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Background: Senescent immune cells exhibit altered gene expression and resistance to apoptosis. The prevalence of these cells increases with age and emerging data implicate senescence-associated maladaptive signaling as a potential contributor to sepsis and septic shock. The senolytic drug fisetin promotes clearance of senescent cells and is hypothesized to mitigate septic responses to infection. Methods: We are conducting a multi-center, randomized, double-blinded, adaptive allocation phase 2 clinical trial to assess the efficacy of the senolytic drug fisetin in preventing clinical deterioration of elderly patients diagnosed with sepsis. We intend to enroll and randomize 220 elderly patients (age > 65) with the clinical diagnosis of sepsis to receive either fisetin as a single oral dose of 20 mg/kg, fisetin in two oral doses of 20 mg/kg each spaced 1 day apart, or placebo. The primary outcome will be changed in the composite of cardiovascular, respiratory, and renal sequential organ failure assessment scores at 7 days from enrollment. Secondary outcomes include quantification of senescent CD3 + cells at 7 days, and 28-day assessments of organ failure-free days, days in an intensive care unit, and all-cause mortality. Discussion: This multi-center, randomized, double-blinded trial will assess the efficacy of fisetin in preventing clinical deterioration in elderly patients with sepsis and measure the effects of this drug on the prevalence of senescent immune cells. We intend that the results of this phase 2 trial will inform the design of a larger phase 3 study. Trial registration: This trial is registered to ClinicalTrials.gov under identifier NCT05758246, first posted on March 7, 2023. [ABSTRACT FROM AUTHOR]

Purpose: Loddo et al. (Br J Cancer 100:959–70, 2009) established the prognostic significance of cell cycle markers and "Cell-Cycle Phenotypes" in breast carcinoma. This study aims to 1) identify prognostic cell-cycle markers in sarcoma, and 2) assess the prognostic potential of specific cell-cycle phenotypes in sarcoma. Methods: Tissue samples from 128 soft tissue sarcomas were stained for four cell cycle-specific markers: Mcm2, Geminin, Plk1, and H3S10ph. Only primary soft tissue tumors (liposarcoma, leiomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma) were included in the analysis. Any tumor coming from a recurrent or metastatic lesion were excluded from the analysis. Three cell-cycle phenotypes (I, II, III) were derived from marker expression patterns. Prognostic significance was evaluated in a subset of primary soft tissue sarcomas using Cox regression for survival analysis. Results: Compared to phenotype I, the phenotype III tumors had a decreased 5-year overall survival (HR 6.81 [2.36–19.61]; p = < 0.001), 5-year disease-free survival (HR 1.07 (1.02–1.18); p = 0.004), and 5-year metastasis-free survival (HR 4.34 [1.58–11.93]; p = 0.004). High expression of Plk1 was associated with decreased 5-year overall survival (HR: 4.04 CI [1.21–6.67; p = 0.02) and 5-year metastasis-free survival (HR: 2.91 CI [1.15–7.37]; p = 0.03). Geminin was also found to have a decreased 5-year overall survival (HR:2.84 CI [1.21–6.67]; p = 0.02). No statistical difference in prognostication were noted between phenotypes and the AJCC system. Conclusions: We identified three unique sarcoma cell cycle phenotypes that have prognostic significance. This performs similarly to the AJCC staging system. [ABSTRACT FROM AUTHOR]

Background: Chronic idiopathic constipation (CIC) is a disorder of gut–brain interaction characterized by a variety of bowel movement‐related and abdominal symptoms. A greater understanding of medication use and satisfaction with symptom control may provide insights to optimize patient care. Therefore, we explored these aspects of the disorder in adults with CIC. Methods: This study assessed data collected from a large nationwide survey of adult participants in the United States, querying demographics, clinical characteristics, and comorbid conditions, as well as medication use, care‐seeking behaviors, and satisfaction with symptom control. Participants were grouped into the CIC cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported. Key Results: Two thousand five hundred and thirty‐three participants with CIC were matched 1:1 to controls. In the CIC cohort, abdominal pain was the most reported symptom leading to medication use: 15.9% of respondents were receiving a prescription medication in addition to an over‐the‐counter medication, while 26.3% were taking neither. In addition, only one‐third were satisfied with the control of their symptoms; however, satisfaction was significantly higher in respondents taking a prescription medication (p < 0.001). The proportion of reported comorbidities was significantly higher in the CIC cohort versus the control cohort, with chronic pain, anxiety, and depression among the highest (p < 0.001 for all). Conclusions and Inferences: This study emphasizes the need for better communication regarding prescription medications and their benefits, with the goal of further improving CIC patients' overall symptoms. [ABSTRACT FROM AUTHOR]

Background: Activation of β2 adrenergic receptors reduces cutaneous mechanical pain thresholds in rats. While β2 adrenergic receptor activation may contribute to mechanisms that underlie temporomandibular joint pain, its effect on masticatory muscle pain sensitivity is uncertain. Objectives: The current study sought to determine the extent to which β adrenergic receptors are expressed by masticatory muscle afferent fibres, and to assess the effect of local activation of these receptors on the mechanical sensitivity of masticatory muscle afferent fibres in rats. Methods: Trigeminal ganglion neurons that innervate the rat (n = 12) masseter muscle and lower lip were identified by tissue injection of fluorescent dyes and were then stained with antibodies against β1 or β2 adrenergic receptors. Extracellular recordings from 60 trigeminal ganglion neurons that innervate the masticatory muscle were undertaken in a second group of anaesthetised rats of both sexes (n = 37) to assess afferent mechanical activation thresholds. Thresholds were assessed before and after injection of the β adrenergic receptor agonists into masticatory muscle. Results: β1 and β2 adrenergic receptor expression was greater in labial skin than in masticatory muscle ganglion neurons (p <.05, one‐way ANOVA, Holm–Sidak test). There was a higher expression of β2 adrenergic receptors in masticatory muscle ganglion neurons in males than in females. The mixed β agonist isoproterenol increased afferent mechanical activation threshold in male but not female rats (p <.05, Mann–Whitney test). In male rats, salbutamol, a β2 selective agonist, also increased afferent mechanical activation threshold but hydralazine, a vasodilator, did not (p <.05, Mann–Whitney test). Conclusion: Activation of β2 adrenergic receptors decreases the mechanical sensitivity of masticatory muscle afferent fibres in a sex‐related manner. [ABSTRACT FROM AUTHOR]

Background/Objectives: Glucagon-like peptide-1 agonists (GLP1As) are increasingly prescribed to treat obesity. While studies document how these medications impact dietary habits, their relationship to consumer food waste is unexplored. Approximately one-third of all food is wasted, which creates substantial economic and environmental damage. The purpose of this study is to assess how consumers alter food waste after beginning GLP1As and to identify factors associated with this relationship. Methods: Retrospectively reported changes in the amount of food wasted since beginning a GLP1A are gathered from a sample of 505 U.S. consumers via a self-administered online survey. Regression analysis yields associations between changes in post-GLP1A-uptake food waste and the length and type of medication use, medication side effects, post-uptake changes in dietary habits, and respondent characteristics. Results: A total of 25% of respondents agree they waste more food since beginning the medication, while 61% disagree. Respondents are significantly less likely to agree with this statement if they have been on the medication a longer time and are significantly more likely to agree if they reported experiencing nausea since beginning the medication. Dietary changes consistent with more vegetable intake are also significantly associated with less waste. Conclusions: Uptake of a novel class of anti-obesity medications may significantly affect food waste patterns. With the potential for widespread adoption of such medications, and given the societal import of reducing food waste, understanding the interaction of these two consumer trends is critical for projecting their joint impact on the food system and for equipping new GLP1A users to limit food waste. [ABSTRACT FROM AUTHOR]

Human exploration of the solar system will expose crew members to galactic cosmic radiation (GCR), with a potential for adverse health effects. GCR particles (protons and ions) move at nearly the speed of light and easily penetrate space station walls, as well as the human body. Previously, we have shown reactivation of latent herpesviruses, including herpes simplex virus, Varicella zoster virus, Epstein–Barr virus, and cytomegalovirus (CMV), during stays at the International Space Station. Given the prevalence of latent CMV and the known propensity of space radiation to cause alterations in many cellular processes, we undertook this study to understand the role of GCR in reactivating latent CMV. Latently infected Kasumi cells with CMV were irradiated with 137Cs gamma rays, 150 MeV protons, 600 MeV/n carbon ions, 600 MeV/n iron ions, proton ions, and simulated GCR. The CMV copy number increased significantly in the cells exposed to radiation as compared with the non-irradiated controls. Viral genome sequencing did not reveal significant nucleotide differences among the compared groups. However, transcriptome analysis showed the upregulation of transcription of the UL49 ORF, implicating it in the switch from latent to lytic replication. These findings support our hypothesis that GCR may be a strong contributor to the reactivation of CMV infection seen in ISS crew members. [ABSTRACT FROM AUTHOR]

Objective: US Hispanics have several health disparities, greater tobacco/nicotine-related illnesses, lower access to smoking cessation, and lower rates of cessation. Understanding cultural constructs linked to tobacco/nicotine use may provide a greater understanding of future cultural adaptations of cessation interventions. This study used a multidimensional acculturation framework, with cultural practices, identity, and values, to test links between measures of acculturation stress, multidimensional acculturation (language-based enculturation and acculturation, cultural identity, familism), and tobacco/nicotine use, and interactions with gender. Design: Participants were 391 adult Latin American immigrants (69% women); 12% self-reported tobacco/nicotine use in the past six months. Results: Path analysis showed acculturative stress, β =.16, and acculturation, β =.20, were positively related to tobacco/nicotine use. Enculturation, familism, and Hispanic cultural identity were not related to tobacco/nicotine use. There were no significant acculturation by enculturation or gender interactions, but women were less likely to use tobacco/nicotine than men, β = −.36. Conclusion: Findings suggest that tobacco/nicotine cessation interventions for Latino immigrants may be enhanced with an emphasis on the mitigation of acculturative stress, attention to the adoption of US cultural practices, and gender. Future research should examine specific sources of acculturative stress or social norms related to tobacco/nicotine use. [ABSTRACT FROM AUTHOR]

Deformed wing virus (DWV) has long been identified as a critical pathogen affecting honeybees, contributing to colony losses through wing deformities, neurological impairments, and reduced lifespan. Since DWV also affects other pollinators, it poses a significant threat to global pollination networks. While honeybees have been the focal point of DWV studies, emerging research indicates that this RNA virus is not host-specific but rather a generalist pathogen capable of infecting a wide range of insect species, including other bee species such as bumblebees and solitary bees, as well as wasps and ants. This expands the potential impact of DWV beyond honeybees to broader ecological communities. The black imported fire ant, Solenopsis richteri, is an economically important invasive ant species. In this study, we describe deformed wing (DW) symptoms in S. richteri. DW alates were found in three of nine (33%) laboratory colonies. The symptoms ranged from severely twisted wings to a single crumpled wing tip. Additionally, numerous symptomatic alates also displayed altered mobility, ranging from an ataxic gait to an inability to walk. Viral replication of DWV was confirmed using a modified strand-specific RT-PCR. Our results suggest that S. richteri can be an alternative host for DWV, expanding our understanding of DWV as a generalist pathogen in insects. However, additional research is required to determine whether DWV is the etiological agent responsible for DW syndrome in S. richteri. [ABSTRACT FROM AUTHOR]

A major challenge in antiviral antibody therapy is keeping up with the rapid evolution of viruses. Our research shows that nanobodies—single-domain antibodies derived from camelids—can be rapidly re-engineered to combat new viral strains through structure-guided in vitro evolution. Specifically, for viral mutations occurring at nanobody-binding sites, we introduce randomized amino acid sequences into nanobody residues near these mutations. We then select nanobody variants that effectively bind to the mutated viral target from a phage display library. As a proof of concept, we used this approach to adapt Nanosota-3, a nanobody originally identified to target the receptor-binding domain (RBD) of early Omicron subvariants, making it highly effective against recent Omicron subvariants. Remarkably, this adaptation process can be completed in less than two weeks, allowing drug development to keep pace with viral evolution and provide timely protection to humans. Author summary: The ongoing fight against viral diseases is made more difficult by the rapid evolution of viruses, which often outpaces current antiviral therapies. Our study addresses this critical issue by demonstrating the flexibility and rapid adaptability of antiviral nanobodies—single-domain antibodies derived from camelids. We have developed a structure-guided in vitro evolution strategy to quickly re-engineer nanobodies, enabling them to neutralize newly emerging viral strains. For viral mutations occurring at nanobody-binding sites, this approach introduces randomized amino acid sequences into nanobody residues near these mutations. Nanobody variants that effectively bind to the mutated viral target are then selected using a phage display library. Using this method, we successfully modified the nanobody Nanosota-3, originally an inhibitor of early Omicron subvariants, into a potent inhibitor of more recent Omicron subvariants. Remarkably, this adaptation process can be completed in under two weeks, significantly narrowing the gap between viral mutation rates and the development of effective therapeutic agents. Our findings have profound implications for antiviral drug development, particularly in light of ongoing global health challenges, providing a pathway to more timely and responsive treatments. [ABSTRACT FROM AUTHOR]

Sarcopenia is the age-related loss of skeletal muscle mass and function. Computed tomography (CT) assessments of sarcopenia utilize measurements of skeletal muscle cross-sectional area (SMA), radiation attenuation (SMRA), and intramuscular adipose tissue (IMAT). Unadjusted SMA is strongly correlated with both height and body mass index (BMI); therefore, SMA must be adjusted for body size to assess sarcopenic low muscle mass fairly in individuals of different heights and BMI. SMA/height (rather than S M A / h e i g h t 2 ) provides optimal height adjustment, and vertebra-specific relative muscle index (RMI) equations optimally adjust for both height and BMI. Since L3 measurement is not available in all CT scans, sarcopenic low muscle mass may be assessed using other levels. Both a mid-vertebral slice and an inferior slice have been used to define ‘L3 SMA’, but the effect of vertebral slice location on SMA measurements is unexplored. Healthy reference values for skeletal muscle measures at mid- and inferior vertebra slices between T10 and L5, have not yet been reported. We extracted T10 through L5 SMA, SMRA, and IMAT at a mid-vertebral and inferior slice using non-contrast-enhanced CT scans from healthy, adult kidney donor candidates between age 18 and 73. We compared paired differences in SMA between the mid-vertebral slice versus the inferior slice. We calculated the skeletal muscle gauge as S M G HT = S M R A ∗ S M I HT . We used allometric analysis to find the optimal height scaling power for SMA. To enable comparisons with other published reference cohorts, we computed two height-adjusted measures; S M I HT = S M A / h e i g h t (optimal) and S M I H T 2 = S M A / h e i g h t 2 (traditional). Using the young, healthy reference cohort, we utilized multiple linear regression to calculate relative muscle index z-scores ( R M I HT , R M I H T 2 ), which adjust for both height and BMI, at each vertebra level. We assessed Pearson correlations of each muscle area measure versus age, height, weight, and BMI separately by sex and vertebra number. We assessed the differences in means between age 18–40 versus 20–40 as the healthy, young adult reference group. We reported means, standard deviations, and sarcopenia cutpoints (mean-2SD and 5th percentile) by sex and age group for all measures. Sex-specific allometric analysis showed that height to the power of one was the optimal adjustment for SMA in both men and women at all vertebra levels. Differences between mid-vertebra and inferior slice SMA were statistically significant at each vertebra level, except for T10 in men. S M I HT was uncorrelated with height, whereas S M I H T 2 was negatively correlated with height at all vertebra levels. Both S M I HT and S M I H T 2 were positively correlated with BMI at all vertebra levels. R M I HT was uncorrelated with BMI, weight, and height (minimal positive correlation in women at L3 inf , L4 mid , and L5 inf ) whereas R M I H T 2 was uncorrelated with BMI, but negatively correlated with height and weight at all levels. There were no significant differences in SMA between 18–40 versus 20–40 age groups. Healthy reference values and sarcopenic cutpoints are reported stratified by sex, vertebra level, and age group for each measure. Height to the power of one (SMA/height) is the optimal height adjustment factor for SMA at all levels between T10 mid through L5 inf . The use of S M A / h e i g h t 2 should be discontinued as it retains a significant negative correlation with height and is therefore biased towards identifying sarcopenia in taller individuals. Measurement of SMA at a mid-vertebral slice is significantly different from measurement of SMA at an inferior aspect slice. Reference values should be used for the appropriate slice. We report sarcopenic healthy reference values for skeletal muscle measures at the mid-vertebral and inferior aspect slice for T10 through L5 vertebra levels. Relative muscle index (RMI) equations developed here minimize correlation with both height and BMI, producing unbiased assessments of relative muscle mass across the full range of body sizes. We recommend the use of these RMI equations in other cohorts. [ABSTRACT FROM AUTHOR]

Food allergies, food sensitivities, and adverse reactions to food represent common reasons for gastroenterology and allergy referral. The epidemiology of these disorders is changing; food allergies are more common than previously thought, and there is a heightened sense of awareness about food sensitivities. Symptoms do not always accurately predict the underlying pathophysiology nor distinguish the underlying etiology. This may lead to unnecessary testing, which is often unrewarding and expensive. Myths and misconceptions about food allergies and sensitivities are common and may lead to unwarranted treatment using untested therapies. Importantly, a missed diagnosis of a true food allergy can have serious consequences. This article discusses the differences between food allergies and sensitivities, including their epidemiology, underlying pathophysiology, key symptoms, and diagnostic criteria, as well as their treatment options. [ABSTRACT FROM AUTHOR]

Pregnant people face increased risk of severe COVID-19. Current guidelines recommend updated COVID-19 vaccination (2023–2024) for those aged ≥6 months, irrespective of pregnancy status. To refine recommendations for pregnant people, further data are needed. Using a test-negative design, we evaluated COVID-19 vaccine effectiveness against medically attended COVID-19 with COVID-19–like illness among pregnant people aged 18 to 45 years during June 2022 to August 2023. When doses were received during pregnancy, vaccine effectiveness was 52% (95% CI, 29%–67%); when received <6 months prior to pregnancy, 28% (95% CI, 11%–42%); and when received ≥6 months prior to pregnancy, 6% (95% CI, −11% to 21%). Pregnant people should stay up-to-date with recommended COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Background: The use of bone–patellar tendon–bone (BPTB) and hamstring tendon (HT) autografts is common in anterior cruciate ligament reconstruction (ACLR). After ACLR, patients typically progress through specific rehabilitation milestones, and graft type may play a role in patient progression. Purpose: To compare the time to meet rehabilitation milestones between BPTB and HT autografts after ACLR. Design: Cohort study; Level of evidence, 3. Methods: This was a single-institution study on patients who underwent ACLR with either BPTB or HT autograft between June 2018 and July 2021. The primary outcomes were time to meet return-to-sport criteria, including >90% limb symmetry index (LSI) for isokinetic quadriceps and hamstring strength, horizontal hop, 4-crossover hop, and single-hop height. The time to satisfaction of each criterion was compared between graft groups using Wilcoxon tests and Cox proportional hazards models. Results: Included in the analysis were 410 participants who underwent ACLR with either BPTB (n = 232) or HT (n = 178). The BPTB group took longer to achieve >90% LSI for knee extension than HT (11.1 ± 4.1 vs 7.63 ± 2.8 months; P <.001). Similarly, the BPTB group took longer than the HT group to achieve >90% LSI for horizontal hop (11.4 ± 3.5 vs 9.82 ± 2.8 months; P <.001), 4-crossover hop (11.8 ± 3.6 vs 10.4 ± 2.8 months; P =.002), and single-hop height testing (11 ± 3.7 vs 8.81 ± 3.2 months; P <.001). The median time to achieve >90% LSI for hamstring strength was similar between groups (7.18 ± 3 vs 7.56 ± 3.1 months; P =.2). Conclusion: Patients that underwent ACLR with BPTB autograft took longer than patients with HT to meet commonly used postoperative rehabilitation milestones. Clinicians should consider these differences when guiding patients regarding graft choice, postoperative expectations, and rehabilitation. [ABSTRACT FROM AUTHOR]

Simple Summary: Liposarcoma is a rare cancer of adipose tissue with limited treatment options. Here, we studied the fuel used by liposarcoma to develop a new strategy for treatment. Liposarcoma was found to rely on the amino acid Asparagine for tumor growth, especially in its most aggressive form. By combining treatments that limit both synthesis and uptake of Asparagine within liposarcoma cells, we demonstrated a unique sensitivity that reduced tumor growth in animal models. Altogether, findings from this study suggest that targeting Asparagine could be a promising new therapy in liposarcoma. Background: mTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS). Methods: Human tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling. Results: Asn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth. Conclusions: Asn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS. [ABSTRACT FROM AUTHOR]

The relationship of Amyotrophic Lateral Sclerosis, Parkinson's disease, and other age-related neurodegenerative diseases with mitochondrial dysfunction has led to our study of the mitochondrial fission gene Drp1 in Drosophila melanogaster and aspects of aging. Previously, the Drp1 protein has been demonstrated to interact with the Drosophila Bcl-2 mitochondrial proteins, and Drp1 mutations can lead to mitochondrial dysfunction and neuronal loss. In this study, the Dopa decarboxylase-Gal4 (Ddc-Gal4) transgene was exploited to direct the expression of Drp1 and Drp1-RNAi transgenes in select neurons. Here, the knockdown of Drp1 seems to compromise locomotor function throughout life but does not alter longevity. The co-expression of Buffy suppresses the poor climbing induced by the knockdown of the Drp1 function. The consequences of Drp1 overexpression, which specifically reduced median lifespan and diminished climbing abilities over time, can be suppressed through the directed co-overexpression of pro-survival Bcl-2 gene Buffy or by the co-knockdown of the pro-cell death Bcl-2 homologue Debcl. Alteration of the expression of Drp1 acts to phenocopy neurodegenerative disease phenotypes in Drosophila, while overexpression of Buffy can counteract or rescue these phenotypes to improve overall health. The diminished healthy aging due to either the overexpression of Drp1 or the RNA interference of Drp1 has produced novel Drosophila models for investigating mechanisms underlying neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Background: Despite the increased risk for people with an intellectual disability developing dementia, post‐diagnostic psychosocial supports such as cognitive stimulation therapy (CST) are not routinely offered and there is limited research examining this intervention with people with intellectual disabilities. The aim of this study was to explore the feasibility of CST for older adults with intellectual disability to support active ageing. Methods: Five client participants attended a 14‐session CST group and four staff attended a focus group. Reflexive thematic analysis was used to investigate the client and staff narratives. Results: Three key themes were generated: (1) Brain Health, (2) Connecting with others, and (3) Barriers and Enablers. Conclusion: Findings indicated the suitability of CST as a way of supporting active ageing for older adults with intellectual disability. This study adds to the growing knowledge about service provision for older adults and their changing needs as they age and identifies clinical implications such as staff training to support intervention adherence. [ABSTRACT FROM AUTHOR]

Background: Orthopedic procedures often require removing bone or pathological tissue, with traditional methods involving instruments like curettes and rongeurs. However, these methods can be time-consuming and lead to increased blood loss. To mitigate these side effects, vacuum-assisted tools have been developed to aid in tissue removal. These devices enable surgeons to suction tissue without discarding it, potentially improving outcomes in conditions such as osteomyelitis or tumor removal while enabling collection of the material for downstream applications. Despite limited research, vacuum-assisted devices show promise beyond bone marrow harvesting. This study assesses infection and clearance rates, estimated blood loss, and total procedure time associated with the use of vacuum-assisted tissue removal, with a goal to understand if these devices can be used for tissue removal across a variety of pathologic conditions. Methods: A retrospective cohort study was conducted on patients undergoing orthopedic procedures with the Avitus® Bone Harvester repurposed from its original design from December 1, 2021, to July 1, 2023. Procedures were categorized into oncology, and debridement for infection cases. Infection cases were further categorized into those secondary to trauma and those involving primary infections (osteomyelitis and periprosthetic joint infection). Clinical variables, including demographics, intraoperative details, complications, and follow-up, were reviewed. Statistical analysis included descriptive statistics computed with R Studio. Results: The study included 44 patients, with debridement for infection cases being the most common (primary infection: 45.5%; infection secondary to trauma: 18.1%), followed by oncology cases (36.4%). In all oncology cases, a definitive diagnosis was established using the device, and no post-operative infections were reported. The infection clearance rate was 85.0% for primary infection cases and 50.0% for cases of infection following trauma. Across the entire cohort, the average blood loss was 314.52 mL (sd: 486.74), and the average total procedure time was 160.93 min (sd: 91.07). The overall reoperation rate was 47.7%, with an unplanned reoperation rate of 11.4%. Conclusion: The vacuum-assisted bone harvester was effectively utilized in a wide range of debridement and curettage procedures across diverse orthopedic surgeries. In oncology cases, the device enabled effective tissue removal with comparable recurrence rates, demonstrating its potential to minimize contamination while preserving tissue for accurate diagnoses. Additionally, a high rate of osteomyelitis eradication was observed in debridement for primary infection cases (85%). Despite the relatively high reoperation rate of 47.7%, it is crucial to interpret this figure within the context of the varied reasons for reoperation. Many of these reoperations were planned as part of a staged approach to treatment or were unrelated to the device's performance. It is crucial to acknowledge that isolating the device's contribution to these results can be difficult. The utilization of the device should be guided by considerations of cost-effectiveness and patient-specific risk factors. [ABSTRACT FROM AUTHOR]

Background: Track PCC includes five geographic surveillance sites to conduct standardized population-based surveillance to estimate and track Post-COVID Conditions (PCC) by age, sex, race/ethnicity, geographic area, severity of initial infection, and risk factors among persons with evidence of SARS-CoV-2 infection (based on the Council of State and Territorial Epidemiologist [CSTE] case definitions for confirmed cases or laboratory-confirmed evidence of infection). Methods: The study will estimate the incidence, prevalence, including temporal trends, and duration and severity of PCC symptoms, among children, adolescents, and adults. PCCs include a broad range of symptoms and conditions that continue or develop after acute SARS-CoV-2 infection or COVID-19 illness. Surveillance includes both passive and active components for diverse populations in Arizona, Indiana, and Utah as well as the Bronx Borough, NY, and part of Philadelphia County, PA. Passive surveillance will utilize electronic health records and health information exchanges within each site catchment area to longitudinally follow persons with COVID-19 to estimate PCC occurring at least 30 days after acute COVID-19 illness. Active surveillance will utilize self-report of PCCs from detailed surveys of persons ages 7 years and older with evidence of SARS-CoV-2 infection in the past 3 months. Respondents will complete follow-up surveys at 6-, 12- and 18-months post-infection. Discussion: These data can help identify which groups are most affected by PCC, and what health differences among demographic groups exist, as well as indicate potential barriers to care. These additional levels of granularity can inform public health action and help direct needed clinical care for patients. [ABSTRACT FROM AUTHOR]

Many neurotransmitter receptors activate G proteins through exchange of GDP for GTP. The intermediate nucleotide-free state has eluded characterization, due largely to its inherent instability. Here we characterize a G protein variant associated with a rare neurological disorder in humans. GαoK46E has a charge reversal that clashes with the phosphate groups of GDP and GTP. As anticipated, the purified protein binds poorly to guanine nucleotides yet retains wild-type affinity for G protein βγ subunits. In cells with physiological concentrations of nucleotide, GαoK46E forms a stable complex with receptors and Gβγ, impeding effector activation. Further, we demonstrate that the mutant can be easily purified in complex with dopamine-bound D2 receptors, and use cryo-electron microscopy to determine the structure, including both domains of Gαo, without nucleotide or stabilizing nanobodies. These findings reveal the molecular basis for the first committed step of G protein activation, establish a mechanistic basis for a neurological disorder, provide a simplified strategy to determine receptor-G protein structures, and a method to detect high affinity agonist binding in cells. Many neurotransmitters act on receptors coupled to GTP-binding G proteins. Here authors report the structure and activity of a mutant that locks the nucleotide-free and receptor-bound state of the G protein, leading to a rare neurological disorder. [ABSTRACT FROM AUTHOR]

Objective To address challenges in large-scale electronic health record (EHR) data exchange, we sought to develop, deploy, and test an open source, cloud-hosted app "listener" that accesses standardized data across the SMART/HL7 Bulk FHIR Access application programming interface (API). Methods We advance a model for scalable, federated, data sharing and learning. Cumulus software is designed to address key technology and policy desiderata including local utility, control, and administrative simplicity as well as privacy preservation during robust data sharing, and artificial intelligence (AI) for processing unstructured text. Results Cumulus relies on containerized, cloud-hosted software, installed within a healthcare organization's security envelope. Cumulus accesses EHR data via the Bulk FHIR interface and streamlines automated processing and sharing. The modular design enables use of the latest AI and natural language processing tools and supports provider autonomy and administrative simplicity. In an initial test, Cumulus was deployed across 5 healthcare systems each partnered with public health. Cumulus output is patient counts which were aggregated into a table stratifying variables of interest to enable population health studies. All code is available open source. A policy stipulating that only aggregate data leave the institution greatly facilitated data sharing agreements. Discussion and Conclusion Cumulus addresses barriers to data sharing based on (1) federally required support for standard APIs, (2) increasing use of cloud computing, and (3) advances in AI. There is potential for scalability to support learning across myriad network configurations and use cases. [ABSTRACT FROM AUTHOR]

Plants employ diverse anti-herbivore defences that can covary to form syndromes consisting of multiple traits. Such syndromes are hypothesized to impact herbivores more than individual defences. We studied 16 species of lowland willows occurring in central Europe and explored if their chemical and physical traits form detectable syndromes. We tested for phylogenetic trends in the syndromes and explored whether three herbivore guilds (i.e., generalist leaf-chewers, specialist leaf-chewers, and gallers) are affected more by the detected syndromes or individual traits. The recovered syndromes showed low phylogenetic signal and were mainly defined by investment in concentration, richness, or uniqueness of structurally related phenolic metabolites. Resource acquisition traits or inducible volatile organic compounds exhibited a limited correlation with the syndromes. Individual traits composing the syndromes showed various correlations to the assemblages of herbivores from the three studied guilds. In turn, we found some support for the hypothesis that defence syndromes are composed of traits that provide defence against various herbivores. However, individual traits rather than trait syndromes explained more variation for all studied herbivore assemblages. The detected negative correlations between various phenolics suggest that investment trade-offs may occur primarily among plant metabolites with shared metabolic pathways that may compete for their precursors. Moreover, several traits characterizing the recovered syndromes play additional roles in willows other than defence from herbivory. Taken together, our findings suggest that the detected syndromes did not solely evolve as an anti-herbivore defence. [ABSTRACT FROM AUTHOR]

Changing distribution and abundance of small pelagic fishes may drive changes in predator distributions, affecting predator availability to fisheries and surveys. However, small pelagics are difficult to survey directly, so we developed a novel method of assessing the aggregate abundance of 21 small pelagic forage taxa via predator stomach contents. We used stomach contents collected from 22 piscivore species captured by multiple bottom trawl surveys within a vector autoregressive spatio-temporal model to assess trends of small pelagics on the Northeast US shelf. The goal was to develop a spatial "forage index" to inform survey and (or) fishery availability in the western North Atlantic bluefish (Pomatomus saltatrix) stock assessment. This spatially resolved index compared favorably with more traditional design-based survey biomass indices for forage species well sampled by surveys. However, our stomach content-based index better represented smaller unmanaged forage species that surveys are not designed to capture. The stomach-based forage index helped explain bluefish availability to the recreational fishery for stock assessment and provided insight into pelagic forage trends throughout the regional ecosystem. [ABSTRACT FROM AUTHOR]

Background: Assisted living (AL) community caregivers are known to report lower quality of hospice care. However, little is known about hospice providers serving AL residents and factors that may contribute to, and explain, differences in quality. We examined the association between hospice providers' AL patient‐day volume and their quality ratings based on Hospice Item Set (HIS) and Consumer Assessment of Healthcare Providers and Systems (CAHPS) Hospice Surveys. Methods: This cross‐sectional study employed information from the Medicare Compare website and Medicare claims data. Medicare‐eligible AL residents were identified using previously validated methods and merged with hospice claims. Linear probability models adjusting for county fixed effects were used to examine the association between hospice provider AL volume, measured as the share of annual hospice patient days from AL residents, and quality measures obtained from HIS and CAHPS. Models controlled for hospice providers' profit status and daily patient census. Results: Higher AL‐volume hospice providers were 7 percentage points more likely to have caregivers reporting lower median scores on domains of pain assessment, dyspnea treatment, and emotional support. Their caregivers also reported lower scores in team communications and training family to provide care. Higher AL‐volume hospice providers also were 5 percentage points less likely to get higher aggregated scores from all CAHPS domains and 7 percentage points less likely to have higher HIS composite scores. Conclusions: Hospice providers serving higher volumes of AL patient days had lower quality scores. In order to identify targeted opportunities for quality improvement, research is needed to understand why lower quality providers are concentrated in the AL market. [ABSTRACT FROM AUTHOR]

Acculturative stress is an important factor that affects health for Latinx immigrants in the US, with multiple studies identifying a link between depression and acculturative stress in this population. However, far fewer studies have examined the specific role and relationship of acculturative stress on mental health service use in this population. Through the lens of Yang's 2016 Model of Immigrant Health Service Use, this study aimed to examine the role of acculturative stress in predicting mental health service use in a sample of Latinx immigrants in the Southeast US. We conducted a secondary data analysis from a longitudinal study of Latinx immigrant health (n = 391). Our study found that while total acculturative stress was not significantly associated with mental health service use in this sample, parenting stress was a significant predictor of mental health service use in the past six months when controlling for covariates (OR: 1.043, 95% CI [1.009, 1.078]). Additionally, important Predisposing and Need for Healthcare factors were significantly associated with mental health service use, specifically: males were less likely to utilize mental health services than females (OR: 0.401, 95% CI [0.166-0.968]), English language acculturation was positively associated with mental health service use (OR: 1.953, 95% CI [1.130, 3.377]), and depression was positively associated with mental health service use (OR: 1.107, 95% CI [1.027, 1.194]). These findings support the need for more culturally sensitive mental health services, and the need to develop strategies to engage males and less acculturated individuals in mental health services to promote health equity among Latinx immigrants. [ABSTRACT FROM AUTHOR]

Background: Symbioses between primary producers and bacteria are crucial for nutrient exchange that fosters host growth and niche adaptation. Yet, how viruses that infect bacteria (phages) influence these bacteria-eukaryote interactions is still largely unknown. Here, we investigate the role of viruses on the genomic diversity and functional adaptations of bacteria associated with pelagic sargassum. This brown alga has dramatically increased its distribution range in the Atlantic in the past decade and is predicted to continue expanding, imposing severe impacts on coastal ecosystems, economies, and human health. Results: We reconstructed 73 bacterial and 3963 viral metagenome-assembled genomes (bMAGs and vMAGs, respectively) from coastal Sargassum natans VIII and surrounding seawater. S. natans VIII bMAGs were enriched in prophages compared to seawater (28% and 0.02%, respectively). Rhodobacterales and Synechococcus bMAGs, abundant members of the S. natans VIII microbiome, were shared between the algae and seawater but were associated with distinct phages in each environment. Genes related to biofilm formation and quorum sensing were enriched in S. natans VIII phages, indicating their potential to influence algal association in their bacterial hosts. In-vitro assays with a bacterial community harvested from sargassum surface biofilms and depleted of free viruses demonstrated that these bacteria are protected from lytic infection by seawater viruses but contain intact and inducible prophages. These bacteria form thicker biofilms when growing on sargassum-supplemented seawater compared to seawater controls, and phage induction using mitomycin C was associated with a significant decrease in biofilm formation. The induced metagenomes were enriched in genomic sequences classified as temperate viruses compared to uninduced controls. Conclusions: Our data shows that prophages contribute to the flexible genomes of S. natans VIII-associated bacteria. These prophages encode genes with symbiotic functions, and their induction decreases biofilm formation, an essential capacity for flexible symbioses between bacteria and the alga. These results indicate that prophage acquisition and induction contribute to genomic and functional diversification during sargassum-bacteria symbioses, with potential implications for algae growth. 1vVC6YGWLCm_DZc419o4RC Video Abstract [ABSTRACT FROM AUTHOR]

Commercial culture of channel catfish (Ictalurus punctatus) occurs in earthen ponds that are characterized by diel swings in dissolved oxygen concentration that can fall to severe levels of hypoxia, which can suppress appetite and lead to suboptimal growth. Given the significance of the hypothalamus in regulating these processes in other fishes, an investigation into the hypothalamus transcriptome was conducted to identify specific genes and expression patterns responding to hypoxia. Channel catfish in normoxic water were compared with catfish subjected to 12 h of hypoxia (20% oxygen saturation; 1.8 mg O2/L; 27°C) followed by 12 h of recovery in normoxia to mimic 24 h in a catfish aquaculture pond. Fish were sampled at 0-, 6-, 12-, 18-, and 24-h timepoints, with the 6- and 12-h samplings occurring during hypoxia. A total of 190 genes were differentially expressed during the experiment, with most occurring during hypoxia and returning to baseline values within 6 h of normoxia. Differentially expressed genes were sorted by function into Gene Ontology biological processes and revealed that most were categorized as "response to hypoxia," "sprouting angiogenesis," and "cellular response to xenobiotic stimulus." The patterns of gene expression reported here suggest that transcriptome responses to hypoxia are broad and quickly reversibly with the onset of normoxia. Although no genes commonly reported to modulate appetite were found to be differentially expressed in this experiment, several candidates were identified for future studies investigating the interplay between hypoxia and appetite in channel catfish, including adm, igfbp1a, igfbp7, and stc2b. NEW & NOTEWORTHY: Channel catfish are an economically important species that experience diel episodic periods of hypoxia that can reduce appetite. This is the first study to investigate their transcriptome from the hypothalamus in a simulated 24-h span in a commercial catfish pond, with 12 h of hypoxia and 12 h of normoxia. The research revealed functional groups of genes relating to hypoxia, angiogenesis, and glycolysis as well as individual target genes possibly involved in appetite regulation. Listen to this article's corresponding podcast at https://apspublicationspodcast.podbean.com/e/channel-catfish-transcriptomic-response-to-hypoxia/. [ABSTRACT FROM AUTHOR]

Self-reported and street race have been associated with health in the U.S. Race is a social construction based on phenotypical classifications rooted in colonialism. Yet, perceptions of race are different in the U.S. than in Latin America. We investigated relationships between self-reported race, street race (i.e., socially assigned race), and the health of U.S. Latinx immigrants in a community-engaged study of immigrant health in North Carolina. Latinx immigrants aged 18–44 years (N = 391) completed measures of self-reported race, street race, and health. Many participants reported that they did not know their race (n = 171; 44%), although to be eligible all identified as Hispanic or Latino/a/x. No significant relationships were observed between street race and health. For self-reported race, participants who declined to respond to the race question were more likely to have poorer mental health than participants who reported a biracial race and worse physical health than those of unknown, white, biracial, and other races. In exploratory analyses, participants who declined to answer the self-reported race question had higher immigration stress and language stress, were more likely to be undocumented, as well as were less bicultural and were less acculturated to the U.S. than participants in some of the other racial groups. The relationship between race and health among Latinx immigrants is complex and may not be explained by traditional racial and ethnic classifications in the U.S. Future research should explore how Latinx immigrants perceive and construct racial identity in the U.S., how they are racialized, and its impact on health. [ABSTRACT FROM AUTHOR]

Multi-stable systems, known for having complex nonlinear dynamics, have been shown in past studies to outperform their linear counterparts when designed for operation in vibration energy harvesters. This work investigates the dynamics and performance of a multi-stable electromagnetic energy harvesting device. The objectives are to enhance the levels of generated power and evaluate the useful bandwidths for the various modes of stability. Nonlinearity is introduced through a set of inclined springs and strongly influenced by the geometric parameters, as the shape of the potential energy curves can be adjusted by the selection of these properties. The effect of the geometric parameters' uncertainties on the potential energy as a result of imperfections in manufacturing and installation, and the performance of the proposed harvester, is examined. A nominal tri-stable configuration is considered, and the sensitivity of the system to input design uncertainties is explored. The system's response bifurcation diagrams and dynamical characteristics as well as the power output under up- and reverse-sweeping excitations are also reported. It is shown that the overall response and effectiveness of the nominal multi-stable harvester may drastically change in terms of resonance regions, periodicity of the motion, and levels of harvested power. A series of mono-stable and bi-stable harvesters arise due to the presence of geometrical uncertainties. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a disorder of gut–brain interaction characterized by abdominal pain and altered bowel habits, with patient‐perceived dissatisfaction of treatment symptom control. We assessed disease burden, satisfaction with medication use, and impact on activities, in participants with IBS with constipation (IBS‐C) and diarrhea (IBS‐D). Methods: This study assessed data from a large, United States survey of adults querying demographics, comorbid conditions, quality of life, medication use, satisfaction with symptom control, and work productivity. Participants were grouped into the IBS‐C or IBS‐D cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported. Key Results: Nine hundred and ten participants with IBS‐C and 669 with IBS‐D were matched to controls. The most reported symptoms were abdominal discomfort for IBS‐C and abdominal pain and abdominal discomfort for IBS‐D. Among the IBS‐C and IBS‐D cohorts, 74.2% and 65.9%, respectively, took prescription and/or over‐the‐counter medication for their symptoms. Respondents were more dissatisfied than satisfied with control of their symptoms. Respondents taking prescription medication(s) with or without over‐the‐counter medication(s) reported better symptom control than respondents only taking over‐the‐counter medications (p < 0.001). There was significantly higher mean presenteeism, work productivity loss, and daily activity impairment (p < 0.001 for all) in respondents with IBS compared with controls. Conclusions and Inferences: This study provides insight into respondents' experiences of IBS symptoms, including the impact on daily activity, as well as satisfaction with control of symptoms and prescription and over‐the‐counter medications. [ABSTRACT FROM AUTHOR]

How do voters react to local candidates who share their policy views but not their party identification, and vice versa? This paper presents findings from a survey experiment that cross-pressured respondents to choose between a co-partisan candidate who does not share their policy views (on housing and homelessness) and an opposing party candidate with some ideological affinity. The majority of respondents chose party over policy, indicating they would vote for co-partisans even if the candidate from the opposing party is closer to their policy positions. However, significant minorities defected and in some circumstances most did. Weak partisans, those with stronger policy views, and those who viewed the issues as highly salient were more likely to defect from their party when cross-pressured. Our findings support revising the expectation that partisanship always takes precedence over policy views and reinforces the view that partisanship may operate differently at the local level. [ABSTRACT FROM AUTHOR]

Aim: To highlight oversimplified quality‐adjusted life year (QALY) calculations and incremental cost‐effectiveness ratios (ICERs) regarding lifestyle metformin and placebo as flaws in the trial‐based (Diabetes Prevention Program) cost‐effectiveness analysis. Materials and Methods: We revised the QALY calculations to conform to convention and calculated appropriate ICERs using both original and revised QALYs results. We used several additional health economics tools to present results, showing the consistency of each method and the added value of each. We presented net monetary benefits, assessed decision uncertainty and calculated net losses. We also used graphics, making correct interpretation clearer and allowing illustration and calculation of technical and economic inefficiencies of treatments that were not cost‐effective. Results: ICERs with either QALY calculation indicated that metformin was technically and economically inefficient and not cost‐effective. There was virtually no decision uncertainty. All methods employed pointed to an identical conclusion. Conclusions: In contrast to original claims, although lifestyle was cost‐effective in diabetes prevention, metformin was not, and acting otherwise imposes significant monetary and health costs. Various available tools of economic evaluation would probably have prevented the original misinterpretation by the authors had they been used. The varied tools implemented here illustrate with a common example their consistency and value to the field, showing how to depict the results in various ways. [ABSTRACT FROM AUTHOR]

CIC‐rearranged sarcomas comprise a group of exceptionally aggressive round‐cell sarcomas. These tumors most commonly demonstrate CIC::DUX4 fusion and show similar histopathology to Ewing sarcomas, though lesions mimicking vascular neoplasms have recently been described. Here, we describe a case of a patient with CIC::DUX4 fusion sarcoma identified using RNA‐based molecular testing who was initially diagnosed with an endothelial neoplasm. The tumor showed extensive vasoformative growth, complete WT1 negativity, and global positive staining for ERG, CD31, and DUX4 by immunohistochemistry. Methylation testing of the tumor clustered more closely with angiosarcomas than with CIC‐rearranged sarcomas. Our findings suggest that CIC::DUX4 fused neoplasms may demonstrate a more diverse phenotypic range than previously appreciated and offer evidence that both molecular and immunohistochemical studies are needed for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Informant report dementia severity staging measures, such as the Quick Dementia Rating System (QDRS) offer clinicians useful diagnostic and staging information. These measures also potentially avoid many of the pitfalls inherent in mental status examinations (e.g., cultural bias, educational bias, floor and ceiling effects). We derive cut points for the QDRS and comprehensively examine their classification accuracy in a large, diagnostically heterogeneous, rural, memory disorder clinic sample. Our findings suggest the QDRS may be helpful when used in the context of a comprehensive diagnostic and staging evaluation. When used in isolation, the QDRS is insufficiently accurate for diagnosis and staging of dementia. [ABSTRACT FROM AUTHOR]

Background: Radiolabeled antibody 131I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic. Methods: Intraventricular radioimmunotherapy (RIT) with 925–1850 MBq (25–50 mCi) of 131I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 min, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3–10 y/o, 10–18 y/o, and 18+. Results: Post-administration exposure rates for patients ranged from 0.16 to 0.46 µSv/hr/MBq at 0.3 m and 0.03–0.08 µSv/hr/MBq at 1 m. Radiation exposure precautions ranged from 1 to 10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with 131I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring. Conclusion: 131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402. [ABSTRACT FROM AUTHOR]

To accomplish the potential of the New‐Space emerging era and facilitate scientific and commercial space exploration, the development of versatile, customized, and affordable space technologies is essential. 3D printing is established as a disruptive technology, enabling the production of complex and lightweight structures with enhanced performance. However, the harsh conditions of the space environment, including atomic oxygen (AO), extreme temperatures, and ionizing radiation, pose significant challenges to the durability and longevity of additive manufacturing‐produced polymers. Until now, there are no additive‐manufacturing polymeric materials that are specifically developed and qualified to withstand space hazards. To address these challenges, novel materials for additive manufacturing, composed of cyanate ester and extended‐bismaleimide are engineered to withstand the extreme conditions in space. The developed materials demonstrate superior thermo‐mechanical properties (flexural stress of 72 MPa and Tg = 260 °C), enhanced durability to AO erosion, ionizing radiation (10 years in orbit), and thermal stability (Td5% = 360 °C). Moreover, it is found that printing orientation governs the AO erosion, thus guiding optimal printing designs for enhanced durability to AO. The materials show improved performance, endurance, and reliability, thus contributing to the development of space‐qualified components and enabling the advancement of additive manufacturing for future space missions. [ABSTRACT FROM AUTHOR]

Virtual reality (VR) is an emerging technology that can enhance experiences and outcomes in mental healthcare. However, mental health therapists have been slow to adopt VR into practice. Implementation of telehealth-based VR therapy (tele-VR) could catalyze adoption and innovation in mental healthcare. To explore therapists' perspectives on tele-VR, we conducted a cross-sectional survey of practicing mental health providers in the United States in June-July 2023. We analyzed 176 completed surveys from therapists, of whom 51.14% had no prior experience with VR, only 6.25% had used VR clinically, and 56.82% had neutral impressions of VR for therapy. Despite therapists' general inexperience with VR, therapists indicated a wide variety of tele-VR simulations (e.g., social situations, flying, heights) and features (e.g., personalized spaces, homework, interactivity) would be moderately to extremely useful for their practices. Therapists also requested additional VR simulations and features for their telehealth clients such as behavioral skills training, exposure therapy, gender identity therapy, and psychological assessments in VR. Therapists rated Health Insurance Portability and Accountability Act compliance, the ability to try VR before buying, affordability for therapists, accessibility for clients, and insurance coverage as the five most influential implementation factors for tele-VR. Overall, therapists were generally inexperienced and neutral about VR for telehealth therapy, but were interested in tele-VR for specific applications. These findings provide actionable directions for future research and collaborative development of therapeutic VR content and features. [ABSTRACT FROM AUTHOR]

The classical amyloid cascade hypothesis postulates that the aggregation of amyloid plaques and the accumulation of intracellular hyperphosphorylated Tau tangles, together, lead to profound neuronal death. However, emerging research has demonstrated that soluble amyloid-β oligomers (SAβOs) accumulate early, prior to amyloid plaque formation. SAβOs induce memory impairment and disrupt cognitive function independent of amyloid-β plaques, and even in the absence of plaque formation. This work describes the development and characterization of a novel anti-SAβO (E3) nanobody generated from an alpaca immunized with SAβO. In-vitro assays and in-vivo studies using 5XFAD mice indicate that the fluorescein (FAM)-labeled E3 nanobody recognizes both SAβOs and amyloid-β plaques. The E3 nanobody traverses across the blood–brain barrier and binds to amyloid species in the brain of 5XFAD mice. Imaging of mouse brains reveals that SAβO and amyloid-β plaques are not only different in size, shape, and morphology, but also have a distinct spatial distribution in the brain. SAβOs are associated with neurons, while amyloid plaques reside in the extracellular matrix. The results of this study demonstrate that the SAβO nanobody can serve as a diagnostic agent with potential theragnostic applications in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Sexual assault is prevalent among undergraduates in Greek-letter organizations (GLO). Prevention efforts promote sexual consent, though few explicitly employ theoretical constructs known to positively influence behavior. This study evaluated theory-informed educational posters promoting sexual consent seeking. Forty undergraduate GLO students (20 female, 20 male) were recruited through in-person, email, and social media solicitation. Data collection was completed March–November 2019 during the spring and fall semesters. A double-blind randomized controlled trial was conducted. Intervention participants viewed theory-informed educational posters promoting sexual consent. The intervention group demonstrated more favorable consent intention (p =.024; η2 = 0.131) and consent subjective norms (p =.040; η2 = 0.109). Intervention group males showed a greater improvement in one of four consent attitudes (p =.045; η2 = 0.211). Brief exposures to theory-informed messaging may help to improve subjective norms and behavioral intent to seek sexual consent among undergraduate GLO members. [ABSTRACT FROM AUTHOR]

Recent advances in automated scoring technology have made it practical to replace multiple-choice questions (MCQs) with short-answer questions (SAQs) in large-scale, high-stakes assessments. However, most previous research comparing these formats has used small examinee samples testing under low-stakes conditions. Additionally, previous studies have not reported on the time required to respond to the two item types. This study compares the difficulty, discrimination, and time requirements for the two formats when examinees responded as part of a large-scale, high-stakes assessment. Seventy-one MCQs were converted to SAQs. These matched items were randomly assigned to examinees completing a high-stakes assessment of internal medicine. No examinee saw the same item in both formats. Items administered in the SAQ format were generally more difficult than items in the MCQ format. The discrimination index for SAQs was modestly higher than that for MCQs and response times were substantially higher for SAQs. These results support the interchangeability of MCQs and SAQs. When it is important that the examinee generate the response rather than selecting it, SAQs may be preferred. The results relating to difficulty and discrimination reported in this paper are consistent with those of previous studies. The results on the relative time requirements for the two formats suggest that with a fixed testing time fewer SAQs can be administered, this limitation more than makes up for the higher discrimination that has been reported for SAQs. We additionally examine the extent to which increased difficulty may directly impact the discrimination of SAQs. [ABSTRACT FROM AUTHOR]

Scientists increasingly draw on fishers' ecological knowledge (FEK) to gain a better understanding of fish biology and ecology, and inform options for fisheries management. We report on a study of FEK among fishers along the Lower Ucayali River in Peru, a region of exceptional productivity and diversity, which is also a major supplier of fish to the largest city in the Peruvian Amazon. Given a lack of available scientific information on stock status, we sought to identify temporal changes in the composition and size of exploited species by interviewing fishers from 18 communities who vary in years of fishing experience since the mid‐1950s. We develop four FEK‐based indicators to assess changes in the fish assemblage and compare findings with landings data. We find an intensification of fishing gear deployed over time and spatiotemporal shifts in the fish assemblage and reported declines in species weight, which point to a fishing‐down process with declines across multiple species. This finding is reflected in a shifting baseline among our participants, whereby younger generations of fishers have different expectations regarding the distribution and size of species. Our study points to the importance of spillover effects from the nearby Pacaya‐Samira National Reserve and community initiatives to support the regional fishery. Reference to fishers' knowledge also suggests that species decline is likely underreported in aggregated landings data. Despite the dynamism and diversity of Amazonian floodplain fisheries, simple FEK‐based indicators can provide useful information for understanding fishing‐induced changes in the fish assemblage. Fishers hold valuable knowledge for fishery management and conservation initiatives in the region. [ABSTRACT FROM AUTHOR]

In this article my aim is to see Karl Llewellyn as a member of the central pragmatist canon. Further, I see Llewellyn not only as a "Legal Pragmatist," but also as developing a full pragmatist philosophy of law. Reading Llewellyn as a pragmatist would greatly add to an extended understanding of early pragmatism. This would show a strong influence of pragmatic thought within the legal academy.. Second, adding Llewellyn to the pragmatist canon would help show pragmatism in action in the world. Llewellyn might be the central theoretical pragmatist of modern US Law. If, as I believe, pragmatism is a philosophy that depends upon an underlying experimentalist attitude towards philosophizing, given his great influence on US law adding Llewellyn brings a large amount of experimentalist data to the tradition. [ABSTRACT FROM AUTHOR]