Human skeletal muscle aging atlas.

Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells and 92,259 single nuclei from 17 donors to map the aging process in the adult human intercostal muscle, identifying cellular changes in each muscle compartment. We found that distinct subsets of muscle stem cells exhibit decreased ribosome biogenesis genes and increased CCL2 expression, causing different aging phenotypes. Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age. Furthermore, we document the function of aging muscle microenvironment in immune cell attraction. Overall, we present a comprehensive human skeletal muscle aging resource ( https://www.muscleageingcellatlas.org/ ) together with an in-house mouse muscle atlas to study common features of muscle aging across species.

Evaluating Sepsis Bundle Compliance as a Predictor for Patient Outcomes at a Community Hospital: A Retrospective Study.

BACKGROUND: Clinicians are encouraged to use the Centers for Medicare & Medicaid Services early management bundle for severe sepsis and septic shock (SEP-1); however, it is unclear whether this process measure improves patient outcomes. PURPOSE: The purpose of this study was to evaluate whether compliance with the SEP-1 bundle is a predictor of hospital mortality, length of stay (LOS), and intensive care unit LOS at a suburban community hospital. METHODS: A retrospective observational study was conducted. RESULTS: A total of 577 patients were included in the analysis. Compliance with the SEP-1 bundle was not a significant predictor for patient outcomes. CONCLUSIONS: SEP-1 compliance may not equate with quality of health care. Efforts to comply with SEP-1 may help organizations develop systems and structures that improve patient outcomes. Health care leaders should evaluate strategies beyond SEP-1 compliance to ensure continuous improvement of outcomes for patients experiencing sepsis.

Step-down multiple testing procedures for the overall population and partitioning subgroups.

Multiple comparisons procedures are described for two-armed studies where there is a primary hypothesis and one or more ordered secondary hypotheses in the scenario where the objective is to test for an effect on the overall population and/or nonoverlapping subgroups that partition the population. This scenario arises when the subgroups are defined by disease etiology or by other patient characteristics such as genetic factors, age, sex, or race, and the treatment may have differential effects in the subgroups. The procedures described control the family-wise error rate in the strong sense at a specified level α.

Engaging Emergency Nurses in Strategies to Address the Social Determinants of Health.

INTRODUCTION: For patients with social needs, emergency departments can be an essential bridge between the health care system and the community. Emergency nurses' knowledge of and engagement in this work need to be examined to ensure that efforts for social determinants of health screening and the resulting community connections are effective. However, there is limited research in this area of nursing practice. The purpose of this study is to describe emergency nurses' knowledge about social needs in their community, assess their knowledge of existing community resources, and examine their perceived confidence to respond to the social needs of their patients. METHODS: A cross-sectional survey was conducted with 243 nurses employed in a large regional health care system. Data were collected using an adapted 81-item social determinants of health survey instrument to measure knowledge of social determinants of health, confidence, and frequency of discussing social determinants of health with emergency department patients and awareness of social resources available in the community. Survey participants were asked about barriers to incorporating social determinants of health into their emergency department workflow and to provide general demographic information. Descriptive statistics were used to analyze study results. RESULTS: Most of the 243 emergency nurse participants believed that addressing social determinants of health was important and that emergency nurses should be involved in issues around social determinants of health. However, most nurses reported limited knowledge about social determinants of health and had very limited knowledge about the resources available in their community to help patients with needs related to food, housing, medical care, and transportation. Nurses reported that although they know that their patients are unlikely to ask for help with social needs during an emergency department visit, they are still unlikely to ask their patients about social needs owing to low confidence about having social needs conversations, limited time, and competing care priorities. Participants advocated for greater case manager presence. Feeling connected to the community was significantly correlated to increased knowledge, confidence, and likelihood to ask about social needs (P < .05). DISCUSSION: The emergency department is a logical place for screening for social determinants of health and connecting patients with social needs to community resources. Emergency nurses included in this study acknowledged that they want to address the social needs of their patients but reported that they lack knowledge about both social determinants of health and more importantly about the resources available to help patients with social needs. In general, they did not feel confident discussing social determinants of health with their patients in the emergency department and are unlikely to ask about social needs. Barriers to screening include time, competing care priorities, and lack of knowledge and support needed from case managers. Findings from this study have implications for supporting emergency nurses employed in institutions that seek to address social influences of health for the patients in their communities.

A human embryonic limb cell atlas resolved in space and time.

Human limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months1. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common2. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.

Leveraging a smartphone to perform time-gated luminescence measurements.

Empowered by advanced on-board sensors, high-performance optics packages and ever-increasing computational power, smartphones have democratized data generation, collection, and analysis. Building on this capacity, many platforms have been developed to enable its use as an optical sensing platform for colorimetric and fluorescence measurements. In this paper, we report the ability to enable a smartphone to perform laboratory quality time-resolved analysis of luminescent samples via the exploitation of the rolling shutter mechanism of the native CMOS imager. We achieve this by leveraging the smartphone's standard image capture applications, commercially available image analysis software, and housing the device within a UV-LED containing case. These low-cost modifications enable us to demonstrate the smartphone's analytical potential by performing tasks ranging from authentication and encryption to the interrogation of packaging, compounds, and physical phenomena. This approach underscores the power of repurposing existing technologies to extend the reach and inclusivity of scientific exploration, opening new avenues for data collection and analysis.

Targetable NOTCH1 rearrangements in reninoma.

Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observe excessive renin and NOTCH1 signalling mRNAs, with a concomitant non-excess of NRARP expression. Re-analysis of previously published reninoma bulk transcriptomes further corroborates our observation of dysregulated Notch pathway signalling in reninoma. Our findings reveal NOTCH1 rearrangements in reninoma, therapeutically targetable through existing NOTCH1 inhibitors, and indicate that unscheduled Notch signalling may be a disease-defining feature of reninoma.

Intrarater and Interrater Reliability of Radiographic Characteristics in Skeletally Immature Patients With Anterior Cruciate Ligament Tears: A PLUTO Study Group Reliability Study.

BACKGROUND: Radiographic measurements of limb alignment in skeletally immature patients with anterior cruciate ligament (ACL) tears are frequently used for surgical decision-making, preoperative planning, and postoperative monitoring of skeletal growth. However, the interrater and intrarater reliability of these radiographic characteristics in this patient population is not well documented. HYPOTHESIS: Excellent reliability across 4 raters will be demonstrated for all digital measures of length, coronal plane joint orientation angles, mechanical axis, and tibial slope in skeletally immature patients with ACL tears. STUDY DESIGN: Cohort study (diagnosis). METHODS: Three fellowship-trained orthopaedic surgeons and 1 medical student performed 2 rounds of radiographic measurements on digital imaging (lateral knee radiographs and long-leg radiographs) of skeletally immature patients with ACL tears. Intrarater and interrater reliability for continuous radiographic measurements was assessed with intraclass correlation coefficients (ICCs) across 4 raters with 95% CIs for affected and unaffected side measurements. Interrater reliability analysis used an ICC (2, 4) structure and intrarater reliability analysis used an ICC (2, 1) structure. A weighted kappa coefficient was calculated for ordinal variables along with 95% CIs for both interrater and intrarater reliability. Agreement statistic interpretations are based on scales described by Fleiss, and Cicchetti and Sparrow: <0.40, poor; 0.40 to 0.59, fair; 0.60 to 0.74, good; and >0.74, excellent. RESULTS: Radiographs from a convenience sample of 43 patients were included. Intrarater reliability was excellent for nearly all measurements and raters. Interrater reliability was also excellent for nearly all reads for all measurements. CONCLUSION: Radiographic reliability of long-leg radiographs and lateral knee x-rays in skeletally immature children with ACL tears is excellent across nearly all measures and raters and can be obtained and interpreted as reliable and reproducible means to measure limb length and alignment. LEVEL OF EVIDENCE: Level III.

Quantifying the impact of the coronavirus 2019 pandemic on youth sports-related injuries in the USA.

The purpose of this study was to estimate monthly and annual trends in youth sports-related injury over the years 2016-2020 using the National Electronic Injury Surveillance System (NEISS) database to measure the impact of COVID-19 on overall and sport-specific rates of injury. Children and adolescents (0-19 years) presenting to USA emergency departments with sport participation injury from 2016 to 2020 were identified. Descriptive statistical analyses were performed of injury patterns. An interrupted time series analysis was applied to estimate changes in injury trends during COVID-19. Proportional changes in injury characteristics during this period were examined. An estimated 5 078 490 sports-related injuries were identified with an annual incidence of 1406 injuries per 100 000 population. Seasonal peaks in injuries occurred during September and May. About 58% of injuries were associated with contact sports, such as basketball, football, and soccer, and the most common injuries were sprains and strains. After the pandemic onset, there was a statistically significant 59% decrease in national youth sports-related injuries compared with the average estimates for 2016-2019. While the distribution of injury characteristics did not appear to change, the location of injury appeared to shift away from school toward alternative settings. A significant reduction in youth sports-related injuries was identified in 2020 coinciding with the COVID-19 pandemic, persisting throughout the rest of the year. No changes in the anatomic or demographic distribution of injuries were identified. This study expands our epidemiologic understanding of youth sports-related injury trends and how they changed following the pandemic onset.

Convergence of Artificial Intelligence and Neuroscience towards the Diagnosis of Neurological Disorders-A Scoping Review.

Artificial intelligence (AI) is a field of computer science that deals with the simulation of human intelligence using machines so that such machines gain problem-solving and decision-making capabilities similar to that of the human brain. Neuroscience is the scientific study of the struczture and cognitive functions of the brain. Neuroscience and AI are mutually interrelated. These two fields help each other in their advancements. The theory of neuroscience has brought many distinct improvisations into the AI field. The biological neural network has led to the realization of complex deep neural network architectures that are used to develop versatile applications, such as text processing, speech recognition, object detection, etc. Additionally, neuroscience helps to validate the existing AI-based models. Reinforcement learning in humans and animals has inspired computer scientists to develop algorithms for reinforcement learning in artificial systems, which enables those systems to learn complex strategies without explicit instruction. Such learning helps in building complex applications, like robot-based surgery, autonomous vehicles, gaming applications, etc. In turn, with its ability to intelligently analyze complex data and extract hidden patterns, AI fits as a perfect choice for analyzing neuroscience data that are very complex. Large-scale AI-based simulations help neuroscientists test their hypotheses. Through an interface with the brain, an AI-based system can extract the brain signals and commands that are generated according to the signals. These commands are fed into devices, such as a robotic arm, which helps in the movement of paralyzed muscles or other human parts. AI has several use cases in analyzing neuroimaging data and reducing the workload of radiologists. The study of neuroscience helps in the early detection and diagnosis of neurological disorders. In the same way, AI can effectively be applied to the prediction and detection of neurological disorders. Thus, in this paper, a scoping review has been carried out on the mutual relationship between AI and neuroscience, emphasizing the convergence between AI and neuroscience in order to detect and predict various neurological disorders.

Diagnostic classification of childhood cancer using multiscale transcriptomics.

The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types.

A Survey on Optimization Techniques for Edge Artificial Intelligence (AI).

Artificial Intelligence (Al) models are being produced and used to solve a variety of current and future business and technical problems. Therefore, AI model engineering processes, platforms, and products are acquiring special significance across industry verticals. For achieving deeper automation, the number of data features being used while generating highly promising and productive AI models is numerous, and hence the resulting AI models are bulky. Such heavyweight models consume a lot of computation, storage, networking, and energy resources. On the other side, increasingly, AI models are being deployed in IoT devices to ensure real-time knowledge discovery and dissemination. Real-time insights are of paramount importance in producing and releasing real-time and intelligent services and applications. Thus, edge intelligence through on-device data processing has laid down a stimulating foundation for real-time intelligent enterprises and environments. With these emerging requirements, the focus turned towards unearthing competent and cognitive techniques for maximally compressing huge AI models without sacrificing AI model performance. Therefore, AI researchers have come up with a number of powerful optimization techniques and tools to optimize AI models. This paper is to dig deep and describe all kinds of model optimization at different levels and layers. Having learned the optimization methods, this work has highlighted the importance of having an enabling AI model optimization framework.

Percutaneous Decommissioning 11 Years After Initial CF-LVAD Placement.

An 80-year-old man with severe nonischemic cardiomyopathy status post left ventricular assist device (LVAD) placement 11 years prior presented for recurrent LVAD alarms from internal driveline fracture. Given his partial myocardial recovery and his preference to avoid surgical procedures, percutaneous LVAD decommissioning was performed by occlusion of the outflow graft and subsequently driveline removal. (Level of Difficulty: Advanced.).

Testicular tumors in the "elderly" population.

Germ cell tumors arise in childhood but peak at around 30 years of age. They are the most common cancers in males under the age of 35. Over 95% arise in the testes while a minority originate in extragonadal sites such as the anterior mediastinum, or mainly in childhood the pineal gland or the sacrococcygeal area. These tumors show an extraordinary sensitivity to chemotherapy (and for seminoma, also to radiation) and cure rates are relatively high even in second or subsequent relapses. Very few data are present in the literature regarding patients diagnosed after 50 years and no specific trials have been conducted in this setting. Nearly all patients reported in the literature had testicular cancers, with occasional reports of extragonadal tumors. Despite the fact that > 50 years may be considered an "elderly" population, these patients are treated with the same cisplatin containing combinations as their younger counterparts with consequent higher toxicity. In this review we will present epidemiological and clinical data from this rare population of patients with testicular cancer.

Preventing spread of aerosolized infectious particles during medical procedures: A lab-based analysis of an inexpensive plastic enclosure.

Severe viral respiratory diseases, such as SARS-CoV-2, are transmitted through aerosol particles produced by coughing, talking, and breathing. Medical procedures including tracheal intubation, extubation, dental work, and any procedure involving close contact with a patient's airways can increase exposure to infectious aerosol particles. This presents a significant risk for viral exposure of nearby healthcare workers during and following patient care. Previous studies have examined the effectiveness of plastic enclosures for trapping aerosol particles and protecting health-care workers. However, many of these enclosures are expensive or are burdensome for healthcare workers to work with. In this study, a low-cost plastic enclosure was designed to reduce aerosol spread and viral transmission during medical procedures, while also alleviating issues found in the design and use of other medical enclosures to contain aerosols. This enclosure is fabricated from clear polycarbonate for maximum visibility. A large single-side cutout provides health care providers with ease of access to the patient with a separate cutout for equipment access. A survey of medical providers in a local hospital network demonstrated their approval of the enclosure's ease of use and design. The enclosure with appropriate plastic covers reduced total escaped particle number concentrations (diameter > 0.01 µm) by over 93% at 8 cm away from all openings. Concentration decay experiments indicated that the enclosure without active suction should be left on the patient for 15-20 minutes following a tracheal manipulation to allow sufficient time for >90% of aerosol particles to settle upon interior surfaces. This decreases to 5 minutes when 30 LPM suction is applied. This enclosure is an inexpensive, easily implemented additional layer of protection that can be used to help contain infectious or otherwise potentially hazardous aerosol particles while providing access into the enclosure.

Theileriosis in naturally infected roan antelope (Hippotragus equinus).

Cases of Theileria-associated mortality are rarely reported in African wild artiodactyls. Descriptions of lesions are limited, particularly in endangered hippotraginids. Here, we analyzed retrospectively the gross and histologic findings in 55 roan antelope (Hippotragus equinus) with fatal natural theileriosis. The most frequently recorded gross findings in 40 cases were widespread petechiae and ecchymoses (72.5%), probable anemia (67.5%), icterus (60%), splenomegaly (60%), hepatomegaly (52.5%), and pulmonary edema (50%). Histologic lesions in 34 cases were characterized by multi-organ infiltrates of parasitized and nonparasitized mononuclear leukocytes (MLs), and fewer multinucleate giant cells (MNGCs). Liver, lung, kidney, adrenal gland, and heart were most consistently infiltrated, followed by spleen and lymph nodes. Leukocytes were phenotyped in lung, liver, kidney, and heart specimens from 16 cases, using immunohistochemistry to detect CD20, CD3, myeloid/histiocyte antigen (MAC387), IBA-1, and CD204 surface receptors. A roan polyclonal anti-Theileria sp. (sable) antibody was applied to the same tissues to identify intraleukocytic parasite antigens. Similar proportions of intravascular and extravascular IBA-1-, CD204-, and MAC387-reactive putative monocyte-macrophages and fewer CD3-positive putative T-lymphocytes were identified in all organs, especially the lungs in infected roan. CD20-positive putative B-lymphocytes were significantly scarcer than in uninfected controls. Intraleukocytic Theileria parasites labeled consistently in affected tissues. Some parasitized and nonparasitized MLs and the MNGCs failed to label with selected leukocyte markers. Fatal theileriosis in roans may largely be the result of multi-organ monocyte-macrophage activation with associated tissue injury and overwhelming systemic inflammation. The identity of the parasitized leukocytes and characteristics of the lymphohistiocytic response require further clarification in roans.

Accounting for delayed entry into observational studies and clinical trials: length-biased sampling and restricted mean survival time.

Individuals in many observational studies and clinical trials for chronic diseases are enrolled well after onset or diagnosis of their disease. Times to events of interest after enrollment are therefore residual or left-truncated event times. Individuals entering the studies have disease that has advanced to varying extents. Moreover, enrollment usually entails probability sampling of the study population. Finally, event times over a short to moderate time horizon are often of interest in these investigations, rather than more speculative and remote happenings that lie beyond the study period. This research report looks at the issue of delayed entry into these kinds of studies and trials. Time to event for an individual is modelled as a first hitting time of an event threshold by a latent disease process, which is taken to be a Wiener process. It is emphasized that recruitment into these studies often involves length-biased sampling. The requisite mathematics for this kind of sampling and delayed entry are presented, including explicit formulas needed for estimation and inference. Restricted mean survival time (RMST) is taken as the clinically relevant outcome measure. Exact parametric formulas for this measure are derived and presented. The results are extended to settings that involve study covariates using threshold regression methods. Methods adapted for clinical trials are presented. An extensive case illustration for a clinical trial setting is then presented to demonstrate the methods, the interpretation of results, and the harvesting of useful insights. The closing discussion covers a number of important issues and concepts.

Group sequential design for randomized trials using "first hitting time" model.

Group sequential design (GSD) has become a popular choice in recent clinical trials as it improves trial efficiency by providing options for early termination. The implementation of traditional tests for survival analysis (eg, the log-rank test and the Cox proportional hazard (PH) model) in the GSD setting has been widely discussed. The PH assumption is required for conventional (sequential) design, it is, however, often violated in practice. As an alternative, some generalized tests have been proposed (eg, the Max-Combo test) and their efficacies have been established. In this article, we explore the application of a more flexible, "first hitting time" based threshold regression (TR) model to GSD. TR assumes that subjects' health status is a latent (unobservable) process, and the clinical event of interest occurs when the latent health process hits a pre-specified boundary. The simulation results supported our findings that, in most cases, this comparable new method can successfully control type I error while providing higher early stopping opportunities in the sequential design, even when non-proportional hazard presents.