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Abstract Background Retained surgical items (RSI) are preventable events that pose a significant risk to patient safety. Current strategies for preventing RSIs rely heavily on manual instrument counting methods, which are prone to human error. This study evaluates the feasibility and performance of a deep learning-based computer vision model for automated surgical tool detection and counting. Methods A novel dataset of 1,004 images containing 13,213 surgical tools across 11 categories was developed. The dataset was split into training, validation, and test sets at a 60:20:20 ratio. An artificial intelligence (AI) model was trained on the dataset, and the model’s performance was evaluated using standard object detection metrics, including precision and recall. To simulate a real-world surgical setting, model performance was also evaluated in a dynamic surgical video of instruments being moved in real-time. Results The model demonstrated high precision (98.5%) and recall (99.9%) in distinguishing surgical tools from the background. It also exhibited excellent performance in differentiating between various surgical tools, with precision ranging from 94.0 to 100% and recall ranging from 97.1 to 100% across 11 tool categories. The model maintained strong performance on a subset of test images containing overlapping tools (precision range: 89.6–100%, and recall range 97.2–98.2%). In a real-time surgical video analysis, the model maintained a correct surgical tool count in all non-transition frames, with a median inference speed of 40.4 frames per second (interquartile range: 4.9). Conclusion This study demonstrates that using a deep learning-based computer vision model for automated surgical tool detection and counting is feasible. The model’s high precision and real-time inference capabilities highlight its potential to serve as an AI safeguard to potentially improve patient safety and reduce manual burden on surgical staff. Further validation in clinical settings is warranted.

Background: Studies examining racial and ethnic disparities in-hospital mortality for patients hospitalized with COVID-19 had mixed results. Findings from patients within academic medical centers (AMCs) are lacking, but important given the role of AMCs in improving health equity. Objective: The purpose of this study is to assess whether minority patients hospitalized with COVID-19 in National COVID Cohort Collaborative (N3C) institutions, which consist predominantly of AMCs, have higher mortality rates relative to White patients. Design: A retrospective analysis of patients hospitalized with COVID-19 was performed. Logistic regression analysis was used to test the primary hypothesis. A separate analysis tested whether there were differences by race and ethnicity during the delta variant phase of the pandemic. Patients: All hospitalized patients with COVID-19 who were above 17 years old were categorized by race and ethnicity as Black, Hispanic, Asian, White, Other, and Unknown. Main Measures: In-hospital mortality for patients with a known hospital outcome formed the primary outcome measure. Race and ethnicity were the primary independent variables. Key Results: There were 103,702 in-hospital Covid-19 admissions with 14,207 (13.7%) hospital deaths. Unadjusted in-hospital mortality for White patients was approximately 26% higher than for Black patients. After multivariable adjustment, none of the racial and ethnic groups had significantly different odds of in-hospital mortality compared to White patients. Only Hispanic patients had an odds ratio greater than one that was insignificant (OR = 1.06; 95% CI = 0.92-1.20). Findings for the delta variant phase were similar with the exception of the unknown category (OR = 1.90; 95% CI = 1.05-3.46). Conclusions: Disparities in-hospital mortality outcomes by race or ethnicity were not found in COVID-19 patients hospitalized in AMCs. AMCs are expected to lead health delivery systems in eliminating disparities associated with structural racism. The null findings are consistent with the hypothesis of no difference in hospital outcomes by race or ethnicity in academic medical centers.

Abstract AidData’s Global Chinese Development Finance Dataset (Version 3.0) provides detailed information about more than 20,000 development projects across 165 low- and middle-income countries financed by 791 official sector Chinese donors and lenders from 2000 to 2021. In this study, we introduce a methodology for identifying the geospatial features of these projects. Our application of the methodology has resulted in the Geospatial Global Chinese Development Finance Dataset (Version 3.0), which captures the geospatial features of 9,405 projects across 148 low- and middle-income countries supported by Chinese grant and loan commitments worth more than USD 830 billion. The dataset provides details for 6,266 projects containing spatial definitions of roads, railways, power plants, transmission lines, buildings, and other precisely geocoded features. It identifies approximate and administrative-level locations for 3,139 additional projects. The methodology, dataset, and the code used to construct the dataset have been made publicly available to facilitate replication and future applications.

In postoperative care, patient education and follow-up are pivotal for enhancing the quality of care and satisfaction. Artificial intelligence virtual assistants (AIVA) and large language models (LLMs) like Google BARD and ChatGPT-4 offer avenues for addressing patient queries using natural language processing (NLP) techniques. However, the accuracy and appropriateness of the information vary across these platforms, necessitating a comparative study to evaluate their efficacy in this domain. We conducted a study comparing AIVA (using Google Dialogflow) with ChatGPT-4 and Google BARD, assessing the accuracy, knowledge gap, and response appropriateness. AIVA demonstrated superior performance, with significantly higher accuracy (mean: 0.9) and lower knowledge gap (mean: 0.1) compared to BARD and ChatGPT-4. Additionally, AIVA’s responses received higher Likert scores for appropriateness. Our findings suggest that specialized AI tools like AIVA are more effective in delivering precise and contextually relevant information for postoperative care compared to general-purpose LLMs. While ChatGPT-4 shows promise, its performance varies, particularly in verbal interactions. This underscores the importance of tailored AI solutions in healthcare, where accuracy and clarity are paramount. Our study highlights the necessity for further research and the development of customized AI solutions to address specific medical contexts and improve patient outcomes.

With abundant information and interconnectedness among people, identifying knowledgeable individuals in specific domains has become crucial for organizations. Artificial intelligence (AI) algorithms have been employed to evaluate the knowledge and locate experts in specific areas, alleviating the manual burden of expert profiling and identification. However, there is a limited body of research exploring the application of AI algorithms for expert finding in the medical and biomedical fields. This study aims to conduct a scoping review of existing literature on utilizing AI algorithms for expert identification in medical domains. We systematically searched five platforms using a customized search string, and 21 studies were identified through other sources. The search spanned studies up to 2023, and study eligibility and selection adhered to the PRISMA 2020 statement. A total of 571 studies were assessed from the search. Out of these, we included six studies conducted between 2014 and 2020 that met our review criteria. Four studies used a machine learning algorithm as their model, while two utilized natural language processing. One study combined both approaches. All six studies demonstrated significant success in expert retrieval compared to baseline algorithms, as measured by various scoring metrics. AI enhances expert finding accuracy and effectiveness. However, more work is needed in intelligent medical expert retrieval.

Summary: Autosomal-dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by the formation of fluid-filled renal cysts, loss of mitochondrial function, decreased fatty acid oxidation, increased glycolysis, and likely renal failure. We previously demonstrated that inducing a state of ketosis ameliorates or reverses PKD progression in multiple animal models. In this study, we compare time-restricted feeding and 48-h periodic fasting regimens in both juvenile and adult Cy/+ rats. Both fasting regimens potently prevent juvenile disease progression and partially reverse PKD in adults. To explore the mechanism of fasting, we administered β-hydroxybutyrate (BHB) to Cy/+ rats and orthologous mouse models of PKD (Pkd1RC/RC, Pkd1-Ksp:Cre). BHB recapitulated the effects of fasting in these models independent of stereoisomer, suggesting the effects of BHB are largely due to its signaling functions. These findings implicate the use of ketogenic metabolic therapy and BHB supplementation as potential disease modifiers of PKD and point toward underlying mechanisms.

Abstract Concurrent resistance and endurance exercise training (CET) has well‐studied benefits; however, inherent hormonal and genetic differences alter adaptive responses to exercise between sexes. Extracellular vesicles (EVs) are factors that contribute to adaptive signaling. Our purpose was to test if EV characteristics differ between men and women following CET. 18 young healthy participants underwent 12‐weeks of CET. Prior to and following CET, subjects performed an acute bout of heavy resistance exercise (AHRET) consisting of 6 × 10 back squats at 75% 1RM. At rest and following AHRET, EVs were isolated from plasma and characteristics and miRNA contents were analyzed. AHRET elevated EV abundance in trained men only (+51%) and AHRET‐induced changes were observed for muscle‐derived EVs and microvesicles. There were considerable sex‐specific effects of CET on EV miRNAs, highlighted by larger variation following the 12‐week program in men compared to women at rest. Pathway analysis based on differentially expressed EV miRNAs predicted that AHRET and 12 weeks of CET in men positively regulates hypertrophy and growth pathways more so than in women. This report highlights sex‐based differences in the EV response to resistance and concurrent exercise training and suggests that EVs may be important adaptive signaling factors altered by exercise training.

Background and objective Various ways exist to display the effectiveness of medical treatment options. This study examined various psychiatric, medical and allied professionals’ understanding and perceived usefulness of eight effect size indices for presenting both dichotomous and continuous outcome data.Methods We surveyed 1316 participants from 13 countries using an online questionnaire. We presented hypothetical treatment effects of interventions versus placebo concerning chronic pain using eight different effect size measures. For each index, the participants had to judge the magnitude of the shown effect, to indicate how certain they felt about their own answer and how useful they found the given effect size index.Findings Overall, 762 (57.9%) participants fully completed the questionnaire. In terms of understanding, the best results emerged when both the control event rate (CER) and the experimental event rate (EER) were presented. The difference in minimal importance difference units (MID unit) was understood worst. Respondents also found CER and EER to be the most useful presentation approach while they rated MID unit as the least useful. Confidence in the risk ratio ranked high, even though it was rather poorly understood.Conclusions and clinical implications For dichotomous outcomes, presenting the effects in terms of the CER and EER could lead to the most correct interpretation. Relative measures including the risk ratio must be supplemented with absolute measures such as the CER and EER. Effects on continuous outcomes were better understood through standardised mean differences than mean differences. These can also be supplemented by dichotomised CER and EER.

The objective of the present review was to evaluate the time-course of recovery of biochemical marker levels and physical performance after strenuous military training, and identify which biomarkers are affected. A systematic literature search was conducted using the databases MedLine (Ovid) and Web of Science (WoS) to identify studies until January 2023. Varying relevant search terms were used, related to military training, Special Forces, physical performance, and biomarkers. Records were based on strict inclusion and exclusion criteria. Twelve studies met the inclusion criteria and were selected for this review. A variety of physiological and psychological markers were measured, and military training lasted from 4 to 62 days, with recovery periods varying from 24 h to 6 weeks. Among these studies, full recovery was observed in two studies, while seven studies showed almost full (79–90%) recovery, and in three studies, 44–63% of markers recovered after the measured recovery period. However, in some studies, additional markers could be defined as recovered, depending on the criterion for recovery. In the majority of the studies, most of the measured variables recovered during the follow-up, but often, some variables remained unrecovered, and at times, only modest recovery was seen. It is important to point out that recovery duration depends on the duration and intensity of the military training stressor. Overall, resolution varies between the markers, and sometimes, recovery might not occur, even after prolonged recovery. Therefore, it is important to measure the recovery status of soldiers with both biomarkers and physical performance markers, especially after strenuous training, to maximize operational capability during prolonged missions.

Medical researchers are increasingly utilizing advanced LLMs like ChatGPT-4 and Gemini to enhance diagnostic processes in the medical field. This research focuses on their ability to comprehend and apply complex medical classification systems for breast conditions, which can significantly aid plastic surgeons in making informed decisions for diagnosis and treatment, ultimately leading to improved patient outcomes. Fifty clinical scenarios were created to evaluate the classification accuracy of each LLM across five established breast-related classification systems. Scores from 0 to 2 were assigned to LLM responses to denote incorrect, partially correct, or completely correct classifications. Descriptive statistics were employed to compare the performances of ChatGPT-4 and Gemini. Gemini exhibited superior overall performance, achieving 98% accuracy compared to ChatGPT-4’s 71%. While both models performed well in the Baker classification for capsular contracture and UTSW classification for gynecomastia, Gemini consistently outperformed ChatGPT-4 in other systems, such as the Fischer Grade Classification for gender-affirming mastectomy, Kajava Classification for ectopic breast tissue, and Regnault Classification for breast ptosis. With further development, integrating LLMs into plastic surgery practice will likely enhance diagnostic support and decision making.

Abstract Objective To assess the impact of reducing saturated fat or fatty foods, or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of mortality and major cancer and cardiometabolic outcomes in adults. Methods We searched MEDLINE, EMBASE, CINAHL, and references of included studies for systematic reviews and meta-analyses (SRMAs) of randomized controlled trials (RCTs) and observational studies in adults published in the past 10 years. Eligible reviews investigated reducing saturated fat or fatty foods or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of cancer and cardiometabolic outcomes and assessed the certainty of evidence for each outcome using, for example, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. We assessed the quality of SRMAs using a modified version of AMSTAR-2. Results were summarized as absolute estimates of effect together with the certainty of effects using a narrative synthesis approach. Results We included 17 SRMAs (13 reviews of observational studies with follow-up 1 to 34 years; 4 reviews of RCTs with follow-up 1 to 17 years). The quality of two-thirds of the SRMAs was critically low to moderate; the main limitations included deficient reporting of study selection, absolute effect estimates, sources of funding, and a priori subgroups to explore heterogeneity. Our included reviews reported > 100 estimates of effect across 11 critically important cancer and cardiometabolic outcomes. High quality SRMAs consistently and predominantly reported low to very low certainty evidence that reducing or replacing saturated fat was associated with a very small risk reduction in cancer and cardiometabolic endpoints. The risk reductions where approximately divided, some being statistically significant and some being not statistically significant. However, based on 2 moderate to high quality reviews, we found moderate certainty evidence for a small but important effect that was statistically significant for two outcomes (total mortality events [20 fewer events per 1000 followed] and combined cardiovascular events [16 fewer per 1000 followed]). Conversely, 4 moderate to high quality reviews showed very small effects on total mortality, with 3 of these reviews showing non-statistically significant mortality effects. Conclusion Systematic reviews investigating the impact of SFA on mortality and major cancer and cardiometabolic outcomes almost universally suggest very small absolute changes in risk, and the data is based primarily on low and very low certainty evidence. Systematic review registration PROSPERO CRD42020172141

Abstract Various approaches have used neural networks as probabilistic models for the design of protein sequences. These "inverse folding" models employ different objective functions, which come with trade-offs that have not been assessed in detail before. This study introduces probabilistic definitions of protein stability and conformational specificity and demonstrates the relationship between these chemical properties and the $$p(\text {structure}|\text {seq})$$ p ( structure | seq ) Boltzmann probability objective. This links the Boltzmann probability objective function to experimentally verifiable outcomes. We propose a novel sequence decoding algorithm, referred to as “BayesDesign”, that leverages Bayes’ Rule to maximize the $$p(\text {structure}|\text {seq})$$ p ( structure | seq ) objective instead of the $$p(\text {seq}|\text {structure})$$ p ( seq | structure ) objective common in inverse folding models. The efficacy of BayesDesign is evaluated in the context of two protein model systems, the NanoLuc enzyme and the WW structural motif. Both BayesDesign and the baseline ProteinMPNN algorithm increase the thermostability of NanoLuc and increase the conformational specificity of WW. The possible sources of error in the model are analyzed.

Abstract To understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p

Traumatic brain injury (TBI) is a leading cause of cognitive disability in adults, often characterized by marked deficits in episodic memory and executive function. Prior studies have found that direct electrical stimulation of the temporal cortex yielded improved memory in epilepsy patients, but it is not clear if these results generalize to patients with a specific history of TBI. Here we asked whether applying closed-loop, direct electrical stimulation to lateral temporal cortex could reliably improve memory in a TBI cohort. Among a larger group of patients undergoing neurosurgical evaluation for refractory epilepsy, we recruited a subset of patients with a history of moderate-to-severe TBI. By analyzing neural data from indwelling electrodes as patients studied and recalled lists of words, we trained personalized machine-learning classifiers to predict momentary fluctuations in mnemonic function in each patient. We subsequently used these classifiers to trigger high-frequency stimulation of the lateral temporal cortex (LTC) at moments when memory was predicted to fail. This strategy yielded a 19% boost in recall performance on stimulated as compared with non-stimulated lists (P = 0.012). These results provide a proof-of-concept for using closed-loop stimulation of the brain in treatment of TBI-related memory impairment.

Abstract Plastic pollution is distributed patchily around the world’s oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.

BackgroundOnly 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response.MethodsWe developed an “immunotumoroid” cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange. Immunohistochemistry was used to detect immune and non-immune cells in cryopreserved source tumors and the resulting immunotumoroids. Immunotumoroid response to ICIs (nivolumab, pembrolizumab, and durvalumab) and chemotherapy (cisplatin, gemcitabine, and paclitaxel) was monitored in real-time with Cytotox Red staining in an Incucyte device, and the immunotumoroid response was compared to retrospective clinical drug responses.ResultsSix of the 13 cases tested grew viable immunotumoroid models, with failed cases attributed to extensive tumor tissue necrosis or excess lymphocytes preventing spheroid formation. One successfully cultured case was excluded from the study due to low TIL infiltration (

Abstract This study compared the structural and cellular skeletal muscle factors underpinning adaptations in maximal strength, power, aerobic capacity, and lean body mass to a 12‐week concurrent resistance and interval training program in men and women. Recreationally active women and men completed three training sessions per week consisting of high‐intensity, low‐volume resistance training followed by interval training performed using a variety upper and lower body exercises representative of military occupational tasks. Pre‐ and post‐training vastus lateralis muscle biopsies were analyzed for changes in muscle fiber type, cross‐sectional area, capillarization, and mitochondrial biogenesis marker content. Changes in maximal strength, aerobic capacity, and lean body mass (LBM) were also assessed. Training elicited hypertrophy of type I (12.9%; p = 0.016) and type IIa (12.7%; p = 0.007) muscle fibers in men only. In both sexes, training decreased type IIx fiber expression (1.9%; p = 0.046) and increased total PGC‐1α (29.7%, p

The Georgia Center for Oncology Research and Education (Georgia CORE) and the Georgia Society of Clinical Oncology (GASCO) held a one-day summit exploring opportunities and evidence-based interventions to address disparities in cancer clinical trials. The purpose of the summit was to identify clear and concise recommendations aimed at decreasing clinical trial accrual disparities in Georgia for rural and minority populations. The summit included expert presentations, panel discussions with leaders from provider organizations throughout Georgia, and breakout sessions to allow participants to critically discuss the information presented. Over 120 participants attended the summit. Recognizing the need for evidence-based interventions to improve clinical trial accrual among rural Georgians and persons of color, summit participants identified four key areas of focus that included: improving clinical trial design, providing navigation for all, enhancing public education and awareness of cancer clinical trials, and identifying potential policy and other opportunities. A comprehensive list of takeaways and action plans was developed in the four key areas of focus with the expectation that implementation of the strategies that emerged from the summit will enhance cancer clinical trial accrual for all Georgians.

Abstract Weight‐bearing physical activity can stimulate bone adaptation. This investigation explored the effect of an acute bout of resistance exercise before and after resistance+interval training on circulating biomarkers of bone metabolism and muscle‐bone crosstalk. Healthy young male and female participants (n = 21 male, 28 ± 4 years; n = 17 female, 27 ± 5 years) performed a 6 × 10 squat test (75% 1RM) before and after a 12‐week resistance+interval training program. Before and after completion of the training program, blood samples were collected at rest, immediately postexercise, and 2 h postexercise. Blood samples were analyzed for βCTX, P1NP, sclerostin, osteocalcin, IGF‐1, and irisin. Significant effects of acute exercise (main effect of time) were observed as increases in concentrations of IGF‐1, irisin, osteocalcin, and P1NP from rest to postexercise. A sex*time interaction indicated a greater decline in βCTX concentration from rest to 2 h postexercise and a greater increase in sclerostin concentration from rest to immediately postexercise in male compared with female participants. Sex differences (main effect of sex) were also observed for irisin and P1NP concentrations. In summary, changes in concentrations of biochemical markers of bone metabolism and muscle‐bone crosstalk were observed in males and females after an acute bout of resistance exercise and following 12 weeks of resistance+interval training.

Abstract Net photosynthetic CO2 assimilation rate (A n) decreases at leaf temperatures above a relatively mild optimum (T opt) in most higher plants. This decline is often attributed to reduced CO2 conductance, increased CO2 loss from photorespiration and respiration, reduced chloroplast electron transport rate (J), or deactivation of Ribulose-1,5-bisphosphate Carboxylase Oxygenase (Rubisco). However, it is unclear which of these factors can best predict species independent declines in A n at high temperature. We show that independent of species, and on a global scale, the observed decline in A n with rising temperatures can be effectively accounted for by Rubisco deactivation and declines in J. Our finding that A n declines with Rubisco deactivation and J supports a coordinated down-regulation of Rubisco and chloroplast electron transport rates to heat stress. We provide a model that, in the absence of CO2 supply limitations, can predict the response of photosynthesis to short-term increases in leaf temperature.

Nest survival drives population demographics of most avian species. Researchers and managers have focused studies on investigating nest success in association with climate, land use change (e.g., agriculture), and predators in the Prairie and Arctic biomes. The Boreal Forest is also an important breeding area for ducks and it has undergone rapid land use change caused by industrial development (e.g., oil and gas; forestry). However, duck nesting ecology has received little attention in this biome. Therefore, we investigated nest survival of upland nesting ducks in the Western Boreal Forest of Alberta, Canada, from 2016–2018. We evaluated how daily nest survival rates (N = 96) were affected by a suite of natural and anthropogenic variables measured at the nest-site (microhabitat) and landscape level (macrohabitat). Nest survival was low (0.212 [85% CI: 0.152–0.282]) and comparable to nest survival estimates for ducks elsewhere in North America, including the Prairies. Nest survival increased with nest age and varied annually. At the microhabitat scale, nest survival increased with greater graminoid, forb, and shrub cover at the nest. At the macrohabitat scale, habitat influenced nest survival at coarse spatial scales with lower survival for nests with greater mineral wetland cover within 2500 m and greater survival with more forest cover within 5000 m. For anthropogenic variables, nests had greater survival with increased densities of pipelines and roads within 90 and 30 m of a nest, respectively. Contrary to our predictions, we did not find evidence that oil and gas development negatively affected duck nest survival. Comparisons with research on nest-site selection reveals both adaptive and maladaptive strategies for nest survival and suggests that some resources might be selected at an adaptive peak. Our findings highlight the importance of investigating the effects of anthropogenic disturbance at multiple scales and life history stages to gain a more nuanced understanding of species responses to land use change.

Specialized cancer treatments have the potential to exploit glutamine dependence to increase patient survival rates. Glutamine diagnostics capable of tracking a patient’s response to treatment would enable a personalized treatment dosage to optimize the tradeoff between treatment success and dangerous side effects. Current clinical glutamine testing requires sophisticated and expensive lab-based tests, which are not broadly available on a frequent, individualized basis. To address the need for a low-cost, portable glutamine diagnostic, this work engineers a cell-free glutamine biosensor to overcome assay background and signal-to-noise limitations evident in previously reported studies. The findings from this work culminate in the development of a shelf-stable, paper-based, colorimetric glutamine test with a high signal strength and a high signal-to-background ratio for dramatically improved signal resolution. While the engineered glutamine test is important progress towards improving the management of cancer and other health conditions, this work also expands the assay development field of the promising cell-free biosensing platform, which can facilitate the low-cost detection of a broad variety of target molecules with high clinical value.

Healthy bone adjusts its traits in an exceptionally coordinated, compensatory process. Recent advancements in skeletal imaging via High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) allows for the in vivo 3-dimensional and longitudinal quantification of bone density, microarchitecture, geometry, and parameters of mechanical strength in response to varying strain stimuli including those resulting from exercise or military training. Further, the voxel size of 61 microns has the potential to capture subtle changes in human bone in as little as 8 weeks. Given the typical time course of bone remodeling, short-term detection of skeletal changes in bone microstructure and morphology is indicative of adaptive bone formation, the deposition of new bone formation, uncoupled from prior resorption, that can occur at mechanistically advantageous regions. This review aims to synthesize existing training-induced HR-pQCT data in three distinct populations of healthy adults excluding disease states, pharmacological intervention and nutritional supplementation. Those included are: 1) military basic or officer training 2) general population and 3) non-osteoporotic aging. This review aims to further identify similarities and contrasts with prior modalities and cumulatively interpret results within the scope of bone functional adaptation.

Abstract Background The health effects of dietary fats are a controversial issue on which experts and authoritative organizations have often disagreed. Care providers, guideline developers, policy-makers, and researchers use systematic reviews to advise patients and members of the public on optimal dietary habits, and to formulate public health recommendations and policies. Existing reviews, however, have serious limitations that impede optimal dietary fat recommendations, such as a lack of focus on outcomes important to people, substantial risk of bias (RoB) issues, ignoring absolute estimates of effects together with comprehensive assessments of the certainty of the estimates for all outcomes. Objective We therefore propose a methodologically innovative systematic review using direct and indirect evidence on diet and food-based fats (i.e., reduction or replacement of saturated fat with monounsaturated or polyunsaturated fat, or carbohydrates or protein) and the risk of important health outcomes. Methods We will collaborate with an experienced research librarian to search MEDLINE, EMBASE, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR) for randomized clinical trials (RCTs) addressing saturated fat and our health outcomes of interest. In duplicate, we will screen, extract results from primary studies, assess their RoB, conduct de novo meta-analyses and/or network meta-analysis, assess the impact of missing outcome data on meta-analyses, present absolute effect estimates, and assess the certainty of evidence for each outcome using the GRADE contextualized approach. Our work will inform recommendations on saturated fat based on international standards for reporting systematic reviews and guidelines. Conclusion Our systematic review and meta-analysis will provide the most comprehensive and rigorous summary of the evidence addressing the relationship between saturated fat modification for people-important health outcomes. The evidence from this review will be used to inform public health nutrition guidelines. Trial registration PROSPERO Registration: CRD42023387377 .

Characterizing the behavior of nuclear reactor plate fuels is vital to the progression of advanced fuel systems. The states of pre- and post-irradiation plates need to be determined effectively and efficiently prior to and following irradiation. Due to the hostile post-irradiation environment, characterization must be completed remotely. Laser-based characterization techniques enable the ability to make robust measurements inside a hot-cell environment. The Laser Shock (LS) technique generates high energy shockwaves that propagate through the plate and mechanically characterizes cladding-cladding interfaces.During an irradiation campaign, two Idaho National Laboratory (INL) fabricated MP-1 plates had a fuel breach in the cladding-cladding interface and trace amounts of fission products were released. The objective of this report is to characterize the cladding-cladding interface strengths in three plates fabricated using different fabrication processes. The goal is to assess the risk in irradiating future developmental and production fuel plates. Prior LS testing has shown weaker and more variability in bond strengths within INL MP-1 reference plates than in commercially produced vendor plates. Three fuel plates fabricated with different fabrication processes will be used to bound the bond strength threshold for plate irradiation insertion and assess the confidence of this threshold value.

Background: Palpitations are a frequent reason for referral to pediatric cardiology providers and diagnostic workup includes ambulatory cardiac monitoring. While common practice, the diagnostic yield is unknown in the pediatric population. The objective is to evaluate the diagnostic yield of 24-h Holter and extended ambulatory cardiac monitoring in pediatric patients with palpitations. Methods and Results: All pediatric patients aged 10–18 years who had ambulatory cardiac monitoring (1–30 days) through the Pocket Electrocardiogram (PocketECG™) system (Medi-Lynx) between January 2016 and July 2020 were included. Patients with an International Classification of Diseases-10 diagnosis code of palpitations (R00.2) during enrollment were evaluated separately. Tachyarrhythmia diagnoses included atrial fibrillation (AF), nonsustained supraventricular tachycardia (nSVT), supraventricular tachycardia (SVT), nonsustained ventricular tachycardia (nVT), and ventricular tachycardia (VT). Age, heart rates, arrhythmia type, and symptomatic transmission data were collected and analyzed. A total of 2388 patients (mean age 11.6 years, 58% F) with the R00.2 code had ambulatory cardiac monitoring (28% 24-h Holter, 72% extended) performed during the study period and there were 6287 total patients (mean age 13.9 years, 54% F) that underwent ambulatory cardiac monitoring (42% 24-h Holter, 58% extended) during that time. Of 2388 patients, 321 (13%) were diagnosed with tachyarrhythmia: AF (9), nSVT (192), SVT (59), and nVT (61). In the overall cohort, 764 (12%) patients were diagnosed with tachyarrhythmia: AF (22), nSVT (478), SVT (85), nVT (177), and VT (2). Symptomatic transmissions with normal cardiac rhythm were common in the R00.2 (n = 1697, 71%) and overall (n = 3848, 61%) groups. No episodes of nSVT, SVT, nVT, or VT were associated with symptomatic transmissions. Conclusion: Ambulatory cardiac monitors are an integral part of the diagnostic workup for pediatric palpitations patients and have demonstrated a high yield of combined positive arrhythmia diagnoses and symptomatic normal transmissions. Further prospective study of this population with the integration of clinical information is warranted.

Research in hockey has found that preparedness and activity alter head impact magnitudes. It is unknown if similar occurrences take place in soccer. Therefore, our study purpose was to determine differences in the magnitudes and frequencies of head impacts due to sex and preparedness. Sixteen female (age: 19 ± 1.05 years, height: 163.68 ± 5.03 cm, mass: 61.36 ± 4.99 kg) and 14 male (age: 20 ± 1.07 years, height: 180.34 ± 5.58 cm, mass: 74.357 ± 8.64 kg) Division III intercollegiate soccer players were included in this study. The independent variables were sex and preparedness (anticipated with good body position, anticipated with poor body position, and unanticipated). xPatch sensors (X2 Biosystems, Seattle, WA, USA) applied over the participants’ right mastoid processes for practices and games provided the frequency and biomechanics of all of the head impacts over 10 g. A total of 860 female and 870 male impacts were verified and coded by preparedness and activity during 1182 female (IR = 727.58, CI = 678.95–776.21) and 801 male (IR = 1086.14, CI = 1013.97–1158.32; IRR = 1.49, CI = 1.36–1.64) exposures. The interaction between sex and preparedness was significant for the combined dependent variables (multivariate F6,3442 = 3.67, p = 0.001, ηp2 < 0.01). Male and female intercollegiate soccer players, although exposed to different frequencies of head impacts, sustained similar magnitude impacts to the head within the preparedness categories. Training interventions should aim at improving technique while sustaining impacts as both sexes often received impacts while unprepared.

The ability to estimate lower-extremity mechanics in real-world scenarios may untether biomechanics research from a laboratory environment. This is particularly important for military populations where outdoor ruck marches over variable terrain and the addition of external load are cited as leading causes of musculoskeletal injury As such, this study aimed to examine (1) the validity of a minimal IMU sensor system for quantifying lower-extremity kinematics during treadmill walking and running compared with optical motion capture (OMC) and (2) the sensitivity of this IMU system to kinematic changes induced by load, grade, or a combination of the two. The IMU system was able to estimate hip and knee range of motion (ROM) with moderate accuracy during walking but not running. However, SPM analyses revealed IMU and OMC kinematic waveforms were significantly different at most gait phases. The IMU system was capable of detecting kinematic differences in knee kinematic waveforms that occur with added load but was not sensitive to changes in grade that influence lower-extremity kinematics when measured with OMC. While IMUs may be able to identify hip and knee ROM during gait, they are not suitable for replicating lab-level kinematic waveforms.

Observations of young star clusters in a variety of galaxies have been used to constrain basic properties related to star formation, such as the fraction of stars found in clusters (Γ) and the shape of the cluster mass function (CMF). However, the results can depend heavily on the reliability of the cluster age-dating process and other assumptions. One of the biggest challenges for successful age-dating lies in breaking the age–reddening degeneracy, where older, dust-free clusters and young, reddened clusters can have similar broadband colors. While this degeneracy affects cluster populations in all galaxies, it is particularly challenging in systems with dusty, extreme star-forming environments. We study the cluster demographics in the luminous infrared galaxy NGC 1614 using Hubble Space Telescope imaging taken in eight optical–near-infrared passbands. For age-dating, we adopt a spectral energy distribution fitting process that limits the maximum allowed reddening by region and includes H α photometry directly. We find that without these assumptions essentially all clusters in the dust-free UV-bright arm that should have ages ≈50–250 Myr are incorrectly assigned ages younger than 10 Myr. We find that this method greatly reduces the number of clusters in the youngest ( τ < 10 Myr) age bin and shows a fairly uniform distribution of massive clusters, the most massive being ≈few × 10 ^7 M _⊙ . A maximum likelihood fit shows that the CMF is well fitted by a power law with an index of approximately −1.8, with no statistically significant high-mass cutoff. We calculate the fraction of stars born in clusters to be Γ _1−10 = 22.4% ± 5.7%. The fraction of stars in clusters decreases quickly over time, with Γ _10−100 = 4.5% ± 1.1% and Γ _100−400 = 1.7% ± 0.4%, suggesting that clusters dissolve rapidly over the first ∼0.5 Gyr. The decreasing fraction of stars in clusters is consistent with the declining shape observed for the cluster age distribution.

We present the largest catalog to date of star clusters and compact associations in nearby galaxies. We have performed a V -band-selected census of clusters across the 38 spiral galaxies of the PHANGS–Hubble Space Telescope (HST) Treasury Survey, and measured integrated, aperture-corrected near-ultraviolet- U-B-V-I photometry. This work has resulted in uniform catalogs that contain ∼20,000 clusters and compact associations, which have passed human inspection and morphological classification, and a larger sample of ∼100,000 classified by neural network models. Here, we report on the observed properties of these samples, and demonstrate that tremendous insight can be gained from just the observed properties of clusters, even in the absence of their transformation into physical quantities. In particular, we show the utility of the UBVI color–color diagram, and the three principal features revealed by the PHANGS-HST cluster sample: the young cluster locus, the middle-age plume, and the old globular cluster clump. We present an atlas of maps of the 2D spatial distribution of clusters and compact associations in the context of the molecular clouds from PHANGS–Atacama Large Millimeter/submillimeter Array. We explore new ways of understanding this large data set in a multiscale context by bringing together once-separate techniques for the characterization of clusters (color–color diagrams and spatial distributions) and their parent galaxies (galaxy morphology and location relative to the galaxy main sequence). A companion paper presents the physical properties: ages, masses, and dust reddenings derived using improved spectral energy distribution fitting techniques.

We use 0.1″ observations from the Atacama Large Millimeter Array (ALMA), Hubble Space Telescope (HST), and JWST to study young massive clusters (YMCs) in their embedded “infant” phase across the central starburst ring in NGC 3351. Our new ALMA data reveal 18 bright and compact (sub-)millimeter continuum sources, of which 8 have counterparts in JWST images and only 6 have counterparts in HST images. Based on the ALMA continuum and molecular line data, as well as ancillary measurements for the HST and JWST counterparts, we identify 14 sources as infant star clusters with high stellar and/or gas masses (∼10 ^5 M _⊙ ), small radii (≲ 5 pc), large escape velocities (6–10 km s ^−1 ), and short freefall times (0.5–1 Myr). Their multiwavelength properties motivate us to divide them into four categories, likely corresponding to four evolutionary stages from starless clumps to exposed H ii region–cluster complexes. Leveraging age estimates for HST-identified clusters in the same region, we infer an evolutionary timeline, ranging from ∼1–2 Myr before cluster formation as starless clumps, to ∼4–6 Myr after as exposed H ii region–cluster complexes. Finally, we show that the YMCs make up a substantial fraction of recent star formation across the ring, exhibit a nonuniform azimuthal distribution without a very coherent evolutionary trend along the ring, and are capable of driving large-scale gas outflows.

We present a new study of the cluster populations in the blue compact dwarf galaxies (BCD) ESO185-IG13, ESO338-IG04, and Haro11, based on new and archival high-resolution images taken by the Hubble Space Telescope, and the first to probe the populations older than ≈100 Myr. BCDs are believed to experience intense bursts of star formation (including at the present day) after long periods of quiescence, but little is known about the timing, frequency, duration, and strength of these bursts or about their star formation histories in general. We find that the cluster population in each of the three galaxies studied here has its own unique distribution of colors and hence a unique cluster and star formation history. From an assumed correlation between the normalization of the cluster mass function and the star formation rate of the host galaxy, we construct cluster-based star formation histories over the past ≈few × Gyr and find that only Haro11 is currently experiencing a burst (≈factor of 10 increase in the rate of star formation for the last ≈20 Myr), whereas ESO185 experienced enhanced star formation (by a factor ≈4) between 10 and 40 Myr ago, and ESO338 has had a fairly constant SFH over the past few Gyr. These findings indicate that not all BCDs are experiencing a burst of star formation at the present day, and that some have been forming stars and clusters at a fairly steady rate (within a factor of ≈2–3) over the past few Gyr. This scenario is similar to the histories of dwarf irregular and dwarf starburst galaxies, which have star formation rates that are 10–1000 times lower than those in BCDs.

We present a comparative study of the molecular gas in two galaxies from the Legacy ExtraGalactic UV Survey (LEGUS) sample: barred spiral NGC 1313 and flocculent spiral NGC 7793. These two galaxies have similar masses, metallicities, and star formation rates, but NGC 1313 is forming significantly more massive star clusters than NGC 7793, especially young massive clusters (10 ^4 M _⊙ ). Using Atacama Large Millimeter/submillimeter Array (ALMA) CO(2–1) observations of the two galaxies with the same sensitivity and resolution (13 pc), we directly compare the molecular gas in these two similar galaxies to determine the physical conditions responsible for their large disparity in cluster formation. By fitting size–line width relations for the clouds in each galaxy, we find that NGC 1313 has a higher intercept than NGC 7793, implying that its clouds have higher kinetic energies at a given size scale. NGC 1313 also has more clouds near virial equilibrium than NGC 7793, which may be connected to its higher rate of massive cluster formation. However, these virially bound clouds do not show a stronger correlation with young clusters than with the general cloud population. We find surprisingly small differences between the distributions of molecular cloud populations in the two galaxies, though the largest of those differences is that NGC 1313 has higher surface densities and lower freefall times.

We compare the molecular cloud properties in subgalactic regions of two galaxies, barred spiral NGC 1313, which is forming many massive clusters, and flocculent spiral NGC 7793, which is forming significantly fewer massive clusters despite having a similar star formation rate to NGC 1313. We find that there are larger variations in cloud properties between different regions within each galaxy than there are between the galaxies on a global scale, especially for NGC 1313. There are higher masses, line widths, pressures, and virial parameters in the arms of NGC 1313 and the center of NGC 7793 than in the interarm and outer regions of the galaxies. The massive cluster formation of NGC 1313 may be driven by its greater variation in environment, allowing more clouds with the necessary conditions to emerge, although no one parameter seems primarily responsible for the difference in star formation. Meanwhile NGC 7793 has clouds that are as massive and have as much kinetic energy as the clouds in the arms of NGC 1313, but have densities and pressures more similar to those in the interarm regions and so are less inclined to collapse and form stars. The cloud properties in NGC 1313 and NGC 7793 suggest that spiral arms, bars, interarm regions, and flocculent spirals each represent distinct environments with regard to molecular cloud populations. We see surprisingly little difference in surface density between the regions, suggesting that the differences in surface densities frequently seen between arm and interarm regions in lower-resolution studies are indicative of the sparsity of molecular clouds, rather than differences in their true surface density.

We present new catalogs of likely globular clusters (GCs) in 17 nearby spiral galaxies studied as part of the PHANGS Hubble Space Telescope (HST) Treasury Survey. The galaxies were imaged in five broadband filters from the near-ultraviolet through the I band. PHANGS-HST has produced catalogs of stellar clusters of all ages by selecting extended sources (from multiple concentration index measurements) followed by morphological classification (centrally concentrated and symmetric or asymmetric, multiple peaks, and contaminants) by visually examining the V -band images and separately by a machine-learning algorithm which classified larger samples to reach fainter limits. From both cluster catalogs, we select an initial list of candidate GCs which have B − V ≥ 0.5 and V − I ≥ 0.73 mag, then remove likely contaminants (including reddened young clusters, background galaxies misclassified by the neural network, and chance superpositions/blends of stars) after a careful visual inspection. We find that ≈86% of the color-selected candidates classified as spherically symmetric and 68% of those classified as centrally concentrated but asymmetric are likely to be GCs. The luminosity functions of the GC candidates in two of our 17 galaxies, NGC 628 and NGC 3627, are atypical, and continue to rise at least 1 mag fainter than the expected turnover near M _V ∼ −7.4. These faint candidate GCs have more extended spatial distributions than their bright counterparts, and may reside in the disk rather than the bulge/halo, similar to faint GCs previously discovered in M101. These faint clusters may be somewhat younger since the age–metallicity degeneracy makes it difficult to determine precise cluster ages from integrated colors once they reach ≈1 Gyr.

Introduction: There are three combination immune checkpoint inhibitor (ICI)–based regimens in the first-line setting for metastatic renal cell carcinoma (mRCC). Currently, there is limited real-world data for clinical outcomes and toxicity in mRCC patients treated with first-line ICI-based regimens. Methods: We performed a retrospective review of 49 mRCC patients treated with ICI-based combination regimens in the standard of care setting at the Winship Cancer Institute of Emory University from 2015–2020. We collected baseline data from the electronic medical record including demographic information and disease characteristics. Immune-related adverse events (irAEs) were collected from clinic notes and laboratory values. The primary clinical outcomes measured were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: The median age was 65 years, and most patients (80%) were males. The majority were White (86%) and had clear cell RCC (83%). Most patients had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 (43%) or 1 (45%). Approximately one-half (49%) had at least three sites of distant metastatic disease. Most patients (88%) received nivolumab and ipilimumab. More than one-half (53%) of patients experienced an irAE, with 13 (27%) patients having treatment delayed and 18% discontinuing treatment for toxicity. The median OS was not reached, and the median PFS was 8.0 months per a Kaplan-Meier estimation. More than half of patients (53%) had a PFS > 6 months, and 22% had PFS > 1 year. The ORR was 33% for the entire cohort, and 7% of patients had a complete response. Conclusion: We presented real-world efficacy and toxicity data for front-line ICI combination treatment regimens. The ORR and median PFS were lower in our cohort of patients compared to the available data in the clinical trial setting. This was likely because of more advanced disease in this study. Future studies should provide additional data that will allow comparisons between different ICI combination regimens for untreated mRCC.

AimsThis study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.MethodsA total of 40 female mice were assigned to four treatment groups (n = 10/group): D+ diet with propylene glycol control, D+ diet with BCP, D-deficient diet with control, and D-deficient diet with BCP. The D+ diet is a commercial basal diet, while the D-deficient diet contains 0.47% calcium, 0.3% phosphorus, and no vitamin D. All the mice were housed in conditions without ultraviolet light. Bone properties were evaluated by X-ray micro-CT. Serum levels of klotho were measured by enzyme-linked immunosorbent assay.ResultsUnder these conditions, the D-deficient diet enhanced the length of femur and tibia bones (p < 0.050), and increased bone volume (BV; p < 0.010) and trabecular bone volume fraction (BV/TV; p < 0.010) compared to D+ diet. With a diet containing BCP, the mice exhibited higher BV and bone mineral density (BMD; p < 0.050) than control group. The trabecular and cortical bone were also affected by vitamin D and BCP. In addition, inclusion of dietary BCP improved the serum concentrations of klotho (p < 0.050). In mice, klotho regulates the expression level of cannabinoid type 2 receptor (Cnr2) and fibroblast growth factor 23 (Fgf23) through CD300a. In humans, data suggest that klotho is connected to BMD. The expression of klotho is also associated with bone markers.ConclusionThese data indicate that BCP enhances the serum level of klotho, leading to improved bone properties and mineralization in an experimental mouse model.Cite this article: Bone Joint Res 2022;11(8):528–540.

Abstract Structures of protein–ligand complexes provide critical information for drug design. Most protein–ligand complex structures are determined using X-ray crystallography, but where crystallography is not able to generate a structure for a complex, NMR is often the best alternative. However, the available tools to enable rapid and robust structure determination of protein–ligand complexes by NMR are currently limited. This leads to situations where projects are either discontinued or pursued without structural data, rendering the task more difficult. We previously reported the NMR Molecular Replacement (NMR2) approach that allows the structure of a protein–ligand complex to be determined without requiring the cumbersome task of protein resonance assignment. Herein, we describe the NMR2 approach to determine the binding pose of a small molecule in a weak protein–ligand complex by collecting sparse protein methyl-to-ligand NOEs from a selectively labeled protein sample and an unlabeled ligand. In the selective labeling scheme all methyl containing residues of the protein are protonated in an otherwise deuterated background. This allows measurement of intermolecular NOEs with greater sensitivity using standard NOESY pulse sequences instead of isotope-filtered NMR experiments. This labelling approach is well suited to the NMR2 approach and extends its utility to include larger protein–ligand complexes.

Abstract Background Early identification of hereditary cancer risk would save lives, but genetic testing (GT) has been inadequate. We assessed i) trends for hereditary breast and ovarian cancer (HBOC), Lynch syndrome, and other GT and ii) factors associated with receipt of GT. Methods We used data from the Arkansas All-Payer Claims Database from January 2013 through June 2018 (commercial, Medicaid), December 2017 (state employee), or December 2016 (Medicare) and identified enrollees with ≥1 month of enrollment. Using Current Procedural Terminology (CPT-4) codes, rates for GT were calculated per 100,000 person-quarters and time series regressions estimated. Second, GT and covariate information for enrollees with 24 months of continuous enrollment were used to estimate separate logistic regression models for each GT category. Results Among 2,520,575 unique enrollees, HBOC testing rates were 2.2 (Medicaid), 22.0 (commercial), 40.4 (state employee), and 13.1(Medicare) per 100,000 person-quarters and increased linearly across all plans. Older age (OR=1.24; 95%CI 1.20 – 1.28), female sex (OR=18.91; 95%CI 13.01 – 28.86), higher comorbidity burden (OR=1.08; 95%CI 1.05 – 1.12), mental disorders (OR=1.53; 95%CI 1.15 – 2.00), and state employee coverage (OR=1.65; 95%CI 1.37 – 1.97) were positively associated with HBOC testing. Less than 1 of 10,000 enrollees received Lynch syndrome testing, while < 5 of 10,000 received HBOC testing. Conclusion GT rates for hereditary cancer syndromes have increased in Arkansas but remain low. Receipt of GT was explained with high discrimination by sex and plan type. Impact Expansion of GT for hereditary cancer risk in Arkansas is needed to identify high-risk individuals who could benefit from risk-reduction strategies.