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We have used surface plasmon resonant metal gratings to induce and probe the dielectric response (i.e., electro-optic modulation) of ionic liquids (ILs) at electrode interfaces. Here, the cross-plane electric field at the electrode surface modulates the refractive index of the IL due to the Pockels effect. This is observed as a shift in the resonant angle of the grating (i.e., Δϕ), which can be related to the change in the local index of refraction of the electrolyte (i.e., Δnlocal). The reflection modulation of the IL is compared against a polar (D2O) and a non-polar solvent (benzene) to confirm the electro-optic origin of resonance shift. The electrostatic accumulation of ions from the IL induces local index changes to the gratings over the extent of electrical double layer (EDL) thickness. Finite difference time domain simulations are used to relate the observed shifts in the plasmon resonance and change in reflection to the change in the local index of refraction of the electrolyte and the thickness of the EDL. Simultaneously using the wavelength and intensity shift of the resonance enables us to determine both the effective thickness and Δn of the double layer. We believe that this technique can be used more broadly, allowing the dynamics associated with the potential-induced ordering and rearrangement of ionic species in electrode–solution interfaces. [ABSTRACT FROM AUTHOR]

Introduction: IL-15 agonists hold promise as immunotherapeutics due to their ability to induce the proliferation and expansion of cytotoxic immune cells including natural killer (NK) and CD8+ T cells. However, they generally have short half-lives that necessitate frequent administration to achieve efficacy. To address this limitation, we have developed a half-life extension technology using hydrogel microspheres (MS). Here, the therapeutic is tethered to MSs by a releasable linker with pre-programed cleavage rates. We previously showed the MS conjugate of single-chain IL-15, MS~IL-15, effectively increased the half-life of IL-15 to approximately 1 week and enhanced the pharmacodynamics. We sought to determine whether the same would be true with a MS conjugate of the IL-15 agonist, receptor-linker IL-15 (RLI). Methods: We prepared a long acting MS conjugate of RLI, MS~RLI. The pharmacokinetics and pharmacodynamics of MS~RLI were measured in C57BL/6J mice and compared to MS~IL-15. The antitumor efficacy of MS~RLI was measured when delivered subcutaneously or intratumorally in the CT26 tumor model and intratumorally in the orthotopic EO771 tumor model. Results: MS~RLI exhibited a half-life of 30 h, longer than most IL-15 agonists but shorter than MS~IL-15. The shorter than expected half-life of MS~RLI was shown to be due to target-mediated-disposition caused by an IL-15 induced cytokine sink. MS~RLI resulted in very potent stimulation of NK and CD44hiCD8+ T cells, but also caused significant injection-site toxicity that may preclude subcutaneous administration. We thus pivoted our efforts toward studying the MS~RLI for long-acting intra-tumoral therapy, where some degree of necrosis might be beneficial. When delivered intra- tumorally, both MS~IL-15 and MS~RLI had modest anti-tumor efficacy, but high anti- metastatic activity. Conclusion: Intra-tumoral MS~RLI and MS~RLI combined with systemic treatment with other agents could provide beneficial antitumor and anti-metastatic effects without the toxic effects of systemic IL-15 agonists. Our findings demonstrate that intra-tumorally administered long-acting IL-15 agonists counter two criticisms of loco-regional therapy: the necessity for frequent injections and the challenge of managing metastases. [ABSTRACT FROM AUTHOR]

Introduction: IL-15 agonists hold promise as immunotherapeutics due to their ability to induce the proliferation and expansion of cytotoxic immune cells including natural killer (NK) and CD8+ T cells. However, they generally have short half-lives that necessitate frequent administration to achieve efficacy. To address this limitation, we have developed a half-life extension technology using hydrogel microspheres (MS). Here, the therapeutic is tethered to MSs by a releasable linker with pre-programed cleavage rates. We previously showed the MS conjugate of single-chain IL-15, MS~IL-15, effectively increased the half-life of IL-15 to approximately 1 week and enhanced the pharmacodynamics. We sought to determine whether the same would be true with a MS conjugate of the IL-15 agonist, receptor-linker IL-15 (RLI). Methods: We prepared a long acting MS conjugate of RLI, MS~RLI. The pharmacokinetics and pharmacodynamics of MS~RLI were measured in C57BL/6J mice and compared to MS~IL-15. The antitumor efficacy of MS~RLI was measured when delivered subcutaneously or intratumorally in the CT26 tumor model and intratumorally in the orthotopic EO771 tumor model. Results: MS~RLI exhibited a half-life of 30 h, longer than most IL-15 agonists but shorter than MS~IL-15. The shorter than expected half-life of MS~RLI was shown to be due to target-mediated-disposition caused by an IL-15 induced cytokine sink. MS~RLI resulted in very potent stimulation of NK and CD44hiCD8+ T cells, but also caused significant injection-site toxicity that may preclude subcutaneous administration. We thus pivoted our efforts toward studying the MS~RLI for long-acting intra-tumoral therapy, where some degree of necrosis might be beneficial. When delivered intra- tumorally, both MS~IL-15 and MS~RLI had modest anti-tumor efficacy, but high anti- metastatic activity. Conclusion: Intra-tumoral MS~RLI and MS~RLI combined with systemic treatment with other agents could provide beneficial antitumor and anti-metastatic effects without the toxic effects of systemic IL-15 agonists. Our findings demonstrate that intra-tumorally administered long-acting IL-15 agonists counter two criticisms of loco-regional therapy: the necessity for frequent injections and the challenge of managing metastases. [ABSTRACT FROM AUTHOR]

The article highlights common and uncommon ocular infections and the challenges in diagnosing and managing these infections. Topics include case of a 73-year-old woman with two days of left eye watery drainage, redness, pain and visual changes and a five-day history of vesicular rash on the left forehead, clinical syndromes, causative pathogens and treatment strategies for infections causing conjunctivitis/keratitis, and a discussion on endophthalmitis associated with injection drug use.

Extremophiles, throughout evolutionary time, have evolved a plethora of unique strategies to overcome hardships associated with the environments they are found in. Modifying their genome, showing a bias towards certain amino acids, redesigning their proteins, and enhancing their membranes and other organelles with specialised chemical compounds are only some of those strategies. Scientists can utilise such attributes of theirs for a plethora of biotechnological and astrobiological applications. Moreover, the rigorous study of such microorganisms regarding their evolution and ecological niche can offer deep insight into science's most paramount inquiries such as how life originated on Earth and whether we are alone in the universe. The intensification of studies involving extremophiles in the future can prove to be highly beneficial for humanity, even potentially ameliorating modern problems such as those related to climate change while also expanding our knowledge about the complex biochemical reactions that ultimately resulted in life as we know it today. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates how storage systems, insect pest infestations, and environmental conditions impact aflatoxin contamination and peanut quality in the southeastern United States. It aims to identify key factors affecting the deterioration of peanut quality and aflatoxin levels in commonly utilized storage facilities for in-shell peanuts. The results indicated that peanuts stored in conventional metal warehouses had higher temperatures and moisture content, leading to increased insect infestations, and aflatoxin contamination compared to those stored in flat storage facilities. A significant correlation was found between elevated temperatures, equilibrium moisture content, and the proliferation of insect pests, which contributed to considerable quality degradation. The findings underscore the critical importance of maintaining optimal storage conditions in storage facilities to preserve peanut quality and prevent aflatoxin contamination, with implications for reducing economic losses and safeguarding public health from aflatoxin exposure. Effective postharvest management is crucial for the U.S. peanut industry, given the humid-subtropical climate that promotes insect pests, Aspergillus mold, and aflatoxin contamination in peanut-producing states. This study surveyed five conventional metal warehouses (CMWs) and thirteen flat storage facilities (FSFs) in northeastern, southeastern, and southwestern Georgia, USA, from December 2022 to July 2023. Peanuts were sampled monthly to assess the temporal abundance and diversity of storage insect pests, damage variables, and aflatoxin levels in farmers' stock peanuts. A monoclonal antibody-based affinity chromatographic assay determined the total aflatoxin levels in samples. The most common insect species, accounting for ~85.73 of the total captured, included Cryptolestes ferrugineus, Tribolium castaneum, Ahasverus advena, Plodia interpunctella, Cadra cautella, Ephestia elutella, Liposcelis spp., and Lachesilla pedicularia. Insect populations peaked in June and July, with similar diversity trends across CMWs and FSFs. Insect-damaged kernels, weight loss, discolored kernels, loose-shelled kernels, moisture content, and aflatoxin levels ranged from 3.02 to 11.45%, 1.11 to 3.60%, 2.11 to 11.20%, 1.56 to 4.91%, 6.89 to 8.85%, and 0.43 to 27.59 ppb, respectively. The high prevalence of insect pests, their damage capabilities, and the aflatoxin levels of infested peanuts highlight the need for an improved IPM strategy in warehouses to ensure safe and sustainable peanut storage in the USA. [ABSTRACT FROM AUTHOR]

This work is devoted to the numerical solution of the Helmholtz equation with variable wave number and including a point source in appropriately truncated infinite domains. Motivated by a two‐dimensional model, we formulate a simplified one‐dimensional model. We study its well posedness via wave number explicit stability estimates and prove convergence of the finite element approximations. As a proof of concept, we present the outcome of some numerical experiments for various wave number configurations. Our experiments indicate that the introduction of the artificial boundary near the source and the associated boundary condition lead to an efficient model that accurately captures the wave propagation features. [ABSTRACT FROM AUTHOR]

The environmental effects of airborne micro‐ and nano‐size plastic particles are poorly understood. Microscopy and chemical analyses of atmospherically deposited particles on snow surfaces at high elevation (2,865–3,690 m) in the Upper Colorado River basin (UCRB; Colorado Rocky Mountains) revealed the presence of black substances intimately associated with microplastic fibers, particles interpreted to have originated as tire matter. Identical and similar particles occur in shredded tires and road‐surface samples. The substance responsible for the black color of all tires is carbon black, a graphitic light‐absorbing tire additive produced by hydrocarbon combustion that homogeneously permeates the mixture of tire polymers and other additives. Such black tire matter may thus exert radiative effects closely similar to those of black carbon. The presence in snow of many organic compound types common to tires, measured by two‐dimensional gas chromatography, suggests that atmospherically deposited black road‐tire‐wear matter is among the light‐absorbing particulates that advance the onset and rate of snow melt in the UCRB. The mass of road‐tire‐wear particles shed from vehicles may be estimated by multiplying measured amounts of eroded tire‐per‐distance traveled by vehicular distances. Under a combination of measurements and assumptions about the amounts and radiative properties of atmospheric tire‐wear particles, the radiative effects of these particles might add about 10%–30% to those effects from black carbon, an estimate ripe for revision. On regional and global scales, the amounts and effects of emitted and deposited tire‐wear matter likely vary by factors of geographic source, transport pathway, and depositional setting. Plain Language Summary: A major source for airborne microplastic particles is road‐tire wear. Microscopy and chemical analyses of wind‐blown particles on dirty, high‐elevation (2,865–3,690 m) snow surfaces in the Colorado Rocky Mountains revealed the presence of black substances intimately mixed with microplastics, particles interpreted as tire matter. Identical and similar particles occur in shredded tires and in samples collected from road surfaces. The black substance responsible for the black color of all tire particles is carbon black that homogeneously permeates the mixture of tire polymers and other additives. The mass of particles produced by road‐tire wear may be estimated by multiplying measured amounts of eroded tire‐per‐distance traveled by vehicular travel distances. Under assumptions of amounts of tire‐wear matter emitted to the atmosphere, their presence as light‐absorbing particles likely contribute to melting of snow and ice as well as to warming the atmosphere. Key Points: Light absorbing particles, as blackened microplastic matter from road‐tire wear, occur in snow of the Colorado Rocky Mountains (2013–2021)The mass of road‐tire‐wear particles annually generated is estimated to be 6,550 kt, of which about 655–1,965 kt might become airborneThe results are relevant to radiation modeling of snow and ice surfaces as well as the atmosphere [ABSTRACT FROM AUTHOR]

Objective: The epidemiology of COVID-19 has substantially changed since its emergence given the availability of effective vaccines, circulation of different viral variants, and re-infections. We aimed to develop models to predict 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applications. Methods: We used comprehensive electronic health records from a national cohort of patients in the Veterans Health Administration (VHA) who tested positive for SARS-CoV-2 between March 1, 2022, and March 31, 2023. Full models incorporated 84 predictors, including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to fit prediction models. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset. Results: Models were trained and tested on 198,174 patients, of whom 8% were hospitalized or died within 30 days of testing positive. AUCs for the full models ranged from 0.80 (hospitalization) to 0.91 (death). Brier scores were close to 0, with the lowest error in the mortality model (Brier score: 0.01). All three models were well calibrated with calibration intercepts <0.23 and slopes <1.05. Parsimonious models performed comparably to full models. Conclusions: We developed prediction models that accurately estimate COVID-19 hospitalization and mortality risk following emergence of the Omicron variant and in the setting of COVID-19 vaccinations and antiviral treatments. These models may be used for risk stratification to inform COVID-19 treatment and to identify high-risk patients for inclusion in clinical trials. [ABSTRACT FROM AUTHOR]

Background and Aims: The European Reference Network on Hepatological Diseases (ERN RARE‐LIVER) launched the prospective, multicentre, quality‐controlled R‐LIVER registry on rare liver diseases. The aim of this study was to assess the presentation and outcome of autoimmune hepatitis (AIH) after 1 year of treatment. Methods: Data were prospectively collected at the time of diagnosis and after 6 and 12 months follow‐up. Complete biochemical response (CBR) was defined as normalization of alanine aminotransferase (ALT) and immunoglobulin G (IgG) serum levels. Results: A total of 231 patients from six European centres were included in the analysis. After 6 months of treatment 50% (106/212), and after 12 months 63% (131/210) of patients reached CBR with only 27% (56/211) achieving a steroid‐free CBR within the first year. Overall, 16 different treatment regimens were administered. Change of treatment, mostly due to intolerance, occurred in 30.4% within the first 6 months. In multivariate analysis, younger age at diagnosis (odds ratio [OR] = 1.03 [95% confidence interval (CI) 1.01–1.05]; p =.007), severe fibrosis (OR.38 [95%.16–.89], p =.026) and change of treatment within the first 6 months (OR.40 [95% CI.2–.86]; p =.018) were associated with a lesser chance of ALT normalization at 12 months follow‐up. Conclusion: The landscape of AIH treatment in Europe is highly heterogeneous, even between expert centres. The results from this first European multicentre prospective registry reveal several unmet needs, highlighted by the overall low rates of CBR and the frequent failure to withdraw corticosteroids. [ABSTRACT FROM AUTHOR]

Streambank erosion in agricultural landscapes contributes high amounts of sediment and total-P to surface water, resulting in the degradation of stream habitats and reduction in ecological services. Moreover, the implication of future climate change on bank erosion is also a growing concern. Streambank erosion rates from riparian forest buffers (RFo), grass filters (GFi), row-crops (RCr) and pastures, including fenced pastures (FPa), rotationally grazed pastures (RPa), intensive rotationally grazed pastures (IPa), and continuously grazed pastures (CPa), in three landform regions of Iowa, were measured over seven years. Bank erosion pins were measured seasonally (spring, summer and fall) in the first five years (2002–2006) and yearly for two more years (2007–2008). It was found that summer and spring seasons are the important ones since the relationships between erosion and precipitation were significantly "strong" in almost all the riparian practices, and precipitation was found to be the main factor driving streambank erosion. Streambank mean soil losses and soil total-P losses from RFo (23.3 tons km−1 yr−1 and 9.8 kg km−1 yr−1, respectively), GFi (31.1 and 9.9) and FPa (44.0 and 23.7) practices were all significantly lower than the grazing pasture practices, including RPa (142.3 and 58), CPa (255 and 105.1), IPa (234.6 and 122.7) and RCr fields (352.9 and 118.9). Also, RPa had significantly lower total-P loss than CPa, IPa and RCr practices (RFo, GFi, FPa < RPa < CPa, IPa, RCr). RCr practices had the highest streambank soil losses among all other riparian practices (RFo, GFi, FPa < RPa < IPa, CPa < RCr). The study showed that riparian conservation practices (RFo, GFi and FPa) showcased significant benefits in mitigating streambank soil loss and associated soil total-P load to streams. However, their effectiveness is highly sensitive to changing climatic conditions and the extent of spatiotemporal variations. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. Methods: This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. Results: 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). Conclusions: Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders. [ABSTRACT FROM AUTHOR]

Background Nirmatrelvir-ritonavir is recommended for persons at risk for severe coronavirus disease 2019 (COVID-19) but remains underutilized. Information on which eligible groups are likely to benefit from treatment is needed. Methods We conducted a target trial emulation study in the Veterans Health Administration comparing nirmatrelvir–ritonavir treated versus matched untreated veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from April 2022 through March 2023. We measured incidence of any hospitalization or all-cause mortality at 30 days. Outcomes were measured for the entire cohort, as well as among subgroups defined by 30-day risk of death or hospitalization, estimated using an ensemble risk prediction model. Results Participants were 87% male with median age 66 years and 16% unvaccinated. Compared with matched untreated participants, those treated with nirmatrelvir-ritonavir (n = 24 205) had a lower 30-day risk for hospitalization (1.80% vs 2.30%; risk difference [RD], −0.50% points [95% confidence interval {CI}: −.69 to −.35]) and death (0.11% vs 0.30%; RD, −0.20 [95% CI: −.24 to −.13]). The greatest reductions in combined hospitalization or death were observed in the highest risk quartile (RD −2.85 [95% CI: −3.94 to −1.76]), immunocompromised persons (RD −1.91 [95% CI: −3.09 to −.74]), and persons aged ≥75 years (RD −1.16 [95% CI: −1.73 to −.59]). No reductions were observed in the 2 lowest risk quartiles or persons younger than 65 years. Conclusions Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death in older veterans, those at highest predicted risk for severe outcomes, and immunocompromised groups. Benefit was not observed in younger veterans or groups at lower predicted risk for hospitalization and death. [ABSTRACT FROM AUTHOR]

Background and Aims: Chronic hepatitis delta represents a major global health burden. Clinical features of hepatitis D virus (HDV) infection vary largely between different regions worldwide. Treatment approaches are dependent on the approval status of distinct drugs and financial resources. Methods: The Hepatitis Delta International Network (HDIN) registry involves researchers from all continents (Wranke, Liver International 2018). We here report long‐term follow‐up data of 648 hepatitis D patients recruited by 14 centres in 11 countries. Liver‐related clinical endpoints were defined as hepatic decompensation (ascites, encephalopathy and variceal bleeding), liver transplantation, hepatocellular carcinoma or liver‐related death. Results: Patient data were available from all continents but Africa: 22% from Eastern Mediterranean, 32% from Eastern Europe and Central Asia, 13% from Central and Southern Europe, 14% from South Asia (mainly Pakistan) and 19% from South America (mainly Brazil). The mean follow‐up was 6.4 (.6–28) years. During follow‐up, 195 patients (32%) developed a liver‐related clinical event after 3.5 (±3.3) years. Liver cirrhosis at baseline and a detectable HDV RNA test during follow‐up were associated with a worse clinical outcome in multivariate regression analysis while patients receiving interferon alfa‐based therapies developed clinical endpoints less frequently. Patients from South Asia developed endpoints earlier and had the highest mortality. Conclusions: The HDIN registry confirms the severity of hepatitis D and provides further evidence for HDV viraemia as a main risk factor for disease progression. Hepatitis D seems to take a particularly severe course in patients born in Pakistan. There is an urgent need to extend access to antiviral therapies and to provide appropriate education about HDV infection. [ABSTRACT FROM AUTHOR]

Acute, high-dose radiation exposure results in life-threatening acute radiation syndrome (ARS) and debilitating delayed effects of acute radiation exposure (DEARE). The DEARE are a set of chronic multi-organ illnesses that can result in early death due to malignancy and other diseases. Animal models have proven essential in understanding the natural history of ARS and DEARE and licensure of medical countermeasures (MCM) according to the FDA Animal Rule. Our lab has developed models of hematopoietic (H)-ARS and DEARE in inbred C57BL/6J and Jackson Diversity Outbred (JDO) mice of both sexes and various ages and have used these models to identify mechanisms of radiation damage and effective MCMs. Herein, aggregate data from studies conducted over decades in our lab, consisting of 3,250 total-body lethally irradiated C57BL/6J young adult mice and 1,188 H-ARS survivors from these studies, along with smaller datasets in C57BL/6J pediatric and geriatric mice and JDO mice, were examined for lifespan and development of thymic lymphoma in survivors up to 3 years of age. Lifespan was found to be significantly shortened in H-ARS survivors compared to age-matched nonirradiated controls in all four models. Males and females exhibited similar lifespans except in the young adult C57BL/ 6J model where males survived longer than females after 16 months of age. The incidence of thymic lymphoma was increased in H-ARS survivors from the young adult and pediatric C57BL/ 6J models. Consistent with our findings in H-ARS, geriatric mice appeared more radioresistant than other models, with a lifespan and thymic lymphoma incidence more similar to nonirradiated controls than other models. Increased levels of multiple pro-inflammatory cytokines in DEARE bone marrow and serum correlated with shortened lifespan and malignancy, consistent with other animal models and human data. Of interest, G-CSF levels in bone marrow and serum 8-11 months after irradiation were significantly increased in females. Importantly, treatment with granulopoietic cytokine MCM for radiomitigation of H-ARS did not influence the long-term survival rate or incidence of thymic lymphoma in any model. Taken together, these findings indicate that the lifespan of H-ARS survivors was significantly decreased regardless of age at time of exposure or genetic diversity, and was unaffected by earlier treatment with granulopoietic cytokines for radiomitigation of H-ARS. [ABSTRACT FROM AUTHOR]

At various times in recent decades, surges have occurred in optimism about the potential for universal influenza vaccines that provide strong, broad, and long-lasting protection and could substantially reduce the disease burden associated with seasonal influenza epidemics as well as the threat posed by pandemic influenza. Each year more than 500 million doses of seasonal influenza vaccine are administered around the world, with most doses being egg-grown inactivated subunit or split-virion vaccines. These vaccines tend to have moderate effectiveness against medically attended influenza for influenza A(H1N1) and influenza B, and somewhat lower for influenza A(H3N2) where differences between vaccine strains and circulating strains can occur more frequently due to antigenic drift and egg adaptations in the vaccine strains. Several enhanced influenza vaccine platforms have been developed including cell-grown antigen, the inclusion of adjuvants, or higher antigen doses, to improve immunogenicity and protection. During the COVID-19 pandemic there was unprecedented speed in development and roll-out of relatively new vaccine platforms, including mRNA vaccines and viral vector vaccines. These new platforms present opportunities to improve protection for influenza beyond existing products. Other approaches continue to be explored. Incremental improvements in influenza vaccine performance should be achievable in the short to medium term. [ABSTRACT FROM AUTHOR]

Background: To overcome the limitations of the term "non-alcoholic fatty liver disease" (NAFLD), the term metabolic-associated steatotic liver disease (MASLD) was introduced. While epidemiologic studies have been conducted on MASLD, there is limited evidence on its associated sex and ethnic variations. Aims: This study assesses the differences across sex and race-ethnicity on the prevalence, associated risk factors and adverse outcomes in individuals with MASLD. Methods: Data retrieved from the National Health and Nutrition Examination Survey between 1999 to 2018 was analyzed. Prevalence, clinical characteristics, and outcomes were evaluated according to sex and race-ethnicity. Adverse outcomes and mortality events were analyzed using multivariate analyses. Results: Of 40,166 individuals included, 37.63% had MASLD. There was a significant increase in MASLD prevalence from 1999 to 2018 among Mexican Americans (Annual Percentage Change [APC] + 1.889%, p < 0.001), other Hispanics (APC + 1.661%, p = 0.013), NH Whites (APC + 1.084%, p = 0.018), NH Blacks (APC + 1.108%, p = 0.007), and females (APC + 0.879%, p = 0.030), but not males. Females with MASLD were at lower risk of all-cause (HR: 0.766, 95%CI 0.711 to 0.825, p < 0.001), cardiovascular disease-related (CVD) (SHR: 0.802, 95% CI 0.698 to 0.922, p = 0.002) and cancer-related mortality (SHR: 0.760, 95% CI 0.662 to 0.873, p < 0.001). Significantly, NH Blacks have the highest risk of all-cause and CVD-related mortality followed by NH Whites then Mexican Americans. Conclusion: There has been an increase in prevalence in most race-ethnicities over time. While the change in definition shows no significant differences in previous associations found in NAFLD, the increased mortality in NH Whites relative to Mexican Americans remains to be explored. [ABSTRACT FROM AUTHOR]

Active transportation, with simple mobility modes such as walking and cycling, could be pivotal in addressing multiple sustainability challenges related to socio-economic, environmental, and public health issues. This paper investigates the facilitators for active transportation and assesses its impact on health, well-being, and urban sustainability. As a result, a multidimensional conceptual framework is developed to analyze the determinants influencing individuals' propensity to engage in active transportation and thereby lead to a sustainable, high-quality way of life. Through an extensive review of the relevant literature, key elements for active transportation, accessibility, and social inclusion are identified, and their potential impact on urban health and sustainability is investigated. Findings suggest that interrelationships between factors such as enhanced infrastructure, safety measures, and improved urban accessibility would significantly encourage active transportation usage. The proposed framework argues for a positive association between active transportation and improved health outcomes, contributing to sustainable urban environments. Furthermore, it is advocated that changing attitudes and mindsets could be achieved by urban planning and policy reforms supporting active transportation, as well as by effectively communicating the multiple benefits for individuals, the economy, and society at large. Comprehensive policy strategies, which include improvements in urban design and increased public awareness of the benefits of active transportation, could establish a paradigm shift for promoting a higher quality of life through a healthy, active, and sustainable urban lifestyle. [ABSTRACT FROM AUTHOR]

Background: Research suggests an association between COVID-19 infection and certain financial hardships in the shorter term and among single-state and privately insured samples. Whether COVID-19 is associated with financial hardship in the longer-term or among socially vulnerable populations is unknown. Therefore, we examined whether COVID-19 was associated with a range of financial hardships 18 months after initial infection among a national cohort of Veterans enrolled in the Veterans Health Administration (VHA)—the largest national integrated health system in the US. We additionally explored the association between Veteran characteristics and financial hardship during the pandemic, irrespective of COVID-19. Methods: We conducted a prospective, telephone-based survey. Out of 600 Veterans with COVID-19 from October 2020 through April 2021 who were invited to participate, 194 Veterans with COVID-19 and 194 matched comparators without a history of infection participated. Financial hardship outcomes included overall health-related financial strain, two behavioral financial hardships (e.g., taking less medication than prescribed due to cost), and seven material financial hardships (e.g., using up most or all savings). Weighted generalized estimating equations were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of financial hardship by COVID-19 status, and to assess the relationship between infection and Veteran age, VHA copay status, and comorbidity score, irrespective of COVID-19 status. Results: Among 388 respondents, 67% reported at least one type of financial hardship since March 2020, with 21% reporting behavioral hardships and 64% material hardships; 8% reported severe-to-extreme health-related financial strain. Compared with uninfected matched comparators, Veterans with a history of COVID-19 had greater risks of severe-to-extreme health-related financial strain (RR: 4.0, CI: 1.4–11.2), taking less medication due to cost (RR: 2.9, 95% CI: 1.0–8.6), and having a loved one take time off work to care for them (RR: 1.9, CI: 1.1–3.6). Irrespective of COVID-19 status, Veterans aged < 65 years had a greater risk of most financial hardships compared with Veterans aged ≥ 65 years. Conclusions: Health-related financial hardships such as taking less medication due to cost and severe-to-extreme health-related financial strain were more common among Veterans with a history of COVID-19 than among matched comparators. Strategies are needed to address health-related financial hardship after COVID-19. Trial registration: NCT05394025, registered 05–27-2022. [ABSTRACT FROM AUTHOR]

Objective: The detection of autoantibodies is essential to diagnose autoimmune hepatitis (AIH). Particularly in children, specificity of autoantibodies decreases due to lower titers being diagnostic and being present not only in AIH but also in other liver diseases. Recently, quantification of polyreactive IgG (pIgG) for detection of adult AIH showed the highest overall accuracy compared to antinuclear antibodies (ANA), anti-smooth muscle antibodies (anti-SMA), anti-liver kidney microsomal antibodies (anti-LKM) and anti-soluble liver antigen/liver pancreas antibodies (anti-SLA/LP). We aimed to evaluate the diagnostic value of pIgG for pediatric AIH. Design: pIgG, quantified using HIP1R/BSA coated ELISA, and immunofluorescence on rodent tissue sections were performed centrally. The diagnostic fidelity to diagnose AIH was compared to conventional autoantibodies of AIH in training and validation cohorts from a retrospective, European multi-center cohort from nine centers from eight European countries composed of existing biorepositories from expert centers (n = 285). Results: IgG from pediatric AIH patients exhibited increased polyreactivity to multiple protein and non-protein substrates compared to non-AIH liver diseases and healthy children. pIgG had an AUC of 0.900 to distinguish AIH from non-AIH liver diseases. pIgG had a 31–73% higher specificity than ANA and anti-SMA and comparable sensitivity that was 6–20 times higher than of anti-SLA/LP, anti-LC1 and anti-LKM. pIgG had a 21–34% higher accuracy than conventional autoantibodies, was positive in 43–75% of children with AIH and normal IgG and independent from treatment response. Conclusion: Detecting pIgG improves the diagnostic evaluation of pediatric AIH compared to conventional autoantibodies, primarily owing to higher accuracy and specificity. [ABSTRACT FROM AUTHOR]

Efficacy of remdesivir for COVID-19 remains unclear. We updated our published systematic review to better inform on the use of remdesivir for COVID-19. We searched for randomized controlled trials (RCTs) among hospitalized COVID-19 patients. Meta-analysis was conducted using an inverse variance, random-effects model, presenting relative risk (RR) or mean difference (MD) and their associated 95% confidence intervals (CIs). Statistical heterogeneity was calculated using the I2 statistic. In addition, we conducted trial sequential analysis (TSA). Outcomes with additional data were clinical progression, hospitalization days, and all-cause mortality. We included nine RCTs (12,876 individuals). Three trials each were of a low, unclear, and a high risk of bias. Compared with no treatment/placebo, remdesivir (100 mg daily, over 10 days) significantly improved clinical progression (RR 1.06, CI 1.02–1.11), but did not significantly reduce hospitalization days (MD −0.48, CI −2.18–1.21) and all-cause mortality (RR 0.92, CI 0.84–1.01). TSA suggested that further information is not required to conclude on the efficacy of remdesivir in improving clinical progression, and that, while more information is required for hospitalization days and all-cause mortality, further RCTs to prove fewer hospitalization days may be futile, as efficacy of remdesivir for this outcome is unlikely. Remdesivir appeared promising for COVID-19, but there is insufficient evidence of its efficacy. High quality RCTs are needed for a stronger evidence base. [ABSTRACT FROM AUTHOR]

Background: Obesity is a major health burden. Preadipocytes proliferate and differentiate in mature adipocytes in the adipogenic process, which could be a potential therapeutic approach for obesity. Deficiency of SIRT6, a stress-responsive protein deacetylase and mono-ADP ribosyltransferase enzyme, blocks adipogenesis. Mutants of SIRT6 (N308K/A313S) were recently linked to the in the long lifespan Ashkenazi Jews. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect adipogenesis at the transcriptional and epigenetic level. Methods: We analyzed the role of SIRT6 wild-type (WT) or SIRT6 centenarian-associated mutant (N308K/A313S) overexpression in adipogenesis, by creating stably transduced preadipocyte cell lines using lentivirus on the 3T3-L1 model. Histone post-translational modifications (PTM: acetylation, methylation) and transcriptomic changes were analyzed by mass spectrometry (LC–MS/MS) and RNA-Seq, respectively, in 3T3-L1 adipocytes. In addition, the adipogenic process and related signaling pathways were investigated by bioinformatics and biochemical approaches. Results: Overexpression of centenarian-associated SIRT6 mutant increased adipogenic differentiation to a similar extent compared to the WT form. However, it triggered distinct histone PTM profiles in mature adipocytes, with significantly higher acetylation levels, and activated divergent transcriptional programs, including those dependent on signaling related to the sympathetic innervation and to PI3K pathway. 3T3-L1 mature adipocytes overexpressing SIRT6 N308K/A313S displayed increased insulin sensitivity in a neuropeptide Y (NPY)-dependent manner. Conclusions: SIRT6 N308K/A313S overexpression in mature adipocytes ameliorated glucose sensitivity and impacted sympathetic innervation signaling. These findings highlight the importance of targeting SIRT6 enzymatic activities to regulate the co-morbidities associated with obesity. [ABSTRACT FROM AUTHOR]

Determining the atomic-level structure of a protein has been a decades-long challenge. However, recent advances in transformers and related neural network architectures have enabled researchers to significantly improve solutions to this problem. These methods use large datasets of sequence information and corresponding known protein template structures, if available. Yet, such methods only focus on sequence information. Other available prior knowledge could also be utilized, such as constructs derived from x-ray crystallography experiments and the known structures of the most common conformations of amino acid residues, which we refer to as partial structures. To the best of our knowledge, we propose the first transformer-based model that directly utilizes experimental protein crystallographic data and partial structure information to calculate electron density maps of proteins. In particular, we use Patterson maps, which can be directly obtained from x-ray crystallography experimental data, thus bypassing the well-known crystallographic phase problem. We demonstrate that our method, CrysFormer, achieves precise predictions on two synthetic datasets of peptide fragments in crystalline forms, one with two residues per unit cell and the other with fifteen. These predictions can then be used to generate accurate atomic models using established crystallographic refinement programs. [ABSTRACT FROM AUTHOR]

BACKGROUND The efficacy, effectiveness, and safety of the approved nirmatrelvir/ritonavir regimen for treatment of laboratory-confirmed mild/moderately severe COVID-19 remains unclear. METHODS We systematically identified randomized controlled trials (RCTs) and realworld studies (RWS; observational studies) of the efficacy/effectiveness and/or safety of the approved nirmatrelvir/ritonavir regimen for COVID-19. We pooled appropriate data (adjusted estimates for RWS) using an inverse variance, random-effects model. We calculated statistical heterogeneity using the I² statistic. Results are presented as relative risk (RR) with associated 95% CI. We further assessed risk of bias/study quality and conducted trial sequential analysis of the evidence from RCTs. RESULTS We included 4 RCTs (4,070 persons) and 16 RWS (1,925,047 persons) of adults (aged ≥18 years). One and 3 RCTs were of low and unclear risk of bias, respectively. The RWS were of good quality. Nirmatrelvir/ritonavir significantly decreased COVID-19 hospitalization compared with placebo/no treatment (RR = 0.17; 95% CI, 0.10-0.31; I² = 77.2%; 2 RCTs, 3,542 persons), but there was no significant difference for decrease of worsening severity (RR = 0.82; 95% CI, 0.66-1.01; I² = 47.5%; 3 RCTs, 1,824 persons), viral clearance (RR = 1.19; 95% CI, 0.93-1.51; I² = 82%; 2 RCTs, 528 persons), adverse events (RR = 1.41; 95% CI, 0.92-2.14; I² = 70.6%; 4 RCTs, 4,070 persons), serious adverse events (RR = 0.82; 95% CI, 0.41-1.62; I² = 0%; 3 RCTs, 3,806 persons), and all-cause mortality (RR = 0.27; 95% CI, 0.04-1.70; I² = 49.9%; 3 RCTs, 3,806 persons), although trial sequential analysis suggested that the current total sample sizes for these outcomes were not large enough for conclusions to be drawn. Real-world studies also showed significantly decreased COVID-19 hospitalization (RR = 0.48; 95% CI, 0.37-0.60; I² = 95.0%; 11 RWS, 1,421,398 persons) and all-cause mortality (RR = 0.24; 95% CI, 0.14-0.34; I² = 65%; 7 RWS, 286,131 persons) for nirmatrelvir/ritonavir compared with no treatment. [ABSTRACT FROM AUTHOR]

Many routes may lead to the transition from a healthy to a diseased phenotype. However, there are not so many routes to travel in the opposite direction; that is, therapy for different diseases. The following pressing question thus remains: what are the pathogenic routes and how can be they counteracted for therapeutic purposes? Human cells contain >500 protein kinases and nearly 200 protein phosphatases, acting on thousands of proteins, including cell growth factors. We herein discuss neurotrophins with pathogenic or metabotrophic abilities, particularly brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), pro-NGF, neurotrophin-3 (NT-3), and their receptor Trk (tyrosine receptor kinase; pronounced "track"). Indeed, we introduced the word trackins, standing for Trk-targeting drugs, that play an agonistic or antagonistic role in the function of TrkBBDNF, TrkCNT−3, TrkANGF, and TrkApro-NGF receptors. Based on our own published results, supported by those of other authors, we aim to update and enlarge our trackins concept, focusing on (1) agonistic trackins as possible drugs for (1a) neurotrophin-deficiency cardiometabolic disorders (hypertension, atherosclerosis, type 2 diabetes mellitus, metabolic syndrome, obesity, diabetic erectile dysfunction and atrial fibrillation) and (1b) neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and multiple sclerosis), and (2) antagonistic trackins, particularly TrkANGF inhibitors for prostate and breast cancer, pain, and arrhythmogenic right-ventricular dysplasia. Altogether, the druggability of TrkANGF, TrkApro-NGF, TrkBBDNF, and TrkCNT−3 receptors via trackins requires a further translational pursuit. This could provide rewards for our patients. [ABSTRACT FROM AUTHOR]

BBT-059, a long-acting PEGylated interleukin-11 (IL-11) analog that is believed to have hematopoietic promoting and anti-apoptotic properties, is being developed as a potential radiation medical countermeasure (MCM) for hematopoietic acute radiation syndrome (H-ARS). This agent has been shown to improve survival in lethally irradiated mice. To further evaluate the drug's toxicity and safety profile, 12 naïve nonhuman primates (NHPs, rhesus macaques) were administered one of three doses of BBT-059 subcutaneously and were monitored for the next 21 days. Blood samples were collected throughout the study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug as well as its effects on complete blood counts, cytokines, vital signs, and to conduct metabolomic studies. No adverse effects were detected in any treatment group during the study. Short-term changes in metabolomic profiles were present in all groups treated with BBT-059 beginning immediately after drug administration and reverting to near normal levels by the end of the study period. Several pathways and metabolites, particularly those related to inflammation and steroid hormone biosynthesis, were activated by BBT-059 administration. Taken together, these observations suggest that BBT-059 has a good safety profile for further development as a radiation MCM for regulatory approval for human use. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings. Aims: To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers. Methods: Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022. We included the domains of HCV treatment, cirrhosis diagnosis, HCC surveillance practices, barriers to surveillance, and interest in risk-stratification tools. We performed descriptive analyses to summarize responses. Tabulations were weighted based on sampling weights accounting for non-response and inter-specialty comparisons were made using chi-squared or t test statistics. Results: After exclusions, 266 responses were included in the final sample (response rate 3.8%). Most respondents (78%) diagnosed cirrhosis using imaging and a minority used non-invasive tests that were blood-based (~ 15%) or transient elastography (31%). Compared to primary care providers, subspecialists were more likely to perform HCC surveillance every 6-months (vs annual) (98% vs 35%, p < 0.0001). Most respondents (80%) believed there were strong data to support HCC surveillance, but primary care providers did not know which liver disease patients needed surveillance. Most providers (> 70%) expressed interest in potential solutions to improve HCC risk-stratification. Conclusions: In this statewide survey, there were great knowledge gaps in HCC surveillance among PCPs and most respondents expressed interest in strategies to increase appropriate HCC surveillance. [ABSTRACT FROM AUTHOR]

Fish parasitology contributes to our understanding of the potential risks posed by diverse groups of parasitic organisms on fish stocks in either wild and culture systems. This study was conducted in May 2023 and aimed at assessing the diversity of endohelminths in the invasive North African catfish Clarias gariepinus (Burchell, 1822) obtained from two freshwater lakes, Naivasha and Ol’Bolossat, in Kenya. Parasitological examination of 66 and 35 fish samples collected from the two lakes respectively was achieved using light and scanning electron microscopy methods. Results revealed endohelminth diversity broadly classified as four digeneans, two nematodes, and one cestode. Seven taxa of endohelminths were found in C. gariepinus samples, but only four of these taxa could be identified up to the species level. Six of the taxa (Diplostomum sp., Tylodelphys mashonense, Plagiorchioidea sp., Paracamallanus cyathopharynx, Contracaecum sp., and Tetracampos ciliotheca) were common in samples from the two lakes. Glossidium pedatum only occurred in samples from Lake Ol’Bolossat. Parasite prevalence ranged from 8.6 (T. mashonense) to 100% (Diplostomum sp., T. ciliotheca, and Contracaecum sp.) and mean intensity from 1.4 (T. mashonense) to 16.9 (Diplostomum sp.). The diversity and richness indices were comparatively higher in fish samples from Lake Ol’Bolossat and attributed to the occurrence of G. pedatum in the Ol’Bolossat. However, parasitic infestation of fish samples from the two lakes depicted close similarity, both in diversity and prevalence. These findings form an important baseline data for further follow-up studies, and they suggest the need for further molecular analyses to fully describe three of the taxa only identified up to the genus level. [ABSTRACT FROM AUTHOR]

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta‐analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta‐analysis was performed using random‐effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower‐middle, 12 in upper‐middle, and only two in high‐income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta‐analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta‐analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high‐income countries. [ABSTRACT FROM AUTHOR]

Arc (also known as Arg3.1) is an activity-dependent immediate early gene product enriched in neuronal dendrites. Arc plays essential roles in long-term potentiation, long-term depression, and synaptic scaling. Although its mechanisms of action in these forms of synaptic plasticity are not completely well established, the activities of Arc include the remodeling of the actin cytoskeleton, the facilitation of AMPA receptor (AMPAR) endocytosis, and the regulation of the transcription of AMPAR subunits. In addition, Arc has sequence and structural similarity to retroviral Gag proteins and self-associates into virus-like particles that encapsulate mRNA and perhaps other cargo for intercellular transport. Each of these activities is likely to be influenced by Arc's reversible self-association into multiple oligomeric species. Here, we used mass photometry to show that Arc exists predominantly as monomers, dimers, and trimers at approximately 20 nM concentration in vitro. Fluorescence fluctuation spectroscopy revealed that Arc is almost exclusively present as low-order (monomer to tetramer) oligomers in the cytoplasm of living cells, over a 200 nM to 5 μM concentration range. We also confirmed that an α-helical segment in the N-terminal domain contains essential determinants of Arc's self-association. [ABSTRACT FROM AUTHOR]

Groundwater is vital for sustainable development, and this study addresses potable water challenges in Shango, North-Central Nigeria. The main goal is to identify optimal sites for new wells and boreholes, utilizing geological and geo-electrical attributes from existing boreholes and wells. Vertical Electrical Sounding (VES) assessed groundwater potential, aquifer protection, and overburden corrosivity. Sixteen VES stations were probed using Schlumberger array with a maximum current electrode spacing (AB/2) of 200 m using a resistivity meter. The data were interpreted using an automatic computer inversion program, IPI2WIN. The VES results revealed five subsurface geo-electric units, with depths to the aquifer ranging from 58 to 68 m, each exhibiting distinct characteristics contributing to the lithological variability of the research area. Hydraulic conductivity ranged from 0.465 to 0.534 m/day, while transmissivity varied from 9.589 m2/day to 26.029 m2/day across different VES points. Regions exhibiting thick layers and low resistivity values indicate high longitudinal conductivity. Furthermore, areas with low protective capacity are susceptible to the risks of pollution and contamination stemming from leaks and waste sites. The study revealed that all VES points are in practically non-corrosive zones, making them suitable for burying underground tanks with extremely low deterioration rates. Based on geoelectrical characteristics, the study area was divided into three groundwater potential zones: low, medium, and high. These findings provide valuable insights into the groundwater potential and protective capacity of the Shango area, while emphasizing on the vulnerability of these regions and highlighting the pressing need for appropriate preventive measures to safeguard against potential environmental hazards. [ABSTRACT FROM AUTHOR]

Background: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). Objective: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. Design: Survey-based non-randomized cohort study with matched comparators. Participants: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. Main Measures: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. Key Results: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. Conclusion: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment. [ABSTRACT FROM AUTHOR]

Background: The Veterans Health Administration provides care to more than 100,000 Veterans with cirrhosis. Aims: This implementation evaluation aimed to understand organizational resources and barriers associated with cirrhosis care. Methods: Clinicians across 145 Department of Veterans Affairs (VA) medical centers (VAMCs) were surveyed in 2022 about implementing guideline-concordant cirrhosis care. VA Corporate Data Warehouse data were used to assess VAMC performance on two national cirrhosis quality measures: HCC surveillance and esophageal variceal surveillance or treatment (EVST). Organizational factors associated with higher performance were identified using linear regression models. Results: Responding VAMCs (n = 124, 86%) ranged in resource availability, perceived barriers, and care processes. In multivariable models, factors independently associated with HCC surveillance included on-site interventional radiology and identifying patients overdue for surveillance using a national cirrhosis population management tool ("dashboard"). EVST was significantly associated with dashboard use and on-site gastroenterology services. For larger VAMCs, the average HCC surveillance rate was similar between VAMCs using vs. not using the dashboard (47% vs. 41%), while for smaller and less resourced VAMCs, dashboard use resulted in a 13% rate difference (46% vs. 33%). Likewise, higher EVST rates were more strongly associated with dashboard use in smaller (55% vs. 50%) compared to larger (57% vs. 55%) VAMCs. Conclusions: Resources, barriers, and care processes varied across diverse VAMCs. Smaller VAMCs without specialty care achieved HCC and EVST surveillance rates nearly as high as more complex and resourced VAMCs if they used a population management tool to identify the patients due for cirrhosis care. [ABSTRACT FROM AUTHOR]

Background: In 2022, there were outbreaks of Mpox where the disease is not endemic. We summarized published full-text epidemiological data from the outbreaks. Methods: A global evidence review (protocol: osf.io/j3kb7) with systematic literature search up to February 09, 2023. We focused on experimental/observational studies of laboratory confirmed Mpox, excluding case reports and case series of < 5 cases. Epidemiological data were pooled using an inverse variance, random-effects model, and pooled estimates presented with associated 95% confidence intervals. Results: We included 66 studies. Mean incubation period was 7.8 days (6.6–9.0 days, 8 studies: 560 cases), reproductive number 1.8 (1.7–1.9, 6 studies), mean duration from symptom onset to diagnosis 5.8 days (4.8–6.8 days, 4 studies: 982 cases), mean symptom duration 17.5 days (14.7–20.2 days, 3 studies: 292 cases), mean serial interval 8.5 days (7.3–9.9 days, 1 study), hospitalisation 6% (4–9%, 26 studies: 5339 cases), and vaccine effectiveness 78% (65–91%, 3 studies: 953 cases). Highly relevant clinical manifestations were pleomorphic skin lesions 82% (68–94%, 26 studies: 4093 cases), anogenital lesions 64% (51–77%, 9 studies: 10,398 cases), fever 54% (50–57%, 52 studies: 25,992 cases), and lymphadenopathy 51% (46–57%, 42 studies: 17,803 cases), with cases mostly men who have sex with men (MSM). Possibly relevant manifestations were perianal lesions, fatigue, asthenia, myalgia, and headache. Conclusions: The 2022 Mpox outbreaks presented with sex-related clinical manifestations and were mostly reported among MSM. [ABSTRACT FROM AUTHOR]

Simple Summary: The sweetpotato whitefly, Bemisia tabaci Gennadius Middle East–Asia Minor 1 (MEAM1), is an economically important vegetable worldwide. This study evaluated the susceptibilities of yellow squash and zucchini cultivars to MEAM1 across three growing seasons in the southeastern United States: summer 2021, fall 2021, and fall 2022. Commercially available cultivars squash and zucchini were examined for resistance to MEAM1 infestations and yield performance. Weekly MEAM1 adult, egg, and nymph counts were conducted over 5 (fall 2022) or 6 (summer and fall 2021) weeks beginning after the third week of planting in each season. In general, MEAM1 adult populations were high at the first week of sampling but decreased in the subsequent weeks. The Zucchini cultivar 'Black Beauty' had the highest number of MEAM1 adults, and 'Green Eclipse Zucchini' had the lowest adult counts in summer 2021. For yellow squash, 'Early Summer' and 'Amberpic 8455' were identified as the cultivars that harbored the highest populations of adults in 2021, whereas 'Golden Goose Hybrid' harbored the least number of adult infestations in fall 2022. Generally, MEAM1 egg counts trailed adult peak populations. For yield performance, 'Gourmet Gold Hybrid', 'Lioness', 'Fortune', and 'Golden Glory' achieved the highest yields. These results provide valuable information for whitefly management in yellow squash and zucchini based on host plant resistance and yield. The sweetpotato whitefly, Bemisia tabaci (Gennadius) Middle East–Asia Minor 1 (MEAM1), causes significant losses to vegetable crops directly by sap-feeding, inducing plant physiological disorders, and elevating the build-up of sooty mold, and indirectly by transmitting plant viruses. In this study, we evaluated the susceptibility of 20 yellow squash and zucchini (Cucurbita pepo) cultivars to MEAM1, across three growing seasons in the southeastern United States. Weekly sampling of the numbers of MEAM1 adults, nymphs, and eggs were conducted from the fourth week after seed sowing and across 6 weeks during the summer and fall of 2021 and five weeks during the fall of 2022. In general, adult whitefly populations were high during the first week of sampling but decreased as the seasons progressed. The zucchini cultivar 'Black Beauty' harbored the most adults, while 'Green Eclipse Zucchini' was the least attractive zucchini cultivar to the adults in fall 2022. For yellow squash, 'Early Summer' (summer 2021) and 'Amberpic 8455' (summer 2021 and fall 2022) were the cultivars with the highest adult populations, while 'Lioness' (summer 2021) and 'Gourmet Gold Hybrid' (fall 2022) harbored the lowest adult counts. The whitefly egg counts across both vegetables trailed those of adults and peaked in the second week of sampling. The counts of nymphs increased as the seasons progressed, but there was a decline after the second week during fall 2021. For the yellow squash cultivars, 'Gourmet Gold Hybrid', (summer 2021 and fall 2022), 'Lioness', and 'Fortune' (summer 2021) recorded the highest yields. For zucchini, 'Golden Glory' (summer 2021) was the top performer. These results provide valuable information for whitefly management in yellow squash and zucchini based on host plant susceptibility and yield. [ABSTRACT FROM AUTHOR]

On-farm losses of peanuts (Arachis hypogaea L. Fabales: Fabaceae) pose a persistent threat to the sustainable production and value of peanuts in the United States. This study presents empirical data on the spatial distribution of subterranean insect pests and various quality aspects of peanuts. Surveys were conducted in 20 randomly selected peanut fields in 10 counties in Northeast, Southeast, and Southwest Georgia. The primary insect pests found in Georgia's peanut production counties were Pangaeus bilineatus (Say), Elasmopalpus lignosellus (Zeller), and Diabrotica undecimpunctata Howardi. In the northeast counties, a high prevalence of P. bilineatus led to a significant increase in insect-damaged pods (%IDP), insect-damaged kernels (%IDK), discolored kernels (%DK), pod weight loss (%PWL), and kernel weight loss (%KWL). Similarly, southeast counties had a high %DK, cracked pods (%CP), and E. lignosellus infestation. In southwest counties, predominantly high D. undecimpunctata infestations resulted in the highest %IDP. Moisture content (%MC) was excessively high in all the counties (22.19%–23.17%). Preharvest aflatoxin contamination in peanuts was prevalent across all studied locations, particularly in counties with a high incidence of P. bilineatus and may cause increased risk in aflatoxin levels along the supply chain. Nevertheless, the diverse regional abundance of insect pests and the widespread presence of aflatoxins in Georgia's peanut fields offer valuable insights for developing integrated pest management strategies targeting subterranean insect pests. This is especially crucial in addressing the impact of P. bilineatus , E. lignosellus , and D. undecimpunctata on aflatoxins content of peanuts and determining the pathway for mitigation of aflatoxin contaminations in peanuts at harvest. [ABSTRACT FROM AUTHOR]

This study combines theoretical modeling and experimental validation to explore anaerobic digestion comprehensively. Developing a computational model is crucial for accurately simulating a digester's performance, considering various feedstocks and operational parameters. The main objective was to adapt the anaerobic digestion model 1 (ADM1) simulation code to align with the laboratory-scale anaerobic digestion reactor's specifications, especially regarding the liquid–gas transfer process. Within this computational framework, users may define model parameters and elucidate processes occurring in compartments reflecting the physical design. The model accurately predicts total concentrations of chemical oxygen demand (COD) as well as the produced biogas, with an average difference of less than 10% between experimental and simulated data. This consistency underscores the reliability and effectiveness of the adapted model in capturing anaerobic digestion nuances under specified conditions. [ABSTRACT FROM AUTHOR]

Background: We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). Methods: A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. Results: A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. Conclusions: The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability. [ABSTRACT FROM AUTHOR]

Background: Sheep is one of the important species of livestock in India contributing to meat production. India has 44 distinct breeds of sheep, out of which 10 are found in Tamil Nadu. The present study describes the characterization of recently registered breed-Katchaikatty sheep, genetic variability and genetic structure of the population by microsatellite marker analysis. Methods: The genomic DNA from 50 unrelated Katchaikatty sheep was amplified with 25 FAO recommended fluorescent tagged ovine-specific microsatellite markers and genotyped on an automated Genetic Analyzer. Microsatellite fragment sizing was performed by Gene Mapper software. In each locus, observed (no) and effective number of microsatellite alleles (ne), allele frequencies, observed (Ho) and expected (He) heterozygosity, heterozygosity deficit estimate (FIS) and Chi-square (X2) test for Hardy-Weinberg equilibrium (HWE) were assessed by POPGENE software and polymorphism information content (PIC) was calculated. Mode-shift analyses were performed for testing the genetic bottleneck by bottleneck software. Result: The study revealed a total of 144 alleles across all the loci. The number of alleles at each locus varied from one to 10 with a mean of 5.76 alleles. The PIC values in the microsatellite loci ranged from 0.34 (OarAE129) to 0.83 (OarFCB48) with an average of 0.59, which showed a high genetic polymorphism. Six out of 25 microsatellite loci studied were in Hardy-Weinberg equilibrium and 19 out of 25 loci showed positive FIS values. The overall mean observed and expected heterozygosity were 0.50 and 0.65 respectively and the estimates elucidated a substantial genetic variability in Katchaikatty sheep population. Mode shift analysis revealed a normal L-shaped curve, describing that the Katchaikatty population had not experienced any genetic bottleneck and remained in mutation-drift equilibrium. [ABSTRACT FROM AUTHOR]

Summary: This work presents details and assesses implicit and adaptive mesh‐free CFD modelling approaches, to alleviate laborious mesh generation in modern CFD processes. A weighted‐least‐squares‐based, mesh‐free, discretisation scheme was first derived for the compressible RANS equations, and the implicit dual‐time stepping was adopted for improved stability and convergence. A novel weight balancing concept was introduced to improve the mesh‐free modelling on highly irregular point clouds. Automatic point cloud generations based on strand and level‐set points were also discussed. A novel, polar selection approach, was also introduced to establish high‐quality point collocations. The spatial accuracy and convergence properties were validated using 2D and 3D benchmark cases. The impact of irregular point clouds and various point collocation search methods were evaluated in detail. The proposed weight balancing and the polar selection approaches were found capable of improving the mesh‐free modelling on highly irregular point clouds. The mesh‐free flexibility was then exploited for adaptive modelling. Various adaptation strategies were assessed using simulations of an isentropic vortex, combining different point refinement mechanisms and collocation search methods. The mesh‐free modelling was then successfully applied to transonic aerofoil simulations with automated point generation. A weighted pressure gradient metric prioritising high gradient regions with large point sizes was introduced to drive the adaptation. The mesh‐free adaptation was found to effectively improve the shock resolution. The results highlight the potential of mesh‐free methods in alleviating the meshing bottleneck in modern CFD. [ABSTRACT FROM AUTHOR]

The prototype high-entropy oxide (HEO) Y0.2La0.2Ce0.2Pr0.2Sm0.2O2−δ represents a particularly complex class of HEOs with significant anion sublattice entropy. The system takes either a fluorite or bixbyite-type crystal structure, depending on synthesis kinetics and thermal history. Here, we synthesize bulk ceramics and epitaxial thin films of Y0.2La0.2Ce0.2Pr0.2Sm0.2O2−δ and use diffraction to explore crystal symmetry and phase. Thin films exhibit the high symmetry fluorite phase, while bulk ceramics adopt the lower symmetry bixbyite phase. The difference in chemical ordering and observed symmetry between vapor-deposited and reactively sintered specimens suggests that synthesis kinetics can influence accessible local atomic configurations, i.e., the high kinetic energy adatoms quench in a higher-effective temperature, and thus higher symmetry structure with more configurational entropy. More generally, this demonstration shows that recovered HEO specimens can exhibit appreciably different local configurations depending on synthesis kinetics, with potential ramifications on macroscopic physical properties. [ABSTRACT FROM AUTHOR]

Rhizobia diversity in the rhizosphere is one of the key promoters of biological nitrogen fixation between host legumes and microsymbionts, although related complex interaction may depend on various factors. This research was intended to assess the abundance of indigenous rhizobia isolates under various soil conditions, as well as their effectiveness to nodulate legumes such as soybeans. Factors such as soil properties and legume species influence the volume and symbiotic effectiveness of native rhizobia to nodulate crop legumes. To investigate the abundance of rhizobia isolates, legume crops were uprooted to obtain nodules for most probable number (MPN) determination of rhizobia isolates, and soybean (Glycine max.) was used to verify the presence of suitable and efficient rhizobia strains for nitrogen fixation. Soil samples were obtained from the holes out of which nodules were collected, and the laboratory analysis included pH, Mg, K, available P, organic C, Ca, and N to establish the correlation between the soil status and number of rhizobia isolates' cells. Significant variations (p‐value <.05) were observed in the cell counts of Rhizobia isolates from Glycine max, Phaseolus vulgaris, Pisum sativum, and Vigna unguiculata, particularly when compared to Arachis hypogaea isolates under acidic conditions. Notably, Pisum sativum and Vigna unguiculata showed consistent performance across all pH conditions. The number of rhizobia isolates was found to be significantly linked to total N and P deficiencies (p <.05). It was also established that total N was dependent on the number of rhizobia cells and that there is a strong correlation between organic carbon and N content. This study highlights the crucial role of understanding and optimizing conditions for rhizobia nodulation in diverse soil environments, emphasizing its potential impact on enhancing biological nitrogen fixation in legumes. [ABSTRACT FROM AUTHOR]