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Summary: Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p 15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114–285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

Sudden cardiac death (SCD), the unexpected death due to acquired or genetic cardiovascular disease, follows distinct 24-hour patterns in occurrence. These 24-hour patterns likely reflect daily changes in arrhythmogenic triggers and the myocardial substrate caused by day/night rhythms in behavior, the environment, and endogenous circadian mechanisms. To better address fundamental questions regarding the circadian mechanisms, the National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death. We present a 2-part report of findings from this workshop. Part 1 summarizes the workshop and serves to identify research gaps and opportunities in the areas of basic and translational research. Among the gaps was the lack of standardization in animal studies for reporting environmental conditions (eg, timing of experiments relative to the light dark cycle or animal housing temperatures) that can impair rigor and reproducibility. Workshop participants also pointed to uncertainty regarding the importance of maintaining normal circadian rhythmic synchrony and the potential pathological impact of desynchrony on SCD risk. One related question raised was whether circadian mechanisms can be targeted to reduce SCD risk. Finally, the experts underscored the need for studies aimed at determining the physiological importance of circadian clocks in the many different cell types important to normal heart function and SCD. Addressing these gaps could lead to new therapeutic approaches/molecular targets that can mitigate the risk of SCD not only at certain times but over the entire 24-hour period.

Sudden cardiac death (SCD) is the sudden, unexpected death due to abrupt loss of heart function secondary to cardiovascular disease. In certain populations living with cardiovascular disease, SCD follows a distinct 24-hour pattern in occurrence, suggesting day/night rhythms in behavior, the environment, and endogenous circadian rhythms result in daily spans of increased vulnerability. The National Heart, Lung, and Blood Institute convened a workshop, Understanding Circadian Mechanisms of Sudden Cardiac Death to identify fundamental questions regarding the role of the circadian rhythms in SCD. Part 2 summarizes research gaps and opportunities in the areas of population and clinical research identified in the workshop. Established research supports a complex interaction between circadian rhythms and physiological responses that increase the risk for SCD. Moreover, these physiological responses themselves are influenced by several biological variables, including the type of cardiovascular disease, sex, age, and genetics, as well as environmental factors. The emergence of new noninvasive biotechnological tools that continuously measure key cardiovascular variables, as well as the identification of biomarkers to assess circadian rhythms, hold promise for generating large-scale human data sets that will delineate which subsets of individuals are most vulnerable to SCD. Additionally, these data will improve our understanding of how people who suffer from circadian disruptions develop cardiovascular diseases that increase the risk for SCD. Emerging strategies to identify new biomarkers that can quantify circadian health (eg, environmental, behavioral, and internal misalignment) may lead to new interventions and therapeutic targets to prevent the progression of cardiovascular diseases that cause SCD.

The current study identified two new climate-resilient groundnut-based cropping systems (GBCSs), viz., groundnut–fenugreek cropping system (GFCS) and groundnut–marigold cropping system (GMCS), with appropriate system-mode bio-compost embedded nutrient management schedules (SBINMSs) for semi-arid South Asia. This 5-year field study revealed that the GMCS along with leaf compost (LC) + 50% recommended dose of fertilizers (RDF50) in wet-season crop (groundnut) and 100% RDF (RDF100) in winter-season crop (marigold) exhibited the highest system productivity (5.13–5.99 t/ha), system profits (US$ 1,767–2,688/ha), and soil fertility (available NPK). Among SBINMSs, the application of 5 t/ha leaf and cow dung mixture compost (LCMC) with RDF50 showed the highest increase (0.41%) in soil organic carbon (SOC) followed by LC at 5 t/ha with RDF50 and RDF100. Legume–legume rotation (GFCS) had significantly higher soil microbial biomass carbon (SMBC) and soil microbial biomass nitrogen (SMBN) than legume–non-legume rotations (groundnut–wheat cropping system (GWCS) and GMCS). Among SBINMSs, the highest SMBC (201 µg/g dry soil) and SMBN (27.9 µg/g dry soil) were obtained when LCMC+RDF50 was applied to groundnut. The SMBC : SMBN ratio was the highest in the GWCS. LC+RDF50 exhibited the highest SMBC : SOC ratio (51.6). The largest increase in soil enzymatic activities was observed under LCMC+RDF50. Overall, the GMCS with LC+RDF50 in the wet season and RDF100 in the winter season proved highly productive and remunerative with better soil bio-fertility. SBINMSs saved chemical fertilizers by ~25%’ in addition to enhanced system productivity and system profits across GBCSs in semi-arid regions of South Asia. Future research needs to focus on studying the potential of diversified production systems on water and environmental footprints, carbon dynamics, and energy productivity under semi-arid ecologies.

Relative proximity theory contributes to the concept of distance in distance education by defining how far a current learning environment is from an ideal learning environment. As in Moore's (1993) theory of transactional distance, it defines distance as a psychosocial phenomenon but provides specificity to Moore's seminal theory for learning at a distance by providing a specific answer to the question "How close are we?" in our continual journey to provide better learning environments for our students and teachers. This paper reports on our development of a statistically valid and reliable scale of relative proximity of transactional distance to measure the remaining distance to ideal. The scale adapts and extends the work by Zhang (2003), Paul et al. (2015), and Weidlich and Bastiaens (2018) and, for the first time, explicitly accounts for differences due to gender and mode of delivery.

Micronutrient malnutrition and suboptimal yields pose significant challenges in rainfed cropping systems worldwide. To address these issues, the implementation of climate-smart management strategies such as conservation agriculture (CA) and system intensification of millet cropping systems is crucial. In this study, we investigated the effects of different system intensification options, residue management, and contrasting tillage practices on pearl millet yield stability, biofortification, and the fatty acid profile of the pearl millet. ZT systems with intercropping of legumes (cluster bean, cowpea, and chickpea) significantly increased productivity (7–12.5%), micronutrient biofortification [Fe (12.5%), Zn (4.9–12.2%), Mn (3.1–6.7%), and Cu (8.3–16.7%)], protein content (2.2–9.9%), oil content (1.3%), and fatty acid profile of pearl millet grains compared to conventional tillage (CT)-based systems with sole cropping. The interactive effect of tillage, residue retention, and system intensification analyzed using GGE statistical analysis revealed that the best combination for achieving stable yields and micronutrient fortification was residue retention in both (wet and dry) seasons coupled with a ZT pearl millet + cowpea–mustard (both with and without barley intercropping) system. In conclusion, ZT combined with residue recycling and legume intercropping can be recommended as an effective approach to achieve stable yield levels and enhance the biofortification of pearl millet in rainfed agroecosystems of South Asia.

Breast cancer in males is rare. Luminal A is the predominant subtype in male breast cancer. Clinical data on triple negative breast cancer in male patients is sparse. This case report will add to the literature on male breast cancers. This is a rare case of a 60-year-old male patient who was diagnosed to have locally advanced breast cancer of triple negative (basal-like) subtype. He received eight cycles of neoadjuvant chemotherapy. He later underwent modified radical mastectomy followed by adjuvant radiotherapy and 6 months of adjuvant capecitabine. He is on regular follow-up for the past 3 years.

Author(s): SangJoon Lee [sup.1] , Rajendra Karki [sup.1] , Yaqiu Wang [sup.1] , Lam Nhat Nguyen [sup.1] , Ravi C. Kalathur [sup.2] , Thirumala-Devi Kanneganti [sup.1] Author Affiliations: (1) Department [...], Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells.sup.1. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively).sup.1. During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors.sup.2-5. Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida. We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases. AIM2 responds to infection with herpes simplex virus 1 or Francisella novicida by driving assembly of a large multi-protein complex containing multiple inflammasome sensors and cell death regulators.

Summary: Type I interferons (IFNs) are essential innate immune proteins that maintain tissue homeostasis through tonic expression and can be upregulated to drive antiviral resistance and inflammation upon stimulation. However, the mechanisms that inhibit aberrant IFN upregulation in homeostasis and the impacts of tonic IFN production on health and disease remain enigmatic. Here, we report that caspase-8 negatively regulates type I IFN production by inhibiting the RIPK1-TBK1 axis during homeostasis across multiple cell types and tissues. When caspase-8 is deleted or inhibited, RIPK1 interacts with TBK1 to drive elevated IFN production, leading to heightened resistance to norovirus infection in macrophages but also early onset lymphadenopathy in mice. Combined deletion of caspase-8 and RIPK1 reduces the type I IFN signaling and lymphadenopathy, highlighting the critical role of RIPK1 in this process. Overall, our study identifies a mechanism to constrain tonic type I IFN during homeostasis which could be targeted for infectious and inflammatory diseases.

Transposition of great arteries (d-TGA) is often associated with various coronary artery (CA) patterns. These anomalous patterns can cause variable clinical symptoms of coronary ischemia including sudden death. CA pattern is one of the major determinants of outcome in TGA postoperatively. An advanced cardiac imaging and a multidisciplinary care approach are essential for a favorable outcome. Here, we describe a novel CA origin pattern in a neonate with d-TGA, who developed myocardial ischemia and required a coronary unroofing procedure for a full recovery.