Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma.

B-cell maturation antigen (BCMA)-targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined. We analyzed outcomes for 72 RRMM patients treated with teclistamab, a CD3 x BCMA bispecific antibody (BsAb), 42% (30/72) of whom had prior BCMA-directed therapy exposure. Malignant plasma cell BCMA expression was present in all BCMA therapy-naïve patients. Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and one of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from one patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen.

Morphological and Molecular Identification of Ulva spp. (Ulvophyceae; Chlorophyta) from Algarrobo Bay, Chile: Understanding the Composition of Green Tides.

Green algae blooms of the genus Ulva are occurring globally and are primarily attributed to anthropogenic factors. At Los Tubos beach in Algarrobo Bay along the central Chilean coast, there have been blooms of these algae that persist almost year-round over the past 20 years, leading to environmental, economic, and social issues that affect the local government and communities. The objective of this study was to characterize the species that form these green tides based on a combination of ecological, morpho-anatomical, and molecular information. For this purpose, seasonal surveys of beached algal fronds were conducted between 2021 and 2022. Subsequently, the sampled algae were analyzed morphologically and phylogenetically using the molecular markers ITS1 and tufA, allowing for the identification of at least five taxa. Of these five taxa, three (U. stenophylloides, U. uncialis, U. australis) have laminar, foliose, and distromatic morphology, while the other two (U. compressa, U. aragoensis) have tubular, filamentous, and monostromatic fronds. Intertidal surveys showed that U. stenophylloides showed the highest relative coverage throughout the seasons and all intertidal levels, followed by U. uncialis. Therefore, we can establish that the green tides on the coast of Algarrobo in Chile are multispecific, with differences in relative abundance during different seasons and across the intertidal zone, opening opportunities for diverse future studies, ranging from ecology to algal biotechnology.

Care, connection, and social distancing: The challenges of baby loss during the COVID-19 pandemic in Aotearoa New Zealand.

PROBLEM: The COVID-19 pandemic hindered access to routine healthcare globally, prompting concerns about possible increases in pregnancy loss and perinatal death. BACKGROUND: PUDDLES is an international collaboration exploring the impact of the COVID-19 pandemic on parents who experience pregnancy loss and perinatal death in seven countries, including Aotearoa New Zealand. AIM: To explore parents' experiences of access to healthcare services and support following baby loss during the COVID-19 pandemic in Aotearoa New Zealand. METHODS: We conducted in-depth, semi-structured interviews with 26 bereaved parents, including 20 birthing mothers, and six non-birthing parents (one mother and five fathers). Types of loss included 15 stillbirths, four late miscarriages, and one neonatal death. Participant ethnicities were broadly representative of Aotearoa New Zealand's multi-ethnic society. Data were analysed using Template Analysis. FINDINGS: Analysis revealed five themes relating to pandemic impact on bereaved parent's experiences. These were: 'Distanced and Impersonal care'; 'Navigating Hospital Rules'; Exclusion of Non-birthing Parents; 'Hindered Access to Social Support'; and 'Continuity of Relational Care'. DISCUSSION: The COVID-19 pandemic exacerbated isolation of bereaved parents through perceived impersonal care by healthcare professionals and restrictions on movement hindered access to social and cultural support. Compassionate bending of the rules by healthcare professionals and community postnatal visits by continuity of care midwives following the bereavement appeared to be mitigating factors. CONCLUSION: Social isolation is an added challenge for parents experiencing baby loss during a pandemic, which may be mitigated by flexible and compassionate care from healthcare professionals, especially continuity of care midwives.

Soybean molasses increases subcutaneous fat deposition while reducing lipid oxidation in the meat of castrated lambs.

This study aimed to evaluate the effect of including soybean molasses (SM) on performance, blood parameters, carcass traits, meat quality, fatty acid and muscle (longissimus thoracis) transcriptomic profiles of castrated lambs. Twenty Dorper × Santa Inês lambs (20.06 ± 0.76 kg BW) were assigned to a randomized block design, stratified by BW, with the following treatments: CON - 0 g/kg of SM and SM20 - 200 g/kg of SM on DM basis, allocated in individual pens. The diet consisted of 840 g/kg concentrate and 160 g/kg corn silage for 76 days, with the first 12 days as an adaptation period and the remaining 64 days on the finishing diet. The SM20 diet increased blood urea concentration (P = 0.03) while reduced glucose concentration (P = 0.04). Lambs fed SM showed higher subcutaneous fat deposition (P = 0.04) and higher subcutaneous adipocyte diameter (P < 0.01), in addition to reduced meat lipid oxidation (P < 0.01). Soybean molasses reduced the quantity of branched-chain fatty acids in longissimus thoracis (P = 0.05) and increased the quantity of saturated fatty acids (P = 0.01). In the transcriptomic analysis, 294 genes were identified as differentially expressed, which belong to pathways such as oxidative phosphorylation, citric acid cycle, and monosaccharide metabolic process. In conclusion, diet with SM increased carcass fat deposition, reduced lipid oxidation, and changed the energy metabolism, supporting its use in ruminant nutrition.

Sustainable behavior begins with sustainable attitudes: Data to assess the relationships between demographics, concerns about transport-related pollution, and willingness for action.

This Data in Brief (DiB) article addresses the relationships among individuals' transport habits, perceptions, and attitudes regarding transport-related pollution, as well as their willingness to act for environmental change. There are presented descriptive statistics, basic comparisons, and bivariate correlations among the core variables of the study. Additionally, the attached dataset appends information from a nationwide sample of 1,250 citizens in the Dominican Republic, with sex, age and habitat distribution proportional to the national census. The research database contains the full set of questions and responses to the research questionnaire, which is also attached to the supplementary files along with its codebook, making it possible to conduct further data explorations for research-related, divulgation, and educational purposes. For more information about the root study, it is advisable to read the paper "Who wants to change their transport habits to help reduce air pollution? A nationwide study in the Caribbean", published in Journal of Transport & Health [1].

Automated Identification of Different Severity Levels of Diabetic Retinopathy Using a Handheld Fundus Camera and Single-Image Protocol.

Purpose: To evaluate the performance of artificial intelligence (AI) systems embedded in a mobile, handheld retinal camera, with a single retinal image protocol, in detecting both diabetic retinopathy (DR) and more-than-mild diabetic retinopathy (mtmDR). Design: Multicenter cross-sectional diagnostic study, conducted at 3 diabetes care and eye care facilities. Participants: A total of 327 individuals with diabetes mellitus (type 1 or type 2) underwent a retinal imaging protocol enabling expert reading and automated analysis. Methods: Participants underwent fundus photographs using a portable retinal camera (Phelcom Eyer). The captured images were automatically analyzed by deep learning algorithms retinal alteration score (RAS) and diabetic retinopathy alteration score (DRAS), consisting of convolutional neural networks trained on EyePACS data sets and fine-tuned using data sets of portable device fundus images. The ground truth was the classification of DR corresponding to adjudicated expert reading, performed by 3 certified ophthalmologists. Main Outcome Measures: Primary outcome measures included the sensitivity and specificity of the AI system in detecting DR and/or mtmDR using a single-field, macula-centered fundus photograph for each eye, compared with a rigorous clinical reference standard comprising the reading center grading of 2-field imaging protocol using the International Classification of Diabetic Retinopathy severity scale. Results: Of 327 analyzed patients (mean age, 57.0 ± 16.8 years; mean diabetes duration, 16.3 ± 9.7 years), 307 completed the study protocol. Sensitivity and specificity of the AI system were high in detecting any DR with DRAS (sensitivity, 90.48% [95% confidence interval (CI), 84.99%-94.46%]; specificity, 90.65% [95% CI, 84.54%-94.93%]) and mtmDR with the combination of RAS and DRAS (sensitivity, 90.23% [95% CI, 83.87%-94.69%]; specificity, 85.06% [95% CI, 78.88%-90.00%]). The area under the receiver operating characteristic curve was 0.95 for any DR and 0.89 for mtmDR. Conclusions: This study showed a high accuracy for the detection of DR in different levels of severity with a single retinal photo per eye in an all-in-one solution, composed of a portable retinal camera powered by AI. Such a strategy holds great potential for increasing coverage rates of screening programs, contributing to prevention of avoidable blindness. Financial Disclosures: F.K.M. is a medical consultant for Phelcom Technologies. J.A.S. is Chief Executive Officer and proprietary of Phelcom Technologies. D.L. is Chief Technology Officer and proprietary of Phelcom Technologies. P.V.P. is an employee at Phelcom Technologies.

Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile.

Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67-5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39-19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72-18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain.

A dynamin superfamily-like pseudoenzyme coordinates with MICOS to promote cristae architecture.

Mitochondrial cristae architecture is crucial for optimal respiratory function of the organelle. Cristae shape is maintained in part by the mitochondrial contact site and cristae organizing system (MICOS) complex. While MICOS is required for normal cristae morphology, the precise mechanistic role of each of the seven human MICOS subunits, and how the complex coordinates with other cristae-shaping factors, has not been fully determined. Here, we examine the MICOS complex in Schizosaccharomyces pombe, a minimal model whose genome only encodes for four core subunits. Using an unbiased proteomics approach, we identify a poorly characterized inner mitochondrial membrane protein that interacts with MICOS and is required to maintain cristae morphology, which we name Mmc1. We demonstrate that Mmc1 works in concert with MICOS to promote normal mitochondrial morphology and respiratory function. Mmc1 is a distant relative of the dynamin superfamily of proteins (DSPs), GTPases, which are well established to shape and remodel membranes. Similar to DSPs, Mmc1 self-associates and forms high-molecular-weight assemblies. Interestingly, however, Mmc1 is a pseudoenzyme that lacks key residues required for GTP binding and hydrolysis, suggesting that it does not dynamically remodel membranes. These data are consistent with the model that Mmc1 stabilizes cristae architecture by acting as a scaffold to support cristae ultrastructure on the matrix side of the inner membrane. Our study reveals a new class of proteins that evolved early in fungal phylogeny and is required for the maintenance of cristae architecture. This highlights the possibility that functionally analogous proteins work with MICOS to establish cristae morphology in metazoans.

An interplay between Ni and Brønsted and Lewis acid sites in the hydrodesulfurization of dibenzothiophene.

NiMo-S2/γ-Al2O3 catalysts are commonly used in hydrotreating to enhance fossil fuel quality. The extensive research on these catalysts reveals a gap in understanding the role of Ni, often underestimated as an inactive sulfide phase or just a MoS2 promoter. In this work, we focused on analyzing whether well-dispersed supported nickel nanoparticles can be active in the hydrodesulfurization of dibenzothiophene. We dispersed Ni by the Strong Electrostatic Adsorption (SEA) method over four supports with different types of acidity: silica (~ neutral acidity), γ-Al2O3 (Lewis acidity), H+-Y zeolite, and microporous-mesoporous H+-Y zeolite (both with Brønsted-Lewis acidity). Our findings reveal that Ni is indeed active in dibenzothiophene hydrodesulfurization, even with alumina and silica as supports, although their catalytic activity declines abruptly in the first hours. Contrastingly, the acid nature of zeolites imparts sustained stability and performance, attributed to robust metal-support interactions. The efficacy of the SEA method and the added mesoporosity in zeolites further amplify catalytic efficiency. Overall, we demonstrate that Ni nanoparticles may perform as a hydrogenating metal in the same manner as noble metals such as Pt and Pd perform in hydrodesulfurization. We discuss some of the probable reasons for such performance and remark on the role of Ni in hydrotreatment.

In Solution Identification of the Lysine-Cysteine Redox Switch with a NOS Bridge in Transaldolase by Sulfur K-Edge X-ray Absorption Spectroscopy.

A novel covalent post-translational modification (lysine-NOS-cysteine) was discovered in proteins, initially in the enzyme transaldolase of Neisseria gonorrhoeae (NgTAL) [Nature 2021, 593, 460-464], acting as a redox switch. The identification of this novel linkage in solution was unprecedented until now. We present detection of the NOS redox switch in solution using sulfur K-edge X-ray absorption spectroscopy (XAS). The oxidized NgTAL spectrum shows a distinct shoulder on the low-energy side of the rising edge, corresponding to a dipole-allowed transition from the sulfur 1s core to the unoccupied σ* orbital of the S-O group in the NOS bridge. This feature is absent in the XAS spectrum of reduced NgTAL, where Lys-NOS-Cys is absent. Our experimental and calculated XAS data support the presence of a NOS bridge in solution, thus potentially facilitating future studies on enzyme activity regulation mediated by the NOS redox switches, drug discovery, biocatalytic applications, and protein design.

Antimicrobial Activity and Phytochemical Characterization of Baccharis concava Pers., a Native Plant of the Central Chilean Coast.

Few sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of Baccharis concava Pers. (sin. B. macraei), a shrub found in the first line and near the Pacific coast. B. concava has been traditionally used by indigenous inhabitants of today's central Chile for its medicinal properties. Few reports exist regarding the phytochemistry characterization and biological activities of B. concava. A hydroalcoholic extract of B. concava was prepared from leaves and small branches. Qualitative phytochemical characterization indicated the presence of alkaloids, steroids, terpenoids, flavonoids, phenolic, and tannin compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive bacteria, Gram-negative bacteria, and pathogenic yeasts. The extract displayed an important antimicrobial effect against Gram-positive bacteria, Candida albicans, and Cryptococcus neoformans but not against Gram-negatives, for which an intact Lipopolysaccharide is apparently the determinant of resistance to B. concava extracts. The hydroalcoholic extract was then fractionated through a Sephadex LH-20/methanol-ethyl acetate column. Afterward, the fractions were pooled according to a similar pattern visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against Staphylococcus aureus. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS, obtaining molecules related to caffeoylquinic acid, dicaffeoylquinic acid, and quercetin, among others. In conclusion, the extracts of B. concava showed strong antimicrobial activity, probably due to the presence of metabolites derived from phenolic acids, such as caffeoylquinic acid, and flavonoids, such as quercetin, which in turn could be responsible for helping with wound healing. In addition, the development of antimicrobial therapies based on the molecules found in B. concava could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.

Association of Park Renovation With Park Use in New York City.

Importance: Equity-driven citywide park redesign and renovation, such as the Community Parks Initiative (CPI), has the potential to increase park use and opportunities for physical activity in underserved communities. Objective: To evaluate changes in patterns of park use following park redesign and renovation in low-income New York City (NYC) neighborhoods. Design, Setting, and Participants: The Physical Activity and Redesigned Community Spaces study was a prospective quality improvement preintervention-postintervention study design with matched control parks. Thirty-three intervention and 21 control neighborhood parks were selected based on specific criteria related to poverty rates, population growth, and population density in park neighborhoods and not having received more than $250 000 in investment in the past 2 decades. Data were collected at baseline (prerenovation) and 2 follow-up points (3 months and 1 year post renovation) between June 5 and December 4 from 2016 to 2022. Participants were individuals observed as users of study parks. Intervention: The CPI, which involved the redesign and renovation of neighborhood parks by the municipal government of New York City. Main Outcomes and Measures: Main outcomes encompassed park use and physical activity levels assessed using the well-validated System for Observing Play and Recreation in Communities. Park use was quantified by total number of park users, categorized by age group (≤20 years vs ≥21 years), sex, and physical activity level (sitting or standing vs walking or vigorous activity). Changes in outcomes between groups were compared via the generalized estimation equation. Results: A total of 28 322 park users were observed across 1458 scans. At baseline, 6343 of 10 633 users (59.7%) were 20 years or younger, 4927 of 10 632 (46.3%) were female and 5705 (53.7%) were male, and 4641 of 10 605 (43.8%) were sitting or standing. Intervention parks showed more net park users compared with control parks from baseline to the final follow-up (difference-in-difference relative rate ratio, 1.69 [95% CI, 1.22-2.35] users/scan; P = .002). The association was driven by a significant increase in adult users at intervention parks and overall decrease in all users at control parks. Park users engaging in sitting or standing at intervention parks increased (difference, 4.68 [95% CI, 1.71-7.62] users/scan; P = .002) and park users engaging in walking or vigorous physical activity at control parks decreased (difference, -7.30 [95% CI, -10.80 to -4.26] users/scan; P < .001) over time. Conclusions and Relevance: In this quality improvement study, park redesign and renovation were positively associated with park use in low-income neighborhoods. However, park renovations may need to be accompanied by other programmatic strategies to increase physical activity.

Heart failure management with ß-blockers: can we do better?

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including ß-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. ß-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, ß-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, ß-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of ß-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a ß-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.

Unscheduled healthcare interactions in multiple myeloma patients receiving T cell redirection therapies.

Outcomes for relapsed/refractory multiple myeloma (RRMM) patients have dramatically improved following the development and now growing utilization of B cell maturation antigen targeted chimeric antigen receptor (CAR) T cell therapy and bispecific antibody (BsAb) therapy. However, healthcare utilization as a quality-of-life metric in these growing populations has not been thoroughly evaluated. We performed a retrospective cohort study evaluating the frequency and cause of unscheduled healthcare interactions (UHIs) among RRMM patients responding to B-cell maturation antigen targeted BsAbs and CAR T cell therapies (N = 46). This included analysis of remote UHIs including calls to physicians' offices and messages sent through an online patient portal. Our results showed that nearly all (89%) RRMM patients receiving these therapies required a UHI during the first 125 days of treatment, with a mean of 3.7 UHIs per patient. RRMM patients responding to BsAbs were significantly more likely to remotely contact their physicians' offices (1.8-fold increase, p = 0.038) or visit an urgent care center (>3-fold increase, p = 0.012) than RRMM patients responding to CAR T cell therapies. This was largely due to increased reports of mild upper respiratory tract infections in BsAb patients. Our results underscore the need to develop preemptive management strategies for commonly reported symptoms that RRMM patients experience while receiving CAR T cell or BsAb therapies. This preemptive management may significantly reduce unnecessary healthcare utilization in this vulnerable patient population.

The (un)controlled body: A grounded theory analysis to conceptualise stigma for women with gestational diabetes mellitus.

Health-related stigma is associated with adverse outcomes including depression, stress and reduced engagement in health behaviours which are particularly harmful in pregnancy and the postpartum. Women with gestational diabetes mellitus (GDM) report negative psychosocial experiences and may be at risk of stigma related to the condition. We aimed to understand women's experiences of GDM-specific stigma. Individual interviews were conducted with n = 53 women living in the UK with a current or past (within 4 years) GDM. Grounded theory methodology was used to analyse the data. Four themes were identified: (1) Preconceptions and misconceptions; (2) Locating, regaining, and negotiating agency; (3) Tension about and resisting the dominant discourse of stigma; and (4) Reclaiming control over the body. GDM-specific stigma was diverse and far reaching and may have broader implications for perinatal mental health and postnatal wellbeing. It is pertinent to investigate possible prospective associations between GDM-specific stigma, and biomedical and mental health outcomes.

One-stage or two-stage elective coronary artery bypass graft surgery and abdominal aortic aneurysm open repair in low and moderate cardiac surgical risk patients.

OBJECTIVES: Coronary artery disease (CAD) and abdominal aortic aneurysm (AAA) are common arterial pathologies that might occur simultaneously; however, there is not enough evidence about the optimal strategy for patients with concomitant indications of coronary artery bypass grafting (CABG) and open repair of the AAA (AAOR). This study aims to present the outcomes in low and moderate cardiac surgical risk patients who underwent one-stage or two-stage elective CABG and AAOR in a middle-income country. METHODS: An observational, retrospective case series study was conducted. Patients who had low and moderate cardiac surgical risk (less than 8% mortality risk on the STS score) and had the concomitant indication for CABG and AAOR between December 2005 and August 2021 were included. Patients were assigned to one of three strategies: Group 1 underwent one-stage surgery for CABG and AAOR, Group 2 underwent two-stage surgery within the same in-patient stay, and Group 3 underwent two-stage surgery in a new in-patient stay within 6 months. RESULTS: Twenty seven, patients with simultaneous requirements of CABG and AAOR were identified, with a mean age of 69.5 ± 6.1 years and 92.6% were male. The most common comorbidities were hypertension at 77.8% and dyslipidemia at 55.6%. The average mortality risk calculated by the STS score was 2.09% ± 1.53%. In Group 1 (n = 9), 1/9 had in-hospital mortality and no reinterventions were needed. In Group 2 (n = 10), 1/10 had in-hospital mortality, and the most common postoperative complication was acute kidney injury 2/10. Furthermore, 2/10 required a reintervention. In Group 3 (n = 8), no in-hospital mortality was present, however, complications such as sepsis, atrial fibrillation, and acute kidney injury occurred in 2/8 patients each, and 2/8 required a reintervention. CONCLUSION: Patients with CAD and AAA that need a concomitant surgical correction with CABG and an AAOR are uncommon in contemporary practice, given the advances in endovascular therapy. When indicated, one-stage surgery can be performed in patients with low cardiac surgical risk, proper patient selection plays a fundamental role and might be performed in experienced centers. However, two-staged surgeries at the same or different inpatient stay may be considered for asymptomatic AAA with close monitoring during the postoperative period. These findings can hold significance for addressing sociodemographic barriers in low and middle-income countries. More robust and extensive studies are needed to make clear comparisons between the different strategies.

Induction of islet autoimmunity to defective ribosomal product of the insulin gene as neoantigen after anti-cancer immunotherapy leading to autoimmune diabetes.

Introduction: The autoimmune response in type 1 diabetes (T1D), in which the beta cells expressing aberrant or modified proteins are killed, resembles an effective antitumor response. Defective ribosomal protein products in tumors are targets of the anti-tumor immune response that is unleashed by immune checkpoint inhibitor (ICI) treatment in cancer patients. We recently described a defective ribosomal product of the insulin gene (INS-DRiP) that is expressed in stressed beta cells and targeted by diabetogenic T cells. T1D patient-derived INS-DRiP specific T cells can kill beta cells and are present in the insulitic lesion. T cells reactive to INS-DRiP epitopes are part of the normal T cell repertoire and are believed to be kept in check by immune regulation without causing autoimmunity. Method: T cell autoreactivity was tested using a combinatorial HLA multimer technology measuring a range of epitopes of islet autoantigens and neoantigen INS-DRiP. INS-DRiP expression in human pancreas and insulinoma sections was tested by immunohistochemistry. Results: Here we report the induction of islet autoimmunity to INS-DRiP and diabetes after ICI treatment and successful tumor remission. Following ICI treatment, T cells of the cancer patient were primed against INS-DRiP among other diabetogenic antigens, while there was no sign of autoimmunity to this neoantigen before ICI treatment. Next, we demonstrated the expression of INS-DRiP as neoantigen in both pancreatic islets and insulinoma by staining with a monoclonal antibody to INS-DRiP. Discussion: These results bridge cancer and T1D as two sides of the same coin and point to neoantigen expression in normal islets and insulinoma that may serve as target of both islet autoimmunity and tumor-related autoimmunity.

Chemical and Redox Noninnocence of Pentane-2,4-dione Bis(S-methylisothiosemicarbazone) in Cobalt Complexes and Their Application in Wacker-Type Oxidation.

Cobalt complexes with multiproton- and multielectron-responsive ligands are of interest for challenging catalytic transformations. The chemical and redox noninnocence of pentane-2,4-dione bis(S-methylisothiosemicarbazone) (PBIT) in a series of cobalt complexes has been studied by a range of methods, including spectroscopy [UV-vis, NMR, electron paramagnetic resonance (EPR), X-ray absorption spectroscopy (XAS)], cyclic voltammetry, X-ray diffraction, and density functional theory (DFT) calculations. Two complexes [CoIII(H2LSMe)I]I and [CoIII(LSMe)I2] were found to act as precatalysts in a Wacker-type oxidation of olefins using phenylsilane, the role of which was elucidated through isotopic labeling. Insights into the mechanism of the catalytic transformation as well as the substrate scope of this selective reaction are described, and the essential role of phenylsilane and the noninnocence of PBIT are disclosed. Among the several relevant species characterized was an unprecedented Co(III) complex with a dianionic diradical PBIT ligand ([CoIII(LSMe••)I]).

Women's experiences of attempted suicide in the perinatal period (ASPEN-study) - a qualitative study.

BACKGROUND: Suicide is a leading cause of maternal death during pregnancy and the year after birth (the perinatal period). While maternal suicide is a relatively rare event with a prevalence of 3.84 per 100,000 live births in the UK [1], the impact of maternal suicide is profound and long-lasting. Many more women will attempt suicide during the perinatal period, with a worldwide estimated prevalence of 680 per 100,000 in pregnancy and 210 per 100,000 in the year after birth [2]. Qualitative research into perinatal suicide attempts is crucial to understand the experiences, motives and the circumstances surrounding these events, but this has largely been unexplored. AIM: Our study aimed to explore the experiences of women and birthing people who had a perinatal suicide attempt and to understand the context and contributing factors surrounding their perinatal suicide attempt. METHODS: Through iterative feedback from a group of women with lived experience of perinatal mental illness and relevant stakeholders, a qualitative study design was developed. We recruited women and birthing people (N = 11) in the UK who self-reported as having undertaken a suicide attempt. Interviews were conducted virtually, recorded and transcribed. Using NVivo software, a critical realist approach to Thematic Analysis was followed, and themes were developed. RESULTS: Three key themes were identified that contributed to the perinatal suicide attempt. The first theme 'Trauma and Adversities' captures the traumatic events and life adversities with which participants started their pregnancy journeys. The second theme, 'Disillusionment with Motherhood' brings together a range of sub-themes highlighting various challenges related to pregnancy, birth and motherhood resulting in a decline in women's mental health. The third theme, 'Entrapment and Despair', presents a range of factors that leads to a significant deterioration of women's mental health, marked by feelings of failure, hopelessness and losing control. CONCLUSIONS: Feelings of entrapment and despair in women who are struggling with motherhood, alongside a background of traumatic events and life adversities may indicate warning signs of a perinatal suicide. Meaningful enquiry around these factors could lead to timely detection, thus improving care and potentially prevent future maternal suicides.