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Endoscopes have been in use for many clinical procedures including biopsy and limited surgery. A biopsy is one of its most common applications. For more than a decade, research is in continuation on various limitations encountered by surgeons in this area like dexterity, manoeuverability and controlling of the scope tip to bring it to an exact point of interest. Existing endoscopes have limitations in number of degrees of freedom. To counter this problem, a 4-degree-of-freedom in vivo robot has been proposed by the authors earlier. This article presents an inverse kinematic solution of the wire-actuated in vivo robot for trajectory control. For this, a kinematic analysis has been performed and the tip positions were obtained analytically. For a known tip position, the length of the wire to be wrapped and un-wrapped is decided from the relational approach and accordingly the desired pulley rotation is performed using the proportional–derivative controller. Simulations have been carried out for three different cases and satisfying results were obtained. [ABSTRACT FROM PUBLISHER]

There is great interest in understanding the role of weight dynamics over the life cycle in predicting the incidence of disease and death. Beginning with a Medline search, we identify, classify, and evaluate the major approaches that have been used to study these dynamics. We identify four types of models: additive models, duration-of-obesity models, additive-weight-change models, and interactive models. We develop a framework that integrates the major approaches and shows that they are often nested in one another, a property that facilitates statistical comparisons. Our criteria for evaluating models are two-fold: the model's interpretability and its ability to account for observed variation in health outcomes. We apply two sets of nested models to data on adults age 50-74 years at baseline in two national probability samples drawn from National Health and Nutrition Examination Survey. One set of models treats obesity as a dichotomous variable and the other treats it as a continuous variable. In three of four applications, a fully interactive model does not add significant explanatory power to the simple additive model. In all four applications, little explanatory power is lost by simplifying the additive model to a duration model in which the coefficients of weight at different ages are set equal to one another. Other versions of a duration-of-obesity model also perform well, underscoring the importance of obesity at early adult ages for mortality at older ages. [ABSTRACT FROM AUTHOR]

Background: Empiric studies find that contextual factors affect individual weight status over and above individual socioeconomic characteristics. Given increasing levels of obesity, researchers are examining how the food environment contributes to unhealthy weight status. An important change to this environment is the increasing availability of away-from-home eating establishments such as restaurants.Methods: This study analyzed the relationship between the restaurant environment and weight status across counties in the United States. Individual data from the 2002-2006 Behavioral Risk Factor Surveillance System (N=714,054) were linked with restaurant data from the 2002 U.S. Economic Census. Fast-food and full-service restaurant density, along with restaurant mix (the ratio of fast-food to full-service restaurants), were assessed.Results: Fast-food restaurant density and a higher ratio of fast-food to full-service restaurants were associated with higher individual-level weight status (BMI and the risk of being obese). In contrast, a higher density of full-service restaurants was associated with lower weight status.Conclusions: Area-level restaurant mix emerged as an important correlate of weight status, with components of the restaurant environment exhibiting differential associations. Hence, it is the availability of fast-food relative to other away-from-home choices that appears salient for unhealthy weight outcomes. Areas with a high density of full-service restaurants were indicative of a more healthful eating environment, suggesting a need for research into the comparative healthfulness of foods served at different types of restaurants. Future prospective studies are required to delineate causal pathways. [ABSTRACT FROM AUTHOR]

Background: Single-country studies document varying time trends in memory function and impairment. Comparative analyses are limited., Methods: We used self-respondent data on adults aged 50+ years in 13 countries from 3 surveys (United States: Health and Retirement Study, 1998-2018; England: English Longitudinal Study of Ageing, 2002-2018; 11 European countries: Survey of Health, Ageing and Retirement in Europe, 2004-2019). Memory is measured with tests of immediate and delayed word recall. Unweighted age- and gender-adjusted mixed effects regression models as well as models with adjustments for additional sociodemographic characteristics and health behaviors were examined. Heterogeneity in trends by gender, age group, and educational attainment was measured., Results: The age-adjusted 10-year improvement in average test score is 0.04 standard deviations (SDs) (95% confidence interval [CI]: 0.03, 0.05) in the United States, 0.17 SDs (95% CI: 0.15, 0.19) in England, and 0.24 SDs (95% CI: 0.23, 0.25) in SHARE countries. Trends are largely similar across gender, age groups, and educational attainment. Regional differences in trends remain after adjustment for potential mechanisms. The difference between the United States and other countries is particularly large under 75 years of age compared to 75 years and older., Conclusions: Pace of improvement in memory function varies strongly across countries. On average, the 11 European countries studied had the fastest improvement, followed by England. The trend in the United States indicates improvement, but at a much slower pace compared to that in England and other European countries. Uncovering the causes for the cross-country heterogeneity in time trends, and in particular the reasons for the comparatively poor performance of the United States, should be both a research and public health priority., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Seafood is abundant in high-quality protein, healthy fats (n-3 and n-6 PUFAs), minerals (calcium, magnesium, copper, selenium, and so on), and vitamin D. Functional compounds in seafood can protect against lifestyle-related diseases. Having had all the merits mentioned, it is also a highly putrefiable food item. To maintain quality and prolong seafood's shelf life, various chemicals have been added, including nitrite, sulfur dioxide, and formaldehyde. In this review, we summarize the uses, the incidence of added formalin contamination, and the approved limit for seafood products. Additionally, worldwide regulations or standards for the use of formalin in seafood products, as well as recent changes relevant to new methods, are highlighted. Although strict limits and regulations have been placed on the utilization of formaldehyde for seafood preservation, there are few incidences reported of formalin/formaldehyde detection in seafood products around Asian countries. In this context, various qualitative and quantitative detection methods for formaldehyde have been developed to ensure the presence of formaldehyde within acceptable limits. Besides this, different rules and regulations have been forced by each country to control formaldehyde incidence. Although it is not an issue of formaldehyde incidence in European countries, strict regulations are implemented and followed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Tracking changes in socioeconomic disparities in diabetes in the U.S. is important to evaluate progress in health equity and guide prevention efforts. Disparities in diabetes prevalence by educational attainment from 2001 to 2020 were investigated., Methods: Using a serial cross-sectional design, data from 33,220 adults aged 30-79 assessed in nine rounds of the National Health and Nutrition Examination Surveys between 2001 and 2020 were analyzed in 2023-2024. Diabetes was defined as self-reported prior diagnosis, elevated glycated hemoglobin (HbA 1c ≥6.5%), or use of diabetes medications. Marginalized age- and covariate-adjusted prevalence differences (PD) and prevalence ratios (PR) of diabetes by educational attainment (less than high school graduation, high school graduation, some college education or associate degree, or college graduation [reference]) by calendar period (2001-2004, 2005-2008, 2009-2012, 2013-2016, 2017-2020) were derived from logistic regression models., Results: From 2001 to 2020, age-adjusted diabetes prevalence was consistently higher among adults without a college degree. Adults without a high school diploma exhibited the largest disparities in both 2001-2004 (PD 8.0%; 95%CI 5.6-10.5 and PR 2.1; 95%CI 1.5-2.6) and 2017-20 (PD 11.0%; 95%CI 6.7-15.2 and PR 2.1; 95%CI 1.5-2.7). Between 2001-2004 and 2017-2020, the absolute disparity in diabetes changed only among adults with a high school diploma (increase from PD 1.7%; 95%CI -0.5- 3.9 to PD 8.8% 95%CI 4.1-13.4, respectively), while the PR did not change in any group. Education-related disparities in diabetes were attenuated after accounting for socio-demographic factors and BMI., Conclusions: From 2001 to 2020, national education-related disparities in diabetes prevalence have shown no signs of narrowing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As powerful activators of the immune system, cytokines have been extensively explored for treating various cancers. But despite encouraging advances and some drug approvals, the broad adoption of cytokine therapies in the clinic has been limited by low response rates and sometimes severe toxicities. This in part reflects an inefficient biodistribution to tumors or a pleiotropic action on bystander cells and tissues. Here, we first review these issues and then argue for the intratumoral delivery of engineered cytokine fusion proteins that have been optimized for tumor retention as a potential solution to overcome these limitations and realize the potential of cytokines as highly effective therapeutics for cancer., Competing Interests: All authors are current or former paid full-time employees of, and own shares and/or stock options of Cullinan Therapeutics, Inc. Cullinan develops CLN-617, one of the modalities discussed in this perspective. The authors declare that this study received funding from Cullinan Therapeutics, Inc. The funder had the following involvement in the study: Cullinan funded the work, paid publication fees, and all authors are current or former Cullinan employees., (Copyright © 2024 Sauer, Rakhra, Wu, Mehta, Michaelson and Baeuerle.)

Background: We sought to evaluate the anatomic and functional lesion development over time at different atrial sites immediately following delivery of pulsed field ablation (PFA)., Methods: Using a porcine model, PFA ablations were performed in the superior vena cava (SVC), right atrial lateral wall (RA), left atrial appendage (LAA), and right superior pulmonary vein (RSPV) using four different PFA profiles. Mapping was done sequentially in 5-20-min increments up to 280-min post lesion delivery for low voltage area (LVA) assessment and conduction velocity. Lesion characteristics were noted with voltage mapping immediately post ablation and at the serial time points., Results: In 9 animals, 33 sites were ablated. None of the four different profiles across all sites showed any statistical difference on acute lesion formation or persistence. Higher tissue contact was observed in the SVC and RSPV and lower tissue contact was observed in the LAA and RA locations. Higher contact areas were noted to have higher density electroanatomic low voltage area (LVA) (12/14 vs 5/18, p = 0.01) and larger lesions on gross pathology (2 /14 vs 6/16, p = 0.01) compared to lower contact areas. Lesion regression occurred in 16/33 sites. Sustained lesions were significantly more prevalent in higher versus lower contact sites (65% vs 38%, p = 0.037)., Conclusion: The development of significant and durable lesions for PFA in a porcine model appears to be dependent on tissue proximity and contact., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite clinical evidence of antitumor activity, the development of cytokine therapies has been hampered by a narrow therapeutic window and limited response rates. Two cytokines of high interest for clinical development are interleukin 2 (IL2) and interleukin 12 (IL12), which potently synergize to promote the activation and proliferation of T cells and NK cells. However, the only approved human IL2 therapy, Proleukin, is rarely used in the clinic due to systemic toxicities, and no IL12 product has been approved to date due to severe dose-limiting toxicities. Here, we describe CLN-617, a first-in-class therapeutic for intratumoral (IT) injection that co-delivers IL2 and IL12 on a single molecule in a safe and effective manner. CLN-617 is a single-chain fusion protein comprised of IL2, leukocyte-associated immunoglobulin-like receptor 2 (LAIR2), human serum albumin (HSA), and IL12. LAIR2 and HSA function to retain CLN-617 in the treated tumor by binding collagen and increasing molecular weight, respectively. We found that IT administration of a murine surrogate of CLN-617, mCLN-617, eradicated established treated and untreated tumors in syngeneic models, significantly improved response to anti-PD1 checkpoint therapy, and generated a robust abscopal response dependent on cellular immunity and antigen cross-presentation. CLN-617 is being evaluated in a clinical trial in patients with advanced solid tumors (NCT06035744)., (©2024 The Authors; Published by the American Association for Cancer Research.)

Aquaculture witnessed a remarkable growth as one of the fastest-expanding sector in the food production industry; however, it faces serious threat from the unavoidable impacts of climate change. Understanding this threat, the present review explores the consequences of climate change on aquaculture production and provides need based strategies for its sustainable management, with a particular emphasis on climate-resilient approaches. The study examines the multi-dimensional impacts of climate change on aquaculture which includes the shifts in water temperature, sea-level rise, ocean acidification, harmful algal blooms, extreme weather events, and alterations in ecological dynamics. The review subsequently investigates innovative scientific interventions and climate-resilient aquaculture strategies aimed at strengthening the adaptive capacity of aquaculture practices. Some widely established solutions include selective breeding, species diversification, incorporation of ecosystem-based management practices, and the implementation of sustainable and advanced aquaculture systems (aquaponics and recirculating aquaculture systems (RAS). These strategies work towards fortifying aquaculture systems against climate-induced disturbances, thereby mitigating risks and ensuring sustained production. This review provides a detailed insight to the ongoing discourse on climate-resilient aquaculture, emphasizing an immediate need for prudent measures to secure the future sustainability of fish food production sector., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Out-of-hospital cardiac arrest is a public health crisis affecting about 356,000 adults and 23,000 children annually in the US with 90% fatality. Early bystander CPR and AED application improve survival. Less than 3% of the US population is CPR trained annually. Since 20% of the US population is at school daily, these represent ideal places to target CPR training. Having standardized state school CPR and AED laws will help with training., Methods: We performed a systemic search of the state-specific laws for school AED and CPR requirements within the US. We used PubMed and Google search using keywords: school CPR mandates, US laws for CPR in schools, US state laws for AED implementation, and gaps in US school CPR and AED. We searched for mandates for schools in other countries for comparison., Results: The state laws for CPR training for high school graduation and AED requirements in US. schools are highly variable, and funding for AEDs is inadequate, especially in schools in lower socio-economic zip codes. Recent AED legislative efforts focus mainly on athletic areas and don't adequately address school size, number of buildings, non-athletic areas, and engagement of student-led advocacy efforts., Conclusion: To improve OHCA survival, we identified potential solutions to consolidate efforts and overcome the barriers-standardize state laws, involve student bodies, increase funding, and allocate appropriate resources. The CPR/AED education needs to start earlier in schools and be part of the standard curriculum rather than implemented as a stopgap check-box mandate., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This investigation focused on the use of mosambi peel extract (MPE) fortification (at 0% to 1.50%, w/w) in silver carp surimi to improve the gelling, textural, and other physicochemical properties of the surimi., Results: The peels were extracted in ethanol (40-100% concentrations, v/v) and water. It was found that 100% ethanol had significantly (P < 0.05) higher yield and total phenolic, flavonoid, and tannin content. The fortification of MPE at optimum level (0.75%) improved the breaking force (55.1%) and gel strength (89.9%) significantly (P < 0.05) in comparison with 0% MPE gel samples. Moreover, 0.75% MPE-fortified gels had higher hydrogen and hydrophobic bonds, higher water-holding capacity, and lower sulfhydryl groups and free amino groups. The myosin heavy chain (MHC) bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) disappeared completely in the MPE-fortified gels. Fortification with MPE affected the secondary structures of protein as shifting of peaks was observed in Fourier-transform infrared (FTIR) spectra. Scanning electron microscopy (SEM) images showed relatively organized finer and denser gel networks in MPE-treated gels., Conclusion: The surimi gels fortified with 0.75% MPE demonstrated improved gelling properties, with an overall higher acceptability than the unfortified gels (0% MPE). The fortified gels also became enriched with bioactive polyphenols, which are generally not present in surimi. This study provides an efficient way to utilize mosambi peel to develop functional surimi and surimi-based products with improved gel ability. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Since 2010, US life expectancy growth has stagnated. Much research on US mortality has focused on working-age adults given adverse trends in drug overdose deaths, other external causes of death, and cardiometabolic deaths in midlife. We show that the adverse mortality trend at retirement ages (65+ y) has in fact been more consequential to the US life expectancy stagnation since 2010, as well as excess deaths and years of life lost in 2019, than adverse mortality trends at working ages. These results reveal that the United States is experiencing a "double jeopardy" that is driven by both mid-life and older-age mortality trends, but more so by older-age mortality. Understanding and addressing the causes behind the worsening mortality trend in older ages will be essential to returning to the pace of life expectancy improvements that the United States had experienced for decades.

Transcatheter aortic valve replacement (TAVR) carries a risk of high-grade AV block requiring cardiac implantable electronic device (CIED) implantation, which has been associated with a higher mortality rate. However, the outcomes of TAVR in patients with preexisting CIEDs are not well understood. We conducted a retrospective analysis of consecutive patients who underwent TAVR from December 2014 to December 2019 at our institution. Patients were categorized into 3 groups: preexisting CIED pre-TAVR (group 1), CIED implanted within 30 days after TAVR (group 2), and no CIED implanted (group 3). Cox proportional hazard was conducted to determine the primary end point of all-cause mortality. A total of 366 patients were included, of whom 93 (25.4%), 51 (13.9%), and 222 (60.7%) comprised group 1, 2, and 3, respectively. The median follow-up time was 2.3 years. The all-cause mortality rate was higher in group 1 than group 2 (hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.09 to 6.18, p = 0.03) and group 3 (HR 1.96, 95% CI 1.24 to 3.08, p = 0.004). On the multivariate analysis, there was no statistically significant difference in mortality among the groups (group 1 vs group 2: HR 1.95, 95% CI 0.70 to 5.44, p = 0.20 and group 1 vs group 3: HR 1.27, 95% CI 0.66 to 2.43, p = 0.47). Preoperative hemoglobin ≤12 g/100 ml was an independent predictor of all-cause mortality (HR 1.75, 95% CI 1.10 to 2.80, p = 0.02). Group 1 had a higher 1 year congestive heart failure readmission rate (29%) than group 2 (17.6%) and group 3 (8.1%; p <0.0001). In conclusion, there was no difference in the adjusted long-term survival based on the CIED grouping. However, patients with preexisting CIEDs had higher all-cause mortality and 1-year congestive heart failure readmission rates owing to their higher co-morbidity burden, irrespective of their Society of Thoracic Surgeons score. This can be taken into account for preoperative risk stratification., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

The objective of this study was to investigate the effects of the kiln (SK-S) and liquid smoking (LS-S) processes on the quality of inulin-fortified emulsion-type Pangasius mince sausages. The moisture content during the storage significantly ( p < 0.05) decreased in C-S (control) sausages and increased ( p < 0.05) in SK-S and LS-S sausages. The protein content decreased ( p < 0.05) in C-S, SK-S, and LS-S throughout the storage period. Initially, among the three processed sausages, LS-S showed a lower pH value, and as the days of storage progressed, all the treatments exhibited a declining trend ( p < 0.05). A significant ( p < 0.05) increase in the PV was observed in all the sausages during the storage days at 5 ± 1 °C, but the intensity of the increase was lower in SK-S and LS-S. The total viable count of C-S and SK-S sausages reached the limit of acceptability (6 log 10 cfu g -1 ) on the 20th day and on the 24th day of storage. The electrophoretic protein pattern of LS-S samples exhibited retention of all bands, indicating the lower proteolysis of MHC, actin, and troponin T in comparison with other treatments. The hardness ( p < 0.05) and cohesiveness ( p > 0.05) values of both SK-S and LS-S reduced as the storage days progressed. The present study indicates that the emulsion-type Pangasius sausages incorporated with inulin powder (2%) exposed to kiln smoking and commercial liquid smoking retained good-to-better sensory attributes up to day 16 (C-S) and day 20 (SK-S and LS-S) under refrigerated storage at 5 ± 1 °C in low-density vacuum polyethylene (LDPE) pouches., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: The aim of the work was to investigate the influence of supplementing pangasius mince-based emulsion sausages with blue agave-derived inulin at 1% (T1), 2% (T2), 3% (T3), 4% (T4), and 5% (T5) on its technological quality attributes and acceptability., Results: The cooking yield of T-2, T-3, and T-4 sausages (96-97%) exhibited no significant difference (P > 0.05), which was higher than the other lots. The T-2 batter exhibited a significant difference with all other treatments, showing the lowest total expressible fluid (12.20%) value, indicating the highest emulsion stability of the batter. There was a significant effect on the diameter reduction of the cooked sausages as the level of inulin increased. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed the proteolysis of raw mince without inulin and new bands in cooked sausage samples were observed. Increasing inulin content increased the hardness of the sausages from 2510.81 ± 114.31 g to 3415.54 ± 75.88. The differential scanning calorimetry melting temperatures of peak 2 of the T-1, T-2, T-3, and T-4 increased as the inulin content increased from 1 to 4%. The scanning electron microscope images exhibited a smooth appearance on the surface as the inulin level increased., Conclusion: The sausages incorporated with the 2% and 3% blue agave plant-derived inulin (T-2 and T-3) showed better sensory overall acceptability scores than the control. The results suggested that the blue agave plant-derived inulin could be efficiently utilized at the 2% and 3% levels to enhance the quality of emulsion-type pangasius sausage. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

In this study, a multiobjective optimization (MOO) approach was utilized for effective decision-making when several variables were changing simultaneously during frying. Carboxy methyl cellulose (CMC), xanthan gum, and carrageenan coatings in different concentrations (0.25-1.50%, w/v) were applied on fish strips to reduce the oil uptake and protein oxidation during frying. The pickup of the strips increased significantly ( p < 0.05) with increasing concentration. The CMC was effective in oil uptake reduction and protein oxidation, as revealed by the lower carbonyl and sulfhydryl contents in the fried strip. The hardness and chewiness of the coated fish strips were found to be declined significantly ( p < 0.05) with increasing coating concentrations. The moisture, lipid, toughness, hardness, cutting force, oiliness, sulfhydryl content (all min), oil uptake reduction, and carbonyl content (both max) were considered as multiple criteria for the MOO technique, and fried strips coated with 1% CMC, followed by 0.75% xanthan gum and 0.75% carrageenan, emerged as the best optimal coating., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

This investigation explored the preparation of surimi gel enhancer from pineapple peel waste, hugely generated by industries and spreading serious environment pollutions. The peel extracted with 100% ethanol had higher bioactive and antioxidant attributes, which was subsequently fortified in tilapia surimi at levels of 0.20%-1.20%, w/w to improve its physiochemical, textural, protein structural and sensorial properties. Our finding demonstrated that surimi gels enriched with 0.80% ethanolic pineapple peel extract (PAPE) exhibited significant (p<0.05) improvement in water holding capacity, breaking force, gel strength, and other textural properties and sensory attributes. Furthermore, the surimi gels fortified with 0.80% PAPE exhibited the elevated levels of hydrogen and hydrophobic interactions, while sulfhydryl and free amino acid contents demonstrated a contrasting trend. The FTIR spectra displayed that the incorporation of PAPE influenced the secondary structure of the protein, as evidenced by shifts in the α-helix to β-sheet peaks. In addition, 0.80% PAPE added gels displayed a compact, uniform, and organized microstructure, featuring small cavities. In summary, the fortification of tilapia surimi gels with 0.80% PAPE could improve gelling and other technological properties with higher sensory scores. This study offers an effective approach to utilize the pineapple peel as a gel enhancer additive for the development of functional surimi and surimi-based products enriched with bioactive compounds., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Despite significant progress in the development of T cell-engaging therapies for various B-cell malignancies, a high medical need remains for the refractory disease setting, often characterized by suboptimal target levels., Methods: To address this issue, we have developed a 65-kDa multispecific antibody construct, CLN-978, with affinities tuned to optimize the killing of low-CD19 expressing tumor cells. CLN-978 bound to CD19 on B cells with picomolar affinity, and to CD3ε on T cells with nanomolar affinity. A serum albumin binding domain was incorporated to extend serum half-life. In this setting, we biophysically characterize and report the activities of CLN-978 in cell co-culture assays, multiple mouse models and non-human primates., Results: Human T cells redirected by CLN-978 could eliminate target cells expressing less than 300 copies of CD19 on their surface. The half-life extension and high affinity for CD19 led to significant antitumor activity in murine lymphoma models at very low doses of CLN-978. In primates, we observed a long serum half-life, deep and sustained depletion of normal B cells, and remarkable tolerability, in particular, reduced cytokine release when CLN-978 was administered subcutaneously., Conclusions: CLN-978 warrants further exploration. An ongoing clinical phase 1 trial is investigating safety, pharmacokinetics, pharmacodynamics, and the initial therapeutic potential of subcutaneously administered CLN-978 in patients with non-Hodgkin's lymphoma., Competing Interests: Competing interests: NKM, KM, BL, PAB, and JSM have ownership in Cullinan Oncology, which is seeking to commercialize CLN-978., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The objective of the current study was to optimize the cook-chill conditions of high-value whiteleg shrimp ( Litopenaeus vannamei ) processed using the sous vide (SV) technique and to assess the effects of various time-temperature combinations on the physicochemical, textural, and sensory qualities. For optimization, a Response Surface Methodology (RSM) approach utilizing a Central Composite Design (CCD) was adopted. Optimum SV cooking conditions to acquire minimum texture (hardness) of 7235 g was 13.48 min and 81.87 °C, expressible moisture of 18.48% was 14.5 min and 84.5 °C, and cook loss of 5.58% was 5 min and 75 °C. Texture (hardness) and expressible moisture decreased while cooking loss increased with increasing time-temperature treatment. Redness and yellowness values increased ( p  < 0.05) with increasing SV cooking time-temperature, but lightness values were nearly consistent in all treatments. With increasing time and temperature, TBARs and total carotenoid content increased ( p  < 0.05). However, the TBARs values were within accepted limits and ranged from 0.05 to 0.08 mg malonaldehyde/kg. Sensory evaluation indicated that all SV cooked samples were well accepted, with overall scores ≥7. These results suggest that the SV cooking temperature and time had a substantial impact on the textural, physicochemical, and sensory characteristics of shrimp. In addition, increasing time-temperature increased cooking and moisture loss, but decreased hardness and higher sensory scores made the product more acceptable to consumers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The mortality impact of the COVID-19 pandemic in Ukraine has remained incomplete. We estimated excess deaths associated with the pandemic in Ukraine during 2020 and 2021. Excess deaths may be attributed directly to SARS-CoV-2 infection or indirectly to deaths associated with social and economic upheavals resulting from the pandemic. Data on all deaths registered in government-controlled Ukraine from 2016-2021 (N = 3,657,475) were utilized. Using a model-based approach, we predicted monthly excess deaths in 2020 and 2021. We estimated 47,578 excess deaths in 2020 as a whole (7.71% of all recorded deaths). This figure reflects both positive (higher than expected) excess deaths from June-December and negative (lower than expected) deaths in January and March-May. From June-December 2020, we estimated 59,363 excess deaths (15.75% of all recorded deaths in those months). In 2021, we estimated 150,049 excess deaths (21.01% of all recorded deaths). Positive excess deaths were detected across age groups even groups younger than 40 years. The number of excess deaths exceeded that of deaths with COVID-19 coded on the death certificate by more than two-fold in 2020, but that difference narrowed in 2021. We furthermore provide provisional estimates of the effect of low vaccine coverage on excess deaths in 2021 drawing from European cross-national evidence and provisional estimates of the hypothetical evolution of the pandemic in 2022 to serve as a rough basis for future studies analyzing the joint impacts of the COVID-19 pandemic and the Russian invasion on Ukrainian demography., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mehta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Obstructive sleep apnea syndrome (OSAS) is an important, modifiable risk factor in the pathophysiology of arrhythmias including atrial fibrillation (AF). The purpose of the study was to evaluate cardiac electrophysiologists' (EPs) perception of OSAS., Methods: We designed a 27-item online Likert scale-based survey instrument entailing several domains: (1) relevance of OSAS in EP practice, (2) OSAS screening and diagnosis, (3) perception on treatments for OSAS, (4) opinion on the OSAS care model. The survey was distributed to 89 academic EP programs in the USA and Canada. While the survey instrument questions refer to the term sleep apnea (SA), our discussion of the diagnosis, management, and research on the sleep disorder is more accurately described with the term OSAS., Results: A total of 105 cardiac electrophysiologists from 49 institutions responded over a 9-month period. The majority of respondents agreed that sleep apnea (SA) is a major concern in their practice (94%). However, 42% reported insufficient education on SA during training. Many (58%) agreed that they would be comfortable managing SA themselves with proper training and education and 66% agreed cardiac electrophysiologists should become more involved in management. Half of EPs (53%) were not satisfied with the sleep specialist referral process. Additionally, a majority (86%) agreed that trained advanced practice providers should be able to assess and manage SA. Time constraints, lack of knowledge, and the referral process are identified as major barriers to EPs becoming more involved in SA care., Conclusions: We found that OSAS is widely recognized as a major concern for EP. However, incorporation of OSAS care in training and routine practice lags. Barriers to increased involvement include time constraints and education. This study can serve as an impetus for innovation in the cardiology OSAS care model., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

To resurrect and establish a low-impact aquaculture practice, gel-based feed applications hold promise. Gel feed is viscoelastic, nutrient-dense, hard, flexible, and appealing, and can be moulded into appealing shapes to ensure rapid acceptance by fish. The purpose of this research is to create a suitable gel feed using various gelling agents and to evaluate its properties and acceptance by a model fish, Pethia conchonius (rosy barb). Three gelling agents, viz. starch, calcium lactate and pectin, were included at 2%, 5%, and 8% in a fish-muscle-based diet. The physical properties of gel feed were standardized using texture profile analysis, sinking velocity, water and gel stability, water holding capacity, proximate composition, and colour. The lowest levels of nutrient leaching protein (0.57 ± 0.15%) and lipid (14.3 ± 14.30%) were observed up to 24 h in the underwater column. The highest score for overall physical and acceptance characteristics was noted for the 5% calcium lactate-based gel feed. Furthermore, a 20-day acceptance feeding experiment was conducted using 5% calcium lactate to examine its suitability as fish feed. The results indicate a better acceptability (3.55 ± 0.19%) and water stability (-2.5 ± 2.5%) of the gel feed compared to the control, with an improvement in nutrient losses. Overall, the study provides an insight into the application of gel-based diets for ornamental fish rearing, besides ensuring an efficient nutrient uptake and minimal leaching to establish a clean aquatic environment.

Policy Points Obesity has emerged as a main threat to future improvements in population health, and there is little evidence that the epidemic is retreating. The traditional model of "calories in, calories out," which has guided public health policy for decades, is increasingly viewed as far too simple a framing to explain the evolution of the epidemic or guide public policy. Advances in the science of obesity, coming from many fields, highlight the structural nature of the risk, which has provided an evidence base to justify and guide policies toward addressing the social and environmental drivers of obesity. Societies and researchers need to play the long game in that widespread reductions in obesity in the short run are unlikely. Nonetheless, there are opportunities. Policies specifically targeting the food environment such as taxing high-calorie beverages and foods, restricting the marketing of junk foods to children, enhancing food labeling, and improving the dietary environment at schools may yield long-run benefits., (© 2023 Milbank Memorial Fund.)

Purpose: The objective was to determine the effects of the anatomic site of a cutaneous melanoma on the survival outcomes of diagnosed individuals., Methods: We conducted a cross-sectional study using data from the Surveillance, Epidemiology, and End Results Program (SEER) Database from 2004-2014 and included 178,892 cases of individuals diagnosed with cutaneous melanoma. Overall survival (OS) for each anatomic site as well as associated demographics, primary site, stage, and pathologic prognostic factors (Breslow's depth of invasion (DOI), level of mitoses, and ulceration), were analyzed., Results: Lower extremity melanoma (LEM) was the most likely to have locoregional nodal spread, yet head and neck melanoma (HNM) was the most likely to present at the most advanced stage of disease (IV). Independent of other factors, HNM was associated with the greatest risk of death (HR 1.90 [95% CI, 1.85-1.96]) compared to other sites, and males experienced worse overall survival (OS) (HR 1.74 [95% CI, 1.70-1.78]) compared to females. The last and greatest risk of death is associated with LEM and HNM, respectively., Conclusion: Given these survival differences, consideration should be given to incorporating the primary site of melanoma into staging to ensure treatment is efficacious as possible.

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural killer (NK) cells as potent effectors of the innate immune response has emerged as a promising modality in immunotherapy. Here, we review therapeutic approaches for selective engagement of NK cells for cancer therapy, with a particular focus on targeting the key activating receptors NK Group 2D (NKG2D) and cluster of differentiation 16A (CD16A).

This review highlights the current evidence on racial, ethnic, and socioeconomic disparities in cardiac arrest outcomes within the United States. Several studies demonstrate that patients from Black, Hispanic, or lower socioeconomic status backgrounds suffer the most from disparities at multiple levels of the resuscitation pathway, including in the provision of bystander cardiopulmonary resuscitation, defibrillator usage, and postresuscitation therapies. These gaps in care may altogether lead to lower survival rates and worse neurological outcomes for these patients. A multisystem, culturally sensitive approach to improving cardiac arrest outcomes is suggested in this article., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Effects of ethanolic extracts of pomegranate peel (PPE) on the gelling and textural characteristics of silver carp surimi gel was investigated. The peels extracted with 100% ethanol exhibited highest total phenolics, tannin and flavonoid contents. The change of the gelling properties of surimi was explained using infrared spectroscopy, chemical interactions, and scanning electronic microscopy images. Greater number of hydrogen bonds and hydrophobic interactions were found in surimi gel fortified with 0.45% PPE. Amongst all the concentrations of PPE, 0.45% level exhibited the lowest sulfhydryl and primary amino groups and this was concurrent with the highest gel strength. The FT-IR analysis showed a gradual reduction of intensity of the amide I band with the increase of PPE concentration, and also shifting to lower value from control to surimi with PPE 0.90%. Absorption bands like C-N stretching from amide II and N-H deformation from amide III were also detected. The SEM images showed that surimi with 0.45% PPE had most ordered, finest and denser gel network, and was closely integrated with higher breaking force, hardness, and WHC. This study showed the potential of functional components of fruit wastes for improving gelling properties of surimi with additional health benefits for the consumers., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Food Scientists & Technologists (India) 2022.)

The effects of ethanolic pineapple peel extract (PPE) powder at various concentrations (0-1.50%, w / w ) on the gelling properties of silver carp surimi were investigated. The pineapple peel extract produced with 0-100% ethanol, revealed that 100% ethanol had the highest bioactive properties. Surimi gels with added PPE powder demonstrated improved gel strength (504.13 ± 11.78 g.cm) and breaking force (511.64 ± 11.80 g) up to 1% PPE addition; however, as PPE concentration increased beyond 1%, the gel strength decreased. Similarly, with the addition of 1% PPE powder, more hydrophobic bonds and fewer sulfhydryl groups and free amino groups were seen. However, the gels with PPE powder added showed a slight reduction in the whiteness of the surimi gels. FTIR analysis indicated that the fortification with PPE powder brought about the secondary structure of myofibrillar proteins; peaks shifted to the β-sheet region (PPE gels) from the α-helix region (control). SEM analysis indicated that the gel with 1% PPE powder had a relatively organized, finer and denser gel architecture. Overall results suggested that the addition of PPE powder up to 1% to the surimi gels enhanced the gelling properties as well as the microstructure of the surimi.

Background and Aims: Invasive hemodynamics may provide a more nuanced assessment of cardiac function and risk phenotyping in patients undergoing cardiac surgery. The systemic pulse pressure (SPP) to central venous pressure (CVP) ratio represents an integrated index of right and left ventricular function and thus may demonstrate an association with valvular heart surgery outcomes. This study hypothesized that a low SPP/CVP ratio would be associated with mortality in valvular surgery patients., Methods: This retrospective cohort study examined adult valvular surgery patients with preoperative right heart catheterization from 2007 through 2016 at a single tertiary medical center (n = 215). Associations between the SPP/CVP ratio and mortality were investigated with univariate and multivariate analyses., Results: Among 215 patients (age 69.7 ± 12.4 years; 55.8% male), 61 died (28.4%) over a median follow-up of 5.9 years. A SPP/CVP ratio <7.6 was associated with increased mortality (relative risk 1.70, 95% confidence interval [CI] 1.08-2.67, p = .019) and increased length of stay (11.56 ± 13.73 days vs. 7.93 ± 4.92 days, p = .016). It remained an independent predictor of mortality (adjusted odds ratio 3.99, 95% CI 1.47-11.45, p = .008) after adjusting for CVP, mean pulmonary artery pressure, aortic stenosis, tricuspid regurgitation, smoking status, diabetes mellitus, dialysis, and cross-clamp time., Conclusions: A low SPP/CVP ratio was associated with worse outcomes in patients undergoing valvular heart surgery. This metric has potential utility in preoperative risk stratification to guide patient selection, prognosis, and surgical outcomes., (© 2022 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

Pulsed field ablation (PFA) has the potential to evolve into an efficient alternative to traditional RF ablation for atrial fibrillation treatment. However, achieving irreversible tissue electroporation is critical to suppressing arrhythmic pathways, raising the need for accurate lesion characterization. To understand the physics behind the tissue response PFA, we propose a quasi-dynamic model that quantifies tissue conductance at end-electroporation and identifies regions that have undergone fully irreversible electroporation (IRE). The model uses several parameters and numerically solves the electrical field diffusion into the tissue by iteratively updating the tissue conductance until equilibrium at end-electroporation. The model yields a steady-state tissue conductance map used to identify the irreversible lesion. We conducted numerical experiments mimicking a lasso catheter featuring nine 3-mm electrodes spaced circumferentially at 3.75 mm and fired sequentially using a 1500 V and 3000 V pulse amplitude. The IRE lesion region has a surface area and volume of 780 mm 2 and 1411 mm 3 , respectively, at 1500 V, and 1178 mm 2 and 2760 mm 3 , respectively, at 3000 V. Lesion discontinuity was observed at 5.0 mm depth with 1500 V, and 7.2 mm depth with 3000 V. This quasi-dynamic model yields tissue conductance maps, predicts irreversible lesion and lesion penumbra at end-electroporation, and confirms larger lesions with higher pulse amplitudes.

Peptide-based cancer vaccines are widely investigated in the clinic but exhibit modest immunogenicity. One approach that has been explored to enhance peptide vaccine potency is covalent conjugation of antigens with cell-penetrating peptides (CPPs), linear cationic and amphiphilic peptide sequences designed to promote intracellular delivery of associated cargos. Antigen-CPPs have been reported to exhibit enhanced immunogenicity compared to free peptides, but their mechanisms of action in vivo are poorly understood. We tested eight previously described CPPs conjugated to antigens from multiple syngeneic murine tumor models and found that linkage to CPPs enhanced peptide vaccine potency in vivo by as much as 25-fold. Linkage of antigens to CPPs did not impact dendritic cell activation but did promote uptake of linked antigens by dendritic cells both in vitro and in vivo. However, T cell priming in vivo required Batf3 -dependent dendritic cells, suggesting that antigens delivered by CPP peptides were predominantly presented via the process of cross-presentation and not through CPP-mediated cytosolic delivery of peptide to the classical MHC class I antigen processing pathway. Unexpectedly, we observed that many CPPs significantly enhanced antigen accumulation in draining lymph nodes. This effect was associated with the ability of CPPs to bind to lymph-trafficking lipoproteins and protection of CPP-antigens from proteolytic degradation in serum. These two effects resulted in prolonged presentation of CPP-peptides in draining lymph nodes, leading to robust T cell priming and expansion. Thus, CPPs can act through multiple unappreciated mechanisms to enhance T cell priming that can be exploited for cancer vaccines with enhanced potency.

Protein antigens are often combined with aluminum hydroxide (alum), the most commonly used adjuvant in licensed vaccines; yet the immunogenicity of alum-adjuvanted vaccines leaves much room for improvement. Here, the authors demonstrate a strategy for codelivering an immunostimulatory cytokine, the interleukin IL-21, with an engineered outer domain (eOD) human immunodeficiency virus gp120 Env immunogen eOD, bound together to alum to bolster the humoral immune response. In this approach, the immunogen and cytokine are co-anchored to alum particles via a short phosphoserine (pSer) peptide linker, promoting stable binding to alum and sustained bioavailability following injection. pSer-modified eOD and IL-21 promote enhanced lymphatic drainage and lead to accumulation of the vaccine in B cell follicles in the draining lymph nodes. This in turn promotes enhanced T follicular helper cell priming and robust germinal center responses as well as increased antigen-specific serum IgG titers. This is a general strategy for codelivery of immunostimulatory cytokine with immunogens providing a facile approach to modulate T cell priming and GC reactions toward enhanced protective immunity using the most common clinical vaccine adjuvant., Competing Interests: D.J.I., Y.A., and T.J.M. are inventors on patent applications related to the technology described in the manuscript., (© 2022 The Authors. Advanced Therapeutics published by Wiley‐VCH GmbH.)

Background: Dementia and cardiovascular diseases contribute to a significant disability and healthcare utilization in the elderly., Objective: The in-hospital treatment patterns and outcomes of heart failure (HF) and acute myocardial infarction (AMI) are not well-studied in this population., Methods: We used the National Inpatient Sample database to identify AMI and HF hospitalizations in adults ≥65 years between 2016 and 2018., Results: A total of 2,466,369 HF hospitalizations (277,900 with dementia [11.3%]) and 1,094,155 AMI hospitalizations (100,365 with dementia [9.2%]) were identified. Patients with dementia were older (mean age 83.8 vs 78.6 years for HF, and 83.0 vs 75.8 years for AMI) with female predominance (59.0% for HF and 56.0% for AMI) than those without dementia. In adjusted analysis, patients with dementia had higher in-hospital mortality (HF 4.7% vs 3.1%, aOR 1.33 [1.27-1.39] and AMI 9.9% vs 5.9%, aOR 1.23 [1.17-1.30]), p < 0.001) and lower mechanical circulatory support utilization. Patients with AMI and dementia were less likely to receive revascularization (including percutaneous coronary intervention, coronary artery bypass grafting, and thrombolysis), vasopressors, and invasive mechanical ventilation. They had a longer mean length of stay (LOS) (5.5 vs 5.3 days for HF and 5.1 vs 4.8 days for AMI, p < 0.001 for both), a lower inflation-adjusted cost of care for AMI ($15,486 vs $23,215, p < 0.001), and higher rates of transfer to rehabilitation facilities., Conclusion: Patients with dementia admitted for HF or AMI had higher in-hospital mortality, a longer LOS, and were less likely to receive aggressive revascularization interventions after AMI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Obesity prevalence among children and adolescents has risen sharply, yet there is a limited understanding of the age-specific dynamics of obesity as there is no single nationally representative cohort following children into young adulthood. Investigators constructed a pooled data set of 5 nationally representative panels and modeled age-specific obesity incidence from childhood into young adulthood., Methods: This longitudinal prospective follow-up used 718,560 person-years of observation in a pooled data set of 5 high-quality nationally representative panels-National Longitudinal Survey of Youth 1979 and 1997, National Longitudinal Study of Adolescent Health, and Early Childhood Longitudinal Study-Kindergarten cohorts of 1998 and 2011-constructed by the authors, covering 1980-2016. Differences in obesity incidence across birth cohorts and disparities in obesity incidence by sex and race/ethnicity (non-Hispanic Black, Hispanic, and non-Hispanic White) were tested in multivariate models. Data were analyzed from September 2018 to October 2021., Results: Obesity incidence increased by approximately 6% for each 1 year of age (hazard ratio=1.06, 95% CI=1.05, 1.07); however, incidence was nonlinear, exhibiting an inverted "U"-shaped pattern before 15 years of age and then rising from adolescence through 30 years. Obesity incidence more than doubled between the cohorts born in 1957-1965 and those born in 1974-1985 during adolescence. There was no significant change among those born in 1991-1994 and 2003-2006 up to age 15 years. Compared with non-Hispanic White children, non-Hispanic Black and Hispanic children had higher obesity incidence in all study cohorts. The magnitude of these disparities on the relative scale remained stable throughout the study period., Conclusions: Although many children become obese before the age of 10, obesity incidence rises from about 15 years into early adulthood, suggesting that interventions are required at multiple developmental stages., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)