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Objective: Drinking more and drinking to cope increase undergraduates' likelihood of experiencing alcohol-related problems (ARP; e.g., driving intoxicated). In accordance with stress-coping models of addiction, anxiety about COVID-19 may motivate undergraduates to drink to cope, leading them to experience more ARP. However, this hypothesis has not been tested. Participants and methods: During fall 2020, 358 undergraduate drinkers (M[subscript age] = 21.18; 69.80% cis-women; 62.30% White) provided data regarding COVID-anxiety, alcohol consumption, drinking to cope, and ARP during an annual student survey. Results: Mediation analysis controlling for alcohol consumption revealed greater COVID-anxiety predicted higher levels of drinking to cope; in turn, higher levels of drinking to cope were associated with more ARP. Additionally, the positive relationship between greater COVID-anxiety and experiencing more ARP was explained entirely by higher levels of drinking to cope. Conclusion: During the pandemic and beyond, university prevention and intervention initiatives should target coping motives for alcohol use to help students avoid ARP.

Sections of a magnesium alloy, AZ31B, joined with tungsten inert gas (TIG) welding, were examined with scanning electrochemical microscopy (SECM) and scanning Kelvin probe force microscopy (SKPFM) to investigate corrosion mechanisms by correlating observed corrosion behavior with weld-affected microstructural variations. Insight into the changing nature of the galvanic couples between weld zones and at localized microgalvanic sites were investigated using SECM and SKPFM to map both electrochemically active regions and Volta potential differences across the weld-affected zones. The formation of an Al-Zn solidification network in the fusion zone (FZ) at and near the TIG weld epicenter differs from the outer heat-affected zone (HAZ), where intermetallic particles (IMPs) are the notable secondary phase from the magnesium matrix. These microstructures were mapped with SKPFM before and after brief exposure to a salt solution, revealing micro-galvanic couples as the main driving force to corrosion initiation and propagation within each zone. The IMPs and Al-Zn solidification network act as strong cathodes and govern the corrosion processes. The galvanic coupling and evolution of the intrinsic corrosion behavior between the weld zones is explained by monitoring the hydrogen evolution reaction (HER) with SECM over time. Anodically induced cathodic activation is confirmed for this welded material, as micro-galvanic couples between microstructural features are found to transition over time to broad electrochemically active areas within the weld-affected zones, resulting in polarity reversal as time of exposure proceeds.

This study introduces Indigenous Case Study (ICS) as a methodology poised to foster decolonized and anti-racist spaces. ICS is a weaving of TribalCrit, critical and Indigenous methodological approaches, and considers contemporary and historical contexts, simultaneously. In the current manuscript, ICS helps reimage campuses through revised policies and practices that work toward the creation of decolonized and inclusive institutions for Native students and communities. ICS allows for deeper analyses as we interrogate the dissonance between university president's statements about race and inclusion, institutional policies and practices, and the experiences of Native students as shared through student stories. We explore historical documents, president speeches, campus events, individual interviews, and researcher auto-narratives in Sharing Circles over the course of five years. The findings situate historical and contemporary campus contexts as we reveal five manifestations of oppression experienced by Native students: exploitation, marginalization, powerlessness, cultural imperialism, and violence. ICS provides circular and methodical methods that offer the opportunity to think in more complex ways as we offer findings and discussions on the cultivation of decolonized and anti-racist spaces.

This study examines how Americans’ narratives of pain are connected to social inequalities using more than 1,500 in-depth interviews collected as part of the American Voices Project. Our novel mixed-method approach to these “big (qualitative) data” uses machine learning and qualitative analysis to demonstrate that discussions of physical pain are prevalent across groups, but narrative content varies by demographics including educational background and gender identity. Our findings demonstrate (1) that pain is commonly described as a challenge that shapes everyday life, (2) that pain narratives often invoke morality and distinction, and (3) that narratives diverge around discussions of unequal medical treatment, illness identities, vulnerability and suffering. We discuss the implications of our findings for scholarship on inequality and experience, social scientific methods, and health policy.

Introduction: Persons experiencing homelessness (PEH) use emergency medical services (EMS) at disproportionately high rates relative to housed individuals due to several factors including disparate access to healthcare. Limited access to care is compounded by higher rates of substance use in PEH. Despite growing attention to the opioid epidemic and housing crisis, differences in EMS naloxone administration by housing status has not been systematically examined. Our objective in this study was to describe EMS administration of naloxone by housing status in the City of Los Angeles.Methods: This was a 12-month retrospective, cross-sectional analysis of electronic patient care reports (ePCRs) for all 9–1–1 EMS incidents attended by the Los Angeles Fire Department (LAFD), the sole EMS agency for the City of Los Angeles during the study period, January-December 2018. During this time, the City had a population of 3,949,776 with an estimated 31,825 (0.8%) PEH. We included in the study individuals to whom LAFD responders had administered naloxone. Housing status is a mandatory field on ePCRs. The primary study outcome was the incidence of EMS naloxone administration by housing status. We used descriptive statistics and logistic regression models to examine patterns by key covariates.Results: There were 345,190 EMS incidents during the study period. Naloxone was administered during 2,428 incidents. Of those incidents 608 (25%) involved PEH, and 1,820 (75%) involved housed individuals. Naloxone administration occurred at a rate of 19 per 1,000 PEH, roughly 44 times the rate of housed individuals. A logistic regression model showed that PEH remained 2.38 times more likely to receive naloxone than their housed counterparts, after adjusting for gender, age, and respiratory depression (odds ratio 2.38, 95% confidence interval 2.15–2.64). The most common impressions recorded by the EMS responders who administered naloxone were the same for both groups: overdose; altered level of consciousness; and cardiac arrest. Persons experiencing homelessness who received naloxone were more likely to be male (82% vs 67%) and younger (41.4 vs 46.2 years) than housed individuals.Conclusion: In the City of Los Angeles, PEH are more likely to receive EMS-administered naloxone than their housed peers even after adjusting for other factors. Future research is needed to understand outcomes and improve care pathways for patients confronting homelessness and opioid use.

Author(s): Corey M. Monley [sup.1] [sup.2] , Bruce S. Liese [sup.2] [sup.3] , Lindsay M. Oberleitner [sup.4] Author Affiliations: (1) https://ror.org/012zs8222, grid.265850.c, 0000 0001 2151 7947, Department of Educational and [...], Gaming Disorder was recently included in the 11.sup.th Edition of the International Classification of Diseases and Internet Gaming Disorder may be introduced in the sixth edition of The Diagnostic and Statistical Manual. Much is not understood about how problems with video games develop. This qualitative study aimed to better understand the development of problematic gaming through focus groups. Eleven young adult "frequent gamers," twelve young adult "non-frequent or non-gamers," and five older adult "non-gamers" discussed vulnerabilities and risk factors of problematic gaming. Participants across all groups believed that problematic gaming developed when people used video games as a primary means of meeting basic psychological needs that were unsatisfied, thwarted, or blocked outside of video games. Frequent and non-frequent gamers, compared to older adult non-gamers, were more likely to view video games as a healthy way to meet basic psychological needs and less likely to stereotype gamers. Video games are equipped to meet basic psychological needs for autonomy, competence, and relatedness. That is, gamers often experience a sense of agency, skill, and connection to others when playing video games. However, problematic gaming may develop when people with unmet psychological needs rely exclusively on video games to meet them. Treatment and prevention approaches to problematic gaming can benefit from greater attention to helping at risk individuals meet needs for autonomy, competence, and relatedness outside of video games.

ABSTRACT: Introduction: This study evaluates the inter-rater reliability and accuracy of radiographs in assessing healing of osteochondral allografts (OCA) in the knee compared with computed tomography (CT) imaging is currently unknown. Methods: A retrospective review patients who underwent OCA transplantation with postoperative knee radiographs obtained at three and six months, and CT scans obtained at six months was conducted. Three board-eligible orthopaedic surgeons independently graded postoperative radiographs, utilizing the grading scale established by Oladeji et al (2017), and the CT scans utilizing the grading scale established by Gelber et al (2021). Their consensus measurements served as a comparative gold standard. Results: Among 44 prospectively imaged grafts, 13 (29.5%) had radiographs at three months and 28 (63.6%) had radiographs available for evaluation at six months. Assessment of radiographic integration demonstrated low reliability (Intraclass correlation coefficient (ICC): -0.02 to 0.14). On CT scan, this improved to fair reliability (κ = 0.29, P

Summary: In contrast to most hematopoietic lineages, megakaryocytes (MKs) can derive rapidly and directly from hematopoietic stem cells (HSCs). The underlying mechanism is unclear, however. Here, we show that DNA damage induces MK markers in HSCs and that G2 arrest, an integral part of the DNA damage response, suffices for MK priming followed by irreversible MK differentiation in HSCs, but not in progenitors. We also show that replication stress causes DNA damage in HSCs and is at least in part due to uracil misincorporation in vitro and in vivo. Consistent with this notion, thymidine attenuated DNA damage, improved HSC maintenance, and reduced the generation of CD41+ MK-committed HSCs. Replication stress and concomitant MK differentiation is therefore one of the barriers to HSC maintenance. DNA damage-induced MK priming may allow rapid generation of a lineage essential to immediate organismal survival, while also removing damaged cells from the HSC pool.

The growing capabilities of synthetic biology and organic chemistry demand tools to guide syntheses toward useful molecules. Here, we present Molecular AutoenCoding Auto-Workaround (MACAW), a tool that uses a novel approach to generate molecules predicted to meet a desired property specification (e.g., a binding affinity of 50 nM or an octane number of 90). MACAW describes molecules by embedding them into a smooth multidimensional numerical space, avoiding uninformative dimensions that previous methods often introduce. The coordinates in this embedding provide a natural choice of features for accurately predicting molecular properties, which we demonstrate with examples for cetane and octane numbers, flash points, and histamine H1 receptor binding affinity. The approach is computationally efficient and well-suited to the small- and medium-size datasets commonly used in biosciences. We showcase the utility of MACAW for virtual screening by identifying molecules with high predicted binding affinity to the histamine H1 receptor and limited affinity to the muscarinic M2 receptor, which are targets of medicinal relevance. Combining these predictive capabilities with a novel generative algorithm for molecules allows us to recommend molecules with a desired property value (i.e., inverse molecular design). We demonstrate this capability by recommending molecules with predicted octane numbers of 40, 80, and 120, which is an important characteristic of biofuels. Thus, MACAW augments classical retrosynthesis tools by providing recommendations for molecules on specification.

No-till cotton producers are focused on saving resources by reducing planting rates, while maintaining yields. A 3-year field experiment was conducted in Shorter, Alabama, USA, to evaluate cotton planted into a roll/crimped cereal rye cover crop seeded at rates of 50 and 101 kg ha−1. Cotton planter performance was also compared between a mechanical planter and an electronic planter at speeds of 5.6 and 11.2 km h−1 along with low and high cotton planting rates (90,193 and 180,387 seeds ha−1). Results indicate that cereal rye seeding rates did not affect its biomass. The emergence rate index (ERI) was influenced by the planter type at the 5.6 km h−1 speed with a higher ERI (9.70% day−1) for the mechanical planter compared to a lower ERI (9.05% day−1) for the electronic planter. The cotton population was proportional to planting rates generating 66,650 and 114,178 plants ha−1 at low and high rates. Standard deviation (STD) of cotton plant spacing had a lower STD for the electronic planter compared to the mechanical planter, but did not affect the cotton yield. The seed cotton yield was not dependent on the cover crop seeding rate, planter type, and speed, but differed among years. Drought in 2019 caused a yield reduction (1844 kg ha−1) compared to higher yields of 3981 kg ha−1 in 2018 and 4152 kg ha−1 in 2020.

Background/Objectives: Although wild poliovirus type 2 has been eradicated, the prolonged transmission of the live- attenuated virus contained in the type-2 oral polio vaccine (OPV2) in under-immunized populations has led to the emergence of circulating vaccine-derived poliovirus type 2 (cVDPV2). The novel OPV2 (nOPV2) was designed to be more genetically stable and reduce the chance of cVDPV2 emergence while retaining comparable immunogenicity to the Sabin monovalent OPV2 (mOPV2). This study aimed to estimate the relative reduction in the emergence risk due to the use of nOPV2 instead of mOPV2. Methods: Data on OPV2 vaccination campaigns from May 2016 to 1 August 2024 were analyzed to estimate type-2 OPV-induced immunity in children under 5 years of age. Poliovirus surveillance data were used to estimate seeding dates and classify cVDPV2 emergences as mOPV2- or nOPV2-derived. The expected number of emergences if mOPV2 was used instead of nOPV2 was estimated, accounting for the timing and volume of nOPV2 doses, the known risk factors for emergence from mOPV2, and censoring due to the incomplete observation period for more recent nOPV2 doses. Results: As of 1 August 2024, over 98% of the approximately 1.19 billion nOPV2 doses administered globally were in Africa. We estimate that approximately 76 (95% confidence interval 69–85) index isolates of cVDPV2 emergences would be expected to be detected by 1 August 2024 if mOPV2 had been used instead of nOPV2 in Africa. The 18 observed nOPV2-derived emergences represent a 76% (74–79%) lower risk of emergence by nOPV2 than mOPV2 in Africa. The crude global analysis produced similar results. Key limitations include the incomplete understanding of the drivers of heterogeneity in emergence risk across geographies and variance in the per-dose risk of emergence may be incompletely captured using known risk factors. Conclusions: These results are consistent with the accumulating clinical and field evidence showing the enhanced genetic stability of nOPV2 relative to mOPV2, and this approach has been implemented in near-real time to contextualize new findings during the roll-out of this new vaccine. While nOPV2 has resulted in new emergences of cVDPV2, the number of cVDPV2 emergences is estimated to be approximately four-fold lower than if mOPV2 had been used instead.

Background Intravenous albumin has limited indications supported by randomised controlled trials, yet it is often prescribed for indications not supported by evidence.Aim To reduce unnecessary transfusion of albumin.Interventions Under the leadership of a multidisciplinary quality improvement team, evidence-based recommendations were disseminated in tandem with a new electronic order set, an educational strategy, qualitative interviews with prescribers and a return policy change to reduce wastage.Implementation and evaluation Interventions were introduced in a staggered fashion. The primary outcome, appropriate use of albumin, was monitored and quantified using pre-intervention and post-intervention audits. Process measures included statistical process run charts of monthly usage of 5% and 25% albumin and wastage. Data on length of stay (hospital and intensive care), new inpatient starts on kidney replacement and mortality were collected as balancing measures.Results Appropriate albumin usage based on indication increased from 30% to 50% (p

BackgroundBlockchain distributed ledger technology is just starting to be adopted in genomics and healthcare applications. Despite its increased prevalence in biomedical research applications, skepticism regarding the practicality of blockchain technology for real-world problems is still strong and there are few implementations beyond proof-of-concept. We focus on benchmarking blockchain strategies applied to distributed methods for sharing records of gene-drug interactions. We expect this type of sharing will expedite personalized medicine.Basic proceduresWe generated gene-drug interaction test datasets using the Clinical Pharmacogenetics Implementation Consortium (CPIC) resource. We developed three blockchain-based methods to share patient records on gene-drug interactions: Query Index, Index Everything, and Dual-Scenario Indexing.Main findingsWe achieved a runtime of about 60 s for importing 4,000 gene-drug interaction records from four sites, and about 0.5 s for a data retrieval query. Our results demonstrated that it is feasible to leverage blockchain as a new platform to share data among institutions.Principal conclusionsWe show the benchmarking results of novel blockchain-based methods for institutions to share patient outcomes related to gene-drug interactions. Our findings support blockchain utilization in healthcare, genomic and biomedical applications. The source code is publicly available at https://github.com/tsungtingkuo/genedrug.

Institutional discovery environments now serve as central resource databases for researchers in the academic environment. Over the last several decades, there have been numerous discovery layer research inquiries centering primarily on user satisfaction measures of discovery system effectiveness. This study focuses on the creation of a largely automated method for evaluating discovery layer quality, utilizing the bibliographic sources from student research projects. Building on past research, the current study replaces a semiautomated Excel Fuzzy Lookup Add-In process with a fully scripted R-based approach, which employs the stringdist R package and applies the Jaro-Winkler distance metric as the matching evaluator. The researchers consider the error rate incurred by relying solely on an automated matching metric. They also use Open Refine for normalization processes and package the tools together on an OSF site for other institutions to use. Since the R-based approach does not require special processing or time and can be reproduced with minimal effort, it will allow future studies and users of our method to capture larger sample sizes, boosting validity. While the assessment process has been streamlined and shows promise, there remain issues in establishing solid connections between research paper bibliographies and discovery layer use. Subsequent research will focus on creating alternatives to paper titles as search proxies that better resemble genuine information-seeking behavior and comparing undergraduate and graduate student interactions within discovery environments., INTRODUCTION There is no denying the ubiquitous nature and importance of discovery environments (DEs) to academic libraries. And further, 'effective optimization of these search platforms should be one of the [...]

Introduction: Persons experiencing homelessness (PEH) use emergency medical services (EMS) at disproportionately high rates relative to housed individuals due to several factors including disparate access to healthcare. Limited access to care is compounded by higher rates of substance use in PEH. Despite growing attention to the opioid epidemic and housing crisis, differences in EMS naloxone administration by housing status has not been systematically examined. Our objective in this study was to describe EMS administration of naloxone by housing status in the City of Los Angeles. Methods: This was a 12-month retrospective, cross-sectional analysis of electronic patient care reports (ePCRs) for all 9–1–1 EMS incidents attended by the Los Angeles Fire Department (LAFD), the sole EMS agency for the City of Los Angeles during the study period, January-December 2018. During this time, the City had a population of 3,949,776 with an estimated 31,825 (0.8%) PEH. We included in the study individuals to whom LAFD responders had administered naloxone. Housing status is a mandatory field on ePCRs. The primary study outcome was the incidence of EMS naloxone administration by housing status. We used descriptive statistics and logistic regression models to examine patterns by key covariates. Results: There were 345,190 EMS incidents during the study period. Naloxone was administered during 2,428 incidents. Of those incidents 608 (25%) involved PEH, and 1,820 (75%) involved housed individuals. Naloxone administration occurred at a rate of 19 per 1,000 PEH, roughly 44 times the rate of housed individuals. A logistic regression model showed that PEH remained 2.38 times more likely to receive naloxone than their housed counterparts, after adjusting for gender, age, and respiratory depression (odds ratio 2.38, 95% confidence interval 2.15–2.64). The most common impressions recorded by the EMS responders who administered naloxone were the same for both groups: overdose; altered level of consciousness; and cardiac arrest. Persons experiencing homelessness who received naloxone were more likely to be male (82% vs 67%) and younger (41.4 vs 46.2 years) than housed individuals. Conclusion: In the City of Los Angeles, PEH are more likely to receive EMS-administered naloxone than their housed peers even after adjusting for other factors. Future research is needed to understand outcomes and improve care pathways for patients confronting homelessness and opioid use.

Background: Acinar ductal metaplasia (ADM) is among the earliest initiating events in pancreatic ductal adenocarcinoma (PDAC) development.Methods: We developed a novel morphology-based screen using organoids from wildtype and p48Cre/+ (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA).Results: Of the 144 compounds screened, nine hits and two additional natural product HDAC inhibitors were validated by dose-response analysis. The class I HDAC inhibitors apicidin and FK228, and the histone methyltransferase inhibitor chaetocin demonstrated pronounced ADM inhibition and reversal without inducing significant cytotoxicity at 1 µM. Thioester prodrug class I HDAC inhibitor largazole attenuated ADM while its disulfide homodimer was effective in both ADM inhibition and reversal. Prioritized compounds were validated for ADM reversal in p48Cre/+; LSL-KrasG12D/+ (KC) mouse organoids using both morphological and molecular endpoints. Molecular index analysis of ADM reversal in KC mouse organoids demonstrated improved activity compared to TSA. Improved prodrug stability translated into a stronger phenotypic and molecular response. RNA-sequencing indicated that angiotensinogen was the top inhibited pathway during ADM reversal.Conclusion: Our findings demonstrate a unique epigenetic mechanism and suggest that the phenotypic screen developed here may be applied to discover potential treatments for PDAC.

The Very Short Introductions series, which now includes Mark Lomolino’s new book Biogeography, aims to give “anyone ... a stimulating and accessible way into a new subject” (p. ii). In such an holistic discipline as biogeography, in such a short book, finding the hooks to engage a diverse audience and represent the field seems like an impossible task. But having co- authored a, if not the discipline’s preeminent, full-size biogeography text (Lomolino et al. 2016), probably few are as well positioned as Lomolino to distil biogeography’s essence.

The mammary epithelial cell (MEC) system is a bilayered ductal epithelium of luminal and basal cells, maintained by a lineage of stem and progenitor populations. Here, we used integrated single-cell transcriptomics and chromatin accessibility analysis to reconstruct the cell types of the mouse MEC system and their underlying gene regulatory features in an unbiased manner. We define differentiation states within the secretory type of luminal cells, which forms a continuous spectrum of general luminal progenitor and lactation-committed progenitor cells. By integrating single-cell transcriptomics and chromatin accessibility landscapes, we identify cis- and trans-regulatory elements that are differentially activated in the specific epithelial cell types and our newly defined luminal differentiation states. Our work provides a resource to reveal cis/trans-regulatory elements associated with MEC identity and differentiation that will serve as a reference to determine how the chromatin accessibility landscape changes during breast cancer.

Viral replication places oncolytic viruses (OVs) in a unique niche in the field of drug pharmacokinetics (PK) as their self-amplification obscures exposure-response relationships. Moreover, standard bioanalytical techniques are unable to distinguish the input from replicated drug products. Here, we combine two novel approaches to characterize PK and biodistribution (BD) after systemic administration of vesicular stomatitis virus pseudotyped with lymphocytic choriomeningitis virus glycoprotein (VSV-GP) in healthy mice. First: to decouple input drug PK/BD versus replication PK/BD, we developed and fully characterized a replication-incompetent tool virus that retained all other critical attributes of the drug. We used this approach to quantify replication in blood and tissues and to determine its impact on PK and BD. Second: to discriminate the genomic and antigenomic viral RNA strands contributing to replication dynamics in tissues, we developed an in situ hybridization method using strand-specific probes and assessed their spatiotemporal distribution in tissues. This latter approach demonstrated that distribution, transcription, and replication localized to tissue-resident macrophages, indicating their role in PK and BD. Ultimately, our study results in a refined PK/BD profile for a replicating OV, new proposed PK parameters, and deeper understanding of OV PK/BD using unique approaches that could be applied to other replicating vectors.

Background:. We aimed to identify how Integra bilayer wound matrix has expanded facial reconstruction options after Mohs surgery due to its reliability in both single- and dual-stage reconstruction. Methods:. A retrospective review of patients undergoing Mohs surgery and alloplastic facial reconstruction with Integra between 2012 and 2022 was performed. Patients who underwent single-stage reconstruction and dual-stage reconstruction with skin graft with at least 90 days of follow-up were included. Results:. One hundred thirty patients with a median age of 76 years were included. Basal cell carcinoma was the most common malignancy (39%). One hundred forty-two lesions were treated and reconstructed same-day with Integra. Lesions most commonly involved the nose (34%) and forehead (22%). The mean postoperative defect size was 26.9 cm2. An estimated 45.5% (n = 60) of defect sites underwent single-stage reconstruction with healing by secondary intention, whereas 54.5% (n = 72) underwent dual-stage reconstruction with skin graft. Integra success rate was 90.2%. Average time to re-epithelialization was 32.2 + 7.3 days. Average time to repigmentation was 169.5 + 14.6 days. The complication rate was 12.8% (n = 17), with 12 undergoing debridement, three needing new Integra graft, and seven needing new skin grafts. Average size for successful healing without complication was 26.6 cm2. Nineteen sites (13.2%) underwent aesthetic improvement procedures, with the majority occurring after dual-stage reconstruction (n = 13). Conclusions:. Integra is a reliable outpatient reconstructive option for facial Mohs defects that can increase the threshold for autologous tissue harvesting and successfully reconstruct large defects of 26.6 cm2 on average with low complication and reoperation rates.