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The National Association of School Psychologists (NASP) emphasizes mental and behavioral health services and family-school-community collaboration as domains within school psychology practice (NASP, 2020). While research outlines best practices in family-based intervention when children exhibit behavioral and emotional concerns, there has been little examination of the current practices of school psychologists within this practice area. This study investigated family intervention practices in schools, school psychologists' involvement in these practices, and their perceived effectiveness. Results indicated that very few practicing school psychologists use family-based interventions in their practice and may lack the knowledge, skills, and training to implement these types of interventions. Implications and future research are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of acute nitrate (NO3−)-rich beetroot juice ingestion on explosive and high-intensity exercise performance, oral microbiota composition, and cognitive flexibility (i.e., function), before and after maximal intermittent running exercise. Fifteen women team-sport athletes were assigned in a randomized, double-blind, crossover design to consume concentrated NO3–-depleted beetroot juice (PL; 0.1 mmol NO3−) and NO3−-rich beetroot juice (BR; 12.0 mmol NO3−) 2.5 h prior to performing a battery of exercise performance tasks and cognitive testing before and after the Yo–Yo intermittent recovery level 1 (YYIR1) running test. Resting plasma [NO3−] and plasma nitrite ([NO2−]) were elevated following BR (P < 0.001). BR did not impact global composition or relative abundance of taxa in the oral microbiome (P > 0.05) or cognitive flexibility before or after exercise (P > 0.05). There was no significant difference in performance during 20-m (PRE, PL: 4.38 ± 0.27 vs. BR: 4.38 ± 0.32 s; POST, PL: 4.45 ± 0.29 vs. BR: 4.43 ± 0.35 s) and 10-m sprints (PRE, PL 2.78 ± 0.15 vs. BR 2.79 ± 0.18 s; POST, PL: 2.82 ± 0.16 vs. BR: 2.81 ± 0.19 s), isokinetic handgrip dynamometry, medicine ball throw, horizontal countermovement jump, or YYIR1 (PL: 355 ± 163 m vs. BR: 368 ± 184 m) between BR and PL (P > 0.05). These findings indicate that acute dietary NO3− may not influence the oral microbiome, explosive and high-intensity exercise performance, or cognitive function in women team-sport athletes. [ABSTRACT FROM AUTHOR]

Introduction: Several clinical outcome assessment (COA) instruments assess Sjögren's disease (Sjögren's) symptoms, but do not provide comprehensive assessment of the health-related quality of life (HRQoL) impact of Sjögren's. This study aimed to develop a patient-reported outcome (PRO) instrument for the assessment of HRQoL, intended for use in clinical trials and clinical practice in the assessment of treatment benefit. Methods: Review of study sponsor proprietary data and qualitative interviews informed the development of a conceptual model, the Sjögren's Related Quality of Life (SRQoL) and patient global impression of severity (PGI-S) and change (PGI-C) items. Combined concept elicitation and cognitive debriefing interviews with patients with Sjögren's explored their HRQoL impact experience and content validity of the SRQoL and PGI items. Results: Twenty participants were interviewed about their Sjögren's experience. Following inductive analysis of interviews, concepts were categorized into eight domains: emotional well-being (e.g., worry and stress; n = 20/20; 100%), sleep (e.g., daytime sleepiness and waking up during the night; n = 20/20; 100%), activities of daily living (e.g., difficulty looking at screens and difficulty driving; n = 20/20; 100%), cognition (e.g., concentration difficulties and word finding difficulties; n = 19/20; 95.0%), physical functioning (e.g., difficulty walking and difficulty exercising; n = 19/20; 95.0%), social and family functioning (e.g., dependent on others and relationship difficulties; n = 17/20; 85.0%), work (n = 15/20; 75.0%), and sexual functioning (n = 12/20; 60.0%). SRQoL and PGI items, instructions, response options, and recall period were well understood and relevant to participants. Conclusions: The SRQoL is a new PRO instrument to assess Sjögren's impact on HRQoL, developed in accordance with regulatory guidance. This study provides considerable insight into the patient experience of Sjögren's and evidence to support the content validity of the SRQoL. Future research should evaluate the psychometric properties of the SRQoL to support its use in clinical trials and clinical practice and further validate its use as an assessment of treatment benefit. Plain Language Summary: Patient and physician completed questionnaires used in clinical trials and clinical practice have previously focused on symptoms. These questionnaires do not cover the full experience of living with Sjögren's, such as differences in symptoms between individual patients, and their use has also been known to result in inaccurate reports. Another way of thinking about patients' experiences is to use a questionnaire to ask about the impact Sjögren's has on patients' health-related quality of life, meaning how Sjögren's might affect their life in different ways including physically, emotionally, and socially. The goal of this study was to develop a new questionnaire (named the Sjögren's-Related Quality of Life [SRQoL] questionnaire) to measure the impact that Sjögren's has on patients' lives. Interviews were conducted with people with Sjögren's to explore their understanding of the new questionnaire and how relevant the content is to their experience of the condition. The results of this study suggest that the SRQoL includes relevant and easy-to-understand questions, suitable for use in future clinical trials and clinical practice, to measure if patients' HRQoL improves with treatment. Future research is needed to confirm that the questionnaire accurately measures the impact of Sjögren's on HRQoL for use with patients with Sjögren's. [ABSTRACT FROM AUTHOR]

Advancements in microscopy techniques and computing technologies have enabled researchers to digitally reconstruct brains at micron scale. As a result, community efforts like the BRAIN Initiative Cell Census Network (BICCN) have generated thousands of whole-brain imaging datasets to trace neuronal circuitry and comprehensively map cell types. This data holds valuable information that extends beyond initial analyses, opening avenues for variation studies and robust classification of cell types in specific brain regions. However, the size and heterogeneity of these imaging data have historically made storage, sharing, and analysis difficult for individual investigators and impractical on a broad community scale. Here, we introduce the Brain Image Library (BIL), a public resource serving the neuroscience community that provides a persistent centralized repository for brain microscopy data. BIL currently holds thousands of brain datasets and provides an integrated analysis ecosystem, allowing for exploration, visualization, and data access without the need to download, thus encouraging scientific discovery and data reuse. [ABSTRACT FROM AUTHOR]

Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigate whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in interspecies virus infection and adaptation. We find that IFITM3-deficient mice and human cells can be infected with low doses of avian influenza viruses that fail to infect WT counterparts, identifying a new role for IFITM3 in controlling the minimum infectious virus dose threshold. Remarkably, influenza viruses passaged through Ifitm3−/− mice exhibit enhanced host adaptation, a result that is distinct from viruses passaged in mice deficient for interferon signaling, which exhibit attenuation. Our data demonstrate that IFITM3 deficiency uniquely facilitates potentially zoonotic influenza virus infections and subsequent adaptation, implicating IFITM3 deficiencies in the human population as a vulnerability for emergence of new pandemic viruses. This study highlights that IFITM3 deficiency lowers the minimum infectious dose of influenza virus, enhances adaptation of influenza viruses to a new host species, and broadly increases infection of human cells by avian and swine influenza viruses. [ABSTRACT FROM AUTHOR]

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Background: Artificial intelligence (AI) has emerged as a powerful tool in various medical fields, including plastic surgery. This study aims to evaluate the performance of ChatGPT, an AI language model, in elucidating historical aspects of plastic surgery and identifying potential avenues for innovation. Methods: A comprehensive analysis of ChatGPT's responses to a diverse range of plastic surgery-related inquiries was performed. The quality of the AI-generated responses was assessed based on their relevance, accuracy, and novelty. Additionally, the study examined the AI's ability to recognize gaps in existing knowledge and propose innovative solutions. ChatGPT's responses were analysed by specialist plastic surgeons with extensive research experience, and quantitatively analysed with a Likert scale. Results: ChatGPT demonstrated a high degree of proficiency in addressing a wide array of plastic surgery-related topics. The AI-generated responses were found to be relevant and accurate in most cases. However, it demonstrated convergent thinking and failed to generate genuinely novel ideas to revolutionize plastic surgery. Instead, it suggested currently popular trends that demonstrate great potential for further advancements. Some of the references presented were also erroneous as they cannot be validated against the existing literature. Conclusion: Although ChatGPT requires major improvements, this study highlights its potential as an effective tool for uncovering novel aspects of plastic surgery and identifying areas for future innovation. By leveraging the capabilities of AI language models, plastic surgeons may drive advancements in the field. Further studies are needed to cautiously explore the integration of AI-driven insights into clinical practice and to evaluate their impact on patient outcomes. Level of Evidence V: 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]

Nonalcoholic fatty liver disease (NAFLD), which shows similar symptoms as fatty liver hemorrhage syndrome (FLHS) in chickens, is the most common cause of chronic liver disease and cancer in humans. NAFLD patients and FLHS in chickens have demonstrated severe liver disorders when infected by emerging strains of human hepatitis E virus (HEV) and avian HEV, respectively. We sought to develop a fatty liver disease chicken model by altering the diet of 3-week-old white leghorn chickens. The high cholesterol, and low choline (HCLC) diet included 7.6% fat with additional 2% cholesterol and 800 mg/kg choline in comparison to 5.3% fat, and 1,300 mg/kg choline in the regular diet. Our diet induced fatty liver avian model successfully recapitulates the clinical features seen during NAFLD in humans and FLHS in chickens, including hyperlipidemia and hepatic steatosis, as indicated by significantly higher serum triglycerides, serum cholesterol, liver triglycerides, cholesterol, and fatty acids. By developing this chicken model, we expect to provide a platform to explore the role of lipids in the liver pathology linked with viral infections and contribute to the development of prophylactic interventions. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) affects roughly 1 in 7500 individuals. While at the population level there is a general pattern of affected muscles, there is substantial heterogeneity in muscle expression across- and within-patients. There can also be substantial variation in the pattern of fat and water signal intensity within a single muscle. While quantifying individual muscles across their full length using magnetic resonance imaging (MRI) represents the optimal approach to follow disease progression and evaluate therapeutic response, the ability to automate this process has been limited. The goal of this work was to develop and optimize an artificial intelligence-based image segmentation approach to comprehensively measure muscle volume, fat fraction, fat fraction distribution, and elevated short-tau inversion recovery signal in the musculature of patients with FSHD. Intra-rater, inter-rater, and scan-rescan analyses demonstrated that the developed methods are robust and precise. Representative cases and derived metrics of volume, cross-sectional area, and 3D pixel-maps demonstrate unique intramuscular patterns of disease. Future work focuses on leveraging these AI methods to include upper body output and aggregating individual muscle data across studies to determine best-fit models for characterizing progression and monitoring therapeutic modulation of MRI biomarkers. [ABSTRACT FROM AUTHOR]

Background: Unintentional injuries disproportionately impact American Indian and Alaska Native (AI/AN) populations. Developing effective and culturally tailored data collection and intervention programs requires an understanding of past prevention efforts in AI/AN communities, but limited peer-reviewed literature on the topic is available. This scoping review aims to summarize efforts that have been published in the Primary Care Provider newsletter, a source of gray literature available through the Indian Health Service. Methods: The research team obtained all injury related articles in the Provider newsletter and excluded those that did not describe an unintentional injury prevention effort. Included articles were organized chronologically and by topic, and outcomes were described in a data abstraction form. Results: A total of 247 articles from the Provider newsletter were screened, and 68 were included in this review. The most number of articles were published in 2007 (n = 15). Many focused not specifically on one tribal community but on the AI/AN community as a whole (n = 27), while others reported that certain tribes were the focus of study but did not identify tribes by name (n = 24). The following is a list of 14 tribal communities explicitly mentioned: Omaha, Cherokee, Ute, Yakama, Chippewa, Apache, Ho-Chunk, The Crow Tribe, Tohono O'odham Nation, Fort Mojave Tribe, Chemehuevi Tribe, The Rosebud Tribe, Navajo, and The Pueblo of Jemez. Published unintentional injury prevention efforts have covered the following 7 topics in AI/AN communities: falls, motor vehicle crashes, poisonings, improving data, burns, children, and other. Conclusion: This scoping review makes available and searchable information on injury prevention work conducted in and for AI/AN communities that is not currently found in the peer-reviewed literature. [ABSTRACT FROM AUTHOR]

Robotic surgery is increasingly utilized in hepatopancreatobiliary (HPB) surgery, but the learning curve is a substantial obstacle hindering implementation. Comprehensive robotic training can help to surmount this obstacle; however, despite the expansion of robotic training into residency and fellowship programs, limited data are available about how this translates into successful incorporation in faculty practice. All operations performed during the first three years of practice of a surgical oncologist at a tertiary care academic institution were retrospectively reviewed. The surgeon underwent comprehensive robotic training during residency and fellowship. 137 HPB operations were performed during the initial three years of practice. Over 80% were performed robotically each year across a spectrum of HPB procedures with a 6% conversion rate. Median operative time, a metric for operative proficiency and evaluation for a learning curve, was similar throughout the study period for each major operation and below several reported optimized operative time benchmarks. The major complications, defined as a Clavien-Dindo of 3 or more, were similar across the experience and comparable to published series. Comprehensive robotic training in residency and fellowship as well as a dedicated, well-trained operative team allows for early attainment of optimized outcomes in a new HPB robotic practice. [ABSTRACT FROM AUTHOR]

Background: Palmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal analgesics/anti-inflammatories. While OTC pain medications can impair strength training adaptations, the mechanism of action of PEA is distinct from these and it may not negatively affect skeletal muscle adaptations to strength training. Methods: The primary aim of this study was to investigate the effects of daily PEA supplementation (350 mg Levagen + equivalent to 300 mg PEA) combined with 8-weeks of resistance training on lean body mass with secondary aims addressing strength, power, sleep, and wellbeing compared to placebo (PLA) in young, healthy, active adults. In a randomized, controlled, double-blinded trial, 52 untrained, recreationally active participants aged 18–35 y were allocated to either the PEA or PLA groups. Participants consumed either 2 × 175 mg Levagen + PEA or identically matched maltodextrin capsules during an 8-week period of whole-body resistance training. This trial assessed the pre- to post- changes in total and regional lean body mass, muscular strength (1-RM bench, isometric mid-thigh pull), muscular power [countermovement jump (CMJ), bench throw], pain associated with exercise training, sleep, and wellbeing compared with the PEA or PLA condition. Results: 48 Participants were included in the final intention to treat (ITT) analysis and we also conducted per protocol (PP) analysis (n = 42). There were no significant between-group differences for total or regional lean muscle mass post-intervention. There was a significantly higher jump height (CMJ) at week 10 in the PEA group compared to the PLA (Adjusted mean difference [95% CI] p-value; ITT: − 2.94 cm [− 5.15, − 0.74] p = 0.010; PP: − 2.93 cm [− 5.31, − 0.55] p = 0.017). The PLA group had higher 1-RM bench press post-intervention compared with the PEA group (ITT: 2.24 kg [0.12, 4.37] p = 0.039; PP: 2.73 kg [0.40, 5.06] p = 0.023). No significant treatment effects were noted for any of the other outcomes. Conclusion: PEA supplementation, when combined with 8 weeks of strength training, did not impair lean mass gains and it resulted in significantly higher dynamic lower-body power when compared with the PLA condition. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p). Key Findings: Palmitoylethanolamide (PEA) is a compound that works as an anti-inflammatory and analgesic for the management of pain that works on different biochemical pathways compared to other over-the-counter analgesics and non-steroidal anti-inflammatories. Our findings indicate that a daily dose of 300 mg of PEA administered during 8-weeks of strength training did not interfere with skeletal muscle hypertrophy gains and may improve lower body power (e.g., jump height) compared to the placebo group. PEA may fill the gap for athletes and the active population as an alternative method of pain management. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection. In this study, the authors identify genetic insertions in the population of hepatitis E virus analyzed in serum samples of a patient with ribavirin treatment failure. They show that these genomic rearrangements promote viral replication without affecting ribavirin sensitivity. [ABSTRACT FROM AUTHOR]

In salt marshes of the Southeastern USA, purple marsh crabs (Sesarma reticulatum), hereafter Sesarma, aggregate in grazing and burrowing fronts at the heads of tidal creeks, accelerating creek incision into marsh platforms. We explored the effects of this keystone grazer and sediment engineer on salt marsh sediment accumulation, hydrology, and carbon (C) and nitrogen (N) turnover using radionuclides (210Pb and 7Be), total hydrolyzable amino acids (THAA), and C and N stable isotopes (δ13C and δ15N) in sediment from paired Sesarma-grazed and un-grazed creeks. Sesarma-grazed-creek sediments exhibited greater bioturbation and tidal inundation compared to sediments in un-grazed creeks, as indicated by larger 210Pb and 7Be inventories. Total organic carbon (TOC) to total nitrogen (TN) weight ratios (C:N) were higher and δ15N values were lower in grazed-creek sediments than in un-grazed-creek sediments, suggesting Sesarma remove and assimilate N in their tissues, and excrete N with lower δ15N values into sediments. In support of this inference, the percent total carbon (TC) and percent TOC declined by nearly half, percent TN decreased by ~ 80%, and the C:N ratio exhibited a ~ threefold increase between Sesarma fore-gut and hind-gut contents. An estimated 91% of Sesarma's diet was derived from Spartina alterniflora, the region's dominant salt marsh plant. We found that, as Sesarma grazing fronts progress across marsh landscapes, they enhance the decay of Spartina-derived organic matter and prolong marsh tidal inundation. These findings highlight the need to better account for the effects of keystone grazers and sediment engineers, like Sesarma, in estimates of the stability and size of blue C stores in coastal wetlands. [ABSTRACT FROM AUTHOR]

Increased left atrial volume and decreased left atrial function have long been associated with atrial fibrillation. The availability of large-scale cardiac magnetic resonance imaging data paired with genetic data provides a unique opportunity to assess the genetic contributions to left atrial structure and function, and understand their relationship with risk for atrial fibrillation. Here, we use deep learning and surface reconstruction models to measure left atrial minimum volume, maximum volume, stroke volume, and emptying fraction in 40,558 UK Biobank participants. In a genome-wide association study of 35,049 participants without pre-existing cardiovascular disease, we identify 20 common genetic loci associated with left atrial structure and function. We find that polygenic contributions to increased left atrial volume are associated with atrial fibrillation and its downstream consequences, including stroke. Through Mendelian randomization, we find evidence supporting a causal role for left atrial enlargement and dysfunction on atrial fibrillation risk. In this study, a deep learning-based model of left atrial size in UK Biobank enabled genome-wide association studies in 35,049 healthy participants. Several lines of evidence, including the PITX2 locus, linked left atrial dysfunction to atrial fibrillation risk. [ABSTRACT FROM AUTHOR]

Introduction: Higher Area Deprivation Index (ADI) scores, indicating higher social deprivation, have been associated with more frequent emergency department (ED) utilization. Access to clinical and social services can help prevent inappropriate ED use. A community-based medical school administering a primary and preventive care program focused on the social determinants of health (SDOH) tracks annual ED utilization by its households. This retrospective study determined household ADI scores and evaluated for associations with ED use. Methods: The ADI uses 17 publicly available variables to assign composite scores of social deprivation at the block group level. The Green Family Foundation Neighborhood Health Education Learning Program at Florida International University provides outreach, clinical, and educational services to > 850 disadvantaged households. We conducted Poisson regression to evaluate the association between households' ADI scores and self-reported ED utilization over 2 calendar years. Results: For both the 2018 and 2019 cohorts, independent Poisson regression results indicate that ED visit count is significantly and inversely associated with ADI raw scores and deciles (p < 0.001). Discussion: Based on findings from earlier studies, we had hypothesized a positive, yet reduced association between annual ED utilization and ADI level but surprisingly, we found an inverse association. The combination of providing primary care and connecting with social and behavioral health services as needed appeared to reverse the expected higher ED use at higher ADI scores. Conclusion: Tracking of ED utilization in association with composite, area-based indices such as the ADI may prove useful for other clinical and community health endeavors focused on SDOH. [ABSTRACT FROM AUTHOR]

Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of the inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd−/−) significantly attenuates influenza virus-induced weight loss, lung dysfunction, lung histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads. Infected Gsdmd−/− mice exhibit decreased inflammatory gene signatures shown by lung transcriptomics. Among these, diminished neutrophil gene activation signatures are corroborated by decreased detection of neutrophil elastase and myeloperoxidase in KO mouse lungs. Indeed, directly infected neutrophils are observed in vivo and infection of neutrophils in vitro induces release of DNA and tissue-damaging enzymes that is largely dependent on GSDMD. Neutrophil depletion in infected WT mice recapitulates the reductions in mortality, lung inflammation, and lung dysfunction observed in Gsdmd−/− animals, while depletion does not have additive protective effects in Gsdmd−/− mice. These findings implicate a function for GSDMD in promoting lung neutrophil responses that amplify influenza virus-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a therapeutic avenue for treating severe influenza. [ABSTRACT FROM AUTHOR]

Stable isotope methods for provenance of unidentified human remains are relatively a newer field of enquiry in forensic archeology. It is of great interest for forensic experts these days. The application of strontium isotope analyses for estimating geolocation of archeological remains is of great interest in bioarcheology and modern forensics. The strontium (Sr) isotope composition of human bones and teeth has been widely used to reconstruct an individual's geo-affiliation, residential mobility, and migration history. Thousands of unknown human remains, reportedly belonging to 282 Indian soldiers of 26th Native Bengal regiment and killed in 1857, were exhumed non-scientifically from an abandoned well situated underneath a religious structure at Ajnala (Amritsar, India). Whether these remains belonged to the individuals, local or non-local to the site, was the important forensic archeological question to be answered by doing their thorough forensic anthropological examinations. In the present study, 27 mandibular teeth (18 s molars, 6 first molars, and 3 premolars) collected from the Ajnala skeletal assemblage were processed for strontium isotope analysis, and the measured ratios were compared with published isotope baseline data to estimate the locality status of these remains. The Sr isotopic values were concentrated in the range of 0.7175 to 0.7270. The comparative analysis of isotopic ratios revealed that most individuals buried in the Ajnala well have 87Sr/86Sr values close to the river as well as groundwater of the Gangetic plain (less radiogenic 87Sr/86Sr ~ 0.716); most likely originated near Varanasi (Uttar Pradesh, India) region, whereas the individuals with higher 87Sr/86Sr ratios (~ 0.7200) probably resided in the West Bengal and Bihar areas where the river as well as groundwater of the Gangetic plain is relatively more radiogenic. Thus, the strontium isotope results reveal that the Ajnala individuals did not grow up or live in the Amritsar region during their childhood, and this observation complemented the previous forensic anthropological and molecular findings. There is very little Indian data on the bioavailable strontium, so the inferences from the present study estimating Sr isotope abundances are expected to provide baseline data for future forensic provenance studies that will contribute to the global efforts of mapping Sr isotope variations by the isotope community. [ABSTRACT FROM AUTHOR]

Purpose: We sought to present the current status of survivorship programs at Dana-Farber Cancer Institute which include the David B. Perini, Jr. Quality of Life Clinic for survivors of childhood cancer, Stop and Shop Neuro-Oncology Outcomes Clinic for pediatric brain tumor survivors, and Adult Survivorship Program for adult cancer survivors including those diagnosed as adults (age 18 years and older) and adult survivors of childhood cancer, in an effort to share best practices as well as challenges. Methods: Description of programs and discussion. Results: Our institutional programs are detailed regarding their history and the multidisciplinary approach and both consultative and long-term care delivery models for pediatric and adult cancer survivors, with the goal of meeting the spectrum of survivorship care needs, from diagnosis and management of long-term effects of cancer-directed therapy and surveillance for subsequent cancer, to healthy lifestyle promotion and psychosocial support. Program investigators conduct research to understand the risks and unmet needs of cancer survivors, and to develop and test interventions to improve care delivery and medical and psychosocial outcomes. There are also educational initiatives detailed. Conclusions: Survivorship programs at Dana-Farber are designed to optimize care and outcomes for cancer survivors including conducting quality improvement initiatives and research to further understand and meet the clinical needs of the large, heterogenous, and growing population cancer survivors into the future. Implications for Cancer Survivors: Programs like ours as well as those ongoing and planned aim to improve the comprehensive care of diverse cancer survivors. [ABSTRACT FROM AUTHOR]

The development of high intensity petawatt lasers has created new possibilities for ion acceleration and nuclear fusion using solid targets. In such laser-matter interaction, multiple ion species are accelerated with broad spectra up to hundreds of MeV. To measure ion yields and for species identification, CR-39 solid-state nuclear track detectors are frequently used. However, these detectors are limited in their applicability for multi-ion spectra differentiation as standard image recognition algorithms can lead to a misinterpretation of data, there is no unique relation between track diameter and particle energy, and there are overlapping pit diameter relationships for multiple particle species. In this report, we address these issues by first developing an algorithm to overcome user bias during image processing. Second, we use calibration of the detector response for protons, carbon and helium ions (alpha particles) from 0.1 to above 10 MeV and measurements of statistical energy loss fluctuations in a forward-fitting procedure utilizing multiple, differently filtered CR-39, altogether enabling high-sensitivity, multi-species particle spectroscopy. To validate this capability, we show that inferred CR-39 spectra match Thomson parabola ion spectrometer data from the same experiment. Filtered CR-39 spectrometers were used to detect, within a background of ~ 2 × 1011 sr−1 J−1 protons and carbons, (1.3 ± 0.7) × 108 sr−1 J−1 alpha particles from laser-driven proton-boron fusion reactions. [ABSTRACT FROM AUTHOR]

Single amino acid (AA) supplementations in foods are increasing, however their potential nutritional and physiological impacts are not fully understood. This study examined the effects of l-lysine (Lys) supplementation on protein quality of diets, serum AA concentrations and associations between the ratio of supplemental Lys to dietary protein (X) with body weight gain (BWG) in Sprague–Dawley male rats. Rats were fed one of 10 diets containing either 7% or 20% casein and supplemented with 0% (Control), 1.5%, 3%, 6% Lys or 6% Lys + 3% l-arginine (Arg) (8 rats/diet group) for 1 week. Lys supplementation reduced the protein quality of the casein-based diets (p < 0.01). BWG was reduced by supplemental Lys when X > 0.18. Free Lys supplementation dose-dependently increased serum Lys levels (p < 0.01), while increased protein-bound Lys (1.4% vs 0.52%) had little effect on serum Lys (p > 0.05). In the 7% casein diets, ≥ 1.5% supplemental Lys reduced serum alanine, asparagine, glycine, isoleucine, leucine, serine, tyrosine, valine, carnitine, ornithine, and increased urea. Supplementation of ≥ 3% Lys additionally reduced tryptophan and increased histidine, methionine and α-aminoadipic acid (α-AAA) compared to the Control (p < 0.05). In the 20% casein diets, addition of ≥ 1.5% Lys reduced serum asparagine and threonine, and ≥ 3% Lys reduced leucine, proline, tryptophan, valine, and ornithine, and 6% Lys reduced carnitine, and increased histidine, methionine, and α-AAA. Overall, this study showed that free Lys supplementation in a Lys-sufficient diet reduced the protein quality of the diets and modified the serum concentrations of many amino acids. Excess free Lys intake adversely affected growth and utilization of nutrients due to AA imbalance or antagonism. Overall lower protein intake increases susceptibility to the adverse effects of Lys supplementation. [ABSTRACT FROM AUTHOR]

The flavivirus envelope protein is a class II fusion protein that drives flavivirus-cell membrane fusion. The membrane fusion process is triggered by the conformational change of the E protein from dimer in the virion to trimer, which involves the rearrangement of three domains, EDI, EDII, and EDIII. The movement between EDI and EDII initiates the formation of the E protein trimer. The EDI-EDII hinge region utilizes four motifs to exert the hinge effect at the interdomain region and is crucial for the membrane fusion activity of the E protein. Using West Nile virus (WNV) NY99 strain derived from an infectious clone, we investigated the role of eight flavivirus-conserved hydrophobic residues in the EDI-EDII hinge region in the conformational change of E protein from dimer to trimer and viral entry. Single mutations of the E-A54, E-I130, E-I135, E-I196, and E-Y201 residues affected infectivity. Importantly, the E-A54I and E-Y201P mutations fully attenuated the mouse neuroinvasive phenotype of WNV. The results suggest that multiple flavivirus-conserved hydrophobic residues in the EDI-EDII hinge region play a critical role in the structure–function of the E protein and some contribute to the virulence phenotype of flaviviruses as demonstrated by the attenuation of the mouse neuroinvasive phenotype of WNV. Thus, as a proof of concept, residues in the EDI-EDII hinge region are proposed targets to engineer attenuating mutations for inclusion in the rational design of candidate live-attenuated flavivirus vaccines. [ABSTRACT FROM AUTHOR]

Background: Back pain occurs commonly in adults and is multifactorial in nature. This study aimed to assess the prevalence and intensity of back pain during young adulthood in subjects with adolescent idiopathic scoliosis (AIS), as well as factors that may be associated with its prognosis. Methods: Subjects with AIS aged 20–39 treated conservatively were included in this study. Patient-reported outcome measures in adulthood involved episodes of back pain, and scales of self-image, depression, anxiety, and stress. Additionally, pain, self-image, and mental health scores were retrieved at the first clinic consultation. Occurrence of back pain was defined as a numeric pain rating scale ≥ 6. Results: 101 participants were enrolled. The prevalence of back pain in the lifetime, past 12 months, past 6 months, past 1 month, past 7 days, and past 24 h were 37%, 35%, 31%, 27%, 23%, and 20%, respectively. Male, self-image, and depression were significant associated factors for the development of back pain at all time points. Furthermore, the analyses of the initial presentation of participants have shown that participants with back pain in adulthood were characterised by poor self-image and mental health during their adolescence. Conclusion: The present study addressed the natural history of back pain in young adults with conservatively treated AIS. Psychological makeup has been shown to constitute the development of back pain and is strongly hinted as an early sign of having back pain in adulthood among subjects with AIS. [ABSTRACT FROM AUTHOR]

Law enforcement officers are the primary individuals called and who respond to situations of heightened concern. They make split-second observations and decisions based on how best to react to given safety situations and those involved. Characteristics of autism spectrum disorders (ASD), if not properly understood and reacted to, may quickly escalate a law enforcement officer call in a negative way, making autism training for law enforcement officers imperative. To ascertain what is known about autism training for law enforcement officers, a scoping review was conducted. Five studies met final inclusion criteria. The trainees, context and development of the training, evaluation procedures, and training outcomes are synthesized to provide guidance for future training implementation teams. Areas for future research are presented. [ABSTRACT FROM AUTHOR]

Defects in parts produced by additive manufacturing, instead of simply being perceived as deleterious, can act as important sources of information associated with the complex physical processes that occur during materials deposition and subsequent thermal cycles. Indeed, they act as materials-state 'fossil' records of the dynamic AM process. The approach of using defects as epoch-like records of prior history has been developed while studying additively manufactured Ti–6Al–4V and has given new insights into processes that may otherwise remain either obscured or unquantified. Analogous to 'epochs,' the evolution of these defects often is characterized by physics that span across a temporal length scale. To demonstrate this approach, a broad range of analyses including optical and electron microscopy, X-ray computed tomography, energy-dispersive spectroscopy, and electron backscatter diffraction have been used to characterize a raster-scanned electron beam Ti–6Al–4V sample. These analysis techniques provide key characteristics of defects such as their morphology, location within the part, complex compositional fields interacting with the defects, and structures on the free surfaces of defects. Observed defects have been classified as banding, spherical porosity, and lack of fusion. Banding is directly related to preferential evaporation of Al, which has an influence on mechanical properties. Lack-of-fusion defects can be used to understand columnar grain growth, fluid flow of melt pools, humping, and spattering events. [ABSTRACT FROM AUTHOR]

Y-box binding protein 1 (YBX1 or YB1) is a therapeutically relevant oncoprotein capable of RNA and DNA binding and mediating protein–protein interactions that drive proliferation, stemness, and resistance to platinum-based therapies. Given our previously published findings, the potential for YB1-driven cisplatin resistance in medulloblastoma (MB), and the limited studies exploring YB1-DNA repair protein interactions, we chose to investigate the role of YB1 in mediating radiation resistance in MB. MB, the most common pediatric malignant brain tumor, is treated with surgical resection, cranio-spinal radiation, and platinum-based chemotherapy, and could potentially benefit from YB1 inhibition. The role of YB1 in the response of MB to ionizing radiation (IR) has not yet been studied but remains relevant for determining potential anti-tumor synergy of YB1 inhibition with standard radiation therapy. We have previously shown that YB1 drives proliferation of cerebellar granular neural precursor cells (CGNPs) and murine Sonic Hedgehog (SHH) group MB cells. While others have demonstrated a link between YB1 and homologous recombination protein binding, functional and therapeutic implications remain unclear, particularly following IR-induced damage. Here we show that depleting YB1 in both SHH and Group 3 MB results not only in reduced proliferation but also synergizes with radiation due to differential response dynamics. YB1 silencing through shRNA followed by IR drives a predominantly NHEJ-dependent repair mechanism, leading to faster γH2AX resolution, premature cell cycle re-entry, checkpoint bypass, reduced proliferation, and increased senescence. These findings show that depleting YB1 in combination with radiation sensitizes SHH and Group 3 MB cells to radiation. [ABSTRACT FROM AUTHOR]

B Correction to: Environ Monit Assess (2020) 192: 458 b https://doi.org/10.1007/s10661-020-08403-1 The original version of this article unfortunately contained errors in Figures 4, 6, 7 and Tables S3, S5 and Table 3. 4 Ranking results for candidate basins within each of 18 hydrologic regions; top-ranked basins are given in Table 3 Graph: Fig. 6 Distribution of candidate basins (all dots), top-two ranked basins (orange dots), and the Delaware River Basin and Colorado-Gunnison Basin (black dots for regions 1 and 15, respectively) by region for the 10 ranking variables (Variables are defined in Table 1, and regions are shown on Fig. [Extracted from the article]

Entrepreneurial ecosystems (EE) are composed not only of startups but also the organizations that support them. Theory has been ambivalent about whether an EE is spatially bounded or includes distant organizations. This exploratory study uses a time series of all Internet industry initial public offerings (IPO) to explore the locational changes not only of startups but also four key EE service providers: lawyers, investment bankers, venture capitalists, and board directors. We find that while the startups became only slightly more concentrated, the EE service providers concentrated more rapidly, as an industry center in Silicon Valley emerged. Our results suggest that over the industry life cycle, industry knowledge exhibits a tendency to spatially concentrate, and this results in a concentration of industry-specific EE service providers that is even greater than the more gradual concentration of startups. As a result, startups, wherever they are located, increasingly source EE services from the industrial knowledge concentration. Plain English Summary: Using the entire life of the Internet industry, we show that entrepreneurial ecosystems are composed of local and extra-local service providers. Moreover, as the industry matured, the generic local entrepreneurial support service providers were replaced by those located in the dominant region which also had developed industry knowledge. The dominant region's support providers effectively became service providers for both local and distant entrepreneurs. The principal implication of this study is that local policymakers should understand and explain to local startups the value of EE members that are extra-local, as these actors may have intimate and current industry-specific knowledge necessary to successfully build their firm. Entrepreneurs should weigh carefully whether it is more efficient to use local EE service providers or those in the region with the greatest industry knowledge. [ABSTRACT FROM AUTHOR]

As commissioned by the Society for Prevention Research, this paper describes and illustrates strategic approaches for reducing health inequities and advancing health equity when adopting an equity-focused approach for applying prevention science evidence-based theory, methodologies, and practices. We introduce an ecosystemic framework as a guide for analyzing, designing, and planning innovative equity-focused evidence-based preventive interventions designed to attain intended health equity outcomes. To advance this process, we introduce a health equity statement for conducting integrative analyses of ecosystemic framework pathways, by describing the role of social determinants, mechanisms, and interventions as factors directly linked to specific health equity outcomes. As background, we present health equity constructs, theories, and research evidence which can inform the design and development of equity-focused intervention approaches. We also describe multi-level interventions that when coordinated can produce synergistic intervention effects across macro, meso, and micro ecological levels. Under this approach, we encourage prevention and implementation scientists to apply and extend these strategic directions in future research to increase our evidence-based knowledge and theory building. A general goal is to apply prevention science knowledge to design, widely disseminate, and implement culturally grounded interventions that incrementally attain specific HE outcomes and an intended HE goal. We conclude with recommendations for conducting equity-focused prevention science research, interventions, and training. [ABSTRACT FROM AUTHOR]

A fundamental challenge in diagnostics is integrating multiple modalities to develop a joint characterization of physiological state. Using the heart as a model system, we develop a cross-modal autoencoder framework for integrating distinct data modalities and constructing a holistic representation of cardiovascular state. In particular, we use our framework to construct such cross-modal representations from cardiac magnetic resonance images (MRIs), containing structural information, and electrocardiograms (ECGs), containing myoelectric information. We leverage the learned cross-modal representation to (1) improve phenotype prediction from a single, accessible phenotype such as ECGs; (2) enable imputation of hard-to-acquire cardiac MRIs from easy-to-acquire ECGs; and (3) develop a framework for performing genome-wide association studies in an unsupervised manner. Our results systematically integrate distinct diagnostic modalities into a common representation that better characterizes physiologic state. A challenge in diagnostics is integrating different data modalities to characterize physiological state. Here, the authors show, using the heart as a model system, that cross-modal autoencoders can integrate and translate modalities to improve diagnostics and identify associated genetic variants. [ABSTRACT FROM AUTHOR]

Florida's coastal salt marshes are vulnerable to both direct and indirect human impacts, including climate change and consequent sea-level rise. For a salt marsh to survive in the face of ongoing sea-level rise, organic and/or mineral sediment must accumulate at a rate equal to or faster than that of sea-level increase. We explored the effects of Late Holocene sea-level variations in the Suwannee River Estuary within the Big Bend region of Florida (USA). We conducted a paleoenvironmental study of a sediment core collected from a salt marsh near Cedar Key, on Florida's Gulf of Mexico coast. The core spans the last ~ 320 years of sediment accumulation. Carbon isotope (δ13C) data and diatom assemblages indicate the salt marsh was relatively stable during that time frame and was dominated by C3 vegetation, likely Juncus roemerianus, but experienced moderate variations in salinity that likely reflect changes in sea-level, with an increase in salinity and marine incursions between ~ 1850 and 1930 CE. Whereas small vertical changes in sea-level have the potential to inundate large areas of the low-gradient salt marsh, as observed during the interval ~ 1850–1930 CE, the salt-marsh vegetation recovered quickly after 1930 CE, indicating that the rate of aggradation and vegetation growth kept pace with the rate of sea-level rise. Despite the apparent resiliency of Big Bend salt marshes and likelihood that they will persist through accretion and migration, we expect to see major changes in salt-marsh ecology if rates of sea-level rise continue to accelerate. [ABSTRACT FROM AUTHOR]

Conducting a critical appraisal is considered as one of the essential steps in any type of qualitative synthesis. While various appraisal tools are available in the literature, the reliability and validity of these tools tend to be limited due to inconsistencies in their conceptualizations and operationalizations. In addition, limited practical guidelines are available for researchers to develop and use these appraisal form for their own synthesis studies. Our goal for this study is to use and modify components of existing tools and work to address the concerns that have been laid out in existing research. Specifically, we set out to (a) keep detailed notes of our development of the appraisal tool over time, (b) attend to the inter-rater reliability and content validity of the appraisal tool, (c) provide a guidance on how to use the tool, and (d) produce an appraisal tool that could be used by all levels of researchers. In this paper, we explain the process we undertook to establish a reliable and valid critical appraisal tool for qualitative syntheses, share the developed 22-question critical appraisal form, and provide an example of how to use the results of a critical appraisal in a sample qualitative synthesis. The developed tool will help focus qualitative synthesis researchers' attention on the transparency and completeness of the information reported in primary studies and thereby increase the credibility of a qualitative synthesis. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the most common diabetic microvascular complication and cause of blindness in adults under the age of 65. Our results suggest that, when comparing transcriptomes of cultures grown in hypoxic conditions versus room-air, cybrids containing mitochondria from African and Asian diabetic subjects ([Afr + Asi]/DM) have some uniquely different transcriptome profiles compared to European/diabetic (Euro/DM) cybrids (e.g., fatty acid metabolism: EnrichR rank 10 in [Afr + Asi]/DM, rank 85 in Euro/DM; Endocytosis: rank 25 in [Afr + Asi]/DM, rank 5 in Euro/DM; Ubiquitin Mediated Proteolysis: rank 34 in [Afr + Asi]/DM, rank 7 in Euro/DM). As determined by both RNA-seq and qRT-PCR results, transcription of the gene encoding oleoyl-ACP hydrolase (OLAH) was significantly increased in [Afr + Asi]/DM cybrids compared to Euro/DM cybrids in hypoxic conditions. Additionally, our results show that in hypoxic conditions, Euro/DM cybrids and [Afr + Asi]/DM cybrids show similar decreases in ROS production. All cybrids showed decreased ZO1-minus protein levels, but their phagocytic functions were not significantly altered in hypoxic conditions. In conclusion, our findings suggest that the "molecular memory" imparted by [Afr + Asi]/DM mtDNA may act through one of the molecular pathways seen in transcriptome analysis, such as fatty acid metabolism, without significantly changing essential RPE functions. [ABSTRACT FROM AUTHOR]

Managing Construction and demolition waste (CDW) is a severe and growing urban challenge, particularly in post-conflict countries. Though Kosovo has significantly rebuilt and developed after the Liberation War, these initiatives have accompanied suboptimal waste management. This research evaluates CDW management in Kosovo by assessing current practices and operations vis-a-vis the legal framework and EU requirements. It identifies instruments and policies capable of ameliorating gaps and proposes a more sustainable and circular CDW management system for Kosovo. Information was primarily collected during on-site visits to Pristina and the surroundings by a cohort of Urban Management Students from the Technische Universität Berlin, students from Kosovo, and the local office of the Gesellschaft für Internationale Zusammenarbeit, GIZ. The analysis identified gaps in Kosovo's CDW management and its observance and enforcement of existing CDW legislation, including an ambiguous licensing system impeding sustainable demolition, storage, and transport; the absence of approved CDW storage options leading to uncontrolled disposal; and an underdeveloped market for recycling and reuse, deterring stakeholders from further pursuit of circular practices. These gaps were compounded by poor recordkeeping, obscuring precise information on CDW streams. Possible instruments and incentives to support Kosovo's transition to a more sustainable CDW management system were then identified. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 Omicron variant is more immune evasive and less virulent than other major viral variants that have so far been recognized1–12. The Omicron spike (S) protein, which has an unusually large number of mutations, is considered to be the main driver of these phenotypes. Here we generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.1 lineage) in the backbone of an ancestral SARS-CoV-2 isolate, and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escaped vaccine-induced humoral immunity, mainly owing to mutations in the receptor-binding motif; however, unlike naturally occurring Omicron, it efficiently replicated in cell lines and primary-like distal lung cells. Similarly, in K18-hACE2 mice, although virus bearing Omicron S caused less severe disease than the ancestral virus, its virulence was not attenuated to the level of Omicron. Further investigation showed that mutating non-structural protein 6 (nsp6) in addition to the S protein was sufficient to recapitulate the attenuated phenotype of Omicron. This indicates that although the vaccine escape of Omicron is driven by mutations in S, the pathogenicity of Omicron is determined by mutations both in and outside of the S protein.Comparisons of a chimeric recombinant version of SARS-CoV-2, the ancestral SARS-CoV-2 strain and an Omicron isolate show that the attenuated virulence of Omicron is caused by mutations in both the spike protein and nsp6. [ABSTRACT FROM AUTHOR]

Understanding vector dispersal capacity is key to assessing the risk of spread of vector borne pathogens. For flying vectors, flight performance is associated with primary and secondary pathogen spread. However, because pathogens induce changes in vector physiology, pathogen status in the vector may impact vector dispersal. In this work, by using flight mills, we assessed the flight performance of Bactericera cockerelli that were infected or not by the plant pathogenic bacterium 'Candidatus Liberibacter solanacearum' (CLso), the causal agent of potato zebra chip disease and vein greening in tomato. Bactericera cockerelli performed short and long-distance flights, but CLso infection status affected the propensity to engage in long flights. CLso-free insects engaged in long flights significantly more often (57%) compared to CLso infected insects (25%). Average distance dispersed for long flyers was 185.33 m for CLso-free insects and 122.99 m for insects infected with CLso. However, distance dispersed was not statistically different by pathogen status of the vector. Maximal flight capacity recorded was 980 m. Overall, our data suggest that CLso reduces the propensity to engage in long distance flights. Our results can be utilized to fine-tune strategies to mitigate CLso establishment in new areas. [ABSTRACT FROM AUTHOR]

MF-LOGP, a new method for determining a single component octanol–water partition coefficients ( LogP ) is presented which uses molecular formula as the only input. Octanol–water partition coefficients are useful in many applications, ranging from environmental fate and drug delivery. Currently, partition coefficients are either experimentally measured or predicted as a function of structural fragments, topological descriptors, or thermodynamic properties known or calculated from precise molecular structures. The MF-LOGP method presented here differs from classical methods as it does not require any structural information and uses molecular formula as the sole model input. MF-LOGP is therefore useful for situations in which the structure is unknown or where the use of a low dimensional, easily automatable, and computationally inexpensive calculations is required. MF-LOGP is a random forest algorithm that is trained and tested on 15,377 data points, using 10 features derived from the molecular formula to make LogP predictions. Using an independent validation set of 2713 data points, MF-LOGP was found to have an average RMSE = 0.77 ± 0.007, MAE = 0.52 ± 0.003, and R 2 = 0.83 ± 0.003. This performance fell within the spectrum of performances reported in the published literature for conventional higher dimensional models ( RMSE = 0.42–1.54, MAE = 0.09–1.07, and R 2 = 0.32–0.95). Compared with existing models, MF-LOGP requires a maximum of ten features and no structural information, thereby providing a practical and yet predictive tool. The development of MF-LOGP provides the groundwork for development of more physical prediction models leveraging big data analytical methods or complex multicomponent mixtures. [ABSTRACT FROM AUTHOR]

For any given body mass index (BMI), individuals vary substantially in fat distribution, and this variation may have important implications for cardiometabolic risk. Here, we study disease associations with BMI-independent variation in visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) fat depots in 40,032 individuals of the UK Biobank with body MRI. We apply deep learning models based on two-dimensional body MRI projections to enable near-perfect estimation of fat depot volumes (R2 in heldout dataset = 0.978-0.991 for VAT, ASAT, and GFAT). Next, we derive BMI-adjusted metrics for each fat depot (e.g. VAT adjusted for BMI, VATadjBMI) to quantify local adiposity burden. VATadjBMI is associated with increased risk of type 2 diabetes and coronary artery disease, ASATadjBMI is largely neutral, and GFATadjBMI is associated with reduced risk. These results – describing three metabolically distinct fat depots at scale – clarify the cardiometabolic impact of BMI-independent differences in body fat distribution. Different location of adipose tissue may have different consequences to cardiometabolic risk. Here the authors report that deep learning enabled accurate prediction of specific adipose tissue volumes, and that after adjustment for BMI, visceral adiposity was associated with increased risk of cardiometabolic disease, while gluteofemoral adiposity was associated with reduced risk. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this study was to explore the utility of islet autoantibody (IAb) levels for the prediction of type 1 diabetes in autoantibody-positive children. Methods: Prospective cohort studies in Finland, Germany, Sweden and the USA followed 24,662 children at increased genetic or familial risk of developing islet autoimmunity and diabetes. For the 1403 who developed IAbs (523 of whom developed diabetes), levels of autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated antigen-2 (IA-2A) were harmonised for analysis. Diabetes prediction models using multivariate logistic regression with inverse probability censored weighting (IPCW) were trained using 10-fold cross-validation. Discriminative power for disease was estimated using the IPCW concordance index (C index) with 95% CI estimated via bootstrap. Results: A baseline model with covariates for data source, sex, diabetes family history, HLA risk group and age at seroconversion with a 10-year follow-up period yielded a C index of 0.61 (95% CI 0.58, 0.63). The performance improved after adding the IAb positivity status for IAA, GADA and IA-2A at seroconversion: C index 0.72 (95% CI 0.71, 0.74). Using the IAb levels instead of positivity indicators resulted in even better performance: C index 0.76 (95% CI 0.74, 0.77). The predictive power was maintained when using the IAb levels alone: C index 0.76 (95% CI 0.75, 0.76). The prediction was better for shorter follow-up periods, with a C index of 0.82 (95% CI 0.81, 0.83) at 2 years, and remained reasonable for longer follow-up periods, with a C index of 0.76 (95% CI 0.75, 0.76) at 11 years. Inclusion of the results of a third IAb test added to the predictive power, and a suitable interval between seroconversion and the third test was approximately 1.5 years, with a C index of 0.78 (95% CI 0.77, 0.78) at 10 years follow-up. Conclusions/interpretation: Consideration of quantitative patterns of IAb levels improved the predictive power for type 1 diabetes in IAb-positive children beyond qualitative IAb positivity status. [ABSTRACT FROM AUTHOR]

Autistic individuals and law enforcement officers are likely to engage under various circumstances within the community. Therefore, law enforcement officers require training on supporting those with autism and better understanding autistic behaviors. Aims for this study include: (1) developing and delivering high quality professional development on autism spectrum disorder (ASD) to support autistic individuals during encounters with law enforcement officers, and (2) examining how law enforcement officers respond to the professional development session. For this study a four-hour, in-person training on autism for law enforcement officers was developed. Law enforcement officers (n = 27) attended the training session. Subsequently, participants completed an open-ended survey gathering perceptions related to the topics covered in the training, thoughts on the feasibility and applicability of content, and transfer to future safety encounters involving autistic individuals. Data was analyzed using a qualitative approach including concept driven thematic coding with constant comparisons. Data yielded themes on experiences with the autistic community, strategies learned from the training, thoughts on specific content, and feedback on the training format. Overall, law enforcement officers reported they felt better prepared, more knowledgeable on the autistic community, and believed the strategies were feasible and applicable to the field. These findings point to the importance of training on autism and that law enforcement officers found it was time well spent. Future directions include examining how training transfers to practice in the field and ways to connect law enforcement officers with the autistic community outside of emergency response. [ABSTRACT FROM AUTHOR]

Purpose: This review aimed to identify effective physical performance tests (PPT) as clinical outcome indicators for detecting and monitoring degenerative cervical myelopathy (DCM). Methods: A comprehensive literature search was performed on seven electronic databases on the effectiveness in detection and monitoring of DCM by PPT. All included studies were reviewed and undergone quality assessments on the risk-of-bias by Newcastle-Ottawa Scale and were pooled by random-effect analysis with level of significance at 0.05. Homogeneity among studies was assessed by I2-statistics and effect of PPT was confirmed by Cohen's d effect size and confidence intervals. Results: Totally, 3111 articles were retrieved, and 19 studies were included for review and meta-analysis. There were 13 studies investigating PPT regarding the upper limbs and 12 studies regarding the lower limbs. Performance in 10-second-Grip-and-Release Test (G&R) and 9-Hole-Peg Test (9HPT) was studied in 10 and 3 articles, respectively, while 10-second-Stepping Test (SST), 30-meter-Walking Test (30MWT) and Foot-Tapping Test (FTT) for lower limbs were studied in 5, 4, and 3 articles correspondingly. Only 1 study utilized the Triangle-Stepping Test. High-quality study with fair risk-of-bias was revealed from Newcastle-Ottawa scale. Large effect size facilitated detection and monitoring in DCM was unveiling for G&R, 9HPT, SST, and 30MWT. FTT, while also effective, was hindered by a high-degree heterogeneity in the meta-analysis. Conclusion: Effective PPT including G&R, 9HPT, SST, 30MWT, and FTT was identified for disease detection and monitoring in DCM. [ABSTRACT FROM AUTHOR]

Noncanonical cofactor biomimetics (NCBs) such as nicotinamide mononucleotide (NMN+) provide enhanced scalability for biomanufacturing. However, engineering enzymes to accept NCBs is difficult. Here, we establish a growth selection platform to evolve enzymes to utilize NMN+-based reducing power. This is based on an orthogonal, NMN+-dependent glycolytic pathway in Escherichia coli which can be coupled to any reciprocal enzyme to recycle the ensuing reduced NMN+. With a throughput of >106 variants per iteration, the growth selection discovers a Lactobacillus pentosus NADH oxidase variant with ~10-fold increase in NMNH catalytic efficiency and enhanced activity for other NCBs. Molecular modeling and experimental validation suggest that instead of directly contacting NCBs, the mutations optimize the enzyme's global conformational dynamics to resemble the WT with the native cofactor bound. Restoring the enzyme's access to catalytically competent conformation states via deep navigation of protein sequence space with high-throughput evolution provides a universal route to engineer NCB-dependent enzymes. Engineering enzymes to accept noncanonical cofactor biomimetics is difficult. Here, the authors establish a self-sufficient growth selection method and demonstrate its application in engineering the Lactobacillus pentosus NADH oxidase to efficiently recycle reduced nicotinamide mononucleotide (NMNH). [ABSTRACT FROM AUTHOR]

Background: The first surge of the COVID-19 pandemic entirely altered healthcare delivery. Whether this also altered the receipt of high- and low-value care is unknown.Objective: To test the association between the April through June 2020 surge of COVID-19 and various high- and low-value care measures to determine how the delivery of care changed.Design: Difference in differences analysis, examining the difference in quality measures between the April through June 2020 surge quarter and the January through March 2020 quarter with the same 2 quarters' difference the year prior.Participants: Adults in the MarketScan® Commercial Database and Medicare Supplemental Database.Main Measures: Fifteen low-value and 16 high-value quality measures aggregated into 8 clinical quality composites (4 of these low-value).Key Results: We analyzed 9,352,569 adults. Mean age was 44 years (SD, 15.03), 52% were female, and 75% were employed. Receipt of nearly every type of low-value care decreased during the surge. For example, low-value cancer screening decreased 0.86% (95% CI, -1.03 to -0.69). Use of opioid medications for back and neck pain (DiD +0.94 [95% CI, +0.82 to +1.07]) and use of opioid medications for headache (DiD +0.38 [95% CI, 0.07 to 0.69]) were the only two measures to increase. Nearly all high-value care measures also decreased. For example, high-value diabetes care decreased 9.75% (95% CI, -10.79 to -8.71).Conclusions: The first COVID-19 surge was associated with receipt of less low-value care and substantially less high-value care for most measures, with the notable exception of increases in low-value opioid use. [ABSTRACT FROM AUTHOR]

In 2018, the giant manta ray was listed as threatened under the U.S. Endangered Species Act. We integrated decades of sightings and survey effort data from multiple sources in a comprehensive species distribution modeling (SDM) framework to evaluate the distribution of giant manta rays off the eastern United States, including the Gulf of Mexico. Manta rays were most commonly detected at productive nearshore and shelf-edge upwelling zones at surface thermal frontal boundaries within a temperature range of approximately 20–30 °C. SDMs predicted highest nearshore occurrence off northeastern Florida during April, with the distribution extending northward along the shelf-edge as temperatures warm, leading to higher occurrences north of Cape Hatteras, North Carolina from June to October, and then south of Savannah, Georgia from November to March as temperatures cool. In the Gulf of Mexico, the highest nearshore occurrence was predicted around the Mississippi River delta from April to June and again from October to November. SDM predictions will allow resource managers to more effectively protect manta rays from fisheries bycatch, boat strikes, oil and gas activities, contaminants and pollutants, and other threats. [ABSTRACT FROM AUTHOR]

Purpose: Although it is evident that some patients with adolescent idiopathic scoliosis (AIS) have proprioceptive deficit in peripheral joints, knowledge on the proprioceptive function of the deformed spine is limited. Nonetheless, spinal proprioception in AIS may be affected three-dimensionally, prior studies only focussed on evaluating peripheral proprioception in single plane. Therefore, this study aimed to develop a novel spinal proprioception assessment using three-dimensional motion analysis in patients with AIS. Methods: Participants were included if they had a primary diagnosis of AIS who did not receive or failed conservative treatments. Three trunk repositioning tests involving flexion-extension, lateral-flexion, and axial-rotation were conducted. A three-dimensional kinematics of the trunk was used as the outcome measures. The proprioceptive acuity was quantified by the repositioning error. The intra-examiner and test-retest reliability were analysed by the intraclass correlation coefficient (ICC). Results: Fifty-nine patients with AIS were recruited. Regarding the trunk flexion–extension test, the single measure ICC showed moderate reliability (0.46) and the average measures ICC demonstrated good reliability (0.72). As for the trunk lateral-flexion test, the reliability of single measure and average measures ICC was moderate (0.44) and good (0.70) reliability, respectively. For the trunk axial-rotation test, the single measure ICC indicated fair reliability (0.32), while the average measures ICC showed moderate reliability (0.59). Conclusion: This is the first study to evaluate the reliability of novel three-dimensional spinal proprioception assessments in patients with AIS. The trunk flexion-extension repositioning test may be preferable clinical test given its highest reliability. [ABSTRACT FROM AUTHOR]