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Background: Teaching students about race and racism is critical to and relevant in psychology classrooms. Objective: We explored whether direct instruction dismantling ideas that race is genetic affects students' race essentialist and other related beliefs. Method: Undergraduate students enrolled in four social psychology courses completed measures of race essentialism and other related beliefs before and after engaging in course-directed activities designed to reduce endorsement of biological essentialist beliefs about race. Results: After class activities, students reported lower levels of general racial essentialist beliefs and estimated that more progress is needed to reduce racial inequality. However, attitudes towards racially minoritized groups or perceived need for anti-racist actions did not shift, and colorblind ideology may have increased. Conclusion: These data provide evidence that essentialism shifts can be accomplished in the psychology classroom, but shifting related beliefs may require additional instruction. Teaching Implications: The class activities described in this research provide a way for instructors to introduce students to a new concept (race essentialism) and change students' beliefs in the genetic underpinning of race.

Abstract Background Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despite some clinical guidelines endorsing the application of lifestyle therapies as a first-line treatment for individuals with mood disorders, there is limited evidence that this recommendation has been widely adopted into routine practice. A key obstacle is the insufficient evidence on whether lifestyle therapies match the clinical and cost effectiveness of psychological therapy, particularly for treating those with moderate to severe symptoms. The HARMON-E Trial seeks to address this gap by conducting a non-inferiority trial evaluating whether a multi-component lifestyle therapy program is non-inferior to psychological therapy on clinical and cost-effectiveness outcomes over 8-weeks for adults with major depressive disorder and bipolar affective disorder. Methods This trial uses an individually randomised group treatment design with computer generated block randomisation (1:1). Three hundred and seventy-eight adults with clinical depression or bipolar affective disorder, a recent major depressive episode, and moderate-to-severe depressive symptoms are randomised to receive either lifestyle therapy or psychological therapy (adjunctive to any existing treatments, including pharmacotherapies). Both therapy programs are delivered remotely, via a secure online video conferencing platform. The programs comprise an individual session and six subsequent group-based sessions over 8-weeks. All program aspects (e.g. session duration, time of day, and communications between participants and facilitators) are matched except for the content and program facilitators. Lifestyle therapy is provided by a dietitian and exercise physiologist focusing on four pillars of lifestyle (diet, physical activity, sleep, and substance use), and the psychological therapy program is provided by two psychologists using a cognitive behavioural therapy approach. Data collection occurs at baseline, 8-weeks, 16-weeks, and 6 months with research assistants blinded to allocation. The primary outcome is depressive symptoms at 8 weeks, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) (minimal clinically important difference = 1.6). A pre-specified within-trial economic evaluation will also be conducted. Discussion Should lifestyle therapy be found to be as clinically and cost effective as psychological therapy for managing mood disorders, this approach has potential to be considered as an adjunctive treatment for those with moderate to severe depressive symptoms. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12622001026718, registered 22nd July 2022. Protocol version: 4.14, 26/06/2024

Abstract Marine spatial planning (MSP) has emerged as a tool to enable marine ecosystem-based management that seeks to balance human demands for ocean space with environmental protection. However, there is a history of thinking about our ocean systems as spaces, not places. As a result, most MSPs have been implemented without consideration of place. The relationship between people and the rest of nature is at the core of the UN SDGs (Sustainable Development Goals). Due to significant knowledge gaps in sociocultural connections, people and their place-based perspectives and needs are often overlooked in the MSP process. New approaches are required to equip societies with information to inform sustainable ocean planning relevant to environmental change and the local sociocultural context. We encourage the inclusion of a distinct place-based characteristic in MSP and argue that bringing in the concepts of space and place from the discipline of geography can enable a broader view of the seascape in MSP. Here, we provide five core considerations of place-based MSP that include: (1) sense of place; (2) social-ecological systems; (3) ocean and human health; (4) multiple ways of knowing; and (5) social knowledge. We review available methods and suggest a multi-evidence-based approach that can highlight dynamic eco-cultural connections between people and the biophysical patterns and processes of interlinked landscapes and seascapes. Moving towards place-based MSP can help to solve three important issues in the current context of global socio-environmental transformations. First, these key concepts are relevant for interdisciplinary science, as solving problems raised by MSP requires more than superimposing spatial layers of scientific knowledge. Second, marine planning and management is less efficient if policies are not integrated and if issues are addressed by each individual sector rather than in a holistic manner. Third, a place-based approach accounts for individual and collective values and may open new ways to solve governance issues. A shift from understanding and managing ocean spaces to including ocean places can support progress towards sustainable and equitable MSP goals.

Abstract Background Multiple sclerosis (MS) is a chronic neurological condition and the leading cause of non-traumatic disability in young adults. MS pathogenesis leads to the death of oligodendrocytes, demyelination, and progressive central nervous system neurodegeneration. Endogenous remyelination occurs in people with MS (PwMS) but is insufficient to repair the damage. Our preclinical studies in mice indicate that endogenous remyelination can be supported by the delivery of repetitive transcranial magnetic stimulation (rTMS). Our phase I trial concluded that 20 sessions of rTMS, delivered over 5 weeks, are safe and feasible for PwMS. This phase II trial aims to investigate the safety and preliminary efficacy of rTMS for PwMS. Methods Participants must be aged 18–65 years, diagnosed with MS by a neurologist, stable and relapse free for 6 months, have an Extended Disability Status Scale (EDSS) between 1.5 and 6 (inclusive), willing to travel to a study site every weekday for 4 consecutive weeks, and able to provide informed consent and access the internet. Participants from multiple centres will be randomised 2:1 (rTMS to sham) stratified by sex. The intervention will be delivered with a Magstim Rapid2 stimulator device and circular 90-mm coil or MagVenture MagPro stimulator device with C100 circular coil, positioned to stimulate a broad area including frontal and parietal cortices. For the rTMS group, pulse intensity will be set at 18% (MagVenture) or 25% (Magstim) of maximum stimulator output (MSO), and rTMS applied as intermittent theta burst stimulation (iTBS) (~ 3 min per side; 600 pulses). For the sham group, the procedure will be the same, but the intensity is set at 0%. Each participant will attend 20 intervention sessions over a maximum of 5 weeks. Outcome measures include MS Functional Composite Score (primary), Fatigue Severity Scale, Hospital Anxiety and Depression Scale, Quality of Life, and Pittsburgh Sleep Quality Index/Numeric Rating Scale and adverse events (secondary) and advanced MRI metrics (tertiary). Outcomes will be measured at baseline and after completing the intervention. Discussion This study will determine if rTMS can improve functional outcomes or other MS symptoms and determine whether rTMS has the potential to promote remyelination in PwMS. Trial registration Registered with Australian New Zealand Clinical Trials Registry, 20 January 2022; ACTRN12622000064707.

Abstract Aim Illicitly manufactured fentanyl and its analogs are the primary drivers of opioid overdose deaths in the United States (U.S.). People who use drugs may be exposed to fentanyl or its analogs intentionally or unintentionally. This study sought to identify strategies used by rural people who use drugs to reduce harms associated with unintentional fentanyl exposure. Methods This analysis focused on 349 semi-structured qualitative interviews across 10 states and 58 rural counties in the U.S conducted between 2018 and 2020. Interview guides were collaboratively standardized across sites and included questions about drug use history (including drugs currently used, frequency of use, mode of administration) and questions specific to fentanyl. Deductive coding was used to code all data, then inductive coding of overdose and fentanyl codes was conducted by an interdisciplinary writing team. Results Participants described being concerned that fentanyl had saturated the drug market, in both stimulant and opioid supplies. Participants utilized strategies including: (1) avoiding drugs that were perceived to contain fentanyl, (2) buying drugs from trusted sources, (3) using fentanyl test strips, 4) using small doses and non-injection routes, (5) using with other people, (6) tasting, smelling, and looking at drugs before use, and (7) carrying and using naloxone. Most people who used drugs used a combination of these strategies as there was an overwhelming fear of fatal overdose. Conclusion People who use drugs living in rural areas of the U.S. are aware that fentanyl is in their drug supply and use several strategies to prevent associated harms, including fatal overdose. Increasing access to harm reduction tools (e.g., fentanyl test strips, naloxone) and services (e.g., community drug checking, syringe services programs, overdose prevention centers) should be prioritized to address the polysubstance-involved overdose crisis. These efforts should target persons who use opioids and other drugs that may contain fentanyl.

During drought, groundwater is often relied on to provide secure drinking water, particularly in rural Africa where other options are limited. However, the technology chosen to access groundwater significantly affects local water security. Here we examine the performance of springs, hand-dug-wells and boreholes in northern Ethiopia through direct high frequency monitoring of water-levels ( n = 19) and water quality ( n = 48) over an 18 month period and gathering information on community impacts of declining water access during the El Niño 2015/2016 drought. We found that shallow boreholes equipped with handpumps were the most reliable water supply, recovering within hours to daily abstraction throughout all conditions. Recovery and performance of most hand-dug-wells and springs declined significantly throughout the extended dry season, although in specific aquifer conditions they were reliable. All sources types had negligible measured contamination from Thermo-tolerant Coliforms through the extended dry season, but were contaminated during the rains marking drought cessation. Boreholes were least affected, median 10 cfu/100 ml, compared to 190 and 59 cfu/100 ml for hand-dug-wells and springs respectively. Many communities who relied solely on springs, wells or rivers experienced severe water shortage in the El Niño drought with mean daily collection times up to 12 h and volumes collected reducing to 3–5 litre per-capita-per-day. This led to reports of violent conflict, missed meals, reduction in school attendance and farm activity and increased health impacts. From this study there is a clear case for improving resilience to drought by installing boreholes equipped with handpumps where feasible even if collection times are >30 min.

Hydro-pedotransfer functions (PTFs) relate easy-to-measure and readily available soil information to soil hydraulic properties (SHPs) for applications in a wide range of process-based and empirical models, thereby enabling the assessment of soil hydraulic effects on hydrological, biogeochemical, and ecological processes. At least more than 4 decades of research have been invested to derive such relationships. However, while models, methods, data storage capacity, and computational efficiency have advanced, there are fundamental concerns related to the scope and adequacy of current PTFs, particularly when applied to parameterise models used at the field scale and beyond. Most of the PTF development process has focused on refining and advancing the regression methods, while fundamental aspects have remained largely unconsidered. Most soil systems are not represented in PTFs, which have been built mostly for agricultural soils in temperate climates. Thus, existing PTFs largely ignore how parent material, vegetation, land use, and climate affect processes that shape SHPs. The PTFs used to parameterise the Richards–Richardson equation are mostly limited to predicting parameters of the van Genuchten–Mualem soil hydraulic functions, despite sufficient evidence demonstrating their shortcomings. Another fundamental issue relates to the diverging scales of derivation and application, whereby PTFs are derived based on laboratory measurements while often being applied at the field to regional scales. Scaling, modulation, and constraining strategies exist to alleviate some of these shortcomings in the mismatch between scales. These aspects are addressed here in a joint effort by the members of the International Soil Modelling Consortium (ISMC) Pedotransfer Functions Working Group with the aim of systematising PTF research and providing a roadmap guiding both PTF development and use. We close with a 10-point catalogue for funders and researchers to guide review processes and research.

Abstract Background Multipurpose prevention technologies (MPTs) are products capable of simultaneously addressing multiple sexual and reproductive health needs such as unwanted pregnancy, STIs including HIV-1, and other reproductive tract infections. MPTs are urgently needed to address the double burden of unplanned pregnancy and HIV. While condoms are currently the only accessible MPTs, they are not solely under a woman’s control, and female condoms face limitations due to poor acceptability and high cost. Methods We conducted a sub-analysis of qualitative data from 39 couples participating in the MTN 045 study to examine the perception of couples on choice and acceptability of a “2 in 1” MPT that combines HIV and pregnancy prevention. Results Couples recognized the benefits of MPTs for HIV and pregnancy prevention but perceptions tied to each indication and a novel prevention technology tool raised important concerns relevant to use of future MPTs. In the study, participants’ perceptions of MPT use were influenced by pregnancy planning. When the timing was less critical, they prioritized HIV prevention. Misinformation about family planning methods, including MPTs, affected decision-making with potential to hinder uptake of future MPTs. Concerns about side effects, such as weight gain and hormonal imbalances, influenced willingness to use MPTs. Conclusion Addressing the myths and misconceptions surrounding the use of contraceptives is crucial in promoting their acceptance and ultimate use. Strategies for addressing the drawbacks women might experience while using a particular product should be in place as new MPTs progress through the development pipeline and approach roll-out.

Abstract Background Low mechanical properties are the main limitation of glass ionomer cements (GICs). The incorporation of elastomeric micelles is expected to enhance the strength of GICs without detrimentally affecting their physical properties and biocompatibility. This study compared the chemical and mechanical properties, as well as the cytotoxicity, of elastomeric micelles-containing glass ionomer cement (DeltaFil, DT) with commonly used materials, including EQUIA Forte Fil (EF), Fuji IX GP Extra (F9), and Ketac Molar (KT). Method Powder particles of GICs were examined with SEM-EDX. Setting kinetics were assessed using ATR-FTIR. Biaxial flexural strength/modulus and Vickers surface microhardness were measured after immersion in water for 24 h and 4 weeks. The release of F, Al, Sr, and P in water over 8 weeks was analyzed using a fluoride-specific electrode and ICP-OES. The toxicity of the material extract on mouse fibroblasts was also evaluated. Results High fluoride levels in the powder were detected with EF and F9. DT demonstrated an initial delay followed by a faster acid reaction compared to other cements, suggesting an improved snap set. DT also exhibited superior flexural strength than other materials at both 24 h and 4 weeks but lower surface microhardness (p 0.05). Conclusions Elastomeric micelles-containing glass ionomer cement (DT) exhibited satisfactory mechanical properties and cytocompatibility compared with other materials. DT could, therefore, potentially be considered an alternative high-strength GIC for load-bearing restorations.

Abstract Background Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra‐articular (IA) administration. Hypothesis/Objectives Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens. Animals Eight healthy neonatal foals. Methods Foals received 3 amikacin treatment protocols: (1) IV‐only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA‐only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 μg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility. Results Foal age was a significant variable. The IV‐only protocol met or exceeded the 30‐minute plasma concentrations considered therapeutic (mean μg/mL [95% confidence interval, CI]) in 7‐ to 9‐day‐old (54.0 [52.2‐56.9]), 14‐ to 16‐day‐old (58.1 [55.2‐61.0]), and 21‐ to 23‐day‐old (66.6 [63.7‐69.6]) foals. Concurrent IV and IA protocol did not reach the 30‐minute concentration considered therapeutic in 7‐ to 9‐day‐old foals (46.5 [43.6‐49.4]) but did in 14‐ to 16‐day‐old (62.9 [60.0‐65.8]) and 21‐to 23‐day‐old (62.6 [59.7‐65.6]) foals. Conclusions and Clinical Importance Concurrent IV and IA administration of amikacin produces 30‐minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.

Abstract Mass mortality of marine animals due to volcanic ash deposition is present in the fossil record but has rarely been documented in real time. Here, using remotely-operated vehicle video footage and analysis of ash collected at the seafloor, we describe the devastating effect of the record-breaking 2022 Hunga submarine volcanic eruption on endangered and vulnerable snail and mussel species that previously thrived at nearby deep-sea hydrothermal vents. In contrast to grazing, scavenging, filter-feeding, and predatory vent taxa, we observed mass mortality, likely due to smothering during burial by thick ash deposits, of the foundation species, which rely on symbiotic chemosynthetic bacteria for the bulk of their nutrition. This is important for our broad understanding of the natural disturbance of marine ecosystems by volcanic eruptions and for predicting the effects of anthropogenic disturbance, like deep-sea mining, on these unique seafloor habitats.

Abstract As a strategy to improve the therapeutic success of chimeric antigen receptor T cells (CART) directed against solid tumors, we here test the combinatorial use of CART and IMSA101, a newly developed stimulator of interferon genes (STING) agonist. In two syngeneic tumor models, improved overall survival is observed when mice are treated with intratumorally administered IMSA101 in addition to intravenous CART infusion. Transcriptomic analyses of CART isolated from tumors show elevated T cell activation, as well as upregulated cytokine pathway signatures, in particular IL-18, in the combination treatment group. Also, higher levels of IL-18 in serum and tumor are detected with IMSA101 treatment. Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion.

Abstract Background Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. Methods We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. Results Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. Conclusions This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.

Background Heart failure (HF) presents a massive burden to health care with a complex pathophysiology that results in HF with reduced left ventricle ejection fraction (EF) or HF with preserved EF. It has been shown that relatively modest changes in protein glycosylation, an essential posttranslational modification, are associated with clinical presentations of HF. We and others previously showed that such aberrant protein glycosylation in animal models can lead to HF. Methods and Results We develop and characterize a novel, tamoxifen‐inducible, cardiomyocyte Mgat1 knockout mouse strain, achieved through deletion of Mgat1, alpha‐1,3‐mannosyl‐glycoproten 2‐beta‐N‐acetlyglucosaminyltransferase, which encodes N‐acetylglucosaminyltransferase I. We investigate the role of hybrid/complex N‐glycosylation in adult HFrEF pathogenesis at the ion channel, cardiomyocyte, tissue, and gross cardiac level. The data demonstrate successful reduction of N‐acetylglucosaminyltransferase I activity and confirm that hybrid/complex N‐glycans modulate gating of cardiomyocyte voltage‐gated calcium channels. A longitudinal study shows that the tamoxifen‐inducible, cardiomyocyte Mgat1 knockout mice present with significantly reduced systolic function by 28 days post induction that progresses into HFrEF by 8 weeks post induction, without significant ventricular dilation or hypertrophy. Further, there was minimal, if any, physiologic or pathophysiologic cardiomyocyte electromechanical remodeling or fibrosis observed before (10–21 days post induction) or after (90–130 days post induction) HFrEF development. Conclusions The tamoxifen‐inducible, cardiomyocyte Mgat1 knockout mouse strain created and characterized here provides a model to describe novel mechanisms and causes responsible for HFrEF onset in the adult, likely occurring primarily through tissue‐level reductions in electromechanical activity in the absence of (or at least before) cardiomyocyte remodeling and fibrosis.

The impact of smoking cessation on long-term clinical outcomes after contemporary percutaneous coronary intervention (PCI) is not well known. We estimated the association of smoking and smoking cessation on the 10-year risk of cardiovascular and non-cardiovascular events in patients after contemporary PCI in a multicenter retrospective cohort of all patients having PCI with second generation drug-eluting stents in the VA Healthcare System between 2008 and 2016. Smoking status, comorbidities and clinical outcomes were extracted from the medical record and the National Death Index. Hazard ratios and 95 % confidence intervals (HR, 95 %CI) were derived from Cox Proportional Hazards Models. Estimates of events prevented from smoking cessation were derived from the differences in absolute risks between subjects who smoked and had stopped smoking. Among 29,001 patients, 10,598 (36.5 %) were current smoking patients, 13,093 (45.1 %) were former smoking patients, and 5,310 (18.3 %) never smoked. Over 10 years, 7,806 (26.9 %) subjects died with non-cardiovascular deaths exceeding cardiovascular deaths. In multivariable models, current smoking was significantly associated with increased long-term risks of all-cause death (HR = 1.27, 95 %CI = 1.19, 1.36), myocardial infarction (HR = 1.32, 95 %CI = 1.21–1.43), cancer death (HR = 2.55, 95 % CI = 2.10, 3.08), and pulmonary death (HR = 4.07, 95 % CI = 2.85, 5.83). Smoking cessation may prevent 18.5 % (95 %CI = 16.0 %, 20.9 %) all-cause deaths, 14.8 % (95 %CI = 9.8 %, 19.6 %) cardiovascular deaths, 42.6 % (95 %CI = 37.7 %, 47.2 %) cancer deaths, and 48.3 % (95 %CI = 41.8 %, 54.2 %) pulmonary deaths among smokers. Stopping smoking will likely have major impacts on non-cardiovascular events as well as cardiovascular events in patients after PCI with second generation drug-eluting stents.

Emphysema is a respiratory disease that causes the progressive loss of lung extracellular matrix (ECM) organisation, subsequently undermining lung integrity and reducing lung function. Fibroblasts must constantly repair damage to the lungs to preserve lung health, however, fibroblast ECM repair is reduced during emphysema, causing ECM damage to outweigh fibroblast ECM maintenance. Current treatments for emphysema fail to address the root causes of emphysematous progression, highlighting the need for novel methods of treating emphysema. Nitrofurantoin is a broad-spectrum antibiotic indicated for the treatment of urinary tract infections that also displays potential as a novel avenue of emphysema treatment. Nitrofurantoin is known to potentially cause fibrotic effects that could be repurposed to increase fibroblast repair and outweigh the progressive ECM damage of the emphysematous lung. Therefore, this study examined the effects of nitrofurantoin treatment on primary human lung fibroblasts derived from emphysema patients to determine if the drug holds potential as a novel treatment for emphysema. Nitrofurantoin was shown to stimulate migration and alter fibroblast morphology by increasing cell area and reducing roundness, suggesting that it could induce an ECM-repair primed phenotype in fibroblasts. Interestingly, nitrofurantoin treatment did not alter collagen-IV, perlecan, periostin or tenascin-C deposition, though fibronectin deposition was significantly upregulated at a higher dosage (20 μg/mL). This study highlighted the nitrofurantoin induced changes to fibroblast motility and morphology that facilitate ECM repair. Thus, nitrofurantoin induced pulmonary fibrosis could be caused by a change in cell phenotype that subsequently upregulates ECM repair, indicating its potential as a treatment for emphysema.

Abstract Background Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. Methods RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. Results Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. Conclusions RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations.

Abstract Background The COVID-19 pandemic has left no one untouched. Resident trainees have been driven to reconsider virtually every component of their daily lives. The purpose of this pilot study is to evaluate the impact of the COVID-19 pandemic on Obstetrics and Gynecology (OBGYN) residency training and education. Methods A cross-sectional pilot study was conducted between 2/2022 and 5/2022. A survey was created and distributed to OBGYN residents. The survey queried the effects of the pandemic on OBGYN residents’ procedure skills training and mental health. Results A total of 95 OBGYN residents across programs affiliated with each American College of Obstetricians and Gynecologists (ACOG) district participated in the survey. Among them, just over half (n = 52, 55%) self-identified as under-represented minorities. A significant majority, 80% (n = 81), felt their gynecological training was inadequate, with 70% of fourth-year residents expressing a lack of confidence in their ability to independently practice gynecology after graduation. This lack of confidence among fourth-year residents suggests a notable disparity in readiness for independent gynecological practice, linked to meeting ACGME requirements before completing their residency (p = 0.013). Among the residents who reported a negative impact of the pandemic on their mental health (n = 76, 80%), about 40% (n = 31) had contemplated self-harm or knew a colleague who considered or attempted suicide (p

Abstract Background Pericytes are multifunctional contractile cells that reside on capillaries. Pericytes are critical regulators of cerebral blood flow and blood–brain barrier function, and pericyte dysfunction may contribute to the pathophysiology of human neurological diseases including Alzheimers disease, multiple sclerosis, and stroke. Induced pluripotent stem cell (iPSC)-derived pericytes (iPericytes) are a promising tool for vascular research. However, it is unclear how iPericytes functionally compare to primary human brain vascular pericytes (HBVPs). Methods We differentiated iPSCs into iPericytes of either the mesoderm or neural crest lineage using established protocols. We compared iPericyte and HBVP morphologies, quantified gene expression by qPCR and bulk RNA sequencing, and visualised pericyte protein markers by immunocytochemistry. To determine whether the gene expression of neural crest iPericytes, mesoderm iPericytes or HBVPs correlated with their functional characteristics in vitro, we quantified EdU incorporation following exposure to the key pericyte mitogen, platelet derived growth factor (PDGF)-BB and, contraction and relaxation in response to the vasoconstrictor endothelin-1 or vasodilator adenosine, respectively. Results iPericytes were morphologically similar to HBVPs and expressed canonical pericyte markers. However, iPericytes had 1864 differentially expressed genes compared to HBVPs, while there were 797 genes differentially expressed between neural crest and mesoderm iPericytes. Consistent with the ability of HBVPs to respond to PDGF-BB signalling, PDGF-BB enhanced and a PDGF receptor-beta inhibitor impaired iPericyte proliferation. Administration of endothelin-1 led to iPericyte contraction and adenosine led to iPericyte relaxation, of a magnitude similar to the response evoked in HBVPs. We determined that neural crest iPericytes were less susceptible to PDGFR beta inhibition, but responded most robustly to vasoconstrictive mediators. Conclusions iPericytes express pericyte-associated genes and proteins and, exhibit an appropriate physiological response upon exposure to a key endogenous mitogen or vasoactive mediators. Therefore, the generation of functional iPericytes would be suitable for use in future investigations exploring pericyte function or dysfunction in neurological diseases.

Wastewater monitoring is an approach to identify the presence or abundance of pathogens within a population. The objective of this scoping review (ScR) was to identify and characterize research on human pathogens and antimicrobial resistance detected in untreated human wastewater and sludge. A search was conducted up to March 2023 and standard ScR methodology was followed. This ScR included 1,722 articles, of which 56.5% were published after the emergence of COVID-19. Viruses and bacteria were commonly investigated, while research on protozoa, helminths, and fungi was infrequent. Articles prior to 2019 were dominated by research on pathogens transmitted through fecal–oral or waterborne pathways, whereas more recent articles have explored the detection of pathogens transmitted through other pathways such as respiratory and vector-borne. There was variation in sampling, samples, and sample processing across studies. The current evidence suggests that wastewater monitoring could be applied to a range of pathogens as a public health tool to detect an emerging pathogen and understand the burden and spread of disease to inform decision-making. Further development and refinement of the methods to identify and interpret wastewater signals for different prioritized pathogens are needed to develop standards on when, why, and how to monitor effectively. HIGHLIGHTS A wide range of pathogens can be detected in wastewater.; 56.5% of studies were published since 2020.; Viruses were the most commonly investigated pathogen type followed by bacteria.; Earlier studies focused on pathogens transmitted through fecal–oral or waterborne pathways.; Additional research is needed to determine which pathogens are conducive to wastewater monitoring and where, when, and how it should be implemented.;

Aggregation is one of the key properties influencing the function of soils, including the soil’s potential to stabilise organic carbon and create habitats for micro-organisms. The mechanisms by which organic matter influences aggregation and alters the pore geometry remain largely unknown. We hypothesised that rapid microbial processing of organic matter and wetting and drying of soil promotes aggregation and changes in pore geometry. Using microcosms of silicate clays and sand with either rapidly decomposable glucose or slowly decomposable cellulose, the degree of aggregation (P

Abstract Atmospheric rivers (ARs) deliver significant and essential precipitation to the western United States (US) with consequential interannual variability. The intensity and frequency of ARs strongly influence reservoir levels, mountain snowpack, and groundwater recharge, which are key drivers of water‐resource availability and natural hazards. Between October 2022 and April 2023, western states experienced exceptionally heavy precipitation from several families of powerful ARs. Using observations of surface‐loading deformation from Global Navigation Satellite Systems, we find that terrestrial water‐storage gains exceeded 100% of normal within vital California watersheds. Independent water‐storage solutions derived from different data‐analysis and inversion methods provide an important measure of precision. The sustained storage increases, which we show are closely associated with ARs at daily‐to‐weekly timescales, alleviated both meteorological and hydrological drought conditions in the region, with a lag in hydrological‐drought improvements. Quantifying water‐storage recovery associated with extreme precipitation after drought advances understanding of an increasingly variable hydrologic cycle.

The Blackfeet Nation in northwestern Montana, United States, is implementing its Agriculture Resource Management Plan (ARMP), an Indigenous-led, sustainable agriculture plan prioritizing economic development for Indigenous producers, intergenerational health and well-being of Amskapi Piikani Blackfeet people, and ecological and cultural sensitivities within this sovereign nation and its traditional territories. Since the passage of the American Indian Agricultural Resource Management Act of 1993, only three Tribes have drafted and finalized Agricultural Resource Management Plans (ARMPs). The Blackfeet ARMP is now being held up as a national model of Tribal sovereignty. “Blackfeet Innovation Pathways to Food Sovereignty,” an Indigenous-led research project, emerged from the Blackfeet Nation’s community-based strategic planning process identifying gaps, systemic barriers and impactful solutions for achieving Blackfeet food sovereignty through the implementation of the Blackfeet Nation ARMP, along with research influenced by the ARMP. This paper provides a community case study of the ongoing process and offers a translational model of sustainable agriculture and food sovereignty within Indigenous lands to improve the economic futures of producers and their families, as well as health outcomes for Native communities.

Summary: The US faces multiple challenges in facilitating the safe, effective, and proactive use of fire as a landscape management tool. This intentional fire use exposes deeply ingrained communication challenges and distinct but overlapping strategies of prescribed fire, cultural burning, and managed wildfire. We argue for a new conceptual model that is organized around ecological conditions, capacity to act, and motivation to use fire and can integrate and expand intentional fire use as a tool. This result emerges from more considered collaboration and communication of values and needs to address the negative consequences of contemporary fire use. When applied as a communication and translation tool, there is potential to lower barriers to faster and more successful collaboration among stakeholders. Such improvements are a vital part of strategies to address climate adaptation, wildfire mitigation, and the well-being of ecosystems.

Fungi and bacteria coexist in many polymicrobial communities, yet the molecular basis of their interactions remains poorly understood. Here, we show that the fungus Candida albicans sequesters essential magnesium ions from the bacterium Pseudomonas aeruginosa. To counteract fungal Mg2+ sequestration, P. aeruginosa expresses the Mg2+ transporter MgtA when Mg2+ levels are low. Thus, loss of MgtA specifically impairs P. aeruginosa in co-culture with C. albicans, but fitness can be restored by supplementing Mg2+. Using a panel of fungi and bacteria, we show that Mg2+ sequestration is a general mechanism of fungal antagonism against gram-negative bacteria. Mg2+ limitation enhances bacterial resistance to polymyxin antibiotics like colistin, which target gram-negative bacterial membranes. Indeed, experimental evolution reveals that P. aeruginosa evolves C. albicans-dependent colistin resistance via non-canonical means; antifungal treatment renders resistant bacteria colistin-sensitive. Our work suggests that fungal-bacterial competition could profoundly impact polymicrobial infection treatment with antibiotics of last resort.

Individuals with Parkinson’s disease (PD) have a higher risk of developing dementia compared to age-matched controls. Rapid eye movement sleep behavior disorder (RBD) and hyposmia can influence symptoms severity. We report associations between polysomnography-assessed sleep architecture, olfactory identification, and cognition. Twenty adults with early-stage PD (mean age 69 ± 7.9; 25% female) completed cognitive assessments, the Brief Smell Identification Test (BSIT), and overnight in-clinic polysomnography. A global cognitive score was derived from principal component analysis. Linear regression models examined associations between sleep variables, BSIT performance, and cognition. Cognitive performance was compared between participants with and without RBD. Deep sleep attainment (β ± SE: 1.18 ± 0.45, p = .02) and olfactory identification (0.37 ± 0.12, p = .01) were associated with better cognition. Light sleep, REM sleep, arousal index, and sleep efficiency were not (all p > .05). Participants with RBD had significantly worse cognition ( t -test = −1.06 ± 0.44, p = .03) compared to those without RBD; none entered deep sleep. Deep sleep attainment was associated with better memory (1.20 ± 0.41, p = .01) and executive function (2.94 ± 1.13, p = .02); sleep efficiency was associated with executive function (0.05 ± 0.02, p = .02). These findings suggest interrelationships between lack of deep sleep, hyposmia, and poorer cognition in PD, particularly among individuals with RBD. Assessing these markers together may improve early identification of high-risk individuals and access to interventions.

Permafrost landscapes are becoming increasingly susceptible to widespread thaw due to climate change. Collating historical and ongoing data are critical for assessing permafrost conditions and spatiotemporal changes. Electrical resistivity tomography (ERT) is a geophysical technique that has become standard practice for characterizing permafrost. However, resistivity data—particularly raw measurements—often go unpublished and unshared, resulting in missed opportunities for knowledge exchange and collaboration. To fill this gap, we created the Canadian Permafrost Electrical Resistivity Survey database and established clear guidelines for data archival and reuse. Here, we present the first release of the database, which currently houses 280 ERT datasets, including standardized metadata, collected between 2008 and 2022 in British Columbia, Labrador, Northwest Territories, Québec, Yukon, and Alaska. These data present unique opportunities to better understand spatial and temporal variability of permafrost conditions across North America.

Summary: Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). Chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify the regulatory targets of ARID1B, BCL11A, FOXP1, TBR1, and TCF7L2, ASD-associated TRs in the developing human and mouse cortex. These TRs shared substantial overlap in the binding sites, especially within open chromatin. The overlap within a promoter region, 1–2,000 bp upstream of the transcription start site, was highly predictive of brain-expressed genes. This signature was observed in 96 out of 102 ASD-associated genes. In vitro CRISPRi against ARID1B and TBR1 delineated downstream convergent biology in mouse cortical cultures. After 8 days, NeuN+ and CALB+ cells were decreased, GFAP+ cells were increased, and transcriptomic signatures correlated with the postmortem brain samples from individuals with ASD. We suggest that functional convergence across five ASD-associated TRs leads to shared neurodevelopmental outcomes of haploinsufficient disruption.

Viral vector gene therapy has immense promise for treating central nervous system (CNS) disorders. Although adeno-associated virus vectors (AAVs) have had success, their small packaging capacity limits their utility to treat the root cause of many CNS disorders. Adenoviral vectors (Ad) have tremendous potential for CNS gene therapy approaches. Currently, the most common vectors utilize the Group C Ad5 serotype capsid proteins, which rely on the Coxsackievirus-Adenovirus receptor (CAR) to infect cells. However, these Ad5 vectors are unable to transduce many neuronal cell types that are dysfunctional in many CNS disorders. The human CD46 (hCD46) receptor is widely expressed throughout the human CNS and is the primary attachment receptor for many Ad serotypes. Therefore, to overcome the current limitations of Ad vectors to treat CNS disorders, we created chimeric first generation Ad vectors that utilize the hCD46 receptor. Using a “humanized” hCD46 mouse model, we demonstrate these Ad vectors transduce cerebellar cell types, including Purkinje cells, that are refractory to Ad5 transduction. Since Ad vector transduction properties are dependent on their capsid proteins, these chimeric first generation Ad vectors open new avenues for high-capacity helper-dependent adenovirus (HdAd) gene therapy approaches for cerebellar disorders and multiple neurological disorders.

Abstract Long‐term records of the flow patterns and dynamics of surge‐type glaciers improve our understanding of their underlying dynamic processes, and are critical to better resolve their contribution to a changing cryosphere. We adapt a modeling approach designed to emulate glacier surging and fold kinematics using the full Stokes ice‐flow model Elmer/Ice to simulate surging of the Dusty Glacier, located in the St. Elias Mountains, Canada. We combine distributed mass‐balance and numerical ice‐flow models to reconstruct the fold kinematics of the 2001–2003 surge of the Dusty Glacier by comparing model results to Landsat‐7 and Sentinel‐2 imagery, and assess the sensitivity of centennial‐scale modeled glacier structure to different mass balance and sliding parameterizations. This study demonstrates the feasibility of using the approach to reconstruct the surface structure kinematics of a surge‐type glacier in nature, highlighting its potential application to other surge‐type glaciers and regions.

Medical librarians work collaboratively across all units and missions of academic medical centers. One area where librarians can provide key expertise is in the building and maintenance of Research Information Management Systems (RIMS). At Penn State, the RIMS implementation team has included a medical librarian, research administrators and marketing staff from the College of Medicine (CoM) since its inception in 2016. As our peer institutions implemented or expanded their own RIMS systems, the CoM team has responded to their questions regarding details about the Penn State RIMS instance. The goal of this commentary is to describe how the CoM team has worked collaboratively within Penn State to address questions related to research output, with special emphasis on details pertaining to questions from other institutions.

Abstract Molecular-glue degraders are small molecules that induce a specific interaction between an E3 ligase and a target protein, resulting in the target proteolysis. The discovery of molecular glue degraders currently relies mostly on screening approaches. Here, we describe screening of a library of cereblon (CRBN) ligands against a panel of patient-derived cancer cell lines, leading to the discovery of SJ7095, a potent degrader of CK1α, IKZF1 and IKZF3 proteins. Through a structure-informed exploration of structure activity relationship (SAR) around this small molecule we develop SJ3149, a selective and potent degrader of CK1α protein in vitro and in vivo. The structure of SJ3149 co-crystalized in complex with CK1α + CRBN + DDB1 provides a rationale for the improved degradation properties of this compound. In a panel of 115 cancer cell lines SJ3149 displays a broad antiproliferative activity profile, which shows statistically significant correlation with MDM2 inhibitor Nutlin-3a. These findings suggest potential utility of selective CK1α degraders for treatment of hematological cancers and solid tumors.

Background: Navicular syndrome is a common cause of forelimb lameness in the horse. Beyond changes to the navicular bone itself, horses with a clinical diagnosis of navicular syndrome often have pathology associated with other components of navicular apparatus, including the navicular bursa, deep digital flexor tendon, collateral sesamoidean ligaments, and impar ligament. Palmar digital neurectomy (PDN) is often used as a salvage procedure for horses diagnosed with navicular syndrome that become unresponsive to medical management. There are many potential complications associated with PDN, some of which are debilitating. Case Description: This report describes two cases of navicular bone fracture with severe deep digital flexor tendinopathy and distal interphalangeal joint subluxation/hyperextension that occurred 12 and 19 weeks after bilateral forelimb PDN. Conclusion: These two cases highlight the importance of proper patient selection prior to PDN due to the high incidence of undiagnosed soft tissue pathology in conjunction with radiographic evidence of navicular syndrome. Advanced imaging of the digit is recommended to identify and characterize any soft tissue pathology associated with the navicular apparatus prior to pursuing PDN to avoid disease progression and catastrophic injury. [Open Vet J 2023; 13(12.000): 1752-1759]

Objective: Postoperative delirium after cardiac surgery is associated with long-term cognitive decline and mortality. We investigated whether increased ICU Confusion Assessment Method scores were associated with greater 30-day mortality and failure to rescue after cardiac surgery. Methods: We studied 4030 patients who underwent a Society of Thoracic Surgeons index operation at the University of Virginia Health System from 2011 to 2021. We obtained all ICU Confusion Assessment Method scores recorded during patients' admission and summarized scores for the first 7 postoperative days. Univariate and multivariable logistic regression analyzed the association between ICU Confusion Assessment Method score/delirium presence and postoperative complications, operative mortality, and failure to rescue. Results: Any episode of ICU Confusion Assessment Method screen-positive delirium and nearly all components of the score were associated with increased 30-day mortality on univariate analysis. We found that a single episode of delirium was associated with increased mortality. Feature 2 (inattention) had the strongest association with poorer outcomes, including failure to rescue in our analysis, as were patients with higher peak Richmond Agitation Sedation Scale scores. Patients with higher mean Richmond Agitation Sedation Scale scores had an association with decreased failure to rescue. Conclusions: A single episode of delirium, as measured using ICU Confusion Assessment Method scores, is associated with increased mortality. Inattention and higher peak Richmond Agitation Sedation Scale scores were associated with failure to rescue. Screening may clarify diagnosing delirium and assessing its implications on mortality and failure to rescue. Our findings suggest the importance of identifying and managing risk factors for delirium to improve patient outcomes and reduce mortality and failure to rescue rates.

* The brown thornbill ( Acanthiza pusilla) is a songbird endemic to eastern Australia with five recognised subspecies within the brown thornbill. The most notable is the King Island brown thornbill ( Acanthiza pusilla magnirostris) of which there are less than 100 remaining and based on expert elicitation are the most likely Australian bird to become extinct in the next 20 years. We sequenced PacBio HiFi reads of the brown thornbill to generate a high-quality reference genome 1.25Gb in size and contig N50 of 20.1Mb. Additionally, we sequenced mRNA from three tissues to generate a global transcriptome to aid with genome annotation. The generation of a reference genome for the brown thornbill provides an important resource to align additional genomic data which will be produced in the near future.

Introduction Many rural communities bear a disproportionate share of drug-related harms. Innovative harm reduction service models, such as vending machines or kiosks, can expand access to services that reduce drug-related harms. However, few kiosks operate in the USA, and their implementation, impact and cost-effectiveness have not been adequately evaluated in rural settings. This paper describes the Kentucky Outreach Service Kiosk (KyOSK) Study protocol to test the effectiveness, implementation outcomes and cost-effectiveness of a community-tailored, harm reduction kiosk in reducing HIV, hepatitis C and overdose risk in rural Appalachia.Methods and analysis KyOSK is a community-level, controlled quasi-experimental, non-randomised trial. KyOSK involves two cohorts of people who use drugs, one in an intervention county (n=425) and one in a control county (n=325). People who are 18 years or older, are community-dwelling residents in the target counties and have used drugs to get high in the past 6 months are eligible. The trial compares the effectiveness of a fixed-site, staffed syringe service programme (standard of care) with the standard of care supplemented with a kiosk. The kiosk will contain various harm reduction supplies accessible to participants upon valid code entry, allowing dispensing data to be linked to participant survey data. The kiosk will include a call-back feature that allows participants to select needed services and receive linkage-to-care services from a peer recovery coach. The cohorts complete follow-up surveys every 6 months for 36 months (three preceding kiosk implementation and four post-implementation). The study will test the effectiveness of the kiosk on reducing risk behaviours associated with overdose, HIV and hepatitis C, as well as implementation outcomes and cost-effectiveness.Ethics and dissemination The University of Kentucky Institutional Review Board approved the protocol. Results will be disseminated in academic conferences and peer-reviewed journals, online and print media, and community meetings.Trial registration number NCT05657106.

Coffee is a critical agricultural commodity and is used to produce premium beverages enjoyed by people worldwide. The microbiome of coffee beans has proven to be an essential tool that improves the flavor profile of coffee by creating aromatic flavor compounds through natural fermentation. This study investigated the natural microbial consortium during the wet process fermentation of coffee onsite in Thailand in order to identify the correlation between microbial diversity and biochemical characteristics including flavor, aroma, and metabolic attributes. Our study found 64 genera of bacteria and 59 genera of yeast/fungi present during the fermentation process. Group of microbes, mainly yeast and lactic acid bacteria, that predominated in the process were significantly correlated with preferable flavor and aroma compounds, including linalyl formate, linalool, cis-isoeugenol, trans-geraniol, and (-)-isopulegol. Some of the detected metabolites were found to be active compounds which could play a role in health.

BackgroundThe COVID-19 pandemic forced the spread of digital health tools to address limited clinical resources for chronic health management. It also illuminated a population of older patients requiring an informal caregiver (IC) to access this care due to accessibility, technological literacy, or English proficiency concerns. For patients with heart failure (HF), this rapid transition exacerbated the demand on ICs and pushed Canadians toward a dyadic care model where patients and ICs comanage care. Our previous work identified an opportunity to improve this dyadic HF experience through a shared model of dyadic digital health. We call this alternative model of care “Caretown for Medly,” which empowers ICs to concurrently expand patients’ self-care abilities while acknowledging ICs’ eagerness to provide greater support. ObjectiveWe present the systematic design and development of the Caretown for Medly dyadic management module. While HF is the outlined use case, we outline our design methodology and report on 6 core disease-invariant features applied to dyadic shared care for HF management. This work lays the foundation for future usability assessments of Caretown for Medly. MethodsWe conducted a qualitative, human-centered design study based on 25 semistructured interviews with self-identified ICs of loved ones living with HF. Interviews underwent thematic content analysis by 2 coders independently for themes derived deductively (eg, based on the interview guide) and inductively refined. To build the Caretown for Medly model, we (1) leveraged the Knowledge to Action (KTA) framework to translate knowledge into action and (2) borrowed Google Sprint’s ability to quickly “solve big problems and test new ideas,” which has been effective in the medical and digital health spaces. Specifically, we blended these 2 concepts into a new framework called the “KTA Sprint.” ResultsWe identified 6 core disease-invariant features to support ICs in care dyads to provide more effective care while capitalizing on dyadic care’s synergistic benefits. Features were designed for customizability to suit the patient’s condition, informed by stakeholder analysis, corroborated with literature, and vetted through user needs assessments. These features include (1) live reports to enhance data sharing and facilitate appropriate IC support, (2) care cards to enhance guidance on the caregiving role, (3) direct messaging to dissolve the disconnect across the circle of care, (4) medication wallet to improve guidance on managing complex medication regimens, (5) medical events timeline to improve and consolidate management and organization, and (6) caregiver resources to provide disease-specific education and support their self-care. ConclusionsThese disease-invariant features were designed to address ICs’ needs in supporting their care partner. We anticipate that the implementation of these features will empower a shared model of care for chronic disease management through digital health and will improve outcomes for care dyads.