [2.48%]), including 47 245 patients (50.26%) who received a diagnosis of early-stage cancer, 19 491 (20.73%) who received a diagnosis of late-stage cancer , and 27 271 (29.01%) with unknown stage. Living outside the main catchment area was associated with higher odds of late-stage cancers for those who received only a diagnosis (odds ratio [OR], 1.50; 95% CI, 1.10-2.05) or only treatment (OR, 1.44; 95% CI, 1.28-1.61) at SKCCC. Non-Hispanic Black patients (OR, 1.16; 95% CI, 1.10-1.23) and those with Medicaid (OR, 1.65; 95% CI, 1.46-1.86) and no insurance at time of treatment (OR, 2.12; 95% CI, 1.79-2.51) also had higher odds of receiving a late-stage cancer diagnosis. Conclusions and Relevance: In this cross-sectional study of CCC data from 2010 to 2019, patients residing outside the main catchment area, non-Hispanic Black patients, and patients with Medicaid or no insurance had higher odds of late-stage diagnoses. These findings suggest that disadvantaged populations and those living outside of the main catchment area of a CCC may face barriers to screening and treatment. Care-sharing agreements among CCCs could address these issues.

Organizational Ethics in Healthcare: A National Survey.

Organizational ethics-defined as the alignment of an institution's practices with its mission, vision, and values-is a growing field in health care not well characterized in empirical literature. To capture the scope and context of organizational ethics work in United States healthcare institutions, we conducted a nationwide convenience survey of ethicists regarding the scope of organizational ethics work, common challenges faced, and the organizational context in which this work is done. In this article, we report substantial variability in the structure of organizational ethics programs and the settings in which it is conducted. Notable findings included disagreement about the activities that comprise organizational ethics and a lack of common metrics used to assess organizational ethics activities. A frequently cited barrier to full engagement in these activities was poor institution-wide understanding about the role and function of organizational ethics resources. These data suggest a tension in the trajectory of organizational ethics' professionalization: while some variability is appropriate to the field's relative youth, inadequate attention to definitions of organizational ethics practice and metrics for success can impede discussions about appropriate institutional support, leadership context, and training for practitioners.

Optimizing Post-Acute Coronary Syndrome Dyslipidemia Management: Insights from the North American Acute Coronary Syndrome Reflective III.

INTRODUCTION: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aimed to investigate this guideline recommendations-to-practice care gap. Specifically, we aimed to identify opportunities where additional lipid-lowering therapies are indicated and explore reasons for the non-prescription of guideline-recommended therapies. METHODS: ACS patients with LDL-C ≥1.81 mmol/L (70 mg/dL) despite maximally tolerated statin ± ezetimibe therapy (including those intolerant of ≥2 statins) were enrolled 1-12 months post-event from 27 Canadian and US sites from September 2018 to October 2020 and followed up for three visits during the 12 months post-event. We determined the proportion of patients who did not achieve Canadian/US guideline-recommended LDL-C thresholds, the number of patients who would have been eligible for additional lipid-lowering therapies, and reasons behind lack of escalation in lipid-lowering therapies when indicated. Individual patient and aggregate practice feedback, including guideline-recommended intensification suggestions, were provided to each physician. RESULTS: Of the 248 patients enrolled in the pilot study (median age 64 [57, 73] years, 31.5% female and STEMI 27.4%), 75.4% were on high-intensity statins on the first visit. A total of 18.5% of those who attended all 3 visits had an LDL-C measured only at the first visit which was above the threshold. After 1 year of follow-up, 51.9% of patients achieved LDL-C thresholds at either visit 2 or 3. In the context of feedback reminding physicians about guideline-directed LDL-C-modifying therapy in their individual participating patients, we observed an increase in the use of ezetimibe and PCSK9 inhibitor therapy at 3-12 months. This was associated with a significant lowering of the mean LDL-C (from 2.93 mmol/L [baseline] to 2.09 mmol/L [3-6 months] to 1.87 mmol/L [6-12 months]) and a significantly greater proportion of patients (from 0% [baseline] to 38.6% [3-6 months] to 53.4% [6-12 months]) achieving guideline-recommended LDL-C thresholds. The most prevalent reasons behind the non-intensification of LDL-C-lowering therapy with ezetimibe and/or PCSK9i were LDL-C levels being close to target, the pre-existing use of other lipid-lowering therapies, patient refusal, and cost. CONCLUSION: Although most patients post-ACS were on high-intensity statin therapy, almost 50% failed to achieve guideline-recommended LDL-C thresholds by 1-year follow-up. Furthermore, additional lipid-lowering therapies in this high-risk group were underprescribed, and this might be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.

Indocyanine Green-Guided Near-Infrared Fluorescence Enhances Vascular Anatomy in Robot-Assisted DIEP Flap Harvest.

SUMMARY: Indocyanine green-guided near-infrared fluorescence imaging has gained clinical acceptance lately. This technology can be particularly advantageous in the case of robotic flap harvest. This article presents a new approach to deep epigastric pedicle dissection using indocyanine green-guided near-infrared fluorescence in the setting of robot-assisted deep inferior epigastric perforator flaps.

Prognostic and therapeutic potential of senescent stromal fibroblasts in prostate cancer.

The stromal component of the tumour microenvironment in primary and metastatic prostate cancer can influence and promote disease progression. Within the prostatic stroma, fibroblasts are one of the most prevalent cell types associated with precancerous and cancerous lesions; they have a vital role in the structural composition, organization and integrity of the extracellular matrix. Fibroblasts within the tumour microenvironment can undergo cellular senescence, which is a stable arrest of cell growth and a phenomenon that is emerging as a recognized hallmark of cancer. Supporting the idea that cellular senescence has a pro-tumorigenic role, a subset of senescent cells exhibits a senescence-associated secretory phenotype (SASP), which, along with increased inflammation, can promote prostate cancer cell growth and survival. These cellular characteristics make targeting senescent cells and/or modulating SASP attractive as a potential preventive or therapeutic option for prostate cancer.

Hi-C metagenome sequencing reveals soil phage-host interactions.

Bacteriophages are abundant in soils. However, the majority are uncharacterized, and their hosts are unknown. Here, we apply high-throughput chromosome conformation capture (Hi-C) to directly capture phage-host relationships. Some hosts have high centralities in bacterial community co-occurrence networks, suggesting phage infections have an important impact on the soil bacterial community interactions. We observe increased average viral copies per host (VPH) and decreased viral transcriptional activity following a two-week soil-drying incubation, indicating an increase in lysogenic infections. Soil drying also alters the observed phage host range. A significant negative correlation between VPH and host abundance prior to drying indicates more lytic infections result in more host death and inversely influence host abundance. This study provides empirical evidence of phage-mediated bacterial population dynamics in soil by directly capturing specific phage-host interactions.

Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer.

The tissue microenvironment in prostate cancer is profoundly altered. While such alterations have been implicated in driving prostate cancer initiation and progression to aggressive disease, how prostate cancer cells and their precursors mediate those changes is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we performed extensive single-cell RNA-sequencing (scRNA-seq) and rigorous molecular pathology of the comparative biology between human prostate cancer and key time points in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues, with validation in a large external data set, revealed that cancer cell-intrinsic activation of MYC signaling was the top up-regulated pathway in human cancers, representing a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Likewise, numerous non-malignant cell states in the tumor microenvironment (TME), including non-cancerous epithelial, immune, and fibroblast cell compartments, were conserved across individuals, raising the possibility that these cell types may be a sequelae of the convergent MYC activation in the cancer cells. To test this hypothesis, we employed a GEMM of prostate epithelial cell-specific MYC activation in two mouse strains. Cell communication network and pathway analyses suggested that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogrammed the TME during carcinogenesis, leading to the emergence of cascading cell state alterations in neighboring epithelial, immune, and fibroblast cell types that paralleled key findings in human prostate cancer. Importantly, among these changes, the progression from a precursor-enriched to invasive-cancer-enriched state was accompanied by a cell-intrinsic switch from pro-immunogenic to immunosuppressive transcriptional programs with coinciding enrichment of immunosuppressive myeloid and Treg cells in the immune microenvironment. These findings implicate activation of MYC signaling in reshaping convergent aspects of the TME of prostate cancer as a common denominator across the otherwise well-documented molecular heterogeneity of human prostate cancer.

Progressive Spreading of DNA Methylation in the GSTP1 Promoter CpG Island across Transitions from Precursors to Invasive Prostate Cancer.

Glutathione S-transferase pi 1 (GSTP1) is lowly expressed in normal prostate luminal cells and becomes induced in most proliferative inflammatory atrophy (PIA) lesions. GSTP1 becomes silenced in prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma (CaP) via cytosine-phospho-guanine (CpG) island promoter hypermethylation. However, GSTP1 methylation patterns in PIA and PIN, and their relationship to patterns in CaP are poorly understood. We used bisulfite genomic sequencing to examine patterns of GSTP1 promoter CpG island methylation in laser capture microdissected benign, PIA, PIN, and CaP regions from 32 subjects that underwent radical prostatectomy. We analyzed 908 sequence clones across 24 normal epithelium, 37 PIA, 18 PIN, and 23 CaP regions, allowing assessment of 34,863 CpG sites with allelic phasing. Normal and PIA lesions were mostly unmethylated with 0.52 and 1.3% of total CpG sites methylated, respectively. PIN and CaP lesions had greater methylation with 24% and 51% of total CpG sites methylated, respectively. The degree of GSTP1 methylation showed progression from PIA << PIN < CaP. PIN lesions showed more partial methylation compared with CaP lesions. Partially methylated lesions were enriched for methylation changes at AP1 and SP1 transcription factor binding sites. These results demonstrate that methylation density in the GSTP1 CpG island in PIN was intermediate relative to that in normal prostate epithelium/PIA and CaP lesions. These results are consistent with gradual spreading of DNA methylation centered at the SP1/AP1 transcription factor binding sites in precursor lesions, with subsequent spreading of methylation across the entire CpG island in transition to CaP. PREVENTION RELEVANCE: DNA hypermethylation at the GSTP1 promoter progressively spreads from being unmethylated in normal prostate to intermediate levels in precursor lesions to extensive methylation in cancer. This molecular progression of GSTP1 promoter methylation patterns in early prostate carcinogenesis could be useful for identification and interception of prostate cancer precursors.

Modeling the accuracy of a novel PCR and antibody ELISA for African swine fever virus detection using Bayesian latent class analysis.

Introduction: Diagnostic test evaluation for African swine fever (ASF) in field settings like Vietnam is critical to understanding test application in intended populations for surveillance and control strategies. Bayesian latent class analysis (BLCA) uses the results of multiple imperfect tests applied to an individual of unknown disease status to estimate the diagnostic sensitivity and specificity of each test, forgoing the need for a reference test. Methods: Here, we estimated and compared the diagnostic sensitivity and specificity of a novel indirect ELISA (iELISA) for ASF virus p30 antibody (Innoceleris LLC.) and the VetAlert™ ASF virus DNA Test Kit (qPCR, Tetracore Inc.) in field samples from Vietnam by assuming that disease status 1) is known and 2) is unknown using a BLCA model. In this cross-sectional study, 398 paired, individual swine serum/oral fluid (OF) samples were collected from 30 acutely ASF-affected farms, 37 chronically ASF-affected farms, and 20 ASF-unaffected farms in Vietnam. Samples were tested using both diagnostic assays. Diagnostic sensitivity was calculated assuming samples from ASF-affected farms were true positives and diagnostic sensitivity by assuming samples from unaffected farms were true negatives. ROC curves were plotted and AUC calculated for each test/sample combination. For comparison, a conditionally dependent, four test/sample combination, three population BLCA model was fit. Results: When considering all assumed ASF-affected samples, qPCR sensitivity was higher for serum (65.2%, 95% Confidence Interval [CI] 58.1-71.8) and OF (52%, 95%CI 44.8-59.2) compared to the iELISA (serum: 42.9%, 95%CI 35.9-50.1; OF: 33.3%, 95%CI 26.8-40.4). qPCR-serum had the highest AUC (0.895, 95%CI 0.863-0.928). BLCA estimates were nearly identical to those obtained when assuming disease status and were robust to changes in priors. qPCR sensitivity was considerably higher than ELISA in the acutely-affected population, while ELISA sensitivity was higher in the chronically-affected population. Specificity was nearly perfect for all test/sample types. Discussion: The effect of disease chronicity on sensitivity and specificity could not be well characterized here due to limited data, but future studies should aim to elucidate these trends to understand the best use of virus and antibody detection methods for ASF. Results presented here will help the design of surveillance and control strategies in Vietnam and other countries affected by ASF.

Predicting Corrosion Damage in the Human Body Using Artificial Intelligence: In Vitro Progress and Future Applications.

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate AI's impact, few studies have led to improved clinical outcomes. In this review, we focus on how AI models implemented in nonorthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be implemented to study fretting, crevice, and pitting corrosion of titanium and cobalt chrome alloys.

No life-history cost of tebufenozide resistance in the smaller tea tortrix moth.

BACKGROUND: Tebufenozide is widely used to control populations of the smaller tea tortrix, Adoxophyes honmai. However, A. honmai has evolved resistance such that straightforward pesticide application is an untenable long-term approach for population control. Evaluating the fitness cost of resistance is key to devising a management strategy that slows the evolution of resistance. RESULTS: We used three approaches to assess the life-history cost of tebufenozide resistance with two strains of A. honmai: a tebufenozide-resistant strain recently collected from the field in Japan and a susceptible strain that has been maintained in the laboratory for decades. First, we found that the resistant strain with standing genetic variation did not decline in resistance in the absence of insecticide over four generations. Second, we found that genetic lines that spanned a range of resistance profiles did not show a negative correlation between their LD50 , the dosage at which 50 % of individuals died, and life-history traits that are correlates of fitness. Third, we found that the resistant strain did not manifest life-history costs under food limitation. Our crossing experiments indicate that the allele at an ecdysone receptor locus known to confer resistance explained much of the variance in resistance profiles across genetic lines. CONCLUSION: Our results indicate that the point mutation in the ecdysone receptor, which is widespread in tea plantations in Japan, does not carry a fitness cost in the tested laboratory conditions. The absence of a cost of resistance and the mode of inheritance have implications for which strategies may be effective in future resistance management efforts. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Strong effects of food quality on host life history do not scale to impact parasitoid efficacy or life history.

Parasitoids are small insects, (e.g., small wasps or flies) that reproduce by laying eggs on or within host arthropods. Parasitoids make up a large proportion of the world's biodiversity and are popular agents of biological control. Idiobiont parasitoids paralyze their hosts upon attack and thus are expected to only target hosts large enough to support offspring development. Host resources generally impact host attributes and life histories including size, development, and life span. Some argue slow host development in response to resource quality increases parasitoid efficacy (i.e., a parasitoid's ability to successfully reproduce on or within a host) due to longer host exposure to parasitoids. However, this hypothesis is not always supported and does not consider variation in other host traits in response to resources that may be important for parasitoids (e.g., variation in host size is known to impact parasitoid efficacy). In this study we test whether trait variation within host developmental stages in response to host resources is more important for parasitoid efficacy and life histories than trait variation across host developmental stages. We exposed seed beetle hosts raised on a food quality gradient to mated female parasitoids and measured the number of hosts parasitized and parasitoid life history traits at the scale of host stage- and age-structure. Our results suggest host food quality does not cascade to impact idiobiont parasitoid life histories despite large food quality effects on host life history. Instead, variation in host life histories across host developmental stages better predicts parasitoid efficacy and life histories, suggesting finding a host in a specific instar is more important for idiobiont parasitoids than finding hosts on or within higher quality resources.

Snekmer: a scalable pipeline for protein sequence fingerprinting based on amino acid recoding.

Motivation: The vast expansion of sequence data generated from single organisms and microbiomes has precipitated the need for faster and more sensitive methods to assess evolutionary and functional relationships between proteins. Representing proteins as sets of short peptide sequences (kmers) has been used for rapid, accurate classification of proteins into functional categories; however, this approach employs an exact-match methodology and thus may be limited in terms of sensitivity and coverage. We have previously used similarity groupings, based on the chemical properties of amino acids, to form reduced character sets and recode proteins. This amino acid recoding (AAR) approach simplifies the construction of protein representations in the form of kmer vectors, which can link sequences with distant sequence similarity and provide accurate classification of problematic protein families. Results: Here, we describe Snekmer, a software tool for recoding proteins into AAR kmer vectors and performing either (i) construction of supervised classification models trained on input protein families or (ii) clustering for de novo determination of protein families. We provide examples of the operation of the tool against a set of nitrogen cycling families originally collected using both standard hidden Markov models and a larger set of proteins from Uniprot and demonstrate that our method accurately differentiates these sequences in both operation modes. Availability and implementation: Snekmer is written in Python using Snakemake. Code and data used in this article, along with tutorial notebooks, are available at http://github.com/PNNL-CompBio/Snekmer under an open-source BSD-3 license. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Genomic Characterization of Prostatic Basal Cell Carcinoma.

Basal cell carcinoma (BCC) of the prostate is a rare tumor. Compared with the more common acinar adenocarcinoma (AAC) of the prostate, BCCs show features of basal cell differentiation and are thought to be biologically distinct from AAC. The spectrum of molecular alterations of BCC has not been comprehensively described, and genomic studies are lacking. Herein, whole genome sequencing was performed on archival formalin-fixed, paraffin-embedded specimens of two cases with BCC. Prostatic BCCs were characterized by an overall low copy number and mutational burden. Recurrent copy number loss of chromosome 16 was observed. In addition, putative driver gene alterations in KIT, DENND3, PTPRU, MGA, and CYLD were identified. Mechanistically, depletion of the CYLD protein resulted in increased proliferation of prostatic basal cells in vitro. Collectively, these studies show that prostatic BCC displays distinct genomic alterations from AAC and highlight a potential role for loss of chromosome 16 in the pathogenesis of this rare tumor type.

Single-cell atlas of epithelial and stromal cell heterogeneity by lobe and strain in the mouse prostate.

BACKGROUND: Evaluating the complex interplay of cell types in the tissue microenvironment is critical to understanding the origin and progression of diseases in the prostate and potential opportunities for intervention. Mouse models are an essential tool to investigate the molecular and cell-type-specific contributions of prostate disease at an organismal level. While there are well-documented differences in the extent, timing, and nature of disease development in various genetically engineered and exposure-based mouse models in different mouse strains and prostate lobes within each mouse strain, the underlying molecular phenotypic differences in cell types across mouse strains and prostate lobes are incompletely understood. METHODS: In this study, we used single-cell RNA-sequencing (scRNA-seq) methods to assess the single-cell transcriptomes of 6-month-old mouse prostates from two commonly used mouse strains, friend virus B/NIH jackson (FVB/NJ) (N = 2) and C57BL/6J (N = 3). For each mouse, the lobes of the prostate were dissected (anterior, dorsal, lateral, and ventral), and individual scRNA-seq libraries were generated. In situ and pathological analyses were used to explore the spatial and anatomical distributions of novel cell types and molecular markers defining these cell types. RESULTS: Data dimensionality reduction and clustering analysis of scRNA-seq data revealed that basal and luminal cells possessed strain-specific transcriptomic differences, with luminal cells also displaying marked lobe-specific differences. Gene set enrichment analysis comparing luminal cells by strain showed enrichment of proto-Oncogene targets in FVB/NJ mice. Additionally, three rare populations of epithelial cells clustered independently of strain and lobe: one population of luminal cells expressing Foxi1 and components of the vacuolar ATPase proton pump (Atp6v0d2 and Atp6v1g3), another population expressing Psca and other stem cell-associated genes (Ly6a/Sca-1, Tacstd2/Trop-2), and a neuroendocrine population expressing Chga, Chgb, and Syp. In contrast, stromal cell clusters, including fibroblasts, smooth muscle cells, endothelial cells, pericytes, and immune cell types, were conserved across strain and lobe, clustering largely by cell type and not by strain or lobe. One notable exception to this was the identification of two distinct fibroblast populations that we term subglandular fibroblasts and interstitial fibroblasts based on their strikingly distinct spatial distribution in the mouse prostate. CONCLUSIONS: Altogether, these data provide a practical reference of the transcriptional profiles of mouse prostate from two commonly used mouse strains and across all four prostate lobes.

Drought patterns: their spatiotemporal variability and impacts on maize production in Limpopo province, South Africa.

Due to global climate change, droughts are likely to become more frequent and more severe in many regions such as in South Africa. In Limpopo, observed high climate variability and projected future climate change will likely increase future maize production risks. This paper evaluates drought patterns in Limpopo at two representative sites. We studied how drought patterns are projected to change under future climatic conditions as an important step in identifying adaptation measures (e.g., breeding maize ideotypes resilient to future conditions). Thirty-year time horizons were analyzed, considering three emission scenarios and five global climate models. We applied the WOFOST crop model to simulate maize crop growth and yield formation over South Africa's summer season. We considered three different crop emergence dates. Drought indices indicated that mainly in the scenario SSP5-8.5 (2051-2080), Univen and Syferkuil will experience worsened drought conditions (DC) in the future. Maize yield tends to decline and future changes in the emergence date seem to impact yield significantly. A possible alternative is to delay sowing date to November or December to reduce the potential yield losses. The grain filling period tends to decrease in the future, and a decrease in the duration of the growth cycle is very likely. Combinations of changed sowing time with more drought tolerant maize cultivars having a longer post-anthesis phase will likely reduce the potential negative impact of climate change on maize.

Evaluation of co-circulating pathogens and microbiome from COVID-19 infections.

Co-infections or secondary infections with SARS-CoV-2 have the potential to affect disease severity and morbidity. Additionally, the potential influence of the nasal microbiome on COVID-19 illness is not well understood. In this study, we analyzed 203 residual samples, originally submitted for SARS-CoV-2 testing, for the presence of viral, bacterial, and fungal pathogens and non-pathogens using a comprehensive microarray technology, the Lawrence Livermore Microbial Detection Array (LLMDA). Eighty-seven percent of the samples were nasopharyngeal samples, and 23% of the samples were oral, nasal and oral pharyngeal swabs. We conducted bioinformatics analyses to examine differences in microbial populations of these samples, as a proxy for the nasal and oral microbiome, from SARS-CoV-2 positive and negative specimens. We found 91% concordance with the LLMDA relative to a diagnostic RT-qPCR assay for detection of SARS-CoV-2. Sixteen percent of all the samples (32/203) revealed the presence of an opportunistic bacterial or frank viral pathogen with the potential to cause co-infections. The two most detected bacteria, Streptococcus pyogenes and Streptococcus pneumoniae, were present in both SARS-CoV-2 positive and negative samples. Human metapneumovirus was the most prevalent viral pathogen in the SARS-CoV-2 negative samples. Sequence analysis of 16S rRNA was also conducted to evaluate bacterial diversity and confirm LLMDA results.

Applying the Peter Parker Principle to Healthcare.

The role of power in healthcare can raise many ethical challenges. Power is ownership, whether given, ceded, or taken of another person's autonomy. When a person has power over someone else, they can control or strongly influence the decision-making freedom of that person. From the principalist perspective1,2 of healthcare ethics, denying a person their freedom to choose should only occur when justifying conditions related to beneficence and nonmaleficence are sufficiently satisfied. In healthcare, it is rare to be able to identify situations where paternalism is justified. However, experience suggests that abusive power in healthcare is used too frequently without justifying criteria.