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Abstract Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development.

Background: In small children with left atrioventricular valve dysfunction, valve repair is preferred but some will require valve replacement. No prosthetic valve has growth potential, bioprostheses have poor durability, and mechanical prostheses have high rates of thromboembolic and hemorrhagic complications. We reviewed our experience with a modified bovine jugular vein valve designed for use in the right ventricular outflow tract (Melody valve, Medtronic) and compared this with contemporary mechanical valve replacement. Methods: We reviewed outcomes of all left-sided atrioventricular valve replacements (AVVR) performed between January 2017 and April 2023 on patients with biventricular circulation less than 5 years old at time of surgery, N = 19. We compared mortality and major morbidity outcomes between mechanical AVVR (mAVVR, n = 14) and Melody AVVR (MAVVR, n=5). Results: MAVVR was performed on younger and smaller patients (5.7 ± 4.2 vs 28.4 ± 22.3 months, P = .002; 6 ± 1.7 vs10 ± 5.1 kg, P = .01). There were 2 early and 1 late death in the mAVVR group, and none in the MAVVR group. There was a trend towards more hemorrhagic and neurologic complications in the mAVVR group (P = .1, 0.28, respectively). Conclusions: In this small series, despite its use in younger and smaller patients, our preliminary experience with the Melody valve compares favorably with our contemporaneous outcomes with mechanical prostheses by way of simpler anticoagulation management with a trend towards better overall outcomes.

Abstract Climate change is a looming threat to marine life, creating an urgent need to develop climate-informed conservation strategies. The Climate Risk Index for Biodiversity was designed to assess the climate risk for marine species in a manner that supports decision-making. Yet, its regional application remains to be explored. Here, we use it to evaluate climate risk for ~2000 species in the northwest Atlantic Ocean, a marine warming hotspot, to explore its capacity to inform climate-considered fisheries management. Under high emissions, harvested species, especially those with the highest economic value, have a disproportionate risk of projected exposure to hazardous climate conditions but benefit the most from emission mitigation. By mapping critical risk areas for 90 fish stocks, we pinpoint locations likely to require additional intervention, such as in the southern Gulf of St. Lawrence for Atlantic cod. Finally, we demonstrate how evaluating climate risk geographically and understanding how it arises can support short- and long-term fisheries management and conservation objectives under climate change.

Abstract Creatine chemical exchange saturation transfer (CrCEST) MRI is an emerging high resolution and noninvasive method for measuring muscle specific oxidative phosphorylation (OXPHOS). However, CrCEST measurements are sensitive to changes in muscle pH, which might confound the measurement and interpretation of creatine recovery time (τCr). Even with the same prescribed exercise stimulus, the extent of acidification and hence its impact on τCr is expected to vary between individuals. To address this issue, a method to measure pH pre- and post-exercise and its impact on CrCEST MRI with high temporal resolution is needed. In this work, we integrate carnosine 1H- magnetic resonance spectroscopy (MRS) and 3D CrCEST to establish “mild” and “moderate/intense” exercise stimuli. We then test the dependence of CrCEST recovery time on pH using different exercise stimuli. This comprehensive metabolic imaging protocol will enable personalized, muscle specific OXPHOS measurements in both healthy aging and myriad other disease states impacting muscle mitochondria.

Abstract Background Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium. Methods We investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice. Articular cartilage (AC) integrity and SCB morphology were assessed in 182 knee joints of 22-25 months old mice using the Osteoarthritis Research Society International (OARSI) scoring system and micro-CT, respectively. Additionally, we explored the effects of methylene blue (MB) and mitoquinone (MitoQ), two agents that affect mitochondrial function, on the prevalence and progression of OA during aging. Results Aged UM-HET3 mice showed a high prevalence of primary OA in both sexes. Significant positive correlations were found between cumulative AC (cAC) scores and synovitis in both sexes, and osteophyte formation in female mice. Ectopic chondrogenesis did not show significant correlations with cAC scores. Significant direct correlations were found between AC scores and inflammatory markers in chondrocytes, including matrix metalloproteinase-13, inducible nitric oxide synthase, and the NLR family pyrin domain containing-3 inflammasome in both sexes, indicating a link between OA severity and inflammation. Additionally, markers of cell cycle arrest, such as p16 and β-galactosidase, also correlated with AC scores. In male mice, no significant correlations were found between SCB morphology traits and cAC scores, while in female mice, significant correlations were found between cAC scores and tibial SCB plate bone mineral density. Notably, MB and MitoQ treatments influenced the disease's progression in a sex-specific manner. MB treatment significantly reduced cAC scores at the medial knee joint, while MitoQ treatment reduced cAC scores, but these did not reach significance. Conclusions Our study provides comprehensive insights into the prevalence and progression of primary OA in aged UM-HET3 mice, highlighting the sex-specific effects of MB and MitoQ treatments. The correlations between AC scores and various pathological factors underscore the multifaceted nature of OA and its association with inflammation and subchondral bone changes.

PURPOSECancer recurrence is an important long-term outcome of cancer survivors that is often not routinely collected and recorded by population-based registries. In this study, we review population-based studies to determine the current availability, landscape, and infrastructure of long-term outcomes, particularly metastatic recurrence, in women initially diagnosed with nonmetastatic breast cancer (MBC).METHODSWe reviewed the literature to identify studies that used population-based registry data to examine the distribution of metastatic recurrence in women diagnosed with non-MBC. Data on outcomes and methods of ascertainment were extracted. Registry infrastructure including sources and funding was also reviewed.RESULTSA total of 23 studies from 11 registries in eight countries spanning Europe, North America, and Oceania were identified and included in the review. Most studies were retrospective in nature and collected recurrence data only for ad hoc studies rather than as part of their routine registration. Definition of recurrence and data sources varied considerably across studies: the cancer-free time interval between the start of follow-up and risk window ranged from the diagnosis of primary tumor (n = 7) to 6 months from diagnosis (n = 1); the start of follow-up differed between initial diagnosis (n = 16) and treatment (n = 7).CONCLUSIONCancer surveillance should encompass outcomes among survivors for research and monitoring. Studies are underway, but more are needed. Cancer registries should be supported to routinely collect recurrence data to allow complete evaluation of MBC as an outcome to be conducted and inform health care providers and researchers of the prognosis of both nonmetastatic and metastatic patients with breast cancer.

Variant calling is fundamental in bacterial genomics, underpinning the identification of disease transmission clusters, the construction of phylogenetic trees, and antimicrobial resistance detection. This study presents a comprehensive benchmarking of variant calling accuracy in bacterial genomes using Oxford Nanopore Technologies (ONT) sequencing data. We evaluated three ONT basecalling models and both simplex (single-strand) and duplex (dual-strand) read types across 14 diverse bacterial species. Our findings reveal that deep learning-based variant callers, particularly Clair3 and DeepVariant, significantly outperform traditional methods and even exceed the accuracy of Illumina sequencing, especially when applied to ONT’s super-high accuracy model. ONT’s superior performance is attributed to its ability to overcome Illumina’s errors, which often arise from difficulties in aligning reads in repetitive and variant-dense genomic regions. Moreover, the use of high-performing variant callers with ONT’s super-high accuracy data mitigates ONT’s traditional errors in homopolymers. We also investigated the impact of read depth on variant calling, demonstrating that 10× depth of ONT super-accuracy data can achieve precision and recall comparable to, or better than, full-depth Illumina sequencing. These results underscore the potential of ONT sequencing, combined with advanced variant calling algorithms, to replace traditional short-read sequencing methods in bacterial genomics, particularly in resource-limited settings.

Craniomaxillofacial (CMF) reconstruction is a challenging clinical dilemma. It often necessitates skin replacement in the form of autologous graft or flap surgery, which differ from one another based on hypodermal/dermal content. Unfortunately, both approaches are plagued by scarring, poor cosmesis, inadequate restoration of native anatomy and hair, alopecia, donor site morbidity, and potential for failure. Therefore, new reconstructive approaches are warranted, and tissue engineered skin represents an exciting alternative. In this study, we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting (IOB), which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting. Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix (adECM) and stem cells (ADSCs), skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies. adECM, even at a very low concentration such as 2 % or less, has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo. Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects, accomplishing near-complete wound closure within two weeks. More importantly, both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame. Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.

Background: Little is known regarding the characteristics, treatment patterns, and outcomes in patients with adult congenital heart disease (ACHD) admitted to cardiac intensive care units (CICUs). Objectives: The authors sought to better define the contemporary epidemiology, treatment patterns, and outcomes of ACHD admissions in the CICU. Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Participating centers contributed prospective data from consecutive admissions during 2-month annual snapshots from 2017 to 2022. We analyzed characteristics and outcomes of admissions with ACHD compared with those without ACHD. Multivariable logistic regression was used to assess mortality in ACHD vs non-ACHD admissions. Results: Of 23,299 CICU admissions across 42 sites, there were 441 (1.9%) ACHD admissions. Shunt lesions were most common (46.1%), followed by right-sided lesions (29.5%) and complex lesions (28.7%). ACHD admissions were younger (median age 46 vs 67 years) than non-ACHD admissions. ACHD admissions were more commonly for heart failure (21.3% vs 15.7%, P

Background Natural killer (NK) cells are being extensively studied as a cell therapy for cancer. These cells are activated by recognition of ligands and antigens on tumor cells. Cytokine therapies, such as IL-15, are also broadly used to stimulate endogenous and adoptively transferred NK cells in patients with cancer. These stimuli activate the membrane protease ADAM17, which cleaves various cell-surface receptors on NK cells as a negative feedback loop to limit their cytolytic function. ADAM17 inhibition can enhance IL-15-mediated NK cell proliferation in vitro and in vivo. In this study, we investigated the underlying mechanism of this process.Methods Peripheral blood mononuclear cells (PBMCs) or enriched NK cells from human peripheral blood, either unlabeled or labeled with a cell proliferation dye, were cultured for up to 7 days in the presence of rhIL-15±an ADAM17 function-blocking antibody. Different fully human versions of the antibody were generated; Medi-1 (IgG1), Medi-4 (IgG4), Medi-PGLALA, Medi-F(ab′)2, and TAB16 (anti-ADAM17 and anti-CD16 bispecific) to modulate CD16A binding. Flow cytometry was used to assess NK cell proliferation and phenotypic markers, immunoblotting to examine CD16A signaling, and IncuCyte-based live cell imaging to measure NK cell antitumor activity.Results The ADAM17 function-blocking monoclonal antibody (mAb) Medi-1 markedly increased early NK cell activation by IL-15. By using different engineered versions of the antibody, we demonstrate involvement by CD16A, an activating Fcγ receptor and well-described ADAM17 substrate. Hence, Medi-1 when bound to ADAM17 on NK cells is engaged by CD16A and blocks its shedding, inducing and prolonging its signaling. This process did not promote evident NK cell fratricide or dysfunction. Synergistic signaling by Medi-1 and IL-15 enhanced the upregulation of CD137 on CD16A+ NK cells and augmented their proliferation in the presence of PBMC accessory cells or an anti-CD137 agonistic mAb.Conclusions Our data reveal for the first time that CD16A and CD137 underpin Medi-1 enhancement of IL-15-driven NK cell activation and proliferation, respectively, with the latter requiring PBMC accessory cells. The use of Medi-1 represents a novel strategy to enhance IL-15-driven NK cell proliferation, and it may be of therapeutic importance by increasing the antitumor activity of NK cells in patients with cancer.

This case report presents a novel, non-pharmacological treatment of Type 2 Diabetes in a 46-year-old male, demonstrating improvements in blood chemistry and psychometric markers after 8 treatments using a Mind-Body Intervention (MBI) called Neuro-Emotional Technique (NET). The patient presented with a diagnosis of Type 2 Diabetes (T2D), pain, psychosocial indicators of stress and anxiety, and a score of 4 on the ACE-Q (Adverse Childhood Experiences Questionnaire) that is consistent with a predisposition to chronic disease and autoimmune disorders. Glucose levels for this patient were above normal levels (typically between 10-15mmol/L where optimal range is between 4-10mmol/L) for at least two months prior to the 4-week NET intervention period, despite the standard use of conventional antidiabetic medications (insulin injections). The patient exhibited numerous indictors of chronic stress that were hypothesised to be underlying his medical diagnosis and a series of 8 NET treatments over a period of 4 weeks was recommended. Psychometric tests and glucose measurements were recorded at baseline (prior to treatment), 4 weeks (at the conclusion of treatment) and at 8 weeks (4 weeks following the conclusion of treatment). Results show that glucose levels were reduced, and self-reported measures of depression, anxiety, stress, distress and pain all decreased from high and extreme levels to within normal ranges after 4 weeks, with ongoing improvement at 8 weeks. McEwen described the concept of allostatic load and the disruptive effects that cumulative stress can have on both mental and physical health. It is hypothesized that NET reduces allostatic load thereby fortifying homeostasis and the salutogenic stress response mechanisms involved in recovery from chronic illness, possibly via the Psycho-Immune-Neuroendocrine (PINE) network. Further studies with larger sample sizes are required to establish whether these results could be extrapolated to a wider population, however the results of this case suggest that it may be beneficial to consider co-management of T2D with an MBI such as NET.

Abstract Background Approximating the recent phylogeny of N phased haplotypes at a set of variants along the genome is a core problem in modern population genomics and central to performing genome-wide screens for association, selection, introgression, and other signals. The Li & Stephens (LS) model provides a simple yet powerful hidden Markov model for inferring the recent ancestry at a given variant, represented as an $$N \times N$$ N × N distance matrix based on posterior decodings. Results We provide a high-performance engine to make these posterior decodings readily accessible with minimal pre-processing via an easy to use package kalis, in the statistical programming language R. kalis enables investigators to rapidly resolve the ancestry at loci of interest and developers to build a range of variant-specific ancestral inference pipelines on top. kalis exploits both multi-core parallelism and modern CPU vector instruction sets to enable scaling to hundreds of thousands of genomes. Conclusions The resulting distance matrices accessible via kalis enable local ancestry, selection, and association studies in modern large scale genomic datasets.

The use of an agonist-antagonist muscle pair for myoelectric control of a transtibial prosthesis requires normalizing the myoelectric signals and identifying their co-contraction signature. Extensive literature has explored the relationship between body posture and lower-limb muscle activation level using surface electromyography (EMG), but it is unknown how these relationships hold after amputation. Using a virtual tracking task, this study compares the effect of three different calibration postures (seated, standing, dynamic) on user tracking ability while in two tracking postures (seated, standing) for 18 able-bodied (AB) subjects and 9 subjects with transtibial (TT) amputation. As expected, AB subjects produced statistically significant differences in muscle activation for gastrocnemius (GAS) when seated vs. standing during calibration (p = 8.8e-4), but not for tibialis anterior (TA) (p = 0.76). TT subjects, however, showed no significant differences in GAS or TA between seated and standing (p = 0.90, 0.60 respectively). It was also determined that normalizing EMG by the global maximum signal observed (standard in biomechanic analysis) is undesirable for myoelectric control. For best general results with this framework, calibration in both seated and dynamic postures is recommended, taking the normalization information from the seated posture and the narrowest co-contraction slopes from the two.

Abstract There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation. Here we utilize a nucleoside analog, 6-Thio-2’-deoxyguanosine (6TdG) currently in phase II clinical trials, that is preferentially incorporated by telomerase into telomeres leading to telomere dysfunction. Using preclinical mouse and human derived models we find low intermittent doses of 6TdG inhibit tumor growth and reduce metastatic burden. Anti-tumor efficacy correlates with a reduction in a subpopulation of cancer initiating like cells (CICs) identified by their expression of L1CAM/CD133 and highest telomerase activity. 6TdG treatment also leads to activation of innate and adaptive anti-tumor responses. Mechanistically, 6TdG depletes CICs and induces type-I interferon signaling leading to tumor immune visibility by activating tumor cell STING signaling. We also observe increased sensitivity to irradiation after 6TdG treatment in both syngeneic and humanized SCLC xenograft models both of which are dependent on the presence of host immune cells. This study underscores the immune-enhancing and metastasis-reducing effects of 6TdG, employing a range of complementary in vitro and in vivo SCLC preclinical models providing a potential therapeutic approach to SCLC.

Abstract Given the importance of coastal upwelling systems to ocean productivity, fisheries, and biogeochemical cycles, their response to climate change is of great interest. However, there is no consensus on future productivity changes in these systems, which may be controlled by multiple drivers including wind‐driven and geostrophic transport, stratification, and source water properties. Here we use an ensemble of regional ocean projections and recently developed upwelling indices for the California Current System to disentangle these sometimes‐competing influences. Some changes are consistent among models (e.g., decreased mixed layer depth), while for others there is a lack of agreement even on the direction of future change (e.g., nitrate concentration in upwelled waters). Despite models' diverging projections of productivity changes, they agree that those changes are predominantly driven by subsurface nitrate concentrations, not by upwelling strength. Our results highlight the need for more attention to processes governing subsurface nutrient changes, not just upwelling strength.

Abstract A global decline in seagrass populations has led to renewed calls for their conservation as important providers of biogenic and foraging habitat, shoreline stabilization and carbon storage. Eelgrass (Zostera marina) occupies the largest geographic range among seagrass species spanning a commensurately broad spectrum of environmental conditions. In Canada, eelgrass is managed as a single phylogroup despite occurring across three oceans and a range of ocean temperatures and salinity gradients. Previous research has focused on applying relatively few markers to reveal population structure of eelgrass, whereas a whole‐genome approach is warranted to investigate cryptic structure among populations inhabiting different ocean basins and localized environmental conditions. We used a pooled whole‐genome re‐sequencing approach to characterize population structure, gene flow and environmental associations of 23 eelgrass populations ranging from the Northeast United States to Atlantic, subarctic and Pacific Canada. We identified over 500,000 SNPs, which when mapped to a chromosome‐level genome assembly revealed six broad clades of eelgrass across the study area, with pairwise FST ranging from 0 among neighbouring populations to 0.54 between Pacific and Atlantic coasts. Genetic diversity was highest in the Pacific and lowest in the subarctic, consistent with colonization of the Arctic and Atlantic oceans from the Pacific less than 300 kya. Using redundancy analyses and two climate change projection scenarios, we found that subarctic populations are predicted to be potentially more vulnerable to climate change through genomic offset predictions. Conservation planning in Canada should thus ensure that representative populations from each identified clade are included within a national network so that latent genetic diversity is protected, and gene flow is maintained. Northern populations, in particular, may require additional mitigation measures given their potential susceptibility to a rapidly changing climate.

Background:. Social media use has grown across healthcare delivery and practice, with dramatic changes occurring in response to the coronavirus (COVID-19) pandemic. The purpose of this study was to conduct a comprehensive systematic review to determine the current landscape of social media use by (1) orthopaedic surgery residencies/fellowship training programs and (2) individual orthopaedic surgeons and the change in use over time. Methods:. We searched 3 electronic databases (PubMed, MEDLINE, and Embase) from their inception to April 2022 for all studies that analyzed the use of social media in orthopaedic surgery. Two reviewers independently determined study eligibility, rated study quality, and extracted data. Methodology was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results:. Twenty-eight studies were included, of which 11 analyzed social media use by orthopaedic surgery residency and fellowship training programs and 17 examined its use by individual orthopaedic surgeons. Among residency and fellowship programs, Instagram was identified as the most common platform used, with 42% to 88% of programs reporting program-specific Instagram accounts, followed by Twitter/X (20%-52%) and Facebook (10%-38%). Social media was most commonly used by programs for recruitment and information dissemination to prospective residency applicants (82% and 73% of included studies, respectively). After the start of the COVID-19 pandemic, there was a 620% and 177% increase in the number of training programs with Instagram and Twitter/X accounts, respectively. Individual use of social media ranged from 1.7% to 76% (Twitter/X), 10% to 73% (Facebook), 0% to 61% (Instagram), 22% to 61% (LinkedIn), and 6.5% to 56% (YouTube). Conclusions:. Instagram, Twitter/X, and Facebook are the premier platforms that patients, residency applicants, and institutions frequent. With the continued growth of social media use anticipated, it will be critical for institutions and individuals to create and abide by guidelines outlining respectful and professional integration of social media into practice. Level of Evidence:. Level IV.

Understanding groundwater-dependent ecosystems (i.e., areas with a relatively shallow water table that plays a major role in supporting vegetation health) is key to sustaining water resources in the western United States. Groundwater-dependent ecosystems (GDEs) in Colorado have non-pristine temporal and spatial patterns, compared to agro-ecosystems, which make it difficult to quantify how these ecosystems are impacted by changes in water availability. The goal of this study is to examine how key hydrosocial parameters perturb GDE water use in time and in space. The temporal approach tests for the additive impacts of precipitation, surface water discharge, surface water mass balance as a surrogate for surface–groundwater exchange, and groundwater depth on the monthly Landsat normalized difference vegetation index (NDVI). The spatial approach tests for the additive impacts of river confluences, canal augmentation, development, perennial tributary confluences, and farmland modification on temporally integrated NDVI. Model results show a temporal trend (monthly, 1984–2019) is identifiable along segments of the Arkansas River at resolutions finer than 10 km. The temporal impacts of river discharge correlate with riparian water use sooner in time compared to precipitation, but this result is spatially variable and dependent on the covariates tested. Spatially, areal segments of the Arkansas River that have confluences with perennial streams have increased cumulative vegetation density. Quantifying temporal and spatial dependencies between the sources and effects of GDEs could aid in preventing the loss of a vulnerable ecosystem to increased water demand, changing climate, and evolving irrigation methodologies.

Background: The successful implementation of an equitable lung cancer screening program requires consideration of factors that influence accessibility to screening services. Methods: Using lung cancer cases in British Columbia (BC), Canada, as a proxy for a screen-eligible population, spatial access to 36 screening sites was examined using geospatial mapping and vehicle travel time from residential postal code at diagnosis to the nearest site. The impact of urbanization and Statistics Canada’s Canadian Index of Multiple Deprivation were examined. Results: Median travel time to the nearest screening site was 11.7 min (interquartile range 6.2–23.2 min). Urbanization was significantly associated with shorter drive time (p < 0.001). Ninety-nine percent of patients with ≥60 min drive times lived in rural areas. Drive times were associated with sex, ethnocultural composition, situational vulnerability, economic dependency, and residential instability. For example, the percentage of cases with drive times ≥60 min among the least deprived situational vulnerability group was 4.7% versus 44.4% in the most deprived group. Conclusions: Populations at risk in rural and remote regions may face more challenges accessing screening services due to increased travel times. Drive times increased with increasing sociodemographic and economic deprivations highlighting groups that may require support to ensure equitable access to lung cancer screening.

This study examined invasive cervical cancer (ICC) incidence trends in British Columbia (BC) by age and stage-at-diagnosis relative to World Health Organization ICC elimination targets (4 per 100,000 persons). Incident ICC cases (1971–2017) were obtained from the BC Cancer Registry. Annual age-standardized incidence rates (ASIRs) per 100,000 persons were generated using the direct method. ASIRs were examined among all ages 15+ years and eight age groups using Joinpoint Regression with the Canadian 2011 standard population. Standardized rate ratios (SRRs) compared stage II–IV (late) versus stage I (early) ASIRs by age (2010–2017). ICC ASIRs did not reach the elimination target. ASIRs declined from 18.88 to 7.08 per 100,000 persons (1971–2017). Stronger declines were observed among ages 45+ years, with the largest decline among ages 70–79 years (AAPC = −3.2%, 95% CI = −3.9% to −2.6%). Among ages 25–69 years, varying levels of attenuation in declining trends and stabilization were observed since the 1980s. SRRs indicated higher rates of late-stage ICC among ages 55+ years (SRR−55–69 years = 1.34, 95% CI = 1.08–1.71). Overall, ICC incidence declined in BC since 1971 but did not reach the elimination target. The pace of decline varied across age groups and increased with age. Continued efforts are needed to progress cervical cancer elimination among all age groups.

Abstract Objectives To assess the cost-effectiveness of cetuximab in combination with chemotherapy fluorouracil, oxaliplatin, and leucovorin (FOLFOX) or fluorouracil, irinotecan and leucovorin (FOLFIRI) compared to standard chemotherapy alone as a first-line treatment for metastatic colorectal cancer (mCRC) with positive KRAS wild type patients in Indonesia. Methods A cost-utility analysis applying Markov model was constructed, with a societal perspective. Clinical evidence was derived from published clinical trials. Direct medical costs were gathered from hospital billings. Meanwhile, direct non-medical costs, indirect costs, and utility data were collected by directly interviewing patients. We applied 3% discount rate for both costs and outcomes. Probabilistic sensitivity analysis was performed to explore the model’s uncertainty. Additionally, using payer perspective, budget impact analysis was estimated to project the financial impact of treatment coverage. Results There was no significant difference in life years gained (LYG) between cetuximab plus FOLFOX/FOLFIRI and chemotherapy alone. The incremental QALY was only one month, and the incremental cost-effectiveness ratio (ICER) was approximately IDR 3 billion/QALY for cetuximab plus chemotherapy. Using 1–3 GDP per capita (IDR 215 million or USD 14,350) as the current threshold, the cetuximab plus chemotherapy was not cost-effective. The budget impact analysis resulted that if cetuximab plus chemotherapy remain included in the benefits package under the Indonesian national health insurance (NHI) system, the payer would need more than IDR 1 trillion for five years. Conclusions The combination of cetuximab and chemotherapy for mCRC is unlikely cost-effective and has a substantial financial impact on the system.

The aim of this study was to determine which characteristics of recreational, collegiate, and professional endurance athletes were associated with training changes due to COVID-19 safety restrictions. A Qualtrics survey was distributed to endurance athletes around the world from June 2020 to February 2021. Significant differences between athlete characteristics and changes in training status were determined using a Chi-squared test (significance p < 0.05). Approximately 66% of the 331 endurance athletes changed their training due to restrictions. Significant group differences were found for age, sex, prior coaching status, prior use of a training program, and athlete primary sport compared to the whole sample. Understanding these factors may allow athletes/coaches to approach training in a different way to help minimize or prevent the effects of detraining for a greater portion of athletes should a COVID-19 variant or any other pandemic emerge in the future.

Abstract Background The pediatric patient-reported outcomes version of the common terminology criteria for adverse event measure was developed and validated for use in pediatric cancer clinical trials to better capture the symptom experiences through direct self-report. The study aim was to develop and validate a Swahili language version of the patient-reported outcomes version of the common terminology criteria for adverse event measure. Methods The pediatric version of 15 core symptom adverse events, and the corresponding questions, were selected from the patient-reported outcomes version of the common terminology criteria for adverse event library, then forward and back translated into Swahili by bilingual translators. The translated items were further refined using concurrent cognitive interviewing. Each round of interviews included five children, ages 8–17 years-old, receiving cancer therapy at Bugando Medical Centre, the cancer referral hospital for Northwest Tanzania, and continued until at least 80% of participants understood the question. Results Three rounds of cognitive interviews were completed involving 13 patients and 5 caregivers. Among patients, 50% of questions (19/38) were fully comprehended after the first interview round. Two Adverse Events (anxiety and peripheral neuropathy) were the most difficult for participants to understand, associated with education level and experience. Goal comprehension was achieved after three rounds of interviews with no further revisions required. All parents in the first cognitive interview group comprehended the survey, with no additional revisions. Conclusion A Swahili patient-reported outcomes version of the common terminology criteria for adverse event was effective in eliciting patient-reported Adverse Events related to cancer treatment, with good comprehension for children aged 8–17 years. This survey is important to incorporate patient self-reporting of symptomatic toxicities and is an effective tool to increase capacity for pediatric cancer clinical trials throughout East Africa, further reducing global disparities in cancer care.

Abstract Despite the numerous hydrological, geological, and ecological benefits produced by floodplain landscapes, floodplains continue to be degraded by human activities at a much higher rate than other landscape types. This large-scale landscape modification has been widely recognized, yet a comprehensive, national dataset quantifying the degree to which human activities are responsible for this degradation has not previously been evaluated. In this research, we analyze floodplain integrity for the contiguous United States by spatially quantifying the impact of anthropogenic stressors on almost 80,000 floodplain units. We demonstrate the prevalence of human modifications through widely available geospatial datasets, which we use to quantify indicators of floodplain integrity for five essential floodplain functions of flood attenuation, groundwater storage, habitat provision, sediment regulation, and organics and solute regulation. Our results show that floodplain degradation is spatially heterogeneous and that the integrity of nearly 70% of floodplains in the United States is poor. We highlight that quantifying the integrity of spatially explicit floodplain elements can allow for restoration efforts to be targeted to the areas in most desperate need of preservation.

Monitoring trends in large mammal populations is a fundamental component of wildlife management and conservation. However, direct estimates of population size and vital rates of large mammals can be logistically challenging and expensive. Indicators that reflect trends in abundance, therefore, can be valuable tools for supporting population monitoring. Polar bears have a relatively simple life history such that a few key variables may be effective indicators for tracking changes in body condition and recruitment that affect abundance. Direct estimates of polar bear abundance are difficult to obtain due to their large home ranges in remote Arctic habitats. Changes in abundance associated with environmental conditions appear to affect polar bears largely via effects on female body condition which influence reproduction and cub survival (i.e., recruitment). Loss of sea ice habitat is further limiting researcher access for population monitoring creating a need for alternative approaches. Here we used relationships established from eight years (2008–2017) of data collected on 439 polar bears in the Chukchi Sea, to transform previously published individual-based relationships with annually available sea ice, atmospheric circulation, and prey body condition variables to predict annual mean body condition and recruitment during 2018–2022. Although annual sample sizes were limited for verifying predicted body condition and recruitment via techniques such as cross-validation, in most cases predicted annual means were closely correlated with observed means for 2008–2017. Summer sea ice and prey body condition remained within or increased relative to levels observed during 2008–2017 and predicted polar bear body condition and recruitment during 2018–2022 were largely within or above observed annual means during 2008–2017. A lack of trend in environmental and ecological variables or polar bear body condition and recruitment metrics during 2008–2022 is suggestive that the Chukchi Sea polar bear population was likely stable during this time. Our results provide support for developing models that predict important population parameters of large mammals based on environmental and ecological indicators. Given that trend information is lacking for 10 of the 19 recognized polar bear populations and is outdated for others, the use of environmental and ecological indicators may be particularly useful for augmenting direct estimates of polar bear vital rates in between periods of data collection. Although demographic assessments for polar bears have primarily focused on correlations with sea ice availability, our study and others highlight that prey health is also an important indicator of polar bear population status.

Despite compelling evidence linking voluntary medical male circumcision (VMMC) with 60-70% HIV risk reduction in sub-Saharan Africa, Zambian men have been especially reluctant to undergo VMMC. The Government of Zambia set targets for VMMC uptake and promoted community-level interventions. Spear & Shield (S&S) is an innovative, evidence-based, service program promoting VMMC uptake while ensuring both VMMC supply and demand. This study assessed the large-scale provincial rollout of the program (S&S2) utilizing the RE-AIM model for translating interventions into the community. The S&S2 study was conducted between November 2015 and December 2020, and sequentially rolled out over four Zambian provinces in 96 clinics; 24 observation clinics received VMMC training only. Local clinic healthcare workers were trained to conduct the VMMC procedure and HIV counselors were trained to lead S&S group sessions. Using the RE-AIM model, primary outcomes were: Reach, the number, proportion, and representativeness of S&S attendees; Effectiveness, the impact of S&S2 on VMMC uptake; Adoption, the number, proportion, and representativeness of clinics implementing S&S2; Implementation, fidelity to the S&S intervention manual; and Maintenance, the extent to which S&S2 became an element of standard care within community clinics. Initially, n = 109 clinics were recruited; 96 were sustained and randomized for activation (Adoption). A total of 45,630 clinic patients (n = 23,236 men and n = 22,394 women) volunteered to attend the S&S sessions (Reach). The S&S2 program ran over 2,866 clinic-months (Implementation). Although the study did not target individual-level VMMCs, ~58,301 additional VMMCs were conducted at the clinic level (Effectiveness). Fidelity to the S&S intervention by group leaders ranged from 42%-95%. Sustainability of the program was operationalized as the number of CHCs initially activated that sustained the program. Intervention delivery ended, however, when study funding ceased (Maintenance). The S&S2 program successfully utilized the RE-AIM model to achieve study goals for implementation and dissemination in four Zambian provinces. Innovative VMMC programs such as S&S2 can improve the uptake of VMMC, one of the most effective strategies in the HIV prevention arsenal.

Apoptosis and clearance of apoptotic cells via efferocytosis are evolutionarily conserved processes that drive tissue repair. However, the mechanisms by which recognition and clearance of apoptotic cells regulate repair are not fully understood. Here, we use single-cell RNA sequencing to provide a map of the cellular dynamics during early inflammation in mouse skin wounds. We find that apoptotic pathways and efferocytosis receptors are elevated in fibroblasts and immune cells, including resident Lyve1+ macrophages, during inflammation. Interestingly, human diabetic foot wounds upregulate mRNAs for efferocytosis pathway genes and display altered efferocytosis signaling via the receptor Axl and its ligand Gas6. During early inflammation in mouse wounds, we detect upregulation of Axl in dendritic cells and fibroblasts via TLR3-independent mechanisms. Inhibition studies in vivo in mice reveal that Axl signaling is required for wound repair but is dispensable for efferocytosis. By contrast, inhibition of another efferocytosis receptor, Timd4, in mouse wounds decreases efferocytosis and abrogates wound repair. These data highlight the distinct mechanisms by which apoptotic cell detection coordinates tissue repair and provides potential therapeutic targets for chronic wounds in diabetic patients.

Summary: Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.

Kaposi sarcoma-associated herpesvirus (KSHV) inflammatory cytokine syndrome (KICS) is a newly described chronic inflammatory disease condition caused by KSHV infection and is characterized by high KSHV viral load and sustained elevations of serum KSHV-encoded IL-6 (vIL-6) and human IL-6 (hIL-6). KICS has significant immortality and greater risks of other complications, including malignancies. Although prolonged inflammatory vIL-6 exposure by persistent KSHV infection is expected to have key roles in subsequent disease development, the biological effects of prolonged vIL-6 exposure remain elusive. Using thiol(SH)-linked alkylation for the metabolic (SLAM) sequencing and Cleavage Under Target & Release Using Nuclease analysis (CUT&RUN), we studied the effect of prolonged vIL-6 exposure in chromatin landscape and resulting cytokine production. The studies showed that prolonged vIL-6 exposure increased Bromodomain containing 4 (BRD4) and histone H3 lysine 27 acetylation co-occupancies on chromatin, and the recruitment sites were frequently co-localized with poised RNA polymerase II with associated enzymes. Increased BRD4 recruitment on promoters was associated with increased and prolonged NF-κB p65 binding after the lipopolysaccharide stimulation. The p65 binding resulted in quicker and sustained transcription bursts from the promoters; this mechanism increased total amounts of hIL-6 and IL-10 in tissue culture. Pretreatment with the BRD4 inhibitors, OTX015 and MZ1, eliminated the enhanced inflammatory cytokine production. These findings suggest that persistent vIL-6 exposure may establish a chromatin landscape favorable for the reactivation of inflammatory responses in monocytes. This epigenetic memory may explain the greater risk of chronic inflammatory disease development in KSHV-infected individuals.

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus and the etiologic agent of Kaposi's sarcoma and hyperinflammatory lymphoproliferative disorders. Understanding the mechanism by which KSHV increases the infected cell population is crucial for curing KSHV-associated diseases. Using scRNA-seq, we demonstrate that KSHV preferentially infects CD14+ monocytes, sustains viral lytic replication through the viral interleukin-6 (vIL-6), which activates STAT1 and 3, and induces an inflammatory gene expression program. To study the role of vIL-6 in monocytes upon KSHV infection, we generated recombinant KSHV with premature stop codon (vIL-6(-)) and its revertant viruses (vIL-6(+)). Infection of the recombinant viruses shows that both vIL-6(+) and vIL-6(-) KSHV infection induced indistinguishable host anti-viral response with STAT1 and 3 activations in monocytes; however, vIL-6(+), but not vIL-6(-), KSHV infection promoted the proliferation and differentiation of KSHV-infected monocytes into macrophages. The macrophages derived from vIL-6(+) KSHV infection showed a distinct transcriptional profile of elevated IFN-pathway activation with immune suppression and were compromised in T-cell stimulation function compared to those from vIL-6(-) KSHV infection or uninfected control. Notably, a viral nuclear long noncoding RNA (PAN RNA), which is required for sustaining KSHV gene expression, was substantially reduced in infected primary monocytes upon vIL-6(-) KSHV infection. These results highlight the critical role of vIL-6 in sustaining KSHV transcription in primary monocytes. Our findings also imply a clever strategy in which KSHV utilizes vIL-6 to secure its viral pool by expanding infected monocytes via differentiating into longer-lived dysfunctional macrophages. This mechanism may facilitate KSHV to escape from host immune surveillance and to support a lifelong infection.

The occurrences of summer hypoxia in coastal California Current can significantly affect the benthic and pelagic habitat and lead to complex ecosystem changes. Model-simulated hypoxia in this region is strongly spatially heterogeneous, and its future changes show uncertainties depending on the model used. Here, we used an ensemble of the new generation Earth system models to examine the present-day and future changes of summer hypoxia in this region. We applied model-specific thresholds combined with empirical bias adjustments of the dissolved oxygen variance to identify hypoxia. We found that, although simulated dissolved oxygen in the subsurface varies across the models both in mean state and variability, after necessary bias adjustments, the ensemble shows reasonable hypoxia frequency compared with a hindcast in terms of spatial distribution and average frequency in the coastal region. The models project increases in hypoxia frequency under warming, which is in agreement with deoxygenation projected consistently across the models for the coastal California Current. This work demonstrated a practical approach of using the multi-model ensemble for regional studies while presenting methodology limitations and gaps in observations and models to improve these limitations.

pdacR is an open-source R package and web-based platform that enables community exploration of pancreatic ductal adenocarcinoma (PDAC) gene expression datasets. pdacR is used to interrogate the specificities of popular PDAC molecular subtypes.

Genomic data provides useful information for public health practice, particularly when combined with epidemiologic data. However, sampling bias is a concern because inferences from nonrandom data can be misleading. In March 2021, the Washington State Department of Health, USA, partnered with submitting and sequencing laboratories to establish sentinel surveillance for SARS-CoV-2 genomic data. We analyzed available genomic and epidemiologic data during presentinel and sentinel periods to assess representativeness and timeliness of availability. Genomic data during the presentinel period was largely unrepresentative of all COVID-19 cases. Data available during the sentinel period improved representativeness for age, death from COVID-19, outbreak association, long-term care facility–affiliated status, and geographic coverage; timeliness of data availability and captured viral diversity also improved. Hospitalized cases were underrepresented, indicating a need to increase inpatient sampling. Our analysis emphasizes the need to understand and quantify sampling bias in phylogenetic studies and continue evaluation and improvement of public health surveillance systems.

Non-volitional control, such as finite-state machine (FSM) impedance control, does not directly incorporate user intent signals, while volitional control, like direct myoelectric control (DMC), relies on these signals. This paper compares the performance, capabilities, and perception of FSM impedance control to DMC on a robotic prosthesis for subjects with and without transtibial amputation. It then explores, using the same metrics, the feasibility and performance of the combination of FSM impedance control and DMC across the full gait cycle, termed Hybrid Volitional Control (HVC). After calibration and acclimation with each controller, subjects walked for two minutes, explored the control capabilities, and completed a questionnaire. FSM impedance control produced larger average peak torque (1.15 Nm/kg) and power (2.05 W/kg) than DMC (0.88 Nm/kg and 0.94 W/kg). The discrete FSM, however, caused non-standard kinetic and kinematic trajectories, while DMC yielded trajectories qualitatively more similar to able-bodied biomechanics. While walking with HVC, all subjects successfully achieved ankle push-off and were able to modulate the magnitude of push-off via the volitional input. Unexpectedly, however, HVC behaved either more similarly to FSM impedance control or to DMC alone, rather than in combination. Both DMC and HVC, but not FSM impedance control, allowed subjects to achieve unique activities such as tip-toe standing, foot tapping, side-stepping, and backward walking. Able-bodied subject (N=6) preferences were split amongst the controllers, while all transtibial subjects (N=3) preferred DMC. Desired performance and ease of use showed the highest correlations with overall satisfaction (0.81 and 0.82, respectively).

Background: We aimed to evaluate midterm patient-reported outcomes and reoperation rates following rotator cuff repair in patients with either rheumatoid arthritis (RA) or other inflammatory arthritis (nonRA-IA) diagnoses. Methods: We identified all patients with either RA or nonRA-IA who underwent a rotator cuff repair at our institution between 2008 and 2018. IA diagnoses included RA, systemic lupus erythematosus, psoriatic arthritis, and other unspecified inflammatory arthritis. We compiled a cohort of 51 shoulders, with an average follow-up time of 7.0 years. The average age was 60 years (range 39-81), and 55% of patients were female. Patients were contacted via phone to obtain patient-reported outcomes surveys. Univariate linear regression was used to evaluate associations between patient characteristics and outcomes. Results: A review of preoperative radiographs demonstrated that 50% of patients presented with some degree of glenohumeral joint inflammatory degeneration. At the final follow-up, the mean visual analog score for pain was 2 (range 0-8), and the mean American Shoulder and Elbow Surgeons score (ASES) was 77 (standard deviation [SD] = 19). The mean subjective shoulder value was 75% (SD = 22%), and the average satisfaction was 9 (SD 1.9). The mean Patient-Reported Outcomes Measurement Information System upper extremity score was 41 (SD = 10.6). Female sex and a complete tear (vs. partial) were both associated with lower ASES scores, whereas no other characteristics were associated with postoperative ASES scores. The 5-year Kaplan-Meier survival estimate free of reoperation was 91.8% (95% confidence interval 83.0-99.8). Conclusions: Rotator cuff repair in patients with RA or other inflammatory arthritis diagnoses resulted in satisfactory patient-reported outcomes that seem comparable to rotator cuff repair when performed in the general population. Furthermore, reoperations were rare, with a 5-year survival rate free of reoperation for any reason of over 90%. Altogether, an inflammatory arthritis diagnosis should not preclude by itself attempted rotator cuff repair surgery in these patients.

Abstract Objective Continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) are main modalities for end stage renal disease (ESRD) patients, and those have been covered by National Health Insurance (NHI) scheme since 2014 in Indonesia. This study aims to update the cost-effectiveness model of CAPD versus HD in Indonesia setting. Results Compared to HD, CAPD provides good value for money among ESRD patients in Indonesia. Using societal perspective, the total costs were IDR 1,348,612,118 (USD 95,504) and IDR 1,368,447,750 (USD 96,908), for CAPD and HD, respectively. The QALY was slightly different between two modalities, 4.79 for CAPD versus 4.22 for HD. The incremental cost-effectiveness ratio (ICER) yields savings of IDR 34,723,527/QALY (USD 2460).

Abstract Background Maize-infecting viruses are known to inflict significant agronomic yield loss throughout the world annually. Identification of known or novel causal agents of disease prior to outbreak is imperative to preserve food security via future crop protection efforts. Toward this goal, a large-scale metagenomic approach utilizing high throughput sequencing (HTS) was employed to identify novel viruses with the potential to contribute to yield loss of graminaceous species, particularly maize, in North America. Results Here we present four novel viruses discovered by HTS and individually validated by Sanger sequencing. Three of these viruses are RNA viruses belonging to either the Betaflexiviridae or Tombusviridae families. Additionally, a novel DNA virus belonging to the Geminiviridae family was discovered, the first Mastrevirus identified in North American maize. Conclusions Metagenomic studies of crop and crop-related species such as this may be useful for the identification and surveillance of known and novel viral pathogens of crops. Monitoring related species may prove useful in identifying viruses capable of infecting crops due to overlapping insect vectors and viral host-range to protect food security.

Abstract Background Historically, the focus of cost-effectiveness analyses has been on the costs to operate and deliver interventions after their initial design and launch. The costs related to design and implementation of interventions have often been omitted. Ignoring these costs leads to an underestimation of the true price of interventions and biases economic analyses toward favoring new interventions. This is especially true in low- and middle-income countries (LMICs), where implementation may require substantial up-front investment. This scoping review was conducted to explore the topics, depth, and availability of scientific literature on integrating implementation science into economic evaluations of health interventions in LMICs. Methods We searched Web of Science and PubMed for papers published between January 1, 2010, and December 31, 2021, that included components of both implementation science and economic evaluation. Studies from LMICs were prioritized for review, but papers from high-income countries were included if their methodology/findings were relevant to LMIC settings. Results Six thousand nine hundred eighty-six studies were screened, of which 55 were included in full-text review and 23 selected for inclusion and data extraction. Most papers were theoretical, though some focused on a single disease or disease subset, including: mental health (n = 5), HIV (n = 3), tuberculosis (n = 3), and diabetes (n = 2). Manuscripts included a mix of methodology papers, empirical studies, and other (e.g., narrative) reviews. Authorship of the included literature was skewed toward high-income settings, with 22 of the 23 papers featuring first and senior authors from high-income countries. Of nine empirical studies included, no consistent implementation cost outcomes were measured, and only four could be mapped to an existing costing or implementation framework. There was also substantial heterogeneity across studies in how implementation costs were defined, and the methods used to collect them. Conclusion A sparse but growing literature explores the intersection of implementation science and economic evaluation. Key needs include more research in LMICs, greater consensus on the definition of implementation costs, standardized methods to collect such costs, and identifying outcomes of greatest relevance. Addressing these gaps will result in stronger links between implementation science and economic evaluation and will create more robust and accurate estimates of intervention costs. Trial registration The protocol for this manuscript was published on the Open Science Framework. It is available at: https://osf.io/ms5fa/ (DOI: 10.17605/OSF.IO/32EPJ).

Follicular lymphoma can transform to a more aggressive histology. Here, the authors use bulk and single cell analysis to create a 26 marker panel which could be used to profile FL samples and predict the risk of transformation using flow cytometry.

Abstract Contemporary analyses of insect population trends are based, for the most part, on a large body of heterogeneous and short‐term datasets of diurnal species that are representative of limited spatial domains. This makes monitoring changes in insect biomass and biodiversity difficult. What is needed is a method for monitoring that provides a consistent, high‐resolution picture of insect populations through time over large areas during day and night. Here, we explore the use of X‐band weather surveillance radar (WSR) for the study of local insect populations using a high‐quality, multi‐week time series of nocturnal moth light trapping data. Specifically, we test the hypotheses that (i) unsupervised data‐driven classification algorithms can differentiate meteorological and biological phenomena, (ii) the diversity of the classes of bioscatterers are quantitatively related to the diversity of insects as measured on the ground and (iii) insect abundance measured at ground level can be predicted quantitatively based on dual‐polarization Doppler WSR variables. Adapting the quasi‐vertical profile analysis method and data clustering techniques developed for the analysis of hydrometeors, we demonstrate that our bioscatterer classification algorithm successfully differentiates bioscatterers from hydrometeors over a large spatial scale and at high temporal resolutions. Furthermore, our results also show a clear relationship between biological and meteorological scatterers and a link between the abundance and diversity of radar‐based bioscatterer clusters and that of nocturnal aerial insects. Thus, we demonstrate the potential utility of this approach for landscape scale monitoring of biodiversity.

Patients treated with Aurora kinase inhibitors experience dose-limiting neutropenia while other cytopenias are rare. Here, Chou et al. show that this cell-type specific side effect is partly explained by loss of drug efflux pump expression during neutrophil differentiation.

Using high-resolution stable isotope and microstructure analyses of otoliths, this study reveals that sardine populations in the western and eastern North Pacific have different early life metabolic and growth rates that respond contrastingly to temperature variations. These findings could explain observations of different responses in these populations to decadal-scale temperature anomalies.

Identification of host antiviral restriction factors could provide targets for antiviral therapy. Here, using a genome-wide CRISPR screen, the authors identify the glycosyltransferase B3GAT1 as a host protein which, when ectopically overexpressed, restricts influenza virus infection in vitro and in mice, as well as other viruses relying on sialic acid for entry.

Abstract Background Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid. Case presentation We present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death. Conclusion Detection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion.

Variable rate irrigation (VRI) is used to save water whilst maintaining crop yields in semiarid regions. A key problem is to be able to inexpensively determine spatial patterns in soil moisture so that VRI zones can be defined. In Southern Idaho, USA, the annual precipitation is low and most fall as winter snow. This research investigates whether snow melt patterns measured using freely available time-series Sentinel 2 imagery from Google Earth Engine can define useful VRI zones for two arable fields (Grace and Rexburg). The normalized difference snow index (NDSI) was computed for each 10 m pixel with snow for all winter images of the fields for 2018–2022. NDSI values were ranked within each image and average ranks were calculated for each month and over several years. The patterns of March NDSI were most similar to patterns in yield and soil moisture observed in previous years. Zones were determined using K-means classification of the mean ranks of March NDSI. Kruskal Wallis H tests showed consistent and significant differences between zones for key soil, plant, and topographic variables. For the Grace site, differences between zones were more consistent in their order of magnitude than VRI zones which were calculated using a labor-intensive method. For the Rexburg site, zones were shown to be better when based on snowmelt data from March 2018 to 2022 rather than just March 2019. It is important to base zones on several years of data because in some years there was no snow observed in the Grace field in March. In locations where the majority of soil moisture comes from snowmelt, basing VRI zones on several years of snowmelt patterns in March is a useful and inexpensive tool for deriving meaningful VRI zones. The code used to automatically extract suitable sentinel images and calculate the NDSI is included so that practitioners can use this approach in other locations.

A direct consequence of Faraday rotation is that the polarized radio sky does not resemble the total intensity sky at long wavelengths. We analyze G137+7, which is undetectable in total intensity but appears as a depolarization feature. We use the first polarization maps from the Canadian Hydrogen Intensity Mapping Experiment. Our 400–729 MHz bandwidth and angular resolution, $17^{\prime} $ – $30^{\prime} $ , allow us to use Faraday synthesis to analyze the polarization structure. In polarized intensity and polarization angle maps, we find a tail extending 10° from the head and designate the combined object, the tadpole . Similar polarization angles, distinct from the background, indicate that the head and tail are physically associated. The head appears as a depolarized ring in single channels, but wideband observations show that it is a Faraday rotation feature. Our investigations of H i and H α find no connections to the tadpole. The tail suggests motion of either the gas or an ionizing star through the interstellar medium; the B2(e) star HD 20336 is a candidate. While the head features a coherent, ∼ −8 rad m ^−2 Faraday depth, Faraday synthesis also identifies multiple components in both the head and tail. We verify the locations of the components in the spectra using QU fitting. Our results show that approximately octave-bandwidth Faraday rotation observations at ∼600 MHz are sensitive to low-density ionized or partially ionized gas, which is undetectable in other tracers.

Precise knowledge of the antenna pointing direction is a key facet to ensure the accuracy of observations from scanning weather radars. The sun is an often-used reference point to aid accurate alignment of weather radar systems and is particularly useful when observed as interference during normal scanning operations. In this study, we combine two online solar interference approaches to determine the pointing accuracy of an X-band mobile weather radar system deployed for 26 months in northern England (54.517°N, 3.615°W). During the deployment, several shifts in the tilt of the radar system are diagnosed between site visits. One extended period of time (>11 months) is shown to have a changing tilt that is independent of human intervention. To verify the corrections derived from this combined approach, quantitative precipitation estimates (QPEs) from the radar system are compared to surface observations: an approach that takes advantage of the variations in the magnitude of partial beam blockage corrections required due to tilting of the radar system close to mountainous terrain. The observed improvements in QPE performance after correction support the use of the derived tilt corrections for further applications using the corrected dataset. Finally, recommendations for future deployments are made, with particular focus on higher latitudes where solar interference spikes show more seasonality than those at mid-latitudes.

Abstract Background Residential treatment is a common approach for treating opioid use disorder (OUD), however, few studies have directly compared it to outpatient treatment. The objective of this study was to compare OUD outcomes among individuals receiving residential and outpatient treatment. Methods A retrospective cohort study used linked data from a state Medicaid program, vital statistics, and the Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episodes Dataset (TEDS) to compare OUD-related health outcomes among individuals treated in a residential or outpatient setting between 2014 and 2017. Multivariable Cox proportional hazards and logistic regression models examined the association between treatment setting and outcomes (i.e., opioid overdose, non-overdose opioid-related and all-cause emergency department (ED) visits, hospital admissions, and treatment retention) controlling for patient characteristics, co-morbidities, and use of medications for opioid use disorders (MOUD). Interaction models evaluated how MOUD use modified associations between treatment setting and outcomes. Results Of 3293 individuals treated for OUD, 957 (29%) received treatment in a residential facility. MOUD use was higher among those treated as an outpatient (43%) compared to residential (19%). The risk of opioid overdose (aHR 1.39; 95% CI 0.73–2.64) or an opioid-related emergency department encounter or admission (aHR 1.02; 95% CI 0.80–1.29) did not differ between treatment settings. Independent of setting, MOUD use was associated with a significant reduction in overdose risk (aHR 0.45; 95% CI 0.23–0.89). Residential care was associated with greater odds of retention at 6-months (aOR 1.71; 95% CI 1.32–2.21) but not 1-year. Residential treatment was only associated with improved retention for individuals not receiving MOUD (6-month aOR 2.05; 95% CI 1.56–2.71) with no benefit observed in those who received MOUD (aOR 0.75; 95% CI 0.46–1.29; interaction p = 0.001). Conclusions Relative to outpatient treatment, residential treatment was not associated with reductions in opioid overdose or opioid-related ED encounters/hospitalizations. Regardless of setting, MOUD use was associated with a significant reduction in opioid overdose risk.