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Weed management is a primary concern of organic farmers. Crop rotation is an important potential management approach for regulating weed seed populations in the soil of organic farming systems. This research was conducted to determine the effect of three organic crop rotations on the weed seedbank during the first 6 yr of a long-term cropping systems experiment at Beltsville, MD. The rotations consisted of (i) a 2-yr corn (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotation, (ii) a 3-yr corn-soybean-wheat (Triticum aestivum L.) rotation, and (iii) a 4-yr corn-soybean-wheat-red clover (Trifolium pratense L.)/orchardgrass (Dactylis glomerata L.) hay rotation. Weed seed populations were determined by a greenhouse emergence assay using soil samples taken in the early spring of each year. The seedbanks of smooth pigweed (Amaranthus hybridus L.) and common lambsquarters (Chenopodium album L.) preceding corn were usually lower following the hay years of the 4-yr rotation or the wheat year of the 3-yr rotation than following the soybean year of the 2-yr rotation. However, annual grass seedbanks preceding corn tended to be higher following the hay years of the 4-yr rotation than following the wheat year of the 3-yr rotation or the soybean year of the 2-yr rotation. Seedbanks in the 3- and 4-yr rotations were similar to those of the 2-yr corn-soybean rotation (higher smooth pigweed and common lambsquarters and lower annual grass) when these longer rotations began with a corn-soybean sequence than with other sequences. Sequences beginning with hay had lower smooth pigweed and common lambsquarters seedbank populations than all other sequences. The seedbank in spring significantly predicted weed abundance at maturity in corn in at least 2 of 4 yr for all species. Results show that longer rotations with more phenologically diverse crops can reduce seedbank populations and abundance of important annual broadleaf weed species in organic production systems.

IMAGING FINDINGS As a ligament injury was suspected to A CT scan of the thorax with con- trast demonstrated a large anterior- mediastinal hematoma measuring 11 x 11 x 3.4-cm compressing the left ven- tricle. Prompt radiologic evalu- ation of the trauma followed by proper management can reduce mortality asso- ciated with the rare, but life-threatening complications of active IMA bleeding, such as hemorrhagic shock and cardiac tamponade 1,2 Chest radiography, usu- ally obtained for the initial evaluation of traumatic chest injury, may show a widened mediastinum, but the signs of hemorrhage may be nonspecific or obscured.3 CT with intravenous con- trast is the more widely used imaging modality for accurately diagnosing tho- racic trauma, especially vascular inju- ries and hemorrhage.2,3 CONCLUSION Though surgical management is the standard treatment for IMA injuries, arterial embolization has been shown to provide a safe, less invasive alter- native in select patients for achieving successful hemostasis, particularly in those who are not good candidates for surgery or have injuries that are not surgically accessible.2,4,5

Incipient ferroelectricity bridges traditional dielectrics and true ferroelectrics, enabling advanced electronic and memory devices. Firstly, we report incipient ferroelectricity in freestanding SrTiO 3 nanomembranes integrated with monolayer MoS 2 to create multifunctional devices, demonstrating stable ferroelectric order at low temperatures for cryogenic memory devices. Our observation includes ultra-fast polarization switching (~10 ns), low switching voltage (<6 V), over 10 years of nonvolatile retention, 100,000 endurance cycles, and 32 conductance states (5-bit memory) in SrTiO 3 -gated MoS 2 transistors at 15 K and up to 100 K. Additionally, we exploit room-temperature weak polarization switching, a feature of incipient ferroelectricity, to construct a physical reservoir for pattern recognition. Our results showcase the potential of utilizing perovskite material properties enabled by advancements in freestanding film growth and heterogeneous integration, for diverse functional applications. Notably, the low 180 °C thermal budget for fabricating the 3D-SrTiO 3 /2D-MoS 2 device stack enables the integration of diverse materials into silicon complementary metal-oxide-semiconductor technology, addressing challenges in compute-in-memory and neuromorphic applications. Sen et al. report the stacking of a perovskite incipient ferroelectric nanomembrane with atomically thin 2D material for a back-end-of-line compatible ferroelectric-like field effect transistors, functioning as a cryogenic memory at 15 K and as an inference engine at room temperature.

Background Effective disease management depends on timely and accurate diagnosis to guide control measures. The capacity to distinguish between individuals in a pathogen population with specific properties such as fungicide resistance, toxin production and virulence profiles is often essential to inform disease management approaches. The genomics revolution has led to technologies that can rapidly produce high-resolution genotypic information to define individual variants of a pathogen species. However, their application to complex fungal pathogens has remained limited due to the frequent inability to culture these pathogens in the absence of their host and their large genome sizes. Results Here, we describe the development of Mobile And Real-time PLant disEase (MARPLE) diagnostics, a portable, genomics-based, point-of-care approach specifically tailored to identify individual strains of complex fungal plant pathogens. We used targeted sequencing to overcome limitations associated with the size of fungal genomes and their often obligately biotrophic nature. Focusing on the wheat yellow rust pathogen, Puccinia striiformis f.sp. tritici ( Pst ), we demonstrate that our approach can be used to rapidly define individual strains, assign strains to distinct genetic lineages that have been shown to correlate tightly with their virulence profiles and monitor genes of importance. Conclusions MARPLE diagnostics enables rapid identification of individual pathogen strains and has the potential to monitor those with specific properties such as fungicide resistance directly from field-collected infected plant tissue in situ. Generating results within 48 h of field sampling, this new strategy has far-reaching implications for tracking plant health threats.

Severe burns result in cardiovascular dysfunction, but responses in the peripheral vasculature are unclear. We hypothesize that severe burns disturb arterial contractility through acute changes in adrenergic and cholinergic receptor function. To address this, we investigated the changes in carotid artery contractility and relaxation following a severe burn. Thirty-four adult Sprague–Dawley male rats received a 40% total body surface area (TBSA) scald burn and fluid resuscitation using the Parkland formula. Control animals received sham burn procedure. Animals were serially euthanized between 6 h and 14 days after burn and endothelium-intact common carotid arteries were used for ex vivo force/relaxation measurements. At 6 h after burn, carotid arteries from burned animals demonstrated a > 50% decrease in cumulative dose-responses to norepinephrine ( p  < 0.05) and to 10 −7  M angiotensin II ( p  < 0.05). Notably, pre-constricted carotid arteries also demonstrated reduced relaxation responses to acetylcholine ( p  < 0.05) 6 h after burn, but not to sodium nitroprusside. Histologic examination of cross-sectional planes revealed significant increases in carotid artery wall thickness in burned rats at 6 h versus 3 days, with increased collagen expression in tunica media at 3 days ( p  < 0.05). Carotid artery dysfunction occurs within 6 h after severe burn, demonstrating decreased sensitivity to adrenergic- and angiotensin II-induced vasoconstriction and acetylcholine-induced relaxation.

Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Bill & Melinda Gates Foundation.

Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions. Bill & Melinda Gates Foundation.

Background CAR-T therapy has revolutionized treatments for many hematologic malignancies, but it has shown far less efficacy against solid tumors. One reason for this lower efficacy in solid tumors is increased antigen heterogeneity. This study utilizes a ligand-based CAR-T approach, which allows targeting of multiple receptors by a single ligand. A high expression of the ligand oncostatin M’s (OSM) receptors, oncostatin M receptor (OSMR), and/or leukemic inhibitory factor receptor (LIFR) were noted in osteosarcoma cell lines and patient samples. Osteosarcoma is a bone cancer where treatment options have been stagnant for close to 40 years. Thus, this study explores the therapeutic potential of OSM ligand-based CAR-T cells against osteosarcoma. Methods Third-generation CAR-T cells expressing human OSM on their surface were created, with the surface expression of OSM confirmed by flow cytometry. Co-incubation of OSM CARs and osteosarcoma in vitro was performed, with cell death assessed via Incucyte and PI detection by flow cytometry. CAR-Ts were injected i.v. into mice with osteosarcoma cell line xenografts, and metastatic osteosarcoma. New patient-derived samples were tested for OSMR and LIFR expression and vulnerability to OSM CAR T cells. A new PDX model (named KKOS) from a patient with metastatic treatment-resistant osteosarcoma was characterized and tested for its susceptibility to OSM CAR T cells. All cytotoxic in vivo experiments were performed with n =3–6 mice per group per experiment. Results OSM-CAR-T cells displayed cytotoxicity against osteosarcoma cell lines and patient samples expressing either one of OSM’s receptors in vitro and in vivo. Large increases in cytokine release, specifically IFNγ, were noted in a target-specific manner. One injection of OSM-CAR-T cells intravenously reduced tumor burden in two different mouse xenograft models. A similar anti-tumor effect was also noted in a metastatic model and a mouse model with multiple implanted KKOS tumors. Conclusions Human ligand-based OSM CAR-T cells displayed anti-tumor effects against multiple osteosarcoma cell lines and patient samples. These effects were demonstrated in vitro, in xenograft models, and against a model simulating metastatic disease. Overall, this data supports the continued study of OSM-CAR-T cells as a new therapeutic avenue for osteosarcoma.

Many medications are available as solid oral dosage forms such as tablets and capsules; however, some people find these medications difficult to swallow. To identify whether certain psychological, oral sensory, and oral motor characteristics contribute to medication swallowing difficulties. A sample of healthy adults from two academic institutions in Brisbane were assessed for their experiences with swallowing solid oral dosage forms, food preferences, and food neophobia. The gag reflex, oral cavity size, fungiform papillae count, and chewing efficacy were also evaluated followed by a capsule-swallowing task. Primary outcome was the incidence of medication swallowing difficulties. Secondary outcomes were the association of medication swallowing difficulties with psychological, oral sensory, and oral motor factors. Of 152 subjects, 32% reported difficulty swallowing tablets or capsules whole. This group was significantly more likely to have had a memory of choking on medications compared to those without medication swallowing difficulties (OR = 7.25, p < 0.05). Current medication swallowing difficulties were significantly associated with a smaller mouth cavity size (OR = 2.98, p < 0.05), a higher density of taste receptors on the tongue (OR = 3.27, p < 0.05), and were higher among those who chewed a jelly candy to non-homogenous particle size (OR = 4.1, p < 0.05). Current medication swallowing difficulties were associated with lower confidence in swallowing large capsules (000 size: OR = 0.47, 00 size: OR = 0.39, p < 0.05). No associations were found between medication swallowing difficulties and the gag reflex or food neophobia. A combination of heightened oral perception characterized by a small oral cavity and high taste sensitivity compounded by a past choking episode on medications may be precipitating factors for medication swallowing difficulties. These factors may be helpful in identifying individuals who are more likely to experience difficulty swallowing medications.

Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Renal failure and toxic acute tubular necrosis (ATN) may be seen following exposure to a variety of therapeutic agents. Zoledronate (Zometa) is a new, highly potent bisphosphonate used in the treatment of hypercalcemia of malignancy. We report the first clinical-pathologic study of nephrotoxicity associated with this agent. A cohort of six patients (four males and two females) with a mean age of 69.2years received bisphosphonate therapy for multiple myeloma (five patients) or Paget's disease (one patient). In all patients, zoledronate was administered at a dose of 4mg intravenously monthly, infused over at least 15 minutes, and the duration of therapy was mean 4.7months (range, 3 to 9months). All patients developed renal failure with a rise in serum creatinine from a mean baseline level of 1.4mg/dL to 3.4mg/dL. Renal biopsy revealed toxic ATN, characterized by tubular cell degeneration, loss of brush border, and apoptosis. Immunohistochemical staining revealed a marked increase in cell cycle-engaged cells (Ki-67 positive) and derangement in tubular Na+,K+-ATPase expression. Importantly, although all patients had been treated with pamidronate prior to zoledronate, no biopsy exhibited the characteristic pattern of collapsing focal segmental glomerulosclerosis observed in pamidronate nephrotoxicity. Following renal biopsy, treatment with zoledronate was discontinued and all six patients had a subsequent improvement in renal function (mean final serum creatinine, 2.3mg/dL at 1 to 4months of follow-up). The close temporal relationship between zoledronate administration and the onset of renal failure and the partial recovery of renal function following drug withdrawal strongly implicate this important and widely used agent in the development of toxic ATN.