Beansaunders8473

S3 and F30 DC019846).

This study was funded by the National Institute on Deafness and Other Communication Disorders and the National Institute on Aging (3UL1-TR002553-03S3 and F30 DC019846).

Pneumonia is a leading cause of childhood morbidity and mortality. This study aimed to estimate the global hospitalisation due to

pneumonia in under-5 children.

We conducted a systematic review and meta-analysis of primary studies following the PRISMA-P guidelines. We searched Medline, Embase, Global Health, CINAHL, Global Index Medicus, Scopus, China National Knowledge Infrastructure, Wanfang, and CQvip. We included studies reporting data on

pneumonia, confirmed by detection of the pathogen in sterile-site samples in under-5 hospitalised children, published in English or Chinese language and conducted between 1st January 1990 and 4th November 2021 and between 1st January 1990 and 30th September 2020, respectively. We excluded those testing upper respiratory tract samples and not reporting data on samples with other bacteria or absence of bacteria. We screened papers against pre-specified criteria, extracted data and assessed the bacteriological quality, and combined epidemiological and microbiologir findings are probably an underestimate because of the unknown and the likely limited sensitivity of current testing methods for Staphylococcal pneumonia diagnosis and widespread reported use of antibiotics before recruitment (in 46% of cases).

is an important cause of hospitalisation for pneumonia in young children globally.

Bill and Melinda Gates Foundation (OPP 1,172,551) through a prime award to John Hopkins University.

Bill and Melinda Gates Foundation (OPP 1,172,551) through a prime award to John Hopkins University.

People who experience incarceration die by suicide at a higher rate than those who have no prior criminal justice system contact, but little is known about the effectiveness of interventions in other criminal justice settings. We aimed to synthesise evidence regarding the effectiveness of interventions to reduce suicide and suicide-related behaviours among people in contact with the criminal justice system.

We searched Embase, PsycINFO, MEDLINE, and grey literature databases for articles published between 1 January 2000 and 1 June 2021. STC-15 The protocol was registered with PROSPERO (CRD42020185989).

Thirty-eight studies (36 primary research articles, two grey literature reports) met our inclusion criteria, 23 of which were conducted in adult custodial settings in high-income, Western countries. Four studies were randomised controlled trials. Two-thirds of studies (n=26, 68%) were assessed as medium quality, 11 (29%) were assessed as high quality, and one (3%) was assessed as low quality. Most had considerabIHR HTA Programme (HTA Project16/159/09).

Data on emergency and critical care (ECC) capacity in low-income countries (LICs) are needed to improve outcomes and make progress towards realizing the goal of Universal Health Coverage.

We developed a novel research instrument to assess public sector ECC capacity and service readiness in LICs. From January 20th to February 18th, 2020 we administered the instrument at all four central hospitals and a simple random sample of nine of 24 district hospitals in Malawi, a landlocked and predominantly rural LIC of 19·1 million people in Southern Africa. The instrument contained questions on the availability of key resources across three domains and was administered to hospital administrators and clinicians from outpatient departments, emergency departments, and inpatient units. Results were used to generate an ECC Readiness Score, with a possible range of 0 to 1, for each facility.

A total of 114 staff members across 13 hospitals completed interviews for this study. Three (33%) district hospitals and all fourrts.

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Department of Emergency Medicine, Brigham and Women's Hospital.

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Department of Emergency Medicine, Brigham and Women's Hospital.Acetylation and phosphorylation are highly conserved posttranslational modifications (PTMs) that regulate cellular metabolism, yet how metabolic control is shared between these PTMs is unknown. Here we analyze transcriptome, proteome, acetylome, and phosphoproteome datasets in E. coli, S. cerevisiae, and mammalian cells across diverse conditions using CAROM, a new approach that uses genome-scale metabolic networks and machine learning to classify targets of PTMs. We built a single machine learning model that predicted targets of each PTM in a condition across all three organisms based on reaction attributes (AUC>0.8). Our model predicted phosphorylated enzymes during a mammalian cell-cycle, which we validate using phosphoproteomics. Interpreting the machine learning model using game theory uncovered enzyme properties including network connectivity, essentiality, and condition-specific factors such as maximum flux that differentiate targets of phosphorylation from acetylation. The conserved and predictable partitioning of metabolic regulation identified here between these PTMs may enable rational rewiring of regulatory circuits.Biological visual system can efficiently handle optical information within the retina and visual cortex of the brain, which suggests an alternative approach for the upgrading of the current low-intelligence, large energy consumption, and complex circuitry of the artificial vision system for high-performance edge computing applications. In recent years, retinomorphic machine vision based on the integration of optoelectronic image sensors and processors has been regarded as a promising candidate to improve this phenomenon. This novel intelligent machine vision technology can perform information preprocessing near or even within the sensor in the front end, thereby reducing the transmission of redundant raw data and improving the efficiency of the back-end processor for high-level computing tasks. In this contribution, we try to present a comprehensive review on the recent progress achieved in this emergent field.Compared with bulk materials, atomically thin two-dimensional (2D) crystals possess a range of unique mechanical properties, including relatively high in-plane stiffness and large bending flexibility. The atomic 2D building blocks can be reassembled into precisely designed heterogeneous composite structures of various geometries with customized mechanical sensing behaviors. Due to their small specific density, high flexibility, and environmental adaptability, mechanical sensors based on 2D materials can conform to soft and curved surfaces, thus providing suitable solutions for functional applications in future wearable devices. In this review, we summarize the latest developments in mechanical sensors based on 2D materials from the perspective of function-oriented applications. First, typical mechanical sensing mechanisms are introduced. Second, we attempt to establish a correspondence between typical structure designs and the performance/multi-functions of the devices. Afterward, several particularly promising areas for potential applications are discussed, following which we present perspectives on current challenges and future opportunities.Abuse of chemical fertilizers and insecticides has created many environmental and human health hazards. We hypothesized that high nitrogen (N) in crops changes insect gut microbiota leading to enhanced insecticide tolerance. We investigated the effect of high N in maize on gut microbiota and insecticide tolerance of the polyphagous pest Spodoptera litura. Bioassays showed that high N applied in both maize plants and artificial diets significantly enhanced larval growth but reduced larval sensitivity to the insecticide methomyl. High N promoted the gut bacterial abundance in the genus Enterococcus. Inoculation with two strains (E. mundtii and E. casseliflavus) isolated from the larval guts increased larval tolerance to methomyl. Incorporation of antibiotics in a high-N diet increased the larval sensitivity to methomyl. These findings suggest that excessive application of N fertilizer to crops can increase insecticide tolerance of insect pests via changing gut microbiota, leading to increased use of insecticides worldwide.Life history theory predicts a trade-off between the quantity and quality of offspring. Short interbirth intervals-the time between successive births-may increase the quantity of offspring but harm offspring quality. In contrast, long interbirth intervals may bolster offspring quality while reducing overall reproductive output. Further research is needed to determine whether this relationship holds among primates, which have intensive parental investment. Using Cox proportional hazards models, we examined the effects of interbirth intervals (short, normal, or long) on infant survivorship using a large demographic dataset (n = 15,852) of captive callitrichine monkeys (marmosets, tamarins, and lion tamarins). In seven of the nine species studied, infants born after short interbirth intervals had significantly higher risks of mortality than infants born after longer interbirth intervals. These results suggest that reproduction in callitrichine primates may be limited by physiologic constraints, such that short birth spacing drives higher infant mortality.The BET-bromodomain protein BRD4 uses two bromodomains to target acetyl-histones and other domains to recruit P-TEFb and other transcription factors to stimulate transcription of proto-oncogenes and key cell identity genes. Recent studies show that its ability to form phase-separated condensates that cluster preferentially at the super-enhancer regions of target genes is key for BRD4 to exert its functions. Here, we describe the identification of a natural product called PCG from polygonum cuspidatum Sieb.et Zucc., a traditional Chinese medicinal herb, that directly binds to BRD4. This binding inhibits BRD4 phase separation, turns dynamic BRD4 nuclear condensates into static aggregates, and effectively shuts down transcription of BRD4-dependent genes. Thus, through PCG we have discovered a BET inhibitor that not only selectively targets BRD4 but also works by suppressing phase separation, a mechanism of action that is different from those of the other known BET inhibitors.Antiplatelet drugs targeting G-protein-coupled receptors (GPCRs), used for the secondary prevention of arterial thrombosis, coincide with an increased bleeding risk. Targeting ITAM-linked receptors, such as the collagen receptor glycoprotein VI (GPVI), is expected to provide a better antithrombotic-hemostatic profile. Here, we developed and characterized an ultra-high-throughput (UHT) method based on intracellular [Ca2+]i increases to differentiate GPVI and GPCR effects on platelets. In 96-, 384-, or 1,536-well formats, Calcium-6-loaded human platelets displayed a slow-prolonged or fast-transient [Ca2+]i increase when stimulated with the GPVI agonist collagen-related peptide or with thrombin and other GPCR agonists, respectively. Semi-automated curve fitting revealed five parameters describing the Ca2+ responses. Verification of the UHT assay was done with a robustness compound library and clinically relevant platelet inhibitors. Taken together, these results present proof of principle of distinct receptor-type-dependent Ca2+ signaling curves in platelets, which allow identification of new inhibitors in a UHT way.