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The titular domain-based local pair natural orbital (DLPNO) approximation is the most widely used method for extending correlated wave function models to large molecular systems, yet its fidelity for intermolecular interaction energies in large supramolecular complexes has not been thoroughly vetted. Non-covalent interactions are sensitive to tails of the electron density and involve nonlocal dispersion that is discarded or approximated if the screening of pair natural orbitals (PNOs) is too aggressive. Meanwhile, the accuracy of the DLPNO approximation is known to deteriorate as molecular size increases. Here, we test the DLPNO approximation at the level of second-order Møller–Plesset perturbation theory (MP2) and coupled-cluster theory with singles, doubles, and perturbative triples [CCSD(T)] for a variety of large supramolecular complexes. DLPNO-MP2 interaction energies are within 3% of canonical values for small dimers with ≲10 heavy atoms, but for larger systems, the DLPNO approximation is often quite poor unless the results are extrapolated to the canonical limit where the threshold for discarding PNOs is taken to zero. Counterpoise correction proves to be essential in reducing errors with respect to canonical results. For a sequence of nanoscale graphene dimers up to ( C 96 H 24 ) 2 , extrapolated DLPNO-MP2 interaction energies agree with canonical values to within 1%, independent of system size, provided that the basis set does not contain diffuse functions; these cause the DLPNO approximation to behave erratically, such that results cannot be extrapolated in a meaningful way. DLPNO-CCSD(T) calculations are typically performed using looser PNO thresholds as compared to DLPNO-MP2, but this significantly impacts accuracy for large supramolecular complexes. Standard DLPNO-CCSD(T) settings afford errors of 2–6 kcal/mol for dimers involving coronene (C24H12) and circumcoronene (C54H18), even at the DLPNO-CCSD(T1) level. [ABSTRACT FROM AUTHOR]

Back pain lifetime incidence is 60%–70%, while 12%–20% of older women have vertebral fractures (VFs), often with back pain. We aimed to provide objective evidence, currently lacking, regarding whether back pain and VFs affect physical activity (PA). We recruited 69 women with recent back pain (age 74.5 ± 5.4 years). Low- (0.5 < g < 1.0), medium- (1.0 ≤ g < 1.5), and high-impact (g ≥ 1.5) PA and walking time were measured (100 Hz for 7 days, hip-worn accelerometer). Linear mixed-effects models assessed associations between self-reported pain and PA, and group differences (VFs from spine radiographs/no-VF) in PA. Higher daily pain was associated with reduced low (β = −0.12, 95% confidence interval, [−0.22, −0.03], p =.013) and medium-impact PA (β = −0.11, 95% confidence interval, [−0.21, −0.01], p =.041), but not high-impact PA or walking time (p >.11). VFs were not associated with PA (all p >.2). Higher daily pain levels but not VFs were associated with reduced low- and medium-impact PA, which could increase sarcopenia and falls risk in older women with back pain. [ABSTRACT FROM AUTHOR]

Oblique shock wave–interface interactions of gases and liquids have been extensively studied in shock tubes using optical methods to measure equation-of-state (EOS) parameters. However, this is difficult with solids due to their opaqueness to visible light. X ray phase contrast imaging (XPCI) has the penetrative strength to probe solids while still being sensitive to mass density and enhancing the visibility of material boundaries. We investigate the accuracy and repeatability of measuring the mean value of the average mass density (areal density divided by thickness) over region S (B S) and flow deflection angle (θ) from XPCI images of a sample. To that end, a Hough transform-based method for measuring θ is developed. To measure B S , the XPCI image intensity probability density function (PDF) is modeled accounting for the spatial distribution of x ray energy, scintillator response, and pulse-to-pulse variation in the x ray intensity. In addition, a Monte Carlo-based algorithm for computing the B S PDF is developed. Both methods are validated on an impact-generated oblique shock wave interacting at a solid polymer-to-polymer interface. This is accomplished through a comparison to hydrodynamic simulations using well-established EOS. Under the modeling framework for the XPCI image intensity, B S is computed with an accuracy of < 0.1 % and precision of 3%–5%, while θ has an uncertainty of 0.2 ° , respectively. This shows that the XPCI-based model that is developed here could be an invaluable tool for high-fidelity testing of hydrodynamic models in shock polar configurations. [ABSTRACT FROM AUTHOR]

Purpose: To report the results of a 2020 international survey of the most commonly used materials and techniques for the fabrication of extraoral maxillofacial prosthetics and to assess the use of 3D technology.Materials and Methods: A 43-question survey was administered via Qualtrics to the members of the American Academy of Maxillofacial Prosthetics, the International Anaplastology Association, and the International Society of Maxillofacial Rehabilitation. The use of current 3D technology in the fabrication of maxillofacial prostheses, as well as barriers to care such as patient cost and insurance coverage, were also assessed.Results: A total of 134 respondents (13%) completed the survey; 96 (73%) reported that they were currently fabricating maxillofacial prostheses and were thus included in the survey. The majority of respondents reported currently using Silastic MDX4-4210 BioMedical Grade Elastomer (DuPont) with either Silastic Medical Adhesive Silicone Type A or Silastic MDX4-4210 crosslinker. Incorporating the use of current CAD/CAM technology was reported by a majority of respondents (58%; 45/77); however, a small cohort (33%, 15/45) reported they were "still experimenting how best to use technology." A total of 39 clinicians (49%) reported that facial prosthetics were most often paid for by the patient (fee for service), with the fee ranging from $10 to $5,500 USD.Conclusion: The results of this survey indicate that current CAD/CAM technology has been adopted and incorporated into the design and fabrication of maxillofacial prostheses. More research is needed to advance CAD/CAM technology as well as the physical and mechanical properties of materials in maxillofacial prosthetics and anaplastology clinical practice. [ABSTRACT FROM AUTHOR]

Prior research finds that individuals with greater exposure to homelessness express more favorable attitudes toward people experiencing homelessness. However, it is unclear whether exposure to more broader forms of housing insecurity (e.g. lack of affordability, poor housing quality, being doubled-up) is linked to perceptions of and attitudes toward homelessness. We thus examined the association between both exposure to homelessness and several broader measures of housing insecurity and perceptions and attitudes toward homelessness. We also assessed whether rurality modified these associations. We used Qualtrics Panels to conduct an online survey of 1270 low- and moderate-income adults, equally split between urban and rural areas nationwide in 2018. The survey included questions assessing experiences and opinions about homelessness and housing insecurity. In multiple regression models, we found that exposure to both homelessness and other forms of housing insecurity were associated with an increased degree of perception of homelessness as beyond individual control and an increased propensity for sympathetic interactions with people experiencing homelessness. Rurality did not modify these relationships. As both homelessness and other forms of housing insecurity are on the rise, these findings may portend a shift toward more favorable attitudes and perceptions of homelessness. [ABSTRACT FROM AUTHOR]

Distress Tolerance (DT) is a transdiagnostic factor that may help better understand vulnerability to mental health problems. This study explores DT among recently incarcerated adults experiencing homelessness (RIHAs). Participants (n = 298) were recruited from an ongoing clinical trial at a homeless shelter in Texas. Cross-sectional linear regression analyses were conducted to examine the relations between DT subconstructs (tolerance, appraisal, regulation, and absorption) and psychosocial factors (depression, aggression, hostility, anxiety, and stress) in a sample of RIHAs. Lower DT absorption was associated with greater depression, aggression, hostility, anxiety, and stress. Lower DT appraisal was associated with greater hostility, anxiety, and stress. Greater DT regulation was associated with lower hostility and stress (ps<.05). DT tolerance was unrelated to any psychosocial factors. DT subscales are associated with psychosocial factors among RIHAs. Future research should assess the feasibility of interventions that enhance DT absorption and appraisal coping among RIHAs. [ABSTRACT FROM AUTHOR]

The objective of this exploratory mixed methods study is to assess the use of hotels/motels among Veterans experiencing housing instability during the COVID-19 pandemic to inform policy and programmatic responses to homelessness during such emergencies. We analyzed qualitative interviews conducted with national-level homeless services leadership and Supportive Services for Veteran Families (SSVF) program providers during October 2020–May 2021 and quantitative data for Veterans who enrolled in SSVF during March–August 2020. A multivariable two-part regression model identified factors associated with receiving hotel/motel-specific financial assistance and associated costs. Qualitative interviews indicated that the use of hotels/motels during COVID-19 offered protection from a contagious disease and a novel mechanism to accommodate high-need Veterans who may have previously been unsheltered or resistant to services. Quantitative analyses found that Veteran households' stays in hotels/motels increased sharply following the onset of the COVID-19 pandemic; this assistance tended to flow to a more vulnerable group (i.e. older, no income, and extensive histories of homelessness). COVID-19 and homelessness are ongoing public health concerns; strategies such as the use of hotels/motels to reduce homelessness and ensure safe options for isolation and quarantine are needed to prevent poor health outcomes for a vulnerable population. [ABSTRACT FROM AUTHOR]

Introduction: Most pregnancies are low-risk. However, sometimes women develop pre-eclampsia. The incidence varies based on different studies (Havers-Borgersen et al., 2023, 10.1136/jech-2023-220829).Pre-eclampsia is characterized by elevated blood pressure, protein in the urine, and excessive swelling and occurs after 20 weeks of pregnancy though in the case of severe symptoms, all may not be required for diagnosis (Bajpai et al., 2023). Many strategies exist to identify women with pre-eclampsia and to treat it. There are known immediate risks to both the mother and fetus. Some of these risks extend beyond the immediate postpartum period. Much less is known regarding the long-term risks. Therefore, the purpose of our study was to conduct a systematic review of the long-term complications related to pre-eclampsia. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to guide this systematic review. PubMed, CINAHL, Medline, Scopus, PschINFO, and Google Scholar were used to identify relevant articles. We focused on articles published within the last 5 years. Search terms were pre-eclampsia and complications, pregnancy-induced hypertension and complications, long-term complications of pre-eclampsia, and long-term follow-up of pre-eclampsia. Results: Two hundred and fifty-eight articles were identified; further analysis identified 91 that seemed relevant. After a thorough review, 19 articles were deemed relevant to identify complications women experience following pre-eclampsia. Discussion: Cardiovascular disease is a major long-term risk. Early-onset pre-eclampsia contributes the greatest risk. Health promotion interventions that target women following a diagnosis of pre-eclampsia are needed. Inadequate knowledge exists to guide efforts to prevent long-term sequelae from pre-eclampsia. Significance: Women who experience pre-eclampsia have significant health risks following the diagnosis. Some risks are immediate (elevated blood pressure) and some risks can take longer to develop (heart disease, diabetes, kidney disease). Because of these risks, it is critical to develop treatment strategies to prevent these risks if possible. There are also risks to the fetus/newborn and these may be amendable to intervention as well. [ABSTRACT FROM AUTHOR]

Emergency department (ED) HIV screening is a key component of the strategy to end the HIV epidemic, reaching populations with limited access to care for screening and early diagnosis. Many screening programs rely primarily on participation from ED nurses; however, little is known about the factors affecting nurse participation in screening. Guided by the Consolidated Framework for Implementation Research, 20 semi-structured interviews were conducted with ED nurses to explore perceptions of HIV screening, barriers and facilitators to participation, and implementation insights. Nurses were categorized as either high adopters or low adopters based on the number of HIV tests ordered 3 months prior to interviews. The Stanford Lightning Report Method, a rapid qualitative analysis approach, was used to analyze field notes. All participants generally agreed that the ED was an appropriate location for screening and that frequent, multimodal education about screening was needed. Integration of screening into standard workflows, education about the public health impact of screening, and the use of peer champions and mentors were identified as important strategies to increase participation. By incorporating these findings into implementation strategies, EDs may be able to increase nurse participation in screening, addressing important health equity issues in HIV diagnosis. [ABSTRACT FROM AUTHOR]

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol−1; aged 64.2 ± 9.4 years; four female] completed a single‐blind, randomised, sham‐controlled, cross‐over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$] = 0.155; ∼2500 m simulated altitude) or normoxic conditions (FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor‐1α]; [interleukin‐6]; [tumour necrosis factor‐α]; [interleukin‐10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon‐like peptide‐1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect‐size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. Key points: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite.In a single‐blind, randomised sham‐controlled, cross‐over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin‐6]; [tumour necrosis factor‐α]; [interleukin‐10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM.Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect‐size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial.Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise). [ABSTRACT FROM AUTHOR]

Background: Ventilator‐associated pneumonia (VAP) is a significant concern in low‐middle‐income countries (LMICs), where the burden of hospital‐acquired infections is high, and resources are low. Evidence‐based guidelines exist for preventing VAP; however, these guidelines may not be adequately utilized in intensive care units of LMICs. Aim: This scoping review examined the literature regarding the use of nursing care bundles for VAP prevention in LMICs, to understand the knowledge, practice and compliance of nurses to these guidelines, as well as the barriers preventing the implementation of these guidelines. Study Design: The review was conducted using Arksey and O'Malley's (2005) five‐stage framework and the PRISMA‐ScR guidelines guided reporting. Searches were performed across six databases: CINAHL, Medline, Embase, Global Health, Scopus and Cochrane, resulting in 401 studies. Results: After screening all studies against the eligibility criteria, 21 studies were included in the data extraction stage of the review. Across the studies, the knowledge and compliance of nurses regarding VAP prevention were reported as low to moderate. Several factors, ranging from insufficient knowledge to a lack of adequate guidelines for VAP management, served as contributing factors. Multiple barriers prevented nurses from adhering to VAP guidelines effectively, including a lack of audit/surveillance, absence of infection prevention and control (IPC) teams and inadequate training opportunities. Conclusions: This review highlights the need for adequate quality improvement procedures and more efforts to conduct and translate research into practice in intensive care units in LMIC. Relevance to Clinical Practice: IPC practices are vital to protect vulnerable patients in intensive care units from developing infections and complications that worsen their prognosis. Critical care nurses should be trained and reinforced to practice effective bundle care to prevent VAP. [ABSTRACT FROM AUTHOR]

Many young people learn about scientific topics online, yet middle school students have trouble identifying where scientific information comes from and what characterizes good sources of scientific information online. In this article, we discuss five lessons we embedded into an NGSS-aligned, sixth-grade comprehensive science course to increase students' scientific information literacy. Drawing on SEP-8, 'obtaining, evaluating, and communicating information,' these lessons gave students an opportunity to search for scientific information, critically evaluate the sources of scientific information, and generate science texts using the information they found. We focused on two concepts—scientific consensus and multiple perspectives—to help students recognize who engages in scientific research, how scientific findings are communicated to the general public, and who else may have important perspectives on socio-scientific issues. [ABSTRACT FROM AUTHOR]

Although mentoring interventions have helped to advance diversity, equity, and inclusion (DEI) goals within STEM fields, even the most efficacious programs can be undermined without intentional cultivation of the broader mentoring ecosystem. This study examines participants from eight campus teams that engaged in a multi-session process of learning about a STEM-mentoring ecosystem (STEM-ME) framework, learning particular terminology, including 'champions' and 'stewards' within the system (i.e. who is advocating for and resourcing mentoring, respectively), and tools to inventory, map and analyze their mentoring ecosystem. Qualitative research, guided by interpretive phenomenological analysis, focused on (a) completed inventory tools, (b) visual mapping exercises, and (c) field notes from meeting sessions. The results indicate that the STEM-ME framework and new terminology facilitated important insights into possible synergies within the system. The opportunity to visualize an institutional ecosystem for concentrations of and gaps in activity helped to identify potential vulnerabilities and places to invest. [ABSTRACT FROM AUTHOR]

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Aims: The aim of this study was to examine the association between women's migrant status (majority, immigrant, descendant) and use of postpartum mental healthcare and investigate whether migration characteristics are associated with mental healthcare use. Methods: Retrospective cohort study. We included all mothers of children born between 2002 and 2018 in 34 municipalities of Denmark who had an identified mental health need as clinically assessed by a child health visitor (CHV) or by a score of 11 or more on the Edinburgh Postpartum Depression Scale (EPDS). Women were followed until the first mental healthcare received 2 years' postpartum, death or emigration. Using Cox regression models, we estimated the time to mental healthcare by migrant status and explored the role of migration characteristics. Results: A total of 29% of women (n = 45,573) had a mental health need identified by the CHV, and 7% (n = 4968) had an EPDS ⩾ 11. Immigrants accounted for 19.5%, and descendants for 4.7% of the sample. Immigrants were at lower risk of using mental healthcare than the majority group (CHV: hazard ratio adjusted (HRa) 0.75 (0.70–0.79), EPDS: HRa 0.67 (0.58–0.78)), as were descendants (CHV: HRa 0.77 (0.70–0.86), EPDS: HRa 0.69 (0.55–0.88)). Among migrants, those not refugees, newly arrived, whose partners were immigrants or descendants, and those originally from Africa showed a lower risk of using postpartum mental healthcare. Conclusions: Our findings emphasize the need to strengthen access to mental healthcare for immigrants and descendants experiencing postpartum mental health concerns and consider migration characteristics as indicators of potential inequalities in access to maternal mental healthcare. [ABSTRACT FROM AUTHOR]

Pregnant and lactating persons in sub-Saharan Africa face a heightened risk of HIV acquisition, due to biological and behavioral factors, combined with limited access to prevention and treatment services. Oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring are promising tools for HIV prevention, and the ring's recent approval in multiple African countries represents a significant advancement in expanding access to HIV prevention. In a nested qualitative study within the MTN-042 trial, we explored the acceptability of study products among pregnant persons in the second and early third trimesters. Interviews were conducted privately, using a semi-structured guide with 77 participants, in participants' preferred language. Topics explored included product acceptability (using the theoretical framework of acceptability), user experience, satisfaction, disclosure, community attitudes, and sexual activity during pregnancy. Interview transcripts were analyzed using Dedoose software. We observed positive attitudes among participants towards the study products, which they found generally user-friendly, despite the added complexities of using them during pregnancy. Participants recognized that consistent and correct use would provide protection for both them and their unborn children. Although initial concerns existed, most of these worries dissipated over time, with study staff support and increased product use experience. These findings emphasize the importance of continued surveillance, support, and education to ensure the successful rollout of new HIV prevention measures during pregnancy. [ABSTRACT FROM AUTHOR]

Background: With nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study. Methods: Sentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys. Results: A total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1–12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were "very" or "completely" satisfied with the clinical utility of the synoptic template (90.0%). Conclusions: Following implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing. [ABSTRACT FROM AUTHOR]

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and posttransplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation. [ABSTRACT FROM AUTHOR]

Biopsy-based histology has been the foundation of disease diagnosis and management for over a century. A long-sought goal in dermatology is the development of an imaging modality with sufficient resolution and compositional detail to noninvasively interrogate skin histology in vivo. Here, we describe a system that achieves this goal using cross-sectionally scanned, multimodal microscopy (cross-modal). Cross-modal combines multiphoton and reflectance confocal microscopy into one compact system with coordinated three-axis scanning that preserves optical resolution in cross-section. A custom pinhole-free mechanism employing finite-infinite conjugates further simplifies and stabilizes confocal alignment. Evaluated in participants ages 9–81 and Fitzpatrick skin types (FST) 1–5, cross-modal images revealed histological details analogous to those obtained from traditional biopsied tissue. We observed dermal elastosis in sun-damaged skin, elevated melanin in pigmented skin, basaloid nests in basal cell carcinoma, and elongated rete ridges in seborrheic keratosis, supporting cross-modal's potential to deliver histological insights noninvasively. [ABSTRACT FROM AUTHOR]

Threats to the future function of forested ecosystems and stability of ecosystem service provisioning due to global change have motivated climate-adaptive forest management strategies that include various forms of tree planting termed "adaptation plantings". Despite the emergence of these strategies, less is known as to how foresters and other natural resource managers perceive or are engaged with adaptation plantings like forest assisted migration (FAM). This knowledge gap is most pronounced in regions like New England and the North Central US (hereafter, the Northeastern US) where tree planting is less common but expected to be an important forest management tool for adaptation. To address this, we surveyed 33 natural resource managers in this region actively engaged in climate change adaptation (i.e., early adopters of the practice) to assess how tree planting for adaptation is currently being pursued against the perceived barriers, opportunities, and potential future engagement with the strategy. Survey respondents overwhelmingly (93.5%) forecast increases in the future use of adaptation plantings in their work in the region, attributed to increased awareness, acceptance, and interest in the practice. Respondents expressed notable interest in strategies related to diversification and most types of FAM (e.g., assisted population expansion and assisted range expansion), but hesitancy to engage with more contentious planting types like afforestation or FAM linked to the long-distance translocation of exotic species (e.g., assisted species migration). Although examples of local enrichment plantings (i.e., non-FAM) proliferate, nineteen of the top twenty most common tree genera planted contain at least one example of FAM in the study region. The most notable barriers reported were themed as 1) biotic and abiotic, 2) information and material, and 3) policy, social, and economic factors. While most respondents report difficulty obtaining adequate planting material from nurseries (i.e., seedlings), over 80% placed orders shortly before planting (< 1 year) which likely generates difficulty in sourcing seedlings suited for a specific site and future range of environmental conditions. Although this study is limited by focusing on subset of natural resource managers who are early adopters of climate change adaptation within the region, valuable inferences into the barriers and trends are possible from this population serving on the front lines of forest adaptation. Together, these results from early adopters suggest a potentially growing need for allocating resources that engage forest stewards in adaptation planning and serve to refine policy, financing, and management practices to support this adaptation strategy in this region and beyond. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether the likelihood of hospital‐acquired complications for older people in Australia differs by whether they have dementia. Study design: Matched cohort study. Setting, participants: People aged 60 years or older with dementia who were admitted to five public hospitals in the South Western Sydney Local Health District, New South Wales, 1 January 2010 to 31 December 2020, and people without dementia admitted during the same period, matched by age, sex, number of medical conditions, and presence of selected specific medical conditions, emergency admission status, history of falls, and admission from a nursing home. Main outcome measures: Hospital‐acquired complications (falls, pressure injuries, delirium, pneumonia, venous thromboembolism, new incontinence, malnutrition, in‐hospital death), by dementia status. Results: A total of 217 459 people aged 60 years or older were admitted to the five hospitals during the study period. The mean age of the 11 393 patients with dementia (83 years; standard deviation [SD], 7.5 years) was higher than that of the 206 065 patients without dementia (73 years; SD, 8.9 years), and the proportion of women slightly larger (55% v 50%). Median hospital length of stay was longer for people with dementia (nine days; interquartile range [IQR], 4–19 days) than for people without dementia (three days; IQR, 1–9 days), and the number of in‐hospital deaths higher (768, 7% v 584, 5%). After propensity score‐based matching, the risks of falls (odds ratio [OR], 4.7; 95% confidence interval [CI], 3.8–5.7), pressure injury (OR, 1.4; 95% CI, 1.1–1.8), delirium (OR, 2.4; 95% CI, 2.0–3.0), and pneumonia (OR, 1.3; 95% CI, 1.01–1.7) were higher for people with dementia than for those without dementia; differences between the two groups in the risks of venous thromboembolism, malnutrition, and incontinence were not statistically significant. Conclusions: Given the greater risk of many hospital‐acquired complications for people with dementia, targeted models of person‐centred care are needed to ensure the best outcomes for these patients. [ABSTRACT FROM AUTHOR]

Optimizing immunologic compatibility in organ transplantation extends beyond the conventional approach of Human Leukocyte Antigen (HLA) antigen matching, which exhibits significant limitations. A broader comprehension of the roles of classical and non-classical HLA genes in transplantation is imperative for enhancing long-term graft survival. High-resolution molecular HLA genotyping, despite its inherent challenges, has emerged as the cornerstone for precise patient-donor compatibility assessment. Leveraging understanding of eplet biology and indirect immune activation, eplet mismatch calculators and the PIRCHE-II algorithm surpass traditional methods in predicting allograft rejection. Understanding minor histocompatibility antigens may also present an opportunity to personalize the compatibility process. While the application of molecular matching in deceased donor organ allocation presents multiple technical, logistical, and conceptual barriers, rendering it premature for mainstream use, several other areas of donor-recipient matching and posttransplant management are ready to incorporate molecular matching. Provision of molecular mismatch scores to physicians during potential organ offer evaluations could potentially amplify long-term outcomes. The implementation of molecular matching in living organ donation and kidney paired exchange programs is similarly viable. This article will explore the current understanding of immunologic matching in transplantation and the potential applications of epitope and non-epitope molecular biology and genetics in clinical transplantation. [ABSTRACT FROM AUTHOR]

Background: Homeless-experienced adults smoke at rates 5 times that of the general adult population, and often have limited access to cessation treatments while homeless. Permanent Supportive Housing (PSH) can be a catalyst for cessation treatment utilization, yet little is known about use of these treatments following PSH entry, or how to tailor and implement cessation care that meets homeless-experienced adults' vulnerabilities. Methods: Using Department of Veterans Affairs (VA) administrative data, we assessed smoking status (ie, current, former, non/never) among a cohort of homeless-experienced Veterans (HEVs) housed in Los Angeles-based PSH. We compared cessation treatment use rates (ie, nicotine replacement therapies, cessation medications, psychosocial counseling) pre- and post-housing using Chi-square tests. Predisposing (ie, demographics), enabling (eg, primary care, benefits), and need characteristics (ie, health, mental health, substance use diagnoses) were examined as correlates of cessation treatment utilization pre- and post-housing in univariable and multivariable logistic regression models. Results: Across HEVs (N = 2933), 48.6% were identified as currently-smoking, 17.7% as formerly-smoking, and 14.0% as non/never smoking. Among currently- and formerly-smoking HEVs (n = 1944), rates of cessation treatment use post-housing were significantly lower, compared to pre-housing, across all treatment types. Health, mental health, and substance use was more prevalent among currently- and formerly-smoking HEVs compared to non/never-smoking HEVs, and most diagnoses were positively associated with utilization univariably. However, in multivariable models, cessation clinic referrals and primary care engagement were the only significant (P <.001) predictors of pre-housing and post-housing cessation treatment utilization. Conclusion: Among HEVs, we found high smoking rates and low cessation treatment utilization pre- and post-PSH entry. Efforts to educate providers about this population's desire to quit smoking, support primary care engagement, and increase cessation clinic referrals may bolster their utilization. For homeless-experienced adults, optimizing cessation treatment accessibility by embedding cessation services within PSH and homeless service settings may reduce utilization impediments. [ABSTRACT FROM AUTHOR]

The olfactory sense is crucial for organisms, facilitating environmental recognition and interindividual communication. Ithomiini butterflies exemplify this importance not only because they rely strongly on olfactory cues for both inter- and intra-sexual behaviors, but also because they show convergent evolution of specialized structures within the antennal lobe, called macroglomerular complexes (MGCs). These structures, widely absent in butterflies, are present in moths where they enable heightened sensitivity to, and integration of, information from various types of pheromones. In this study, we investigate chemosensory evolution across six Ithomiini species and identify possible links between expression profiles and neuroanatomical. To enable this, we sequenced four new high-quality genome assemblies and six sex-specific antennal transcriptomes for three of these species with different MGC morphologies. With extensive genomic analyses, we found that the expression of antennal transcriptomes across species exhibit profound divergence, and identified highly expressed ORs, which we hypothesize may be associated to MGCs, as highly expressed ORs are absent in Methona , an Ithomiini lineage which also lacks MGCs. More broadly, we show how antennal sexual dimorphism is prevalent in both chemosensory genes and non-chemosensory genes, with possible relevance for behavior. As an example, we show how lipid-related genes exhibit consistent sexual dimorphism, potentially linked to lipid transport or host selection. In this study, we investigate the antennal chemosensory adaptations, suggesting a link between genetic diversity, ecological specialization, and sensory perception with the convergent evolution of MCGs. Insights into chemosensory gene evolution, expression patterns, and potential functional implications enhance our knowledge of sensory adaptations and sexual dimorphisms in butterflies, laying the foundation for future investigations into the genetic drivers of insect behavior, adaptation, and speciation. [ABSTRACT FROM AUTHOR]

Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. In addition to motor symptoms, a variety of other neurological and psychiatric symptoms may occur in affected individuals, including supranuclear gaze palsy and cognitive decline. Although psychotic symptoms are often reported, response to antipsychotic therapy is not well described in previous case reports/series. As such, we describe treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis. His disease was caused by a homozygous novel loss-of-function ATP13A2 variant (NM_022089.4, c.1970_1975del) that was characterized in this study. Our patient exhibited a good response to quetiapine monotherapy, which he has so far tolerated well. We also reviewed the literature and summarized all previous descriptions of antipsychotic treatment response. Although its use has infrequently been described in Kufor-Rakeb syndrome, quetiapine is commonly used in other degenerative parkinsonian disorders, given its lower propensity to cause extrapyramidal symptoms. As such, quetiapine should be considered in the treatment of Kufor-Rakeb syndrome-associated psychosis when antipsychotic therapy is deemed necessary. [ABSTRACT FROM AUTHOR]

An occupational health study was conducted inside reinforced-concrete earth-covered munitions storage magazines (ECMs) at Fort Wingate Depot Activity (FWDA), a former military facility near Gallup, New Mexico. A two-phased approach was used: (1) HEPA vacuuming of bulk dust and (2) wipe sample verification post-vacuuming. Site-specific occupational health criteria were derived to evaluate potential risk from inhalation of bulk dust (Phase 1) and dermal contact of residual dust (Phase 2). In Phase 1, no explosives detections exceeded site-specific screening criteria. Any explosives detected, with or without criteria were carried forward into Phase 2. In Phase 2, no exceedances were noted for detected explosives with criterion. Using structure/reactivity characteristics within the explosives category, surrogates were assigned to the six (6) explosives without occupational health screening criteria. Based upon structural similarities within the analysis category, assignments of surrogates to explosives without criteria did not adversely impact the study conclusions. In Phase 1, lead was detected in bulk dust in all 35 igloos and all detections exceeded the applicable criterion for commercial/industrial workers. In Phase 2, all lead detections in wipe samples were below the wipe screening criteria. Study results indicated the ECM interiors posed no unacceptable dermal occupational risk for explosives or lead residues following bulk dust removal. High-efficiency particulate air (HEPA) filter vacuuming of interior bulk dust in ECMs at FWDA reduced occupational risk/hazard for exposure via inhalation and dermal contact for commercial/industrial worker activities under worst-case exposure conditions. Both phases of this sampling design are widely applicable, provided the site-specific assumptions made for this study are evaluated for suitability to another specific application and adjusted if needed. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is associated with increased morbidity in patients with advanced liver disease, but it is particularly challenging for these patients to preserve skeletal muscle mass during weight loss and accelerating sarcopenia is a concern. Alternate‐day modified fasting (ADMF) may be particularly effective for weight loss in patients with concomitant cirrhosis and obesity due to preservation of fat‐free mass (FFM). Methods: A weight loss program featuring either ADMF or a continuous low‐calorie diet (LCD) was evaluated in a 24‐week randomized clinical trial in 20 adult patients with Child‐Pugh Class A cirrhosis and obesity. Participants were randomized to either ADMF (n = 11) or LCD (n = 9). Both groups received a remotely delivered exercise program. Body composition, sarcopenia measures, and functional outcomes were assessed pre‐post. Results: Thirteen participants completed the intervention (Age = 57 ± 10; BMI = 37.7 ± 5.8 kg/m2). The median body weight lost in ADMF was 13.7 ± 4.8 kg (13.9% of initial body weight), while LCD lost 9.9 ± 6.9 kg (10.7% of initial body weight). Total body fat percentage decreased in both groups (ADMF: −4.1 ± 4.0%; LCD = −2.8 ± 1.4%). Fat‐free mass accounted for 34 ± 20% of total weight loss in ADMF and 38 ± 10% in LCD. Functional measures, such as timed chair stands, improved in both groups. Conclusion: This pilot study demonstrates the feasibility of the ADMF and LCD interventions to produce significant weight loss while improving body composition in patients with cirrhosis and obesity. Further research is needed to validate these findings in larger cohorts and to assess changes in muscle quality and visceral fat. Trial Registration: ClinicalTrials.gov Identifier: NCT05367596. [ABSTRACT FROM AUTHOR]

Background: Children with medical complexity (CMC) have high healthcare utilization and face unique challenges during hospital admissions. The evidence describing their experiences of inpatient care is distributed across disciplines. The aim of this scoping review was to map the evidence related to the inpatient experience of care for CMC and their families, particularly related to key aspects and methodological approaches, and identify gaps that warrant further study. Methods: This scoping review was conducted in accordance with JBI methodology and included all studies that reported experiences of acute hospital care for CMC/families. All study designs were included. Databases searched included EMBASE, CINAHL Plus with Full Text, Web of Science, MEDLINE(R) and APA PsycInfo from 2000 to 2022. Details about the participants, concepts, study methods and key findings were abstracted using a data abstraction tool. A thematic analysis was conducted. Results: Forty‐nine papers were included: 27 qualitative studies, 10 quantitative studies, six mixed methods studies, two descriptive studies and four reviews. Some quantitative studies used validated instruments to measure experience of care, but many used non‐validated surveys. There were a few interventional studies with a small sample size. Results of thematic analysis described the importance of negotiating care roles, shared decision‐making, common goal setting, relationship‐building, communication, sharing expertise and the hospital setting itself. Conclusion: CMC and families value relational elements of care and partnering through sharing expertise, decision‐making and collaborative goal‐setting when admitted to hospital. Patient or Public Contribution: This review was conducted in alignment with the principles of patient and family engagement. The review was conceptualized, co‐designed and conducted with the full engagement of the project's parent–partner. This team member was involved in all stages from constructing the review question, to developing the protocol, screening articles and drafting this manuscript. Practitioner Points: Qualitative research describes key elements of inpatient experience of care for CMC and their families as relationships, communication, respect for parent/provider expertise and the hospital setting. There is less evidence on measuring experience of care using quantitative methodology, particularly using validating instruments. This would be helpful to support the evaluation of inpatient interventions to improve the experiences of CMC. [ABSTRACT FROM AUTHOR]

Whilst studies of child welfare inequalities have identified the impact of socio-economic deprivation on child protection rates, little is known about how this relates to intervention with adults who have care and support needs. This article examines the impact of area-level deprivation on adult safeguarding (AS) rates in Northern Ireland (NI). Routinely gathered statistics for community AS referrals (2015–2017) were linked to area-level deprivation across NI using service users' postcode. The relationship between deprivation and the screening, investigation and safeguarding planning stages of intervention was examined. Our analysis identified a clear social gradient in relation to AS referrals; the higher the level of deprivation, the higher the rates of AS screening and protection plans. Findings for investigations showed more variability. Further research is needed to explore the factors associated with areas of high deprivation that shape AS social work responses. To our knowledge, this is the first time AS rates have been explored in relation to deprivation. The study findings, that structural factors play a significant role in AS interventions, will help to determine how and where social work interventions are best focused, helping to shape policy and AS theory. [ABSTRACT FROM AUTHOR]

This paper seeks to illuminate new perspectives on the concept of crisis in globalised higher education (HE) by focusing on knowledge generated by doctoral research. Doctoral research is a significant part of research and knowledge building in HE, particularly in science, and doctoral students contribute to the research capacity and knowledge building of institutions. This source of knowledge offers alternative perspectives on crisis in HE, providing a rich source of research which is often under‐consulted. Using the British Library's digital repository EThOS, a collection of around 637,000 doctoral studies carried out in British universities, the research harnesses Generative Artificial Intelligence approaches in order to analyse the ways in which crisis is defined and constructed in doctoral research since 2000. Through a pilot study using a prototype of a new AI tool, the paper offers both conceptual and methodological insights into constructions of crisis in this under‐used field of research. [ABSTRACT FROM AUTHOR]

Ebola disease (EBOD) in humans is a severe disease caused by at least four related viruses in the genus Orthoebolavirus, most often by the eponymous Ebola virus. Due to human‐to‐human transmission and incomplete success in treating cases despite promising therapeutic development, EBOD is a high priority in public health research. Yet despite almost 50 years since EBOD was first described, the sources of these viruses remain undefined and much remains to be understood about the disease epidemiology and virus emergence and spread. One important approach to improve our understanding is detection of antibodies that can reveal past human infections. However, serosurveys routinely describe seroprevalences that imply infection rates much higher than those clinically observed. Proposed hypotheses to explain this difference include existence of common but less pathogenic strains or relatives of these viruses, misidentification of EBOD as something else, and a higher proportion of subclinical infections than currently appreciated. The work presented here maps B‐cell epitopes in the spike protein of Ebola virus and describes a single epitope that is cross‐reactive with an antigen seemingly unrelated to orthoebolaviruses. Antibodies against this epitope appear to explain most of the unexpected reactivity towards the spike, arguing against common but unidentified infections in the population. Importantly, antibodies of cross‐reactive donors from within and outside the known EBOD geographic range bound the same epitope. In light of this finding, it is plausible that epitope mapping enables broadly applicable specificity improvements in the field of serology. [ABSTRACT FROM AUTHOR]

The chemotherapeutic agent cisplatin accumulates in the kidneys, leading to acute kidney injury (AKI). Preclinical and clinical studies have demonstrated sex-dependent outcomes of cisplatin-AKI. Deranged histone deacetylase (HDAC) activity is hypothesized to promote the pathogenesis of male murine cisplatin-AKI; however, it is unknown whether there are sex differences in the kidney HDACs. We hypothesized that there would be sex-specific Hdac expression, localization, or enzymatic activity, which may explain sexual dimorphic responses to cisplatin-AKI. In normal human kidney RNA samples, HDAC10 was significantly greater in the kidneys of women compared with men, whereas HDAC1, HDAC6, HDAC10, and HDAC11 were differentially expressed between the kidney cortex and medulla, regardless of sex. In a murine model of cisplatin-AKI (3 days after a 15 mg/kg injection), we found few sex- or cisplatin-related differences in Hdac kidney transcripts among the mice. Although Hdac9 was significantly greater in female mice compared with male mice, HDAC9 protein localization did not differ. Hdac7 transcripts were greater in the inner medulla of cisplatin-AKI mice, regardless of sex, and this agreed with a greater HDAC7 abundance. HDAC activity within the cortex, outer medulla, and inner medulla was significantly lower in cisplatin-AKI mice but did not differ between the sexes. In agreement with these findings, a class I HDAC inhibitor did not improve kidney injury or function. In conclusion, even though cisplatin-AKI was evident and there were transcript level differences among the different kidney regions in this model, there were few sex- or cisplatin-dependent effects on kidney HDAC localization or activity. NEW & NOTEWORTHY: Kidney histone deacetylases (HDACs) are abundant in male and female mice, and the inner medulla has the greatest HDAC activity. A low dose of cisplatin caused acute kidney injury (AKI) in these mice, but there were few changes in kidney HDACs at the RNA/protein/activity level. A class I HDAC inhibitor failed to improve AKI outcomes. Defining the HDAC isoform, cellular source, and interventional timing is necessary to determine whether HDAC inhibition is a therapeutic strategy to prevent cisplatin-AKI in both sexes. [ABSTRACT FROM AUTHOR]

Purpose: We sought to identify trends and characteristics associated with the availability of tailored mental health services for individuals involved in the criminal justice system and ordered to treatment by a court, nationally in the US and by state. Methods: We used National Mental Health Services Survey to identify outpatient mental health treatment facilities in the US (2016 n = 4744; 2018 n = 4626; 2020 n = 4869). We used clustered multiple logistic regression to identify changes over time as well as facility- and state-level factors associated with the availability of specialty court-ordered services. Results: Slightly more than half of the outpatient mental health treatment facilities offered specialized services for individuals ordered to treatment by a court, with wide variation between states. Nationally, there was a significant increase in the odds of offering court-ordered treatment in 2020 compared to 2016 (aOR = 1.16, 95% CI = 1.06–1.27, p < 0.01). Notable associations included offering integrated substance use treatment (versus none, aOR = 2.95, 95% CI = 2.70–3.22, p < 0.0001) and offering trauma therapy (versus none, aOR = 2.05, 95% CI = 1.85–2.27, p < 0.0001). Conclusion: The availability of mental health services for individuals ordered to treatment by a court is growing nationally but several states are lagging behind. Court ordered treatment is a promising strategy to improve health and reduce reliance on the carceral system as a healthcare provider. At the same time, we express caution around disparities within behavioral health courts and advocate for equity in access to incarceration alternatives. [ABSTRACT FROM AUTHOR]

Adopting diverse perspectives is increasingly important for athletic trainers (ATs) to provide care that fosters inclusion for all patients. Despite the NATA's commitment to diversity, NATA membership remains approximately 80% White. Additionally, although ATs work with people from ethnically diverse backgrounds with unique body expression and body-size characteristics, it is unknown whether athletic training textbooks represent this diversity. To investigate diversity characteristics of images including patients and clinicians within athletic training textbooks. Cross-sectional study. Twenty percent (n = 15) of athletic training and health care textbooks included on the Board of Certification reference list were selected. Twenty percent of chapters from those textbooks were then randomly selected for inclusion. Descriptive statistics were calculated for person (athlete, nonathlete, clinician), setting (athletic venue, clinic, physician office, other), and demographic categories (perceived skin tone, race/ethnicity, age, gender, body size, body expression). Chi-square tests of goodness of fit were performed to determine significant differences between categories, and χ2 tests of independence were performed to determine differences across person type and category and across textbook domain and category. One thousand six hundred sixty-seven people were assessed from 1190 images. Images depicted statistically more persons with light skin tone (86%) assumed to be White (86%), young adults (75%) of average weight (95%), with no body expression diversity (95%). There were no major differences in subject characteristic majorities across person type or textbook domain. Like other health care professions, a lack of image diversity was demonstrated within athletic training textbooks. To better recruit diverse students to the athletic training profession, and to prepare professional students to provide culturally competent and patient-centered care, these resources should better represent the diversity of ATs and their patients. [ABSTRACT FROM AUTHOR]

Down syndrome predisposes individuals to haematological abnormalities, such as increased number of erythrocytes and leukaemia in a process that is initiated before birth and is not entirely understood1–3. Here, to understand dysregulated haematopoiesis in Down syndrome, we integrated single-cell transcriptomics of over 1.1 million cells with chromatin accessibility and spatial transcriptomics datasets using human fetal liver and bone marrow samples from 3 fetuses with disomy and 15 fetuses with trisomy. We found that differences in gene expression in Down syndrome were dependent on both cell type and environment. Furthermore, we found multiple lines of evidence that haematopoietic stem cells (HSCs) in Down syndrome are ‘primed’ to differentiate. We subsequently established a Down syndrome-specific map linking non-coding elements to genes in disomic and trisomic HSCs using 10X multiome data. By integrating this map with genetic variants associated with blood cell counts, we discovered that trisomy restructured regulatory interactions to dysregulate enhancer activity and gene expression critical to erythroid lineage differentiation. Furthermore, as mutations in Down syndrome display a signature of oxidative stress4,5, we validated both increased mitochondrial mass and oxidative stress in Down syndrome, and observed that these mutations preferentially fell into regulatory regions of expressed genes in HSCs. Together, our single-cell, multi-omic resource provides a high-resolution molecular map of fetal haematopoiesis in Down syndrome and indicates significant regulatory restructuring giving rise to co-occurring haematological conditions.Using single-cell and multi-omics data of fetal blood, a high-resolution molecular map of dysregulated haematopoiesis in Down syndrome is provided. [ABSTRACT FROM AUTHOR]

Friedreich's ataxia (FA) is an autosomal recessive disorder caused by reduced frataxin (FXN) expression in mitochondria, where the lethal component is cardiomyopathy. Using the conditional Fxnflox/null::MCK-Cre knock-out (Fxn-cKO) mouse model, we discovered significant sex differences in the progression towards heart failure, with Fxn-cKO males exhibiting a worse cardiac phenotype, low survival rate, kidney and reproductive organ deficiencies. These differences are likely due to a decline in testosterone in Fxn-cKO males. The decrease in testosterone was related to decreased expression of proteins involved in cholesterol transfer into the mitochondria: StAR and TSPO on the outer mitochondrial membrane, and the cholesterol side-chain cleavage enzyme P450scc and ferredoxin on the inner mitochondrial membrane. Expression of excitation-contraction coupling proteins (L-type calcium channel, RyR2, SERCA2, phospholamban and CaMKIIδ) was decreased significantly more in Fxn-cKO males. This is the first study that extensively investigates the sexual dimorphism in FA mouse model with cardiac calcium signaling impairment. Sexual dimorphism is identified in a mouse model of Friedreich's ataxia, with males exhibiting a worse cardiac phenotype, low survival rate, as well as kidney and reproductive organ deficiencies. [ABSTRACT FROM AUTHOR]

Background: Adolescent smoking is associated with significant health and social risks. Previous research has demonstrated the effectiveness of interventions based on behavior change theories in preventing adolescent smoking uptake. However, evidence from the theory-based perspective of evaluation is limited, especially for how such complex interventions work, and how they work when implemented in different contextual settings. Method: A comparative qualitative analysis was conducted to explore various influences on behavior change among participants taking part in two smoking prevention interventions in Northern Ireland and Bogotá. Twenty-seven focus groups were conducted in 12 schools (6 in Northern Ireland and 6 in Bogota, n = 195 pupils participated; aged 11–15 years). The Theoretical Domains Framework guided a content analysis of the data. Results: We found similarities across settings in terms of knowledge, skills, and beliefs related to smoking or vaping behavior change, as well as differences in contextual resources and social influence. Different environmental resources included availability to purchase tobacco products in the neighborhoods and previous information about tobacco risk. Participants in both interventions perceived behavioral change outcomes related to personal skills and intention to not smoke or vape. Conclusion: These findings have highlighted how both individual factors and contextual resources influence behavior change for smoking prevention in practice. Local contextual factors and social influences affecting pupils should be taken into account in the implementation and evaluation of health behavior change interventions. In particular, this study supports using social and contextual influence strategies in interventions to reduce the onset of adolescent smoking and vaping. [ABSTRACT FROM AUTHOR]

We show that, in almost every n$$ n $$‐vertex random directed graph process, a copy of every possible n$$ n $$‐vertex oriented cycle will appear strictly before a directed Hamilton cycle does, except of course for the directed cycle itself. Furthermore, given an arbitrary n$$ n $$‐vertex oriented cycle, we determine the sharp threshold for its appearance in the binomial random directed graph. These results confirm, in a strong form, a conjecture of Ferber and Long. [ABSTRACT FROM AUTHOR]

We develop a Bayesian method for aggregating partial ranking data using the Thurstone model. Our implementation is a JAGS graphical model that allows each individual to rank any subset of items, and provides an inference about the latent true ranking of the items and the relative expertise of each individual. We demonstrate the method by analyzing data from new experiments that collected partial ranking data. In one experiment, participants were assigned subsets of items to rank; in the other experiment, participants could choose how many and which items they ranked. We show that our method works effectively for both sorts of partial ranking in applications to US city populations and the chronology of US presidents. We discuss the potential of the method for studying the wisdom of the crowd and other research problems that require aggregating incomplete or partial rankings. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is an end-stage treatment for knee osteoarthritis that relieves pain and loss of mobility, but patient satisfaction and revision rates require improvement. One cause for TKA revision is joint instability, which may be due to improper ligament balancing. A better understanding of the relationship between prosthesis design, alignment, and ligament engagement is necessary to improve component designs and surgical techniques to achieve better outcomes. We investigated the biomechanical effects of ligament model complexity and ligament wrapping during laxity tests using a virtual joint motion simulator. There was little difference in kinematics due to ligament complexity or ligament wrapping. [ABSTRACT FROM AUTHOR]

Reactive chlorine species (RCS) like sodium hypochlorite (NaOCl) are potent oxidizing agents and widely used biocides in surface disinfection, water treatment, and biofilm elimination. Moreover, RCS are also produced by the human immune system to kill invading pathogens. However, bacteria have developed mechanisms to survive the damage caused by RCS. Using the comprehensive Pseudomonas aeruginosa PA14 transposon mutant library in a genetic screen, we identified a total of 28 P. aeruginosa PA14 mutants whose biofilms showed increased susceptibility to NaOCl in comparison to PA14 WT biofilms. Of these, ten PA14 mutants with a disrupted apaH, PA0793, acsA, PA1506, PA1547, PA3728, yajC, queA, PA3869, or PA14_32840 gene presented a 4-fold increase in NaOCl susceptibility compared to wild-type biofilms. While none of these mutants showed a defect in biofilm formation or attenuated susceptibility of biofilms toward the oxidant hydrogen peroxide (H2O2), all but PA14_32840 also exhibited a 2–4-fold increase in susceptibility toward the antibiotic ciprofloxacin. Further analyses revealed attenuated levels of intracellular ROS and catalase activity only for the apaH and PA1547 mutant, providing insights into the oxidative stress response in P. aeruginosa biofilms. The findings of this paper highlight the complexity of biofilm resistance and the intricate interplay between different mechanisms to survive oxidative stress. Understanding resistance strategies adopted by biofilms is crucial for developing more effective ways to fight resistant bacteria, ultimately contributing to better management of bacterial growth and resistance in clinical and environmental settings. [ABSTRACT FROM AUTHOR]

Metabolic diseases such as obesity and type 2 diabetes are marked by insulin resistance1,2. Cells within the arcuate nucleus of the hypothalamus (ARC), which are crucial for regulating metabolism, become insulin resistant during the progression of metabolic disease3–8, but these mechanisms are not fully understood. Here we investigated the role of a specialized chondroitin sulfate proteoglycan extracellular matrix, termed a perineuronal net, which surrounds ARC neurons. In metabolic disease, the perineuronal net of the ARC becomes augmented and remodelled, driving insulin resistance and metabolic dysfunction. Disruption of the perineuronal net in obese mice, either enzymatically or with small molecules, improves insulin access to the brain, reversing neuronal insulin resistance and enhancing metabolic health. Our findings identify ARC extracellular matrix remodelling as a fundamental mechanism driving metabolic diseases.Experiments in mice show that the perineural net has a key role in metabolic disease by controlling insulin access to neurons in the arcuate nucleus of the hypothalamus. [ABSTRACT FROM AUTHOR]

Genetic diagnosis plays a crucial role in rare diseases, particularly with the increasing availability of emerging and accessible treatments. The International Rare Diseases Research Consortium (IRDiRC) has set its primary goal as: "Ensuring that all patients who present with a suspected rare disease receive a diagnosis within one year if their disorder is documented in the medical literature". Despite significant advances in genomic sequencing technologies, more than half of the patients with suspected Mendelian disorders remain undiagnosed. In response, IRDiRC proposes the establishment of "a globally coordinated diagnostic and research pipeline". To help facilitate this, IRDiRC formed the Task Force on Integrating New Technologies for Rare Disease Diagnosis. This multi-stakeholder Task Force aims to provide an overview of the current state of innovative diagnostic technologies for clinicians and researchers, focusing on the patient's diagnostic journey. Herein, we provide an overview of a broad spectrum of emerging diagnostic technologies involving genomics, epigenomics and multi-omics, functional testing and model systems, data sharing, bioinformatics, and Artificial Intelligence (AI), highlighting their advantages, limitations, and the current state of clinical adaption. We provide expert recommendations outlining the stepwise application of these innovative technologies in the diagnostic pathways while considering global differences in accessibility. The importance of FAIR (Findability, Accessibility, Interoperability, and Reusability) and CARE (Collective benefit, Authority to control, Responsibility, and Ethics) data management is emphasized, along with the need for enhanced and continuing education in medical genomics. We provide a perspective on future technological developments in genome diagnostics and their integration into clinical practice. Lastly, we summarize the challenges related to genomic diversity and accessibility, highlighting the significance of innovative diagnostic technologies, global collaboration, and equitable access to diagnosis and treatment for people living with rare disease. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent form of programmed cell death that is influenced by biological processes such as iron metabolism and senescence. As brain iron levels increase with aging, ferroptosis is also implicated in the development of age-related pathologic conditions such as Alzheimer's disease (AD) and related dementias (ADRD). Indeed, inhibitors of ferroptosis have been shown to be protective in models of degenerative brain disorders like AD/ADRD. Given the inaccessibility of the living human brain for metabolic studies, the goal of this work was to characterize an in vitro model for understanding how aging and iron availability influence neuronal iron metabolism and ferroptosis. First, the human (SH-SY5Y) and mouse (Neuro-2a) neuroblastoma lines were terminally differentiated into mature neurons by culturing in all-trans-retinoic acid for at least 72 h. Despite demonstrating all signs of neuronal differentiation and maturation, including increased expression of the iron storage protein ferritin, we discovered that differentiation conferred ferroptosis resistance in both cell lines. Gene expression data indicates differentiated neurons increase their capacity to protect against iron-mediated oxidative damage by augmenting cystine import, and subsequently increasing intracellular cysteine levels, to promote glutathione production and glutathione peroxidase activity (GPX). In support of this hypothesis, we found that culturing differentiated neurons in cysteine-depleted media sensitized them to GPX4 inhibition, and that these effects are mitigated by cystine supplementation. Such findings are important as they provide guidance for the use of in vitro experimental models to investigate the role of ferroptosis in neurodegeneration in pathologies such as ADRD. [ABSTRACT FROM AUTHOR]