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•Among 259 patients receiving CAR T cells for lymphoma, 26% had weight loss, defined as >5% reduction in body mass index in the preceding 3 months.•Patients with weight loss had worse complete remission rates, overall survival, and event-free survival, after multivariable adjustment.

The functional activation of the androgen receptor (AR) and its interplay with the aberrant Hh/Gli cascade are pivotal in the progression of castration-resistant prostate cancer (CRPC) and resistance to AR-targeted therapies. Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation. Despite lacking a transactivation domain, t-Gli3 relies on androgen receptor variant 7 (AR-V7) for its action. Mechanistically, Gsk3β activation led to the t-Gli3 generation, and inhibition of Gsk3β supported the accumulation of full-length Gli3 expression through a non-canonical mechanism. Knockdown of Gsk3β (Gsk3β KD) reduces CRPC cell proliferation, induces apoptosis via mitochondrial fragmentation, and triggers metabolomic reprogramming. The in vivo studies with Gsk3β KD cells in the mouse prostate resulted in tumor growth retardation compared to scramble cells. RNA-seq HALLMARK Gene Set Enrichment Analysis (GSEA) analysis of Gsk3β KD revealed a positive enrichment of apoptosis, tumor suppressor gene, and negative enrichment of oncogenic pathway. Furthermore, combinational use of a Gsk3β inhibitor with anti-Smo or Gli1 significantly inhibited the CRPC cell growth, which is resistant to individual Smo or Gli1 inhibitor targeting. Intriguingly, solely targeting Gli3 showed effectiveness in inhibiting CRPC cell growth. Overall, our study underscores the clinical significance of Gli3, emphasizing t-Gli3, and provides novel insights into the interplay of the Gsk3β/t-Gli3/AR-V7 axis in CRPC.

Bleeding is common in patients with haematological malignancies undergoing intensive therapy. We aimed to assess the effect of tranexamic acid on preventing bleeding and the need for platelet transfusions.

The study involves the impact of Instagram food vloggers on customer intentions to visit restaurants, aiming on the part of credibility, attractiveness, homophily, and parasocial relationships. The research employs a quantitative survey methodology, targeting Instagram users who follow food vloggers. It analyses the collected data using PLS-SEM and SPSS to comprehend relationships between influencer characteristics and restaurant visit intentions. Findings reveal that credibility and parasocial relationships have a significant influence on restaurant visit intentions. Attractiveness, while influential on credibility, does not directly affect visit intentions, highlighting the importance of vlogger-subscriber relationships over superficial traits. The study involves the emerging sector of influencer marketing research by focusing on the food industry and highlighting the paramount importance of credibility and parasocial relationships in influencing consumer behaviour, offering valuable insights for marketers and vloggers alike.

Patients undergoing CD19 chimeric antigen receptor (CAR)–T cell therapy exhibit multiple immune deficits that may increase their susceptibility to infections. Invasive fungal infections (IFIs) are life-threatening events in the setting of hematologic diseases. However, there is ongoing debate regarding the optimal role and duration of antifungal prophylaxis in this specific patient population. The objective of this study was to provide a comprehensive overview of the evolution of IFI prophylactic strategies over time and to assess IFI incidence rates in a cohort of patients with relapsed or refractory (R/R) lymphoma treated with CAR-T cell therapy. A single-center retrospective study was conducted on a cohort of patients with R/R B cell lymphoma treated with CD19 CAR-T cell therapy between April 2016 and March 2023. Group A (April 2016–August 2020) consisted of patients primarily treated with fluconazole, irrespective of their individual IFI risk profile. In Group B (September 2020–March 2023) antifungal prophylaxis was recommended only for high-risk patients. Overall, 330 patients were included. Antifungal prophylaxis was prescribed to 119/142 (84%) patients in Group A and 58/188 (31%) in Group B (P< .001). Anti-mold azoles were prescribed to 8 (5.6%) patients in Group A and 21 (11.2%) patients in Group B. In Group A, 42 (29%) patients were switched to another antifungal, 9 (21%) because of toxicity, with 6 cases of transaminitis and 3 cases of prolonged QTc. In Group B, 21 (11.2%) patients were switched to the antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following revised guidelines. No difference was found in liver toxicity between the two groups at infusion, day 10, and day 30. No significant differences were observed between the groups. IFIs following CAR-T cell therapy were rare, with 1 case of cryptococcal meningoencephalitis in group A (.7%) and 1 case of invasive aspergillosis in Group B (.5%), both occurring in patients on micafungin prophylaxis. In this large single-center cohort of patients with R/R lymphoma treated with CAR-T cells, we show that individualized prophylaxis, alongside careful management of CAR-T cell–related toxicities such as CRS, was associated with a very low IFI rate, avoiding the risk of unnecessary toxicities, drug–drug interactions, and high costs.

Polymeric materials are commonly used as the outermost layer in spacecraft passive thermal control. However, in geostationary earth orbit environments, the polymeric layer is susceptible to environmental hazards, particularly electrostatic charges. In this study, we develop a graphene-based coating on a polymeric polyimide (Kapton®) and discuss its suitability in simulated harsh space environments for electrostatic dissipation. An about 80–100 nm thick conducting reduced graphene oxide (rGO) coating was developed on Kapton® by a simple and cost-effective spray technique while ensuring minimal variation in the thermo-optical properties and hence the equilibrium temperature. The spaceworthiness and stability of the coating were evaluated through simulated space environment tests, including thermal cycling, thermal vacuum, relative humidity, adhesion, and aging tests. Structural, optical, and electrical properties were found to be preserved after spaceworthiness tests, demonstrating the durability of the coating in harsh space environments. Furthermore, field emission scanning electron microscopy demonstrated significant electron charging on uncoated Kapton®, with a gradual reduction in charge buildup for GO-coated Kapton®, and almost negligible charging on rGO-coated Kapton®when subjected to electron bombardment at 10, 15, and 20 kV. Kelvin probe force microscopy further confirmed the enhanced electrostatic dissipative properties, showing a notable decrease in surface potential from 300 mV for uncoated Kapton®to 60 mV for rGO-coated Kapton®. These findings suggest that the developed graphene-based coating holds promise as a space-survivable solution for electrostatic dissipation in a spacecraft.

Numerous longitudinal studies have traced the nutritional trajectories of a child. However, there is a paucity of literature about the factors that set the direction of it. The present study is here to fill this research gap. The study aims to determine the role of socioeconomic factors and livelihood strategies in stunting trajectories. The study has utilized the Young Lives longitudinal data collected in 2001, 2004 and 2009, from undivided Andhra Pradesh, India. This paper uses the Nutrition transition matrix to understand the different dimensions of stunting trajectories. Further, Multinomial logistic regression has been applied to determine the factors associated with it. The study validates the notion of nutritional trajectories among children. Multinomial regression analysis shows that a decrease in household size, the use of clean energy and an increase in the age and education of the mother decreases the probability of being stunted. The children from Scheduled Castes, Scheduled Tribes and a female child are more prone to being malnourished. Socio-economic factors play an important role in nutritional trajectories. The caregiver’s education, wealth Index, provision of safe drinking water, safe cooking energy, toilet facilities, and access to electricity play a vital role in nutritional trajectories. A child’s health and nutrition-related factors such as vaccination, institutional delivery and so on play a role in this regard. The study recommends the strengthening of socioeconomic indicators for positive nutritional trajectories. Targeted steps should be taken through health infrastructure development, employment generation programes, improvement in health-related accessibility and, awareness towards nutritious foods.

An 8-port modified-shielded quarter mode substrate integrated waveguide (MS-QMSIW) multiple-input-multiple–output (MIMO) antenna for WLAN applications is presented in this letter. The MIMO antenna comprises four MS-QMSIW resonators that are placed adjacent to each other, sharing the via side walls. Each MS-QMSIW resonator is inset fed orthogonally through a pair of microstrip feed lines. It utilizes the TE110 mode of the QMSIW resonator for the radiations at 5.5 GHz. The designed MIMO antenna can be easily re-designed in a 4.6 GHz to 6.4 GHz frequency band by varying one of the design parameters without changing the overall size. The isolation between the antenna elements is better than 22 dB over the entire operating band. The antenna exhibits a gain of 5.75 dBi and a radiation efficiency of better than 85%.

Due to their flexible geometry, in-plane selective area grown (SAG) nanowires (NWs) encompass the advantages of vapor–liquid–solid NWs and planar structures. The complex interplay of growth kinetics and NW dimensions provides new pathways for crystal engineering; however, their growth mechanisms remain poorly understood. We analyze the growth mechanisms of GaAs(Sb) and InGaAs/GaAs(Sb) in-plane SAG NWs using molecular beam epitaxy (MBE). While GaAs(Sb) NWs consistently follow a layer-by-layer growth, the InGaAs/GaAs(Sb) growth transitions from step-flow to layer-by-layer and layer-plus-island depending on the InGaAs thickness and the NW dimensions. We extract the diffusion lengths of Ga adatoms along the [11̅0] and [110] directions under As2during GaAs(Sb) growth. Our results indicate that Sb may inhibit the layer-by-layer to step-flow transition. Our findings show that different growth modes can be achieved in the MBE of in-plane SAG NWs grown on the same substrate and highlight the importance of the interplay with NW dimensions.

•AI interpretation of pretransplant ECG images is a novel diagnostic tool to predict transplant arrhythmia risk.•AI-ECG prediction of AF also informed the risk of mortality after allo transplantation.

Occupationally acquired COVID-19 is a hazard for healthcare workers (HCWs). In four hospitals of the Metro North Hospitals and Health Service in Queensland, Australia, we invited HCWs to report the nature of any anaesthesia interactions with COVID-19-positive and COVID-19-suspect patients. This was to assist workforce planning in future pandemics. Data collection consisted of three phases; 1) participating HCWs recorded details of episodes of care (EOCs) with COVID-19-positive or COVID-19-suspect patients; 2) these HCWs were invited to complete a follow-up survey about their own health status regarding COVID-19 infections; 3) electronic health records were used to assess patient demographics, infectious status and outcomes. Between 21 March 2020 and 17 May 2022, 63 anaesthesia HCWs reported 90 EOCs with 67 unique patients. The median (interquartile range (IQR)) age of the HCWs was 40.5 years (34–46); 55% (34/62) were male, 62% (39/63) were consultants and 21% (13/63) were registrars. The median (IQR) age of patients was 39 (28–63) years. Personal protective equipment (PPE) was deemed to be appropriate by the HCWs in (86/88) 98% of the EOCs. Twenty-four HCWs (38%) responded to a follow-up survey. Of 12 HCWs who subsequently tested positive to COVID-19, only four had cared for a COVID-19-positive patient in the two weeks prior to their diagnosis. Most responding HCWs perceived they contracted COVID-19 in the community, experiencing mild illness. We found relatively low COVID-19 case numbers, high PPE use and low transmission of COVID-19 within the hospital setting.

•New-onset CRS and ICANS are rare after 2 weeks for axi-cel, tisa-cel, and liso-cel, making flexible monitoring beyond 14 days seem safe.•NRM beyond day 28 is largely driven by infection and highlights the need to monitor for late effects and complications.

•Bridging radiotherapy (BRT) for chemotherapy-refractory CNS lymphoma achieves rapid cytoreduction before CART.•CNS-BRT is associated with a favorable CNS response profile and CART–associated neurotoxicity profile.

AbstractRecent discoveries of microplastics in cities, suburbs, and even remote locations, far from microplastic source regions, have raised the possibility of long-distance transmission of microplastics in many ecosystems. A little is known scientifically about the threat that it posed to the environment by microplastics. The problem’s apparent size necessitates the rapid development of reliable scientific advice regarding the ecological risks of microplastics. These concerns are brought on by the lack of consistent sample and identification techniques, as well as the limited physical analysis and understanding of microplastic pollution. This review provides insight regarding some unaddressed issues about the occurrence, fate, movement, and impact of microplastics, in general, with special emphasis on primary microplastics. The approaches taken in the earlier investigations have been analyzed and different recommendations for future research have been suggested.

Splenic leukocytes, particularly macrophage-expressed lipoxygenases, facilitate the biosynthesis of resolution mediators essential for cardiac repair. Next, we asked whether deletion of 12/15 lipoxygenase (12/15LOX) in macrophages impedes the resolution of inflammation following myocardial infarction (MI). Using 12/15flox/floxand LysMcre scheme, we generated macrophage-specific 12/15LOX (Mɸ-12/15LOX−/−) mice. Young C57BL/6J wild-type and Mɸ-12/15LOX−/−male mice were subjected to permanent coronary ligation microsurgery. Mice were monitored at day 1 (d1) to d5 (as acute heart failure [AHF]) and to d56 (chronic HF) post-MI, maintaining no MI as d0 naïve control animals. Post ligation, Mɸ-12/15LOX−/−mice showed increased survival (88% vs 56%) and limited heart dysfunction compared with wild-type. In AHF, Mɸ-12/15LOX−/−mice have increased biosynthesis of epoxyeicosatrienoic acid by 30%, with the decrease in D-series resolvins, protectin, and maresin by 70% in the infarcted heart. Overall, myeloid cell profiling from the heart and spleen indicated that Mɸ-12/15LOX−/−mice showed higher immune cells with reparative Ly6Clowmacrophages during AHF. In addition, the detailed immune profiling revealed reparative macrophage phenotype (Ly6Clow) in Mɸ-12/15LOX−/−mice in a splenocardiac manner post-MI. Mɸ-12/15LOX−/−mice showed an increase in myeloid population that coordinated increase of T regulatory cells (CD4+/Foxp3+) in the spleen and injured heart at chronic HF compared with wild-type. Thus, macrophage-specific deletion of 12/15LOX directs reparative macrophage phenotype to facilitate cardiac repair. The presented study outlines the complex role of 12/15LOX in macrophage plasticity and T regulatory cell signaling that indicates that resolution mediators are viable targets to facilitate cardiac repair in HF post-MI.Macrophage-derived bioactive lipids promote the safe clearance of inflammation (resolution), thus modulating macrophage-specific 12/15 lipoxygenase restores structure, function, and survival after heart attack in mice.

•The cumulative incidence of subsequent malignancies after CAR T cells was 14%.•Solid tumors were seen in 6.1% of patients after CAR T cell therapy.•Skin cancers were noted in 4.2% of patients after CAR T cell therapy.•Hematologic malignancies were seen in 4.5% of CAR T cell therapy recipients.

•Letermovir prevents csCMV in allogenic HCT pts at high and standard-risk for CMV.•Total cost of care was compared for letermovir prophylaxis versus preemptive therapy.•For high-risk pts, letermovir decreases total cost of care through day+180.•For standard-risk pts, letermovir reduces inpatient cost of care through day+180.•Standard-risk pts benefit from letermovir by lower input room and pharmacy costs.

The role of livestock ownership in related animal-source foods’ (ASFs) consumption and in determining a child’s nutritional status is well explored in a wide range of countries. However, there is a paucity of Indian literature in this context. The current study aims to fill this research gap. The objective of the paper is to establish the relationship between livestock ownership, ASFs’ consumption, dietary diversity, and dietary adequacy among children in India. Further, the study also investigates the impact of livestock ownership on a child’s nutritional status. The study has utilized the Young Lives longitudinal data, collected in 2001, 2004, and 2009 from undivided Andhra Pradesh, India. Multilevel linear and nonlinear mixed models have been used in the study. The study finds a significant association between livestock ownership and ASFs’ consumption among children. Livestock ownership enhances related ASFs’ consumption, dietary diversity score, and dietary adequacy of the household members, including children. Large ruminants are used for income generation, which help in diversifying the consumption basket. However, there is no significant association between livestock ownership and children’s nutritional status, the consumption of ASFs and children’s nutritional status. Education plays a determining role in children’s nutritional status. The engagement of less-educated women in livestock ownership may cause the absence of association. The provision of safe drinking water and toilet facilities help in reducing water-related diseases and diarrhoea frequency among adults and children that positively impact nutritional outcomes.

ABSTRACTWhile satellite-based remote sensing techniques are often used for studying and visualizing the heat distribution in cities, they are limited in terms of spatial resolution, view bias, and revisit times. In comparison, modern Unmanned Aerial Vehicles (UAVs) equipped with infrared sensors allow very fine-scale (cm) data to be collected over smaller areas. We present a user study (n = 66) that outlines how satellite and drone-sourced thermal pseudo-color images compare in terms of map reading performance on three representative map reading tasks, how the choice of colormap affects map reading, and how a new shading augmentation to thermal maps based on high-resolution digital surface models can support interaction. Additionally, users provided explicit preferences indicating an inclination toward the shading augmentation, for the recently designed rainbow-style colormap turbo, and the cmocean thermal/FLIR ironbow colormap. However, we detail how user preferences and map reading performance are not always well aligned and are linked to issues of information content and visual clutter.

•Patients with multiple myeloma previously treated with T-cell redirection therapy have a significantly lower risk of developing CRS with Tec.•Patients with high-risk cytogenetic features were at a low risk of developing CRS with Tec.

New approaches such as selective area growth (SAG), where crystal growth is lithographically controlled, allow the integration of bottom-up grown semiconductor nanomaterials in large-scale classical and quantum nanoelectronics. This calls for assessment and optimization of the reproducibility between individual components. We quantify the structural and electronic statistical reproducibility within large arrays of nominally identical selective area growth InAs nanowires. The distribution of structural parameters is acquired through comprehensive atomic force microscopy studies and transmission electron microscopy. These are compared to the statistical distributions of the cryogenic electrical properties of 256 individual SAG nanowire field effect transistors addressed using cryogenic multiplexer circuits. Correlating measurements between successive thermal cycles allows distinguishing between the contributions of surface impurity scattering and fixed structural properties to device reproducibility. The results confirm the potential of SAG nanomaterials, and the methodologies for quantifying statistical metrics are essential for further optimization of reproducibility.

IMPORTANCE: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. OBJECTIVE: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. INTERVENTIONS: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. MAIN OUTCOMES AND MEASURES: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). RESULTS: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: −0.86 mm2; 95% CI, −1.15 to −0.57; P &lt; .001; pegcetacoplan every other month: −0.69 mm2; 95% CI, −0.98 to −0.39; P &lt; .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: −0.17 mm2; 95% CI, −0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. CONCLUSIONS AND RELEVANCE: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613

Objective: To develop a digitally enabled adherence platform (DEAP) using evidence-based adherence promotion strategies through iterative testing with patients, design specialists, and adherence experts.Method: Adolescents and young adults (AYAs) with a kidney transplant from a large, midwestern transplant program were recruited to participate in this study. Through an iterative process, we conducted focus groups, individual interviews, empathy interviews/mapping, and usability testing and evaluation to develop and refine the initial version of DEAP.Results: Three empathy maps were created to assess the unique needs of patients, caregivers, and healthcare providers. Eleven patients were then recruited to participate in usability testing of the platform. Platform engagement was high with nine of the 11 participants viewing their initial messages/surveys, usability was rated as high (M= 81.88, SD= 9.61, range = 67.5–95.0), and user-friendliness was rated as excellent (M= 5.88, SD= 0.74, range = 5.0–7.0). Participants also noted multiple opportunities for improving the look and design of DEAP.Conclusions: Engaging with multiple stakeholders and piloting a small usability study have demonstrated support for the acceptability and usability of DEAP, a mobile health platform to address barriers to taking immunosuppression medication for AYAs who have received kidney transplants. Future work is planned to develop a better patient and clinician user experience, increase personalization, and facilitate patient–clinician engagement using this platform.Implications for Impact Statement Up to 40% of adolescents and young adults (AYAs) who have undergone kidney transplants do not take their immunosuppression medication as prescribed, which can lead to devastating consequences including organ rejection. DEAP (digitally enabled adherence platform), a web-based system, was designed using an iterative process with input from key stakeholders with features to assess adherence barriers and provide solutions through problem-solving. Preliminary usability testing suggests it is acceptable and easy to use, demonstrating its potential to address suboptimal adherence and improve health outcomes.

Introduction: Nutrition plays an important role in management of acute pancreatitis (AP) and decreases its severity and infectious complications. Various formulations of enteral nutrition (EN) are available and are costly. For developing countries, cost and availability is a major issue and kitchen-based diet should be explored in patients with AP. Aim: Comparison of kitchen-based diet with a commercially available polymeric formulation in terms of various outcomes in patients with AP within 14 days after the onset of pain. Methods: Sixty patients (39 male, mean age 36.1 ± 12.7 years) of moderately severe and severe AP of any etiology were randomized (30 in each group) to either kitchen-based diet or commercial polymeric formulation group. Outcome measures were refeeding pain, tolerability, infectious complications, mortality, total hospital/intensive care unit stay; and change in serum C-reactive protein (CRP), transferrin and pre albumin. Results: There was no significant difference in baseline demographic and biochemical parameters in both groups. No difference was observed in refeeding pain (7.1% vs 8%, p= 0.99), tolerability (28.6% vs 12%, p= 0.17), infectious complications (57.14% vs 36%, p= 0.12), mortality (31.7% vs 20%, p= 0.69), hospital stay (19.5 vs 23.5 days, p= 0.86), CRP (74.4 vs 59 mg/L, p= 0.97), transferrin levels (23.6 vs 25.6 mg/dL, p= 0.75) and pre albumin (9.45 vs 13.09 mg/dL, p= 0.68) in both groups. Conclusion: Kitchen-based diet is comparable to commercial polymeric formulation for the early initiation of enteral nutrition in patients with severe or moderately severe acute pancreatitis. Clinical trial registration: Trial registered with the Clinical Trials registry-India (CTRI/2018/01/011188).