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Abstract Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre‐symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti‐lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11‐dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell‐dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ‐binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization‐independent T cell‐mediated effects, even against an established CNS infection by a lethal neurotropic virus.

Background: Weight bias is characterised by negative attitudes towards people with a higher weight and is widespread in healthcare. Primary care professionals sometimes avoid discussing weight with patients due to concerns about upsetting them, insufficient training, resources, or referral pathways. There is, however, a responsibility for primary care professionals to address the health needs of patients, which may require discussing weight. Objective: The current study aimed to understand primary care professionals and trainee perceptions of the appropriateness of weight-centric, weight-inclusive/holistic, and avoidant approaches for discussing weight with higher weight individuals when patients were and were not seeking weight management advice. Design: Mixed methods design. Participants: Primary care professionals and trainees (N = 112) within Australia. Approach: Participants first completed an online survey and provided demographic data and completed measures of implicit and explicit weight bias. Secondly, participants viewed simulated patient consultations, reflecting each of the three approaches (weight-centric, weight-inclusive/holistic, and avoidant) in a weight-related and non-weight related context. Participants then evaluated the appropriateness of the language and strategies used. Key results: The participants showed, on average, low to moderate levels of explicit weight bias but high levels of implicit weight bias. For the consultations, language and strategies of the holistic approach were considered the most appropriate in both contexts. In the weight-related consultation, language used in the weight-centric and avoidant approaches were deemed equally inappropriate. However, weight-centric strategies were considered more appropriate than avoidant strategies. In the non-weight related consultation, the language and strategies of the avoidant approach were considered more appropriate than those of the weight-centric approach. Conclusions: Primary care professionals and trainees favoured the holistic approach to discussing weight when patients presented with weight-related or non-weight related concerns. These findings have potential practical implications for health professional education. [ABSTRACT FROM AUTHOR]

The Western Vardar ophiolite, a thrust sheet of oceanic crust and mantle obducted onto the Adriatic passive margin in the Late Jurassic, crops out along the entire Balkan Peninsula. The Mirdita Ophiolite forms the northern Albanian segment of this unit. In northeast Albania near Bajram Curri, a 200–700 m thick metamorphic sole is preserved at its base. The assembly of obducted mantle rocks and metamorphic sole constitutes a plate interface that formed during the intraoceanic subduction stage preceding obduction; we call this a fossil intraoceanic plate interface in this paper. This setting allows to study the interrelated tectonometamorphic evolution and rock-water interaction between the subducted and exhumed metamorphic sole and concomitant mantle wedge serpentinization in the overlying units. We combined detailed lithological and structural mapping with micro-scale analyses along this plate interface. Three tectonic units were distinguished. Mylonitic harzburgites overlie a tightly folded, tectonised subophiolitic mélange along a SE-dipping contact that defines the fossil intraoceanic plate interface. The tectonised subophiolitic mélange itself was separated into a structurally lower non-metamorphic broken formation and a higher metamorphic sole, separated by an isoclinally folded thrust. Within the metamorphic sole, the temperature and degree of deformation increase towards the structural top. Shear sense indicators in calcschists of the metamorphic sole show top to the west transport of the overriding units. All metamorphic sole lithologies were overprinted at lower greenschist-facies conditions, reflecting their exhumation from intraoceanic subduction. Corresponding microstructures indicate mineral growth at isotropic stresses, suggesting that deformation migrated into structurally lower, frontally accreted non-metamorphic units of the sub-ophiolitic mélange marking the start of obduction onto the passive Adriatic margin. Ongoing westward transport led to folding of the entire sub-ophiolitic succession. Harzburgites are more deformed towards the plate interface, forming a mylonitic fabric. There, harzburgites contain accessory Cr-rich spinel and the foliation is dissected by multiple generations of veins containing serpentine and magnetite. Vein density is highest along the plate interface and decreases up-section, suggesting that serpentinisation was triggered by devolatilisation reactions in the sediments of the metamorphic sole that were subducting below the harzburgites, and the upwards migration of volatiles into the overlying mantle wedge. [ABSTRACT FROM AUTHOR]

Background: The Oakland Score predicts risk of 30-day adverse events among hospitalized patients with lower gastrointestinal bleeding (LGIB) possibly identifying patients who may be safe for discharge. The Oakland Score has not been studied among emergency department (ED) patients with LGIB. The Oakland Score composite outcome includes re-bleeding, defined as additional blood transfusion requirements and/or a further decrease in hematocrit (Hct) >/= 20% after 24 h in clinical stability; red blood cell transfusion; therapeutic intervention to control bleeding, including surgery, mesenteric embolization, or endoscopic hemostasis; in-hospital death, all cause; and re-admission with further LGIB within 28 days. Prediction variables include age, sex, previous LGIB admission, systolic blood pressure, heart rate, and hemoglobin concentration, and scores range from 0 to 35 points, with higher scores indicating greater risk. Methods: Retrospective cohort study of adult (≥ 18 years old) patients with a primary ED diagnosis of LGIB across 21 EDs from March 1st, 2018, through March 1st, 2020. We excluded patients who were more likely to have upper gastrointestinal bleeding (esophago-gastroduodenoscopy without LGIB evaluation), patients who left against medical advice or prior to ED provider evaluation, ED patients without active health plan membership, and patients with incomplete Oakland Score variables. We assessed predictive accuracy by reporting the area under the receiver operator curve (AUROC) and sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios at multiple clinically relevant thresholds. Results: We identified 8,283 patients with LGIB, 52% were female, mean age was 68, 49% were non-White, and 27% had an adverse event. The AUROC for predicting an adverse event was 0.85 (95% CI 0.84–0.86). There were 1,358 patients with an Oakland Score of

Climate is the primary factor influencing the feasibility of agricultural production. Given the context of climate change, prospective studies become imperative for anticipating potential consequences on plant development and the adaptation of agricultural systems. The objective of this study is to compare two methods based on the calculation of climatic indicators, which can reveal risks of production losses. The first method relies on agroclimatic indicators (AGIs), computed on fixed calendar dates corresponding to plant development phases. The second method employs phenoclimatic indicators (PHI), calculated between previously simulated phenological stage dates. To provide a concrete comparison and account for a range of potential climate scenarios, the cultivation of soft winter wheat (Triticum aestivum) in Clermont-Ferrand is used as an example for horizons 2060 and 2100 under the RCP 4.5 and 8.5 scenarios (using the ALADIN63_CNRM-CM5 model from Météo-France). A comparison of the two methods yields contrasting results. It emphasizes the effectiveness of PHIs in closely approximating the conditions encountered by a specific plant, without undermining the significance of AGIs in interpreting changes in diverse climatic parameters that affect plant development overall. The AGIs indicate a rise in water deficit and hot days for soft wheat in 2060 and 2100. Meiosis would be less susceptible to low temperatures, and bolting would benefit from a slightly higher cumulative radiation. Conversely, depending on the chosen sowing dates, the PHIs indicate that heat days and water deficit would not be more pronounced than in the reference period, owing to the earlier physiological maturity date of the grains. However, advancing the bolting date on the calendar would expose it to a lack of radiation and low temperatures. Consequently, recommendations for adaptation and transition in the agricultural sector may vary significantly between the results of AGIs and those of PHIs. [ABSTRACT FROM AUTHOR]

Purpose: Emergency laparotomy can result in a range of physical and neuropsychiatric postoperative complaints, potentially impacting quality of life. This study aimed to assess the effect of emergency laparotomy on health-related quality of life (HRQoL) and how HRQoL influences the risk of readmission. Method: HRQoL was assessed in patients undergoing emergency laparotomy during a 1-year period. Patients who completed the baseline HRQoL evaluation underwent a reassessment on postoperative day (POD) 30, 90, and 180. HRQoL was measured with the EQ5D index, and patients were categorized in ‘high’ and ‘low’ HRQoL. A decrease from high baseline HRQoL to low HRQoL by POD 30 was classified as ‘acquired low HRQoL’. Results: All 215 patients who completed the baseline HRQoL evaluation were followed. On average, patients reported a lower mean (M) HRQoL from baseline (M = 0.876, standard deviation (SD) = 0.171) to POD 30 (M = 0.735, SD = 0.260). On POD 90, HRQoL had somewhat improved (M = 0.763, SD = 0.298), and by POD 180 HRQoL had returned to normal (M = 0.853, SD = 0.235). From the full-record population (n = 73), 20.5% acquired low HRQoL of whom 33% had not recovered by POD180. For patients with acquired low HRQoL, the risk of 180-day readmission was increased, and days alive and out of hospital within 180 days was reduced. Conclusion: For most patients, HRQoL has returned to normal within 180 days after emergency laparotomy. However, patients who acquired low HRQoL after the procedure had an increased risk of long-term readmission. [ABSTRACT FROM AUTHOR]

Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating condition with high mortality and morbidity. The outcome measures used in aSAH clinical research vary making it challenging to compare and combine different studies. Additionally, there may be a mismatch between the outcomes prioritized by patients, caregivers, and health care providers and those selected by researchers. We conducted an international, online, multiple round Delphi study to develop consensus on domains (where a domain is a health concept or aspect) prioritized by key stakeholders including those with lived experience of aSAH, health care providers, and researchers, funders, or industry professionals. One hundred seventy-five people participated in the survey, 59% of whom had lived experience of aSAH. Over three rounds, 32 domains reached the consensus threshold pre-defined as 70% of participants rating the domain as being critically important. During the fourth round, participants ranked the importance of each of these 32 domains. The top ten domains ranked highest to lowest were (1) Cognition and executive function, (2) Aneurysm obliteration, (3) Cerebral infarction, (4) Functional outcomes including ability to walk, (5) Delayed cerebral ischemia, (6) The overall quality of life as reported by the SAH survivor, (7) Changes to emotions or mood (including depression), (8) The basic activities of daily living, (9) Vasospasm, and (10) ICU complications. Our findings confirm that there is a mismatch between domains prioritized by stakeholders and outcomes used in clinical research. Our future work aims to address this mismatch through the development of a core outcome set in aSAH research. [ABSTRACT FROM AUTHOR]

Loud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we investigate the specific underlying cognitive processes during auditory perceptual decision-making that are impacted by NIHL. Gerbils were trained to perform an auditory decision-making task that involves discriminating between slow and fast presentation rates of amplitude-modulated (AM) noise. Decision-making task performance was assessed across pre- versus post-NIHL sessions within the same gerbils. A single exposure session (2 h) to loud broadband noise (120 dB SPL) produced permanent NIHL with elevated threshold shifts in auditory brainstem responses (ABRs). Following NIHL, decision-making task performance was tested at sensation levels comparable to those prior to noise exposure in all animals. Our findings demonstrate NIHL diminished perceptual acuity, reduced attentional focus, altered choice bias, and slowed down evidence accumulation speed. Finally, video-tracking analysis of motor behavior during task performance demonstrates that NIHL can impact sensory-guided decision-based motor execution. Together, these results suggest that NIHL impairs the sensory, cognitive, and motor factors that support auditory decision-making. [ABSTRACT FROM AUTHOR]

Form-function relationships often have tradeoffs: if a material is tough, it is often inflexible, and vice versa. This is particularly relevant for the elephant trunk, where the skin should be protective yet elastic. To investigate how this is achieved, we used classical histochemical staining and second harmonic generation microscopy to describe the morphology and composition of elephant trunk skin. We report structure at the macro and micro scales, from the thickness of the dermis to the interaction of 10 μm thick collagen fibers. We analyzed several sites along the length of the trunk to compare and contrast the dorsal-ventral and proximal-distal skin morphologies and compositions. We find the dorsal skin of the elephant trunk can have keratin armor layers over 2 mm thick, which is nearly 100 times the thickness of the equivalent layer in human skin. We also found that the structural support layer (the dermis) of the elephant trunk contains a distribution of collagen-I (COL1) fibers in both perpendicular and parallel arrangement. The bimodal distribution of collagen is seen across all portions of the trunk, and is dissimilar from that of human skin where one orientation dominates within a body site. We hypothesize that this distribution of COL1 in the elephant trunk allows both flexibility and load-bearing capabilities. Additionally, when viewing individual fiber interactions of 10 μm thick collagen, we find the fiber crossings per unit volume are five times more common than in human skin, suggesting that the fibers are entangled. We surmise that these intriguing structures permit both flexibility and strength in the elephant trunk. The complex nature of the elephant skin may inspire the design of materials that can combine strength and flexibility. Advanced microscopy shows that the skin along the elephant's trunk is anisotropic; elephant skin has an armor thicker than an Armadillo shell, with entangled protein fibers that provide additional stiffness. [ABSTRACT FROM AUTHOR]

Objective: Our primary objective was to determine the frequency and type of substance use in youth presenting to our pediatric ED (PED). Our secondary objective was to identify characteristics associated with higher-risk substance use. Methods: We conducted a tablet-based, anonymous, self-administered screening for substance use using a modified version of the Screening to Brief Intervention (S2BI) tool among a convenience sample of 383 patients 12–21 years presenting to an urban, academic PED from February to July 2023. Patients' attitudes toward ED screening and interventions for substance use also were collected. The frequency and type of substance use was analyzed by age group. Ordinal logistic regression was used to identify characteristics associated with higher-risk use (monthly or more substance use) and lower-risk use (past year use), as compared to no past year use. Results: Among 14-17-year-olds (n = 144), 38% reported substance use in the past year; 25% had higher-risk use. Among 18–21-year-olds (n = 172), 67% reported substance use in the past year; 48% had higher-risk use. Alcohol, cannabis, and tobacco were most commonly used. Substance use was rare for 12–13-year-olds. Compared to youth 14–17 years, youth 18–21 years were more likely to have either higher-risk use (aOR 3.81, 95% CI (2.24–6.47)) or lower-risk use (aOR 2.74 (1.41–5.35)), rather than no use. Compared to Asian patients, Non-Hispanic White patients (aOR 5.23 (1.07–25.66)) and Hispanic patients (aOR 3.18 (1.06–9.58)) were more likely to have higher-risk use than no use. Most patients reported that it was important for youth to be asked about substance use in the ED and to be offered help for substance use. Conclusion: Youth substance use was common in this urban, academic PED, and many patients reported higher-risk use. These findings support future research to determine the best practices for ED substance use screening and ED-based interventions for youth. [ABSTRACT FROM AUTHOR]

Most people who seek mental health treatment cannot access it. Certain groups (e.g., Medicaid enrollees and the uninsured) face particularly severe treatment access barriers along the care continuum. We interviewed 31 clinicians across two studies about their perspectives working in New York City's public mental health system. Because every clinician across both studies reported gaps in the system, we deployed an emergent, "serendipitous finding" approach and qualitatively analyzed the interviews together. Clinicians described three public mental health system gaps. First, many treatment-seekers must wait long periods of time to receive care and some never receive it at all. Second, patients with more serious challenges cannot access longer-term, higher-intensity, or specialized treatment. Third, some patients receiving high-intensity services may benefit from lower-intensity mental health support that is better integrated with medical and social service support. Coordinated and sustained financial investments at every step of the mental healthcare continuum are needed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of prophylactic mesh placement in reducing the incidence of parastomal hernias following colostomy, ileostomy, and ileal conduit formation. Methods: A systematic review identified relevant studies evaluating parastomal hernia incidence with prophylactic mesh use during stoma formation. Pairwise meta-analysis and network meta-analysis using Bayesian modeling were performed. Results: 25 studies, consisting of 16 randomized control trials (RCT), 6 follow up studies, and 3 retrospective cohort studies, were included. Prophylactic mesh led to significantly fewer parastomal hernias beyond 6 months follow-up (OR 0.43, 95% CI 0.33–0.58). Hernias were reduced with mesh for both ileal conduits and colostomies. When analyzing hazard ratios (HRs), only 6 studies were included, and a statistically significant difference was observed among both randomized controlled trials (RCTs) (HR 0.75 [0.53, 0.92], p = 0.01) and non-RCTs (HR 0.57 [0.36, 0.92], p = 0.02). Network meta-analysis found the retromuscular approach with mesh had the lowest hernia rate. Regression was non-significant for variations between study types. Conclusion: This meta-analysis demonstrated prophylactic mesh placement during ostomy creation significantly reduced parastomal hernia risk, more prominently beyond 6 months, consistently across randomized trials and observational studies for urologic and gastrointestinal ostomies. The retromuscular technique was most effective. [ABSTRACT FROM AUTHOR]

Two studies examined the effects of race on the think manager-think male effect, which has shown men in general to be viewed more similarly to successful managers than women in general. The first study directly manipulated the race of the male or female target in the think manager-think-male framework and examined the effects on two key measures of agency – competence and assertiveness – as well as on communality. Results indicated that the differences in agency characterizations between men and successful managers and women and successful managers that are emblematic of the think-manager-think-male effect were not always evident. While the think manager-think male effect was observed for men and women "in general" as well as for men and women designated as White, it did not hold for Black and Asian targets, whose characterizations were influenced not only by gender stereotypes but also by racial stereotypes. Additionally, a potential "think manager-think female" effect, as indicated by greater overlap in communality ratings between women in general and successful managers than between men in general and successful managers held for targets who were White and Black, but not for those who were Asian. A follow-up study focused on potential implications of the findings from the first study and indicated that competence was believed to be more important than either communality or assertiveness, while communality was believed to be more important than assertiveness in determining managerial success. These results raise questions about the universality of the think-manager-think-male effect and the scope of its generalizability. These findings also add to the growing concern about the precision and application of gender bias research findings when attention is not paid to crucial intersecting identities such as race. [ABSTRACT FROM AUTHOR]

Gender norms shape expectations for how women and men should behave, and those who deviate from these norms are often punished, both socially and professionally. However, these penalties do not always occur, and sometimes women and men are even rewarded for engaging in counter-stereotypic behaviors. At present, we do not have a clear theoretical understanding of why and when people will react positively or negatively to gender norm violations. In this paper, we combine the predictions of role congruity, status incongruity hypothesis, and expectancy-violation theories to propose a unified theory for predicting reactions to counter-stereotypic women and men. The model proposed here provides an explanation for why both penalties and rewards occur for counter-stereotypic behaviors and explains why women risk penalties for engaging in masculine-stereotypic behaviors, generally, while men are only penalized for a narrow subset of feminine-stereotypic behaviors. This unified framework advances our understanding of reactions to gender norm violations and provides a foundation for future research aimed at identifying and preventing gender inequality in society. [ABSTRACT FROM AUTHOR]

Background: Omadacycline offers a potential advancement in the management of infections in people with cystic fibrosis (CF) because of its spectrum of activity, intrapulmonary penetration, and oral bioavailability. A prospective single-dose, single-arm study was conducted to characterize the pharmacokinetic (PK) profile of omadacycline in people with CF, considering the known alterations in PK observed in this population (NCT04460586, 2020-07-01). Methods: Plasma samples were obtained from nine adults with CF who received a single dose of intravenous omadacycline 100 mg over 0.5 h followed by a 1-week washout and an oral dose of omadacycline 300 mg. The data were analyzed using noncompartmental PK. Results: The maximum plasma concentration (Cmax) and area under the curve extrapolated to infinity (AUC0-∞) after intravenous administration of omadacycline were similar between healthy volunteers and people with CF. The absorption kinetics of oral omadacycline, encompassing both the rate (Cmax and time to Cmax [tmax]) and the extent (AUC0-∞), also showed consistency between healthy volunteers and people with CF. The absolute bioavailability of the oral tablet formulation of omadacycline in people with CF (31.2%) was also consistent with that observed in healthy volunteers (34.5%). In comparing the two routes of administration, intravenous omadacycline 100 mg provided plasma exposures equivalent to those with oral omadacycline 300 mg in people with CF, as evidenced by geometric mean ratios for both AUC0-∞ (0.9381; 90% confidence intervals [CI] 0.6783–1.2975) and Cmax (0.7746; 90% CI 0.5478–1.0951). Conclusions: Overall, the similarity in plasma PK observed in this study when comparing healthy volunteers and infected patients indicates that no dosing alterations are necessary when using omadacycline in people with CF. [ABSTRACT FROM AUTHOR]

Duplication, accessory slips, and division of the rectus capitis posterior muscles are rare anatomical variations. Here we report a case of unilateral doubling of rectus capitis posterior major, and doubling of rectus capitis posterior minor with an accessory slip originating from the spinous process of the second cervical vertebra. The gross anatomical characteristics, clinical significance, and relationship of suboccipital musculature to the cervical myodural bridge is discussed in this report. Knowledge of rectus capitis posterior muscle variations may be of interest to clinicians practicing surgical approaches to the posterior cervical region due to the close proximity of the variations to typical muscular and neurovascular structures of the suboccipital region and potential association with the cervical myodural bridge. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVD) are among the leading causes of mortality in the western world, and high blood pressure is among the greatest risk factors for CVD. Given that most of a person's waking hours are spent in sedentary behaviors, understanding the cardiovascular impact of a sedentary lifestyle is imperative. Although limiting sedentary time is encouraged in public health messaging, individual reviews analyzing its impact on clinically relevant cardiovascular outcomes such as blood pressure and CVD exhibit conflicting results. Objective: We conducted an umbrella review of systematic reviews and meta-analyses synthesizing the effects of sedentary time/behaviors on blood pressure or CVD. Methods: To be included, studies had to be a systematic review and/or meta-analysis that studied the impact of sedentary time or a sedentary posture on blood pressure or CVD incidence/mortality. The review was preregistered in PROSPERO (CRD4202342568) and conducted in May 2023. The Joanna Briggs Institute and Risk of Bias in Systematic Reviews tools assessed study quality. PRISMA reporting was followed. Results: Our umbrella review screened 2215 citations with 40 review studies meeting our inclusion criteria (n = 22 meta-analyses) that included 234 unique individual studies of 3,769,755 unique participants. The average study quality was high (9.2 ± 1.7 out of 11). A minority of studies (n = 7/20) supported that less sedentary time was associated with lower blood pressure, with reviews of interventional studies typically not observing a consistent effect (n = 9/12), whereas reviews of cross-sectional studies observed a positive effect (n = 5/7). When hypertension rates were used as the outcome, most (n = 3/4) studies observed a deleterious impact of sedentary time. For CVD incidence/mortality, less sedentary time or screen time was consistently associated with a lower CVD incidence/mortality (n = 17/23), with studies exhibiting a null effect generally including small sample sizes and being of a lower study quality. Total sedentary time and specific behaviors (i.e., television and screen time) exhibited similar findings. Conclusions: Based on a high quality of evidence and large sample size, existing systematic reviews and meta-analyses demonstrate the negative impact of sedentary behaviors on CVD incidence/mortality, with conflicting reports for blood pressure that vary based on the study design. [ABSTRACT FROM AUTHOR]

Despite its presence in everyday life, cultural appropriation is not well understood, perhaps because its definition, bounds, and conditions have not been clearly unpacked. The present study uses a between-subjects, mixed-methods approach and culinary-related scenarios to address possible factors that constitute appropriation (e.g., actor background and intent). Utilizing a sample of emerging adults from a small, liberal arts university (N = 167, 52% female, 65% white), results suggest that an actor's background is not the sole factor in deeming an act appropriative. Rather, intent appears to be an even more pertinent factor to examine. Participants believe that it is possible to engage with cultural products or practices in a respectful manner, further emphasizing the role intent plays in perceptions of appropriation. Although our results help define the bounds of cultural appropriation, future research should consider connections between authenticity and appropriation as well as how observer background might impact perceptions of appropriation. [ABSTRACT FROM AUTHOR]

Indigenous communities at ground zero for extractive industry, industrial pollution, and climate change battle extant development agendas under coloniality that drive cycles of consumption. In this scheme bolstered by neoliberal policies, stewarding biocultural diversity is a clarion call and heavy responsibility for Indigenous community members and students as well as for educational and scientific collaborators. This article examines knowledge construction within coloniality and its link to science and science education as a tool of hegemonic rationality and modernity that is at odds with the planetary balance sought within Indigenous intelligence and Indigenous knowledge systems. Drawing from translanguaging theories and biocultural diversity education, we consider how multiple epistemologies shape and are shaped by transknowledging as restorative and healing practices of sciences education towards Indigenous self-determination. [ABSTRACT FROM AUTHOR]

School reentry after inpatient psychiatric hospitalization requires careful coordination between multiple team members to ensure stability across transitions, given documented negative academic and socioemotional impacts in the post-discharge period. Existing investigations are limited by the fact that no articles examine the perspectives of multiple participant types simultaneously. We conducted a qualitative study of multiple children transitioning out of psychiatric hospitalization and their adult reentry team members, utilizing thematic analysis informed by grounded theory. Across 16 semi-structured interviews, we analyzed perspectives from 17 participants: four children, four parents, five school staff, and four hospital staff. We identified four key themes informing an overarching theory: 1) Centering the socioemotional role of school; 2) Clarifying what constitutes good communication; 3) Reconciling multiple sources of authority; and 4) Navigating limitations with creativity. Together, these themes converge into two new theoretical concepts. First, stereovision represents the synthesis of multiple "lines of sight," which cross to create a densely interactional system. Second, patchworking represents the cobbling together of case-by-case solutions to develop an adequate support plan in the face of multiple limitations or barriers. In conclusion, by incorporating the above four thematic findings into a novel theoretical framework, we argue that when navigating school reentry after psychiatric hospitalization, children and adults must use stereovision and patchworking to create a strong, flexible support fabric. These reflections increase representation of child and adult team member voices in the literature and inform future school–hospital–family partnerships for school reentry after psychiatric hospitalization. [ABSTRACT FROM AUTHOR]

Background: Diagnostic methods for native vertebral osteomyelitis (NVO) often yield inconclusive results. Image-guided spine biopsies for culture are specific but diagnose NVO in only 50% of cases. Pre-exposure to antimicrobials further reduces diagnostic yield. Our study assesses the value of neutrophil percentage in disc space fluid and vertebral body (DS/VB) samples for diagnosing NVO. Methods: Adults referred for spine biopsy at Mayo Clinic from August 2022 to September 2023 were consented and enrolled at the time of biopsy. Following routine specimen collection, the biopsy needle was rinsed in saline into an EDTA tube for cell analysis. NVO diagnosis required organism identification in spine tissue or blood and/or positive histopathology, and consistent symptoms and imaging. Results: Sixty-eight patients were prospectively enrolled, comprising 14 with NVO and 54 with alternative diagnoses. The median biopsy sample polymorphonuclear (PMN) percentage for NVO patients was 80.5% (IQR 72.5–85.2), compared to 64.5% (IQR 54.0–69.0) for those without NVO (p < 0.001). Nine (64.3%) NVO patients received antibiotics within 10 days prior to spine biopsy. As a continuous measure, PMN differential showed a moderately strong ability in classifying NVO status with an area under ROC curve of 0.795; an optimal point on the curve of 71.5% corresponded to a sensitivity of 78.6%, specificity of 79.6%, negative predictive value of 93.5% and positive predictive value of 50.0%. Conclusion: PMN differential in DS/VB biopsies may serve as an effective diagnostic tool in the evaluation of patients with NVO particularly in ambiguous cases with an initially negative spine biopsy. Future efforts will aim to implement these findings within routine clinical practice. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation and atrial flutter represent the most prevalent clinically significant cardiac arrhythmias. While the CHA2DS2-VASc score is commonly used to inform anticoagulation therapy decisions for patients with these conditions, its predictive power is limited. Therefore, we sought to improve risk prediction for left atrial appendage thrombus (LAAT), a known risk factor for stroke in these patients. Methods: We developed and validated an explainable machine learning model using the eXtreme Gradient Boosting algorithm with 5 × 5 nested cross-validation. The primary outcome was to predict the probability of LAAT in patients with atrial fibrillation and atrial flutter who underwent transesophageal echocardiogram prior to cardioversion. Our algorithm used 37 demographic, comorbid, and transthoracic echocardiographic variables. Results: A total of 795 patients were included in our analysis. LAAT was present in 11.3% of the patients. The average age of patients was 63.3 years and 34.7% were women. Patients with LAAT had significantly lower left ventricular ejection fraction (29.9% vs 43.5%; p < 0.001), lower E' lateral velocity (5.7 cm vs. 7.9 cm; p < 0.001) and higher E/A ratio (2.6 vs 1.8; p = 0.002). Our machine learning model achieved a high AUC of 0.79, with a high specificity of 0.82, and modest sensitivity of 0.57. Left ventricular ejection fraction was the most important variable in predicting LAAT. Patients were split into 10 buckets based on the percentile of their predicted probability of having thrombus. The lower the percentile (e.g., 10%), the lower the probability of having thrombus. Using a cutoff point of 0.16 which includes 10.0% of the patients, we can rule out thrombus with 100% confidence. Conclusion: Using machine learning, we refined the predictive power of predicting LAAT and explained the model. These results show promise in providing better guidance for anticoagulation therapy and cardioversion in AF and AFL patients. [ABSTRACT FROM AUTHOR]

Background: Feminizing fronto-orbital reconstruction involves one of four possibilities with the Ousterhout Type III anterior table frontal sinus osteotomy and setback performed in most patients while the Type I reduction recontouring is reserved for patients without frontal sinuses or thick anterior tables. However, patients with frontal sinuses and either a moderately thick anterior table or a shallow frontal sinus in the sagittal plane represent an intermediate morphology. For such morphologies, we introduce the novel Type I+ fronto-orbital reconstruction technique, consisting of frontal bone recontouring supplemented with anterior table reconstruction and split cranial bone graft. Methods: Transgender and gender non-conforming patients who underwent Type I+ or Type III feminizing fronto-orbital reconstruction (2019–2023) were included for retrospective review and comparison of techniques. Results: In the 123 patients (mean age 32.2 ± 9.5 years) included, 6.5% underwent Type I+ and 94.5% underwent Type III feminizing fronto-orbital reconstruction. Morphologically, Type I+ patients displayed a shallower frontal sinus compared to Type III patients (median anterior to posterior table depth 4.1[interquartile range, IQR, 1.1-5.0] versus 9.8[IQR 7.5-12.0]mm, p<0.001). At the maximum prominence, Type I+ patients also demonstrated thicker anterior tables compared to Type III patients (median 6.6[IQR 5.0-8.8] versus 2.2[IQR 0.4-4.7]mm, p=0.001). Patients receiving Type I+ procedures underwent an anterior table reduction of 2.7±1.2mm versus 4.2 ± 1.2mm for Type III procedures in the sagittal plane (p=0.002). Conclusions: The current work introduces a novel solution to an intermediate frontal sinus phenotype for gender-affirming facial feminization surgery. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

The La Prele site (ca. 12,940 cal BP) is a deeply buried, single-component mammoth kill and campsite in Wyoming (USA). The site was discovered eroding from a creek bank 3 m deep within a 7-m tall terrace scarp, and prior investigations have primarily focused on excavations accessible from the creek bank, using heavy machinery to remove sterile overburden to access the deeply buried deposits. This approach has allowed excavations to occur safely outside of deep pits, but it has limited our ability to assess the total size and density of the site. To determine total site extent, we conducted systematic bucket auger testing of the La Prele site terrace, attempting 189 augers between 1.6 m and 6.2 m deep across the landform. We use a simulation and other mathematical procedures to infer artifact density from auger artifact counts and interpolate artifact densities across the site using GIS. We determine that La Prele is around 4500 m2 in area and likely contains a buried bison bonebed and two additional artifact concentrations comparable to or exceeding the size and density of previously excavated areas. We use these insights to infer Early Paleoindian group size, concluding that around 30 people occupied La Prele. [ABSTRACT FROM AUTHOR]

Patient-reported outcomes (PROs) are crucial endpoints in multiple myeloma (MM) randomized controlled trials (RCTs), yet there is significant variability in their methodology and reporting. Our study aimed to (a) identify the most commonly pre-specified PRO domains in MM RCTs and those most responsive to modern therapies, and (b) examine the association between PROs and progression-free survival (PFS)/overall survival (OS). We performed a systematic review of MM RCTs that used EORTC QLQ-C30 and published between 01/2014–06/2023. The association between PFS/OS and PRO was explored using Fisher's exact test or Pearson's Chi-squared test. Thirty-five RCTs were identified, with PROs as secondary or exploratory endpoints in all studies. About one-third of RCTs (n=11, 31.4%) pre-specified at least one EORTC QLQ-C30 domain, with the most common domains being Global health status/Quality of life (GHS/QoL) (n = 10, 90.9%), Physical Functioning (n = 6, 54.5%), Fatigue (n = 6, 54.5%), and Pain (n = 6, 54.5%). A statistically significant and/or clinically meaningful difference in at least one EORTC QLQ-C30 domain between arms was seen in 23/35 trials (65.7%), with the most common domains showing improvement being GHS/QoL (12/23 trials), Pain (11/23 trials), Fatigue (9/23 trials), and Physical Functioning (9/23 trials). PRO was noted to be concordant with PFS in 19/33 (57.6%) trials (p = 0.398), and with OS in 22/31 (71%) trials (p = 0.018). Our study identified key PRO domains that can be potentially used as primary endpoint in MM RCTs. Additionally, significant association between PROs and OS highlight the importance of integrating PROs to better capture treatment efficacy. [ABSTRACT FROM AUTHOR]

This study explores the role of individual and local marriage market characteristics in whether recently wed U.S. residents "imported" a spouse instead of marrying someone already present in the country. Our findings indicate that U.S. natives and immigrants whose spouse is a "marriage migrant" (someone who arrived in the U.S. the same year as the marriage occurred) are positively selected along some dimensions but negatively along others. The results also suggest that U.S. immigration policy plays an important role in whether immigrants bring in a spouse. We further investigate the trade-offs in spouse characteristics associated with having a marriage-migrant spouse. Marriage-migrant spouses are more likely than other spouses to have characteristics that their spouse may find desirable, such as being relatively younger and less likely to have been previously married. Among naturalized citizens, differences in spousal characteristics between marriage migrants and other spouses are notably large, showcasing the desirability of someone who can easily sponsor a spouse for permanent residence. [ABSTRACT FROM AUTHOR]

The article discusses the impact of global climate change on aquatic ecosystems, emphasizing the vulnerability of water bodies to climate-induced changes. It highlights the challenges faced by freshwater management in adapting to uncertain climatic conditions and the need for scientists to contribute to climate-proof water management. The text also underscores the importance of proactive climate adaptation strategies, reliable forecasts, and multi-level approaches to sustain aquatic ecosystems and ensure human well-being. The article concludes by advocating for new adaptation strategies, robust engineering solutions, and science-based decision-making to address the challenges posed by climate change. [Extracted from the article]

Phytoplankton blooms create harmful toxins, scums, and taste and odor compounds and thus pose a major risk to drinking water safety. Climate and land use change are increasing the frequency and severity of blooms, motivating the development of new approaches for preemptive, rather than reactive, water management. While several real-time phytoplankton forecasts have been developed to date, none are both automated and quantify uncertainty in their predictions, which is critical for manager use. In response to this need, we outline a framework for developing the first automated, real-time lake phytoplankton forecasting system that quantifies uncertainty, thereby enabling managers to adapt operations and mitigate blooms. Implementation of this system calls for new, integrated ecosystem and statistical models; automated cyberinfrastructure; effective decision support tools; and training for forecasters and decision makers. We provide a research agenda for the creation of this system, as well as recommendations for developing real-time phytoplankton forecasts to support management. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of prophylactic mesh placement in reducing the incidence of parastomal hernias following colostomy, ileostomy, and ileal conduit formation. Methods: A systematic review identified relevant studies evaluating parastomal hernia incidence with prophylactic mesh use during stoma formation. Pairwise meta-analysis and network meta-analysis using Bayesian modeling were performed. Results: 25 studies, consisting of 16 randomized control trials (RCT), 6 follow up studies, and 3 retrospective cohort studies, were included. Prophylactic mesh led to significantly fewer parastomal hernias beyond 6 months follow-up (OR 0.43, 95% CI 0.33–0.58). Hernias were reduced with mesh for both ileal conduits and colostomies. When analyzing hazard ratios (HRs), only 6 studies were included, and a statistically significant difference was observed among both randomized controlled trials (RCTs) (HR 0.75 [0.53, 0.92], p = 0.01) and non-RCTs (HR 0.57 [0.36, 0.92], p = 0.02). Network meta-analysis found the retromuscular approach with mesh had the lowest hernia rate. Regression was non-significant for variations between study types. Conclusion: This meta-analysis demonstrated prophylactic mesh placement during ostomy creation significantly reduced parastomal hernia risk, more prominently beyond 6 months, consistently across randomized trials and observational studies for urologic and gastrointestinal ostomies. The retromuscular technique was most effective. [ABSTRACT FROM AUTHOR]

School refusal (SR) is a form of school attendance problem (SAP) that requires specific mental health care. Despite improvements in the definition of SAPs, the course of SR is not well characterized. To explore three-year patterns of SR course in children, as reported by their parents, we deployed an anonymous web-based survey. We defined SR onset as the absence of ≥ 2 school weeks during one academic year, combined with emotional distress. We defined standard SR trajectories using sequence analysis of parents' recollection of three consecutive years of school attendance. We obtained 1970 responses, 1328 (67%) completed by a parent and meeting the definition of SR. Of these, 729 (55%) responses included three years of school attendance recollection. We identified five prototypical trajectories of SR: two profiles for children: beaded absences (n = 272), and rapid recovery (n = 132); and three for adolescents: prolonged recovery (n = 93), gradual decline (n = 89), and rapid decline (n = 143). We found five distinct trajectories of retrospective recall of SR course. Through pattern recognition, this typology could help with timely identification of SR and implementation of evidence-based interventions to optimize outcomes. Prospective replication of these findings and their field application is warranted. [ABSTRACT FROM AUTHOR]

Erythroderma, an inflammatory skin condition characterized by widespread erythema with variable degrees of exfoliation, pustulation, or vesiculobullous formation, is associated with high morbidity and mortality. Determining the underlying cause of erythroderma frequently presents a diagnostic challenge, which may contribute to the condition's relatively poor prognosis. This review covers the clinical presentation, pathophysiology, diagnosis, and treatment of erythroderma. It discusses similarities and differences among the many underlying etiologies of the condition and differences between erythrodermic and non-erythrodermic presentations of the same dermatosis. Finally, this article explores current research that may provide future tools in the diagnosis and management of erythroderma. [ABSTRACT FROM AUTHOR]

Australian tidal wetlands differ in important respects to better studied northern hemisphere systems, an artefact stable to falling sea levels over millennia. A network of Surface Elevation Table-Marker Horizon (SET-MH) monitoring stations has been established across the continent to assess accretionary and elevation responses to sea-level rise. This network currently consists of 289 SET-MH installations across all mainland Australian coastal states and territories. SET-MH installations are mostly in mangrove forests but also cover a range of tidal marsh and supratidal forest ecosystems. Mangroves were found to have higher rates of accretion and elevation gain than all the other categories of tidal wetland, a result attributable to their lower position within the tidal frame (promoting higher rates of accretion) higher biomass (with potentially higher rates of root growth), and lower rates of organic decomposition. While Australian tidal marshes in general show an increase in elevation over time, in 80% of locations, this was lower than the rate of sea-level rise. High rates of accretion did not translate into high rates of elevation gain, because the rate of subsidence in the shallow substrate increased with higher accretion rates (r2 = 0.87). The Australian SET-MH network, already in many locations spanning two decades of measurement, provides an important benchmark against which to assess wetland responses to accelerating sea-level rise in the decades ahead. [ABSTRACT FROM AUTHOR]

Background: Atypical intradermal smooth muscle neoplasm, also commonly termed cutaneous leiomyosarcoma, is a soft tissue tumor with a low risk of aggressive behavior. These lesions arise in the dermis with possible superficial subcutaneous extension, demonstrate cytologic atypia, and often show mitotic activity. Methods: A retrospective review of patient demographics, tumor characteristics, and treatment methods was conducted in a consecutive series of patients presenting to MD Anderson Cancer Center (MDACC) from 2002 to 2021 (n = 95). All pathology was reviewed by MDACC pathologists and determined to be atypical intradermal smooth muscle neoplasm. Results: Median age at diagnosis was 58 years (range 22–86), and 74% were male. Ninety-five percent (n = 90) of patients identified as White, non-Hispanic. Most tumors were slow-growing, solitary, and painless nodules. Tumors were in the lower extremities (44.2%), followed by the upper extremity (28.4%), trunk (22.1%), and head and neck (5.2%). All patients (n = 44, 46.3%) who had a punch/incisional biopsy for diagnostic purposes had a subsequent tumor excision. Unplanned excision or excisional biopsy was performed on the remaining 46 (48%) patients. Of this subset, 41 of the 46 aforementioned patients (89%) had positive margins and underwent re-excision. Final pathology in 25/38 (66%) re-excision specimens was negative for residual tumor despite an initial positive margin. Two patients in the cohort had local recurrence 2 and 3 years after initial surgery. Both patients had positive margins, underwent excision of the recurrent tumor, and remain free of disease. After median follow-up of 6.9 years (range 1 day–18 years), 5-year recurrence-free survival was 96% and overall survival (OS) of the entire cohort was 78%. Conclusion: In this study of consecutive patients presenting with atypical intradermal smooth muscle neoplasm, we found good OS and local control after definitive surgical excision with negative margins, including excisional biopsy with close margins. Atypical intradermal smooth muscle neoplasm is unlikely to metastasize and has an excellent prognosis. Guidelines to determine optimal surveillance strategies for these patients should be revisited. [ABSTRACT FROM AUTHOR]

Purpose: Symptom management among patients diagnosed with advanced cancer is a high priority in clinical care that often involves the support of a family caregiver. However, limited studies have examined parallel patient and caregiver symptom burden and associations with their own and each other's quality of life (QOL). This study seeks to identify patient and caregiver symptom clusters and investigate associations between identified clusters and demographic, clinical, and psychosocial factors (cognitive appraisals and QOL). Methods: This study was a secondary analysis of self-reported baseline survey data collected from a randomized clinical trial of 484 adult advanced cancer patients and their caregivers. Latent class analysis and factor analysis were used to identify symptom clusters. Bivariate statistics tested associations between symptom clusters and demographic, clinical, and psychosocial variables. Results: The most prevalent symptom for patients was energy loss/fatigue and for caregivers, mental distress. Low, moderate, and high symptom burden subgroups were identified at the patient, caregiver, and dyad level. Age, gender, race, income, chronic conditions, cancer type, and treatment type were associated with symptom burden subgroups. Higher symptom burden was associated with more negative appraisals of the cancer and caregiving experience, and poorer QOL (physical, social, emotional, functional, and overall QOL). Dyads whose caregivers had more chronic conditions were more likely to be in the high symptom burden subgroup. Conclusion: Patient and caregiver symptom burden influence their own and each other's QOL. These findings reinforce the need to approach symptom management from a dyadic perspective. [ABSTRACT FROM AUTHOR]

The cultural construal of leadership as masculine impedes women's attainment of leader roles. This research examined whether adding feminine demands to a leader role relieved the greater stress experienced by women than men in a job interview for a leadership position and considered the processes that mediated women's less favourable interview outcomes. In a hiring simulation, management students (N = 209; 112 women, 97 men) interviewed for a leader role framed by either stereotypically feminine or masculine role requirements. As shown by the stress biomarker salivary cortisol, the feminine role framing alleviated women's, but not men's, physiological stress response during the interview. However, under both masculine and feminine role framing, women, compared with men, reported lesser fit, expected poorer interview performance, appraised greater threat relative to challenge, and evaluated their performance less favourably, as did external raters. An additional vignette study (N = 305; 189 women, 111 men, 5 diverse) found that the feminine role framing increased the leader role's communal demands but still conveyed strong agentic demands not different from those of the masculine role. In conclusion, although a feminine role framing alleviated women's physiological stress response, it did not change their less favourable outcomes, as indicated by participants' self-reports and others' reports. [ABSTRACT FROM AUTHOR]

Purpose: To describe program characteristics and outcomes of a residential substance use recovery program serving pregnant and parenting women in a rural and urban location. Description: This assessment of administrative records from April 1, 2020 through March 31, 2022, included women in a rural (n = 140) and urban (n = 321) county in Kentucky. Assessment: This retrospective case study used descriptive and non-parametric analyses to assess the population and examine differences between locations, race, and ethnicity for women served. Logistic regression tested predictors of goal achievement by community. Of 461 women served, 65 (14.1%) delivered a baby while in treatment; 62 of which were considered healthy. 13% of the women were Black, 83.1% non-Hispanic (NH) white, and 3.7% were other races/biracial; 1.3% were Hispanic. The mean age was 30.92 years (SD 6.23) and treatment duration was 90.11 days (SD 67.70). Program goals were achieved by 312 (67.7%). There were no differences in rates of goal achievement or treatment duration by race, ethnicity, or age and no difference in the rate of achievement by location in univariate analyses. However, treatment duration was positively associated with program success in both communities. In the urban community, Black women were 8% more likely to successfully complete the program compared to NH white women (OR = 9.77 [95% CI 1.21,79.18; p = 0.033]) after controlling for confounders. Insufficient sample size for non-white women in the rural community prohibited evaluation. Conclusions: Duration of time in the program best predicted successful completion for women in recovery. These findings have policy implications. Significance: Women having difficulties with substance use are typically of childbearing age. Integrated programs are needed to address the multi-factorial needs of these women. Models suggest that optimal care involves services that are co-located or closely aligned. The current evaluation contributes to the literature by examining outcomes for women in recovery. This case study examines client outcomes at a community-based residential treatment program and found evidence that the length of stay was associated with achievement of program goals. Lastly, contrary to previous reports, Black women in an urban community had an 8% greater probability of successful completion compared to white women. [ABSTRACT FROM AUTHOR]

Obesity-induced β cell dysfunction contributes to the onset of type 2 diabetes. Nevertheless, elucidating epigenetic mechanisms underlying islet dysfunction at single cell level remains challenging. Here we profile single-nuclei RNA along with enhancer marks H3K4me1 or H3K27ac in islets from lean or obese mice. Our study identifies distinct gene signatures and enhancer states correlating with β cell dysfunction trajectory. Intriguingly, while many metabolic stress-induced genes exhibit concordant changes in both H3K4me1 and H3K27ac at their enhancers, expression changes of specific subsets are solely attributable to either H3K4me1 or H3K27ac dynamics. Remarkably, a subset of H3K4me1+H3K27ac- primed enhancers prevalent in lean β cells and occupied by FoxA2 are largely absent after metabolic stress. Lastly, cell-cell communication analysis identified the nerve growth factor (NGF) as protective paracrine signaling for β cells through repressing ER stress. In summary, our findings define the heterogeneous enhancer responses to metabolic challenges in individual β cells. β cell dysfunction contributes to the onset of type 2 diabetes. Here the authors profile single-nuclei RNA along with enhancer marks H3K4me1 or H3K27ac in islets and suggest highly heterogeneous enhancer states in response to metabolic challenges. [ABSTRACT FROM AUTHOR]

Background: It is unclear how patient-reported outcomes (PROs) change longitudinally after breast cancer surgery. We sought to compare trends in PROs among patients who underwent lumpectomy versus mastectomy over the first year after surgery. Patients and Methods: Newly diagnosed stage 0–III female patients with breast cancer who underwent lumpectomy or mastectomy at an academic breast center between June 2019 and March 2023 were invited to participate in a longitudinal PRO study. Enrolled patients received the BREAST-Q™ module, a validated tool measuring domains, such as satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. Scores for each domain were compared between the lumpectomy and mastectomy groups over the first year after surgery. Linear mixed models were used to estimate the change in PRO scores over time. Results: The cohort included 203 who underwent lumpectomy and 144 who underwent mastectomy. Patients who underwent lumpectomy were older, more likely to receive adjuvant radiation and endocrine therapy, and less likely to receive adjuvant chemotherapy. Patients who underwent lumpectomy demonstrated greater increases in scores over time for satisfaction with breasts, psychosocial well-being, and sexual well-being compared with patients who underwent mastectomy, after adjusting for the abovementioned covariates and receipt of reconstruction. The lumpectomy group had a larger decline in physical well-being over time compared with the mastectomy group. Conclusions: Patients who underwent lumpectomy demonstrated greater satisfaction with their breasts, psychosocial well-being, and sexual well-being but worse physical well-being over the first year after surgery compared with patients who underwent mastectomy. These results may help inform early-stage breast cancer patients making decisions about their surgical care. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 JN.1 with an additional L455S mutation on spike when compared with its parental variant BA.2.86 has outcompeted all earlier variants to become the dominant circulating variant. Recent studies investigated the immune resistance of SARS-CoV-2 JN.1 but additional factors are speculated to contribute to its global dominance, which remain elusive until today. Here, we find that SARS-CoV-2 JN.1 has a higher infectivity than BA.2.86 in differentiated primary human nasal epithelial cells (hNECs). Mechanistically, we demonstrate that the gained infectivity of SARS-CoV-2 JN.1 over BA.2.86 associates with increased entry efficiency conferred by L455S and better spike cleavage in hNECs. Structurally, S455 altered the mode of binding of JN.1 spike protein to ACE2 when compared to BA.2.86 spike at ACE2H34, and modified the internal structure of JN.1 spike protein by increasing the number of hydrogen bonds with neighboring residues. These findings indicate that a single mutation (L455S) enhances virus entry in hNECs and increases immune evasiveness, which contribute to the robust transmissibility of SARS-CoV-2 JN.1. We further evaluate the in vitro and in vivo virological characteristics between SARS-CoV-2 BA.2.86/JN.1 and EG.5.1/HK.3, and identify key lineage-specific features of the two Omicron sublineages that contribute to our understanding on Omicron antigenicity, transmissibility, and pathogenicity. Here, the authors show that a single mutation in JN.1 spike, L455S, confers better spike cleavage and enhances virus infectivity in differentiated primary human nasal epithelial cells while increasing immune evasiveness, contributing to the efficient spread of JN.1. [ABSTRACT FROM AUTHOR]

Purpose: Cancer care for lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other sexuality and gender diverse (LGBTQIA +) individuals is marked by disparities stemming from a history of discrimination, stigma, and systemic inequities. For LGBTQIA + individuals seeking cancer care, cancer center websites may be a first point of contact with healthcare. Two complementary studies sought to evaluate the LGBTQIA + inclusivity of cancer centers’ websites. Methods: The authors conducted two studies in 2022–2023, reviewing the websites of National Cancer Institute (NCI)-designated cancer centers and Children’s Oncology Group (COG)-designated health systems and cancer centers. Reviewers manually searched websites and coded several Yes/No criteria for LGBTQIA + inclusivity. Results: Among the 65 NCI cancer centers’ websites in 2023, 66% included a nondiscrimination statement, 71% mentioned LGBTQIA + health disparities, 65% included LGBTQIA + tailored resources, and 66% had articles about LGBTQIA + health. There was a trend of increased inclusivity across categories from 2022 to 2023. Among the 204 COG-designated health system websites in 2023, there were 60 pediatric care websites and 144 lifespan care websites. A total of 79.9% of COG health system websites referenced LGBTQIA + patients (80.0% of pediatric and 79.9% of lifespan sites), 16.7% of COG cancer center websites referenced LGBTQIA + patients in the context of cancer care (6.7% of pediatric and 20.8% of lifespan sites), and 82.4% yielded results when search terms were input (83.3% of pediatric and 81.9% of lifespan sites). Conclusions: Adult and pediatric cancer centers’ websites have varying levels of LGBTQIA + inclusivity based on nondiscrimination statements, articles, and the availability of LGBTQIA + resources. While there have been some improvements in inclusivity on the NCI-designated cancer centers’ websites between 2022 and 2023, there is a need for further improvement. [ABSTRACT FROM AUTHOR]

Purpose: The emergency midline laparotomy is a commonly performed procedure with a burst abdomen being a critical surgical complication requiring further emergency surgery. This study aimed to investigate the clinical outcomes of patients with burst abdomen after emergency midline laparotomy. Methods: A single-center, prospective, observational cohort study of patients undergoing emergency midline laparotomy during a two-year period was done. Abdominal wall closure followed a standardized technique using monofilament, slowly absorbable suture in a continuous suturing technique with a suture-to-wound ratio of at least 4:1. Treatment of burst abdomen was surgical. Data, including intra-hospital postoperative complications, were collected and registered chronologically based on journal entries. The primary outcome was to describe postoperative complications, length of stay, and the overall morbidity based on the Comprehensive Complication Index (CCI), stratified between patients who did and did not suffer from a burst abdomen during admission. Results: A total of 543 patients were included in the final cohort, including 24 patients with burst abdomen during admission. The incidence of burst abdomen after emergency midline laparotomy was 4.4%. Patients with a burst abdomen had a higher total amount of complications per patient (median of 3, IQR 1.3–5.8 vs. median of 1, IQR 0.0–3.0; p = 0.001) and a significantly higher CCI (median of 53.0, IQR 40.3–94.8 vs. median of 21.0, IQR 0.0–42.0; p = < 0.001). Conclusion: Patients with burst abdomen had an increased risk of postoperative complications during admission as well as a longer and more complicated admission with multiple non-surgical complications. [ABSTRACT FROM AUTHOR]

Purpose: Cancer registries offer an avenue to identify cancer clusters across large populations and efficiently examine potential environmental harms affecting cancer. The role of known metal carcinogens (i.e., cadmium, arsenic, nickel, chromium(VI)) in breast and colorectal carcinogenesis is largely unknown. Historically marginalized communities are disproportionately exposed to metals, which could explain cancer disparities. We examined area-based metal exposures and odds of residing in breast and colorectal cancer hotspots utilizing state tumor registry data and described the characteristics of those living in heavy metal-associated cancer hotspots. Methods: Breast and colorectal cancer hotspots were mapped across Kentucky, and area-based ambient metal exposure to cadmium, arsenic, nickel, and chromium(VI) were extracted from the 2014 National Air Toxics Assessment for Kentucky census tracts. Among colorectal cancer (n = 56,598) and female breast cancer (n = 77,637) diagnoses in Kentucky, we used logistic regression models to estimate Odds Ratios (ORs) and 95% Confidence Intervals to examine the association between ambient metal concentrations and odds of residing in cancer hotspots, independent of individual-level and neighborhood risk factors. Results: Higher ambient metal exposures were associated with higher odds of residing in breast and colorectal cancer hotspots. Populations in breast and colorectal cancer hotspots were disproportionately Black and had markers of lower socioeconomic status. Furthermore, adjusting for age, race, tobacco and neighborhood factors did not significantly change cancer hotspot ORs for ambient metal exposures analyzed. Conclusion: Ambient metal exposures contribute to higher cancer rates in certain geographic areas that are largely composed of marginalized populations. Individual-level assessments of metal exposures and cancer disparities are needed. [ABSTRACT FROM AUTHOR]

Introduction: Mechanical forces provide critical biological signals to cells. Within the distal lung, tensile forces act across the basement membrane and epithelial cells atop. Stretching devices have supported studies of mechanical forces in distal lung epithelium to gain mechanistic insights into pulmonary diseases. However, the integration of curvature into devices applying mechanical forces onto lung epithelial cell monolayers has remained challenging. To address this, we developed a hammock-shaped platform that offers desired curvature and mechanical forces to lung epithelial monolayers. Methods: We developed hammocks using polyethylene terephthalate (PET)-based membranes and magnetic-particle modified silicone elastomer films within a 48-well plate that mimic the alveolar curvature and tensile forces during breathing. These hammocks were engineered and characterized for mechanical and cell-adhesive properties to facilitate cell culture. Using human small airway epithelial cells (SAECs), we measured monolayer formation and mechanosensing using F-Actin staining and immunofluorescence for cytokeratin to visualize intermediate filaments. Results: We demonstrate a multi-functional design that facilitates a range of curvatures along with the incorporation of magnetic elements for dynamic actuation to induce mechanical forces. Using this system, we then showed that SAECs remain viable, proliferate, and form an epithelial cell monolayer across the entire hammock. By further applying mechanical stimulation via magnetic actuation, we observed an increase in proliferation and strengthening of the cytoskeleton, suggesting an increase in mechanosensing. Conclusion: This hammock strategy provides an easily accessible and tunable cell culture platform for mimicking distal lung mechanical forces in vitro. We anticipate the promise of this culture platform for mechanistic studies, multi-modal stimulation, and drug or small molecule testing, extendable to other cell types and organ systems. [ABSTRACT FROM AUTHOR]

Declining physical function with aging is associated with structural and functional brain network organization. Gaining a greater understanding of network associations may be useful for targeting interventions that are designed to slow or prevent such decline. Our previous work demonstrated that the Short Physical Performance Battery (eSPPB) score and body mass index (BMI) exhibited a statistical interaction in their associations with connectivity in the sensorimotor cortex (SMN) and the dorsal attention network (DAN). The current study examined if components of the eSPPB have unique associations with these brain networks. Functional magnetic resonance imaging was performed on 192 participants in the BNET study, a longitudinal and observational trial of community-dwelling adults aged 70 or older. Functional brain networks were generated for resting state and during a motor imagery task. Regression analyses were performed between eSPPB component scores (gait speed, complex gait speed, static balance, and lower extremity strength) and BMI with SMN and DAN connectivity. Gait speed, complex gait speed, and lower extremity strength significantly interacted with BMI in their association with SMN at rest. Gait speed and complex gait speed were interacted with BMI in the DAN at rest while complex gait speed, static balance, and lower extremity strength interacted with BMI in the DAN during motor imagery. Results demonstrate that different components of physical function, such as balance or gait speed and BMI, are associated with unique aspects of brain network organization. Gaining a greater mechanistic understanding of the associations between low physical function, body mass, and brain physiology may lead to the development of treatments that not only target specific physical function limitations but also specific brain networks. [ABSTRACT FROM AUTHOR]

The shift to higher orbits requires larger space structures that are assembled on-orbit. These large space structures experience problematic vibrations at low frequencies, especially during robotic assembly in space. Beyond active vibration control, which is expensive and often infeasible, current passive mitigation strategies are limited. Here, struts of the space frame are transformed to resonant metamaterials via periodically placed resonators along their length, providing a pathway for energy exhaustion. Simple and multi-degree of freedom resonators were successfully applied to struts to mitigate vibrations of frequencies <500 Hz. In frames, a dependence on resonator layout relative to the excitation point is demonstrated. [ABSTRACT FROM AUTHOR]

Using ex vivo microscopy, virtual pathology can improve histological procedures by providing pathology images in near real-time without tissue destruction. Several emerging and promising approaches leverage fast-acting small-molecule fluorescent stains to replicate traditional pathology structural contrast, combined with rapid optical sectioning microscopes. However, several vital challenges must be addressed to translate virtual pathology into the clinical environment. One such challenge is selecting robust, reliable, and repeatable staining protocols that can be adopted across institutions. In this work, we addressed the effects of dye selection and staining protocol on image quality in rapid point-of-care imaging settings. For this purpose, we used structured illumination microscopy to evaluate fluorescent dyes currently used in the field of ex vivo virtual pathology, in particular, studying the effects of staining protocol and temporal and photostability on image quality. We observed that DRAQ5 and SYBR gold provide higher image quality than TO-PRO3 and RedDot1 in the nuclear channel and Eosin Y515 in the extracellular/cytoplasmic channel than Atto488. Further, we found that TO-PRO3 and Eosin Y515 are less photostable than other dyes. Finally, we identify the optimal staining protocol for each dye and demonstrate pan-species generalizability. [ABSTRACT FROM AUTHOR]