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Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, and B cell and CD4+ T cell responses emerged after vaccination. Five vaccinees developed serum autologous tier 2 nAbs (ID50 titer, 1:28-1:8647) after two to three doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes., (© 2024 Hahn et al.)

The resurgence of interest in sodium-ion batteries (SIBs) is largely driven by their natural abundance and favourable cost, apart from their comparable electrochemical performance when compared with lithium-ion batteries (LIBs). The uneven geographic distribution of the raw materials required for LIBs has also contributed to this. The solid-state electrolyte (SSE) is typically one of the vital components for energy storage in SIBs and for achieving high electrochemical performances. SSEs are preferred over liquid electrolytes primarily due to their enhanced safety and stability, apart from the option of achieving higher energy density. A single sodium-ion selective conductor minimises dendrite formation and cell polarisation, among many other benefits over binary ionic conductors in battery operation. Here, we demonstrate the first example of a sulfonated supramolecular organic two-dimensional (2D) nanosheet as a novel class of single sodium-ion conductors prepared from the self-assembly of a functionalised guanidinium ion (AD-1). Solvent-assisted exfoliation of the bulk powder in water yielded nanosheet morphology, whereas nanotube morphology was achieved in isopropanol (IPA). In contrast, self-assembly with systematic water/IPA solvent ratio variations produced marigold, sunflower, and nanorod morphologies. Thermodynamic parameters, crystallinity, elemental composition, and varying natures of hydrogen bonding in five distinct morphologies were determined using microscopic and spectroscopic studies. The single Na + conducting properties of each morphology are correlated in terms of morphology, crystallinity, and the solvent used to achieve that specific morphology. Importantly, with high crystallinity and directional ion channels, 2D nanosheet morphology exhibits the highest single Na + -ion conductivity of 3.72 × 10 -4 S cm -1 with an activation energy of 0.28 eV, showing a moderately high Na + -ion transference number of 0.83 at room temperature without incorporating any additional sodium salts and organic solvents. This report is believed to be the first to show the significance of nanostructure morphologies in achieving high single-Na + -ion transport., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field., Competing Interests: Competing interests: The authors declare the following competing interests: J.C. is a founder and shareholder of Unity Biotechnology, which develops senolytic drugs. M.J.S., C.M.C. and Mayo Clinic have intellectual property related to this research. Research in the M.J.S. and D.J.B. laboratory is reviewed by the Mayo Clinic Conflict of Interest Review Board and conducted in compliance with Mayo Clinic Conflict of Interest policies. D.J.B. has a potential financial interest related to this research; he is a co-inventor on patents held by Mayo Clinic and patent applications licensed to or filed by Unity Biotechnology and a Unity Biotechnology shareholder. N. Slavov is a founding director and CEO of Parallel Squared Technology Institute, which is a non-profit research institute., (© 2024. Springer Nature Limited.)

Fluorescent molecules or materials with high photoluminescence quantum yields and stability towards photobleaching are ideally suited for multiplex imaging. Despite complying with such properties, perovskite nanocrystals (Pv-NCs) are rarely used for bioimaging owing to their toxicity and limited stability in aqueous media and towards human physiology. We aim to address these deficiencies by designing core-shell structures with Pv-NCs as the core and surface-engineered silica as the shell (SiO 2 @Pv-NCs) since silica is recognized as a biologically benign carrier material and is known to be excreted through urine. The post-grafting methodology is adopted for developing [SiO 2 @Pv-NCs]tpm and [SiO 2 @Pv-NCs]tsy (tpm: triphenylphosphonium ion, tsy: tosylsulfonamide) for specific imaging of mitochondria and endoplasmic reticulum (ER) of the live HeLa cell, respectively. A subtle difference in their average fluorescence decay times ([SiO 2 @Pv-NCs]tpm: tpm τ av = 3.1 ns and [SiO 2 @Pv-NCs]tsy: tsy τ av = 2.1 ns) is used for demonstrating a rare example of perovskite nanocrystals in fluorescence lifetime multiplex imaging., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: This study sought to examine how daily mind wandering is related to loneliness, felt connection to others, and school belonging among college students. Participants: Three samples ( n  = 209, n  = 173, and n  = 266) from two US campuses were recruited. Methods: Data were collected via ecological momentary assessment over the course of two academic quarters in one sample and an academic semester in two samples. Results: Social well-being declined throughout the academic term in all samples. Lower day-to-day mind wandering predicted lower loneliness at the next time point and was concurrently related to a higher felt connection to others and higher school belonging. Thoughts about the past and future were associated with lower social well-being than present-focused thoughts. Conclusions: This study supports the proposition that promoting present-centered attention can benefit college students' social well-being and alleviate their feelings of loneliness and isolation that they often experience.

Ethnopharmacological Relevance: Achyranthes ferruginea (A. ferruginea) Roxb. is a common plant used in traditional medicine in Asia and Africa. It has a variety of local names, including "Gulmanci" in Nigeria, "Dangar" in Pakistan, "Thola" in Ethiopia, and "Roktoshirinchi" in Bangladesh. It is edible and has several ethnomedical uses for a wide range of illnesses, including hysteria, dropsy, constipation, piles, boils, asthma, and shigellosis. However, the neuropharmacological and analgesic potential of A. ferruginea remains uninvestigated., Aim of the Study: To assess the neuropharmacological and analgesic potential of A. ferruginea through a multifaceted approach encompassing both experimental and computational models., Materials and Methods: Methanol was used to extract the leaves of A. ferruginea. It was then fractionated with low to high polar solvents (n-hexane, chloroform, ethyl acetate, and water) to get different fractions, including chloroform fraction (CLF). The study selected CLF at different doses and conducted advanced chemical element and proximate analyses, as well as phytochemical profiling using GC-MS. Toxicological studies were done at 300 μg per rat per day for 14 days. Cholinesterase inhibitory potential was checked using an in-vitro colorimetric assay. Acetic acid-induced writhing (AAWT) and formalin-induced licking tests (FILT) were used to assess anti-nociceptive effects. The forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM), hole board test (HBT), and light and dark box test (LDB) were among the behavioral tests used to assess depression and anxiolytic activity. Network pharmacology-based analysis was performed on selected compounds using the search tool for interacting chemicals-5 (STITCH 5), Swiss target prediction tool, and search tool for the retrieval of interacting genes and proteins (STRING) database to link their role with genes involved in neurological disorders through gene ontology and reactome analysis., Results: Qualitative chemical element analysis revealed the presence of 15 elements, including Na, K, Ca, Mg, P, and Zn. The moisture content, ash value, and organic matter were found to be 11.12, 11.03, and 88.97%, respectively. GC-MS data revealed that the CLF possesses 25 phytoconstituents. Toxicological studies suggested the CLF has no effects on normal growth, hematological and biochemical parameters, or cellular organs after 14 days at 300 μg per rat. The CLF markedly reduced the activity of both acetylcholinesterase and butyrylcholinesterase (IC 50 : 56.22 and 13.22 μg/mL, respectively). Promising dose-dependent analgesic activity (p < 0.05) was observed in chemically-induced pain models. The TST and FST showed a dose-dependent substantial reduction in immobility time due to the CLF. Treatment with CLF notably increased the number of open arm entries and time spent in the EPM test at doses of 200 and 400 mg/kg b.w. The CLF showed significant anxiolytic activity at 200 mg/kg b.w. in the HBT test, whereas a similar activity was observed at 400 mg/kg b.w. in the EPM test. A notable increase in the amount of time spent in the light compartment was observed in the LDB test by mice treated with CLF, suggesting an anxiolytic effect. A network pharmacology study demonstrated the relationship between the phytochemicals and a number of targets, such as PPARA, PPARG, CHRM1, and HTR2, which are connected to the shown bioactivities., Conclusions: This study demonstrated the safety of A. ferruginea and its efficacy in attenuating cholinesterase inhibitory activity, central and peripheral pain, anxiety, and depression, warranting further exploration of its therapeutic potential., 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Biobehavioral rhythms are biological, behavioral, and psychosocial processes with repeating cycles. Abnormal rhythms have been linked to various health issues, such as sleep disorders, obesity, and depression., Objective: This study aims to identify links between productivity and biobehavioral rhythms modeled from passively collected mobile data streams., Methods: In this study, we used a multimodal mobile sensing data set consisting of data collected from smartphones and Fitbits worn by 188 college students over a continuous period of 16 weeks. The participants reported their self-evaluated daily productivity score (ranging from 0 to 4) during weeks 1, 6, and 15. To analyze the data, we modeled cyclic human behavior patterns based on multimodal mobile sensing data gathered during weeks 1, 6, 15, and the adjacent weeks. Our methodology resulted in the creation of a rhythm model for each sensor feature. Additionally, we developed a correlation-based approach to identify connections between rhythm stability and high or low productivity levels., Results: Differences exist in the biobehavioral rhythms of high- and low-productivity students, with those demonstrating greater rhythm stability also exhibiting higher productivity levels. Notably, a negative correlation (C=-0.16) was observed between productivity and the SE of the phase for the 24-hour period during week 1, with a higher SE indicative of lower rhythm stability., Conclusions: Modeling biobehavioral rhythms has the potential to quantify and forecast productivity. The findings have implications for building novel cyber-human systems that align with human beings' biobehavioral rhythms to improve health, well-being, and work performance., (©Runze Yan, Xinwen Liu, Janine M Dutcher, Michael J Tumminia, Daniella Villalba, Sheldon Cohen, John D Creswell, Kasey Creswell, Jennifer Mankoff, Anind K Dey, Afsaneh Doryab. Originally published in JMIR AI (https://ai.jmir.org), 18.04.2024.)

Varicella zoster virus (VZV) is a highly contagious human herpes virus responsible for causing chickenpox (varicella) and shingles (herpes zoster). Despite the approval of a highly effective vaccine, Shingrix ® , the global incidence of herpes zoster is increasing and the economic burden to the health care system and society are substantial due to significant loss of productivity and health complications, particularly among elderly and immunocompromised individuals. This is primarily because access to the vaccines remains mostly limited to countries within developed economies, such as USA and Canada. Therefore, similarly effective vaccines against VZV that are more accessible to the rest-of-the-world are necessary. In this study, we aimed to evaluate immunogenicity and memory response induced by three mRNA-LNP-based vaccine candidates targeting VZV's surface glycoprotein E (gE). C57BL/6 mice were immunized with each candidate vaccine, and humoral and cellular immune responses were assessed. Our results demonstrate that the mRNA-LNP-based vaccine candidates elicited robust and durable humoral responses specific to the gE antigen. Notably, mice vaccinated with the mRNA-LNP vaccines exhibited significantly higher antigen-specific T-cell cytokine production compared to the group receiving Shingrix ® , the current standard of care vaccine. Additionally, mRNA-LNP vaccines induced long-lasting memory response, as evidenced by detection of persistent gE-specific Long-Lived Plasma Cells (LLPCs) and memory T cells four months after final immunization. These findings underscore the potential of our mRNA-LNP-based vaccine candidates in generating potent immune responses against VZV, offering promising prospects for their clinical development as an effective prophylactic vaccine against herpes zoster., (© 2024. The Author(s).)

Competing Interests: Conflict of interestThe authors declare no competing interests.

Ethnopharmacological Relevance: Drynaria quercifolia is an epiphytic fern distributed all over Bangladesh with traditional use in treating neurological disorders and other ailments. Although several pharmacological activities of D. quercifolia have been investigated, the neuroprotective potential of this plant is still unexplored., Aim of Study: In this study, we evaluated the in vitro anticholinesterase and antioxidant activities of D. quercifolia and the neuroprotective effect in scopolamine-induced memory-impaired mouse model., Materials and Methods: The crude methanol extract (DCM) of the plant was fractionated to prepare n-hexane (DHF), chloroform (DCF), ethyl acetate (DEF), and aqueous (DAF) factions. All the fractions were evaluated for anticholinesterase activity by modified Ellman's method and the antioxidant activity by several in vitro assays such as DPPH and hydroxyl free radicals scavenging, reducing power, and inhibition of brain lipid peroxidation. The effect of the most active fractions (both DCF and DEF) on learning and memory was assessed in scopolamine-induced mouse model of memory-impairment by Morris water maze tasks. Biochemical assays were performed in brain tissue. The active compound was isolated and characterized by chromatographic, spectroscopic, and molecular docking methods., Results: Phytochemical analysis demonstrated a high content of phenolic and flavonoid in DEF. In vitro studies revealed a strong antioxidant power of DEF and anticholinesterase activity of DCF. Both the DCF and DEF significantly (P˂0.05) reduced the escape latency time in the Morris's water maze tasks, and increased the time spent in the northeast quadrant in the probe trial. Biochemical data demonstrated that treatment with DCF and DEF at different doses significantly (P˂0.0001) inhibited acetylcholinesterase activity, restored GSH levels, and reduced MDA levels in the brain of scopolamine-induced memory-impaired mice, indicating the protective effect of D. quercifolia, possibly by acetylcholinesterase inhibition and oxidative stress prevention. Chromatographic methods of separation led to he isolation of catechin and protocatechuric acid from DEF and 3,4-dihydroxy benzoic acid from DCF. The structure of the compounds was determined by studies of their 1 H-NMR spectra. Molecular docking as well as in vitro study suggests the anticholinesterase and antioxidant activity of the isolated compounds., Conclusion: Our study suggested that the extracts of D. quercifolia, due to anticholinesterase and antioxidant activity, ameliorate the scopolamine-induced memory impairment in mice and thus may represent therapeutics in the treatment of Alzheimer's disease., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nonalcoholic Fatty Liver Disease (NAFLD) is proving to be a globally prevalent condition. Moreover, NAFLD may be an independent risk factor associated with higher cardiovascular (CVD) morbidity and mortality. Further studies are needed to assess whether NAFLD needs to be included in the atherosclerotic risk score algorithms or whether patients with NAFLD need to be screened early on to assess their CVD risk especially since imaging such as positron emission tomography can be used to assess both NAFLD and CV disease at the same time. Therefore employing cardiovascular imaging modalities to investigate the incidence, extent, and nature of atherosclerotic lesions in NAFLD may be beneficial. Additionally, whether treating NAFLD halts the progression of CVD on imaging remains to be seen. Further research to delineate NAFLD and CVD associations, deciphering screening imaging modalities, and investigating targeted interventions could improve CVD morbidity and mortality in NAFLD., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors confirm that neither the manuscript nor any part of it was written or published or is under consideration for publication elsewhere., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the effects of a mobile health (mHealth) intervention, HerBeat, compared with educational usual care (E-UC) for improving exercise capacity (EC) and other patient-reported outcomes at 3 mo among women with coronary heart disease., Methods: Women were randomized to the HerBeat group (n = 23), a behavior change mHealth intervention with a smartphone, smartwatch, and health coach or to the E-UC group (n = 24) who received a standardized cardiac rehabilitation workbook. The primary endpoint was EC measured with the 6-min walk test (6MWT). Secondary outcomes included cardiovascular disease risk factors and psychosocial well-being., Results: A total of 47 women (age 61.2 ± 9.1 yr) underwent randomization. The HerBeat group significantly improved on the 6MWT from baseline to 3 mo ( P = .016, d = .558) while the E-UC group did not ( P = .894, d =-0.030). The between-group difference of 38 m at 3 mo was not statistically significant. From baseline to 3 mo, the HerBeat group improved in anxiety ( P = .021), eating habits confidence ( P = .028), self-efficacy for managing chronic disease ( P = .001), diastolic blood pressure ( P = .03), general health perceptions ( P = .047), perceived bodily pain ( P = .02), and waist circumference ( P = .008) while the E-UC group showed no improvement on any outcomes., Conclusions: The mHealth intervention led to improvements in EC and several secondary outcomes from baseline to 3 mo while the E-UC intervention did not. A larger study is required to detect small differences between groups. The implementation and outcomes evaluation of the HerBeat intervention was feasible and acceptable with minimal attrition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Several COVID-19 vaccines, some more efficacious than others, are now available and deployed, including multiple mRNA- and viral vector-based vaccines. With the focus on creating cost-effective solutions that can reach the low- and medium- income world, GreenLight Biosciences has developed an mRNA vaccine candidate, GLB-COV2-043, encoding for the full-length SARS-CoV-2 Wuhan wild-type spike protein. In pre-clinical studies in mice, GLB-COV2-043 induced robust antigen-specific binding and virus-neutralizing antibody responses targeting homologous and heterologous SARS-CoV-2 variants and a T H 1-biased immune response. Boosting mice with monovalent or bivalent mRNA-LNPs provided rapid recall and long-lasting neutralizing antibody titers, an increase in antibody avidity and breadth that was held over time and generation of antigen-specific memory B- and T- cells. In hamsters, vaccination with GLB-COV2-043 led to lower viral loads, reduced incidence of SARS-CoV-2-related microscopic findings in lungs, and protection against weight loss after heterologous challenge with Omicron BA.1 live virus. Altogether, these data indicate that GLB-COV2-043 mRNA-LNP vaccine candidate elicits robust protective humoral and cellular immune responses and establishes our mRNA-LNP platform for subsequent clinical evaluations., (© 2023. The Author(s).)

Rabies is a fatal but preventable zoonotic disease with an approximately 100% case fatality rate. The most common way to contract rabies is through the bite of a rabid animal. Post-exposure prophylaxis (PEP) by vaccination and/or immunoglobulin therapy is the most effective measure for rabies prevention. The effectiveness of vaccination depends on the level of completion of vaccination. In Bangladesh, no previous studies were conducted to evaluate adherence to government recommendations for post-exposure rabies vaccine among animal-bite cases. We conducted a cross-sectional study to collect information about adherence to government recommendations for post-exposure rabies vaccine. A total of 457 animal bite victims were selected to collect data and follow up after one month of enrollment. The majority of participants (58%, n = 265, 95% CI: 53-63%) had a history of animal bites. Most of the participants (77%) were advised to receive three doses of vaccine and 100% of them completed 3-dose of vaccine. Among the 4-dose recommended group of participants (n = 105), 78% completed full vaccination. Of the 457 participants, 20% received post-exposure vaccine on the day of bite/scratch and the majority of the participants (66%, n = 303, 95% CI: 62-71%) received post-exposure vaccine on the day between the first and third day of bite or scratch. Increasing awareness of the importance of timely vaccination is the key to reducing the time gap between animal bites and intake of the first dose post-exposure vaccine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tamanna 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.)

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, and senescent cells have emerged as key contributors to its pathogenesis. Senescent cells exhibit cell cycle arrest and secrete a range of proinflammatory factors, termed the senescence-associated secretory phenotype (SASP), which promotes tissue dysfunction and exacerbates CVD progression. Omics technologies, specifically transcriptomics and proteomics, offer powerful tools to uncover and define the molecular signatures of senescent cells in cardiovascular tissue. By analyzing the comprehensive molecular profiles of senescent cells, omics approaches can identify specific genetic alterations, gene expression patterns, protein abundances, and metabolite levels associated with senescence in CVD. These omics-based discoveries provide insights into the mechanisms underlying senescence-induced cardiovascular damage, facilitating the development of novel diagnostic biomarkers and therapeutic targets. Furthermore, integration of multiple omics data sets enables a systems-level understanding of senescence in CVD, paving the way for precision medicine approaches to prevent or treat cardiovascular aging and its associated complications.

Providers' disrespect and abuse of patients is a recognized but understudied issue affecting quality of care and likely affecting healthcare utilization. Little research has examined this issue among people living with HIV (PWH) who inject drugs, despite high stigmatization of this population. No research has examined this issue in the context of Russia. This study assesses patients' reports of disrespect and abuse from providers as a barrier to healthcare and examines the association between these reports and HIV care outcomes.We conducted a cross-sectional analysis of the associations between disrespect/abuse from health providers as a barrier to care and the following HIV care outcomes: (i) anti-retroviral treatment (ART) uptake ever, (ii) past 6-month visit to HIV provider, and (iii) CD4 count. Participants (N = 221) were people living with HIV who injected drugs and were not on ART at enrollment.Two in five participants (42%) reported a history disrespect/abuse from a healthcare provider that they cited as a barrier to care. Those reporting this concern had lower odds of ever use of ART (adjusted odds ratio 0.46 [95% CI 0.22, 0.95]); we found no significant associations for the other HIV outcomes. We additionally found higher representation of women among those reporting prevalence of disrespect/abuse from provider as a barrier to care compared to those not reporting this barrier (58.1% versus 27.3%).Almost half of this sample of PWH who inject drugs report disrespect/abuse from a provider as a barrier to healthcare, and this is associated with lower odds of receipt of ART but not with other HIV outcomes studied. There is need for improved focus on quality of respectful and dignified care from providers for PWH who inject drugs, and such focus may improve ART uptake in Russia., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cellular senescence is a state of irreversible growth arrest with profound phenotypic changes, including the senescence-associated secretory phenotype (SASP). Senescent cell accumulation contributes to aging and many pathologies including chronic inflammation, type 2 diabetes, cancer, and neurodegeneration. Targeted removal of senescent cells in preclinical models promotes health and longevity, suggesting that the selective elimination of senescent cells is a promising therapeutic approach for mitigating a myriad of age-related pathologies in humans. However, moving senescence-targeting drugs (senotherapeutics) into the clinic will require therapeutic targets and biomarkers, fueled by an improved understanding of the complex and dynamic biology of senescent cell populations and their molecular profiles, as well as the mechanisms underlying the emergence and maintenance of senescence cells and the SASP. Advances in mass spectrometry-based proteomic technologies and workflows have the potential to address these needs. Here, we review the state of translational senescence research and how proteomic approaches have added to our knowledge of senescence biology to date. Further, we lay out a roadmap from fundamental biological discovery to the clinical translation of senotherapeutic approaches through the development and application of emerging proteomic technologies, including targeted and untargeted proteomic approaches, bottom-up and top-down methods, stability proteomics, and surfaceomics. These technologies are integral for probing the cellular composition and dynamics of senescent cells and, ultimately, the development of senotype-specific biomarkers and senotherapeutics (senolytics and senomorphics). This review aims to highlight emerging areas and applications of proteomics that will aid in exploring new senescent cell biology and the future translation of senotherapeutics.

BACKGROUNDCellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDL-cholesterol (HDL-C) but is not suitable as a routine clinical assay.METHODSWe developed an HDL-specific phospholipid efflux (HDL-SPE) assay to assess HDL functionality based on whole plasma HDL apolipoprotein-mediated solubilization of fluorescent phosphatidylethanolamine from artificial lipid donor particles. We first assessed the association of HDL-SPE with prevalent coronary artery disease (CAD): study I included NIH severe-CAD (n = 50) and non-CAD (n = 50) participants, who were frequency matched for sex, BMI, type 2 diabetes mellitus, and smoking; study II included Japanese CAD (n = 70) and non-CAD (n = 154) participants. We also examined the association of HDL-SPE with incident CVD events in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study comparing 340 patients with 340 controls individually matched for age, sex, smoking, and HDL-C levels.RESULTSReceiver operating characteristic curves revealed stronger associations of HDL-SPE with prevalent CAD. The AUCs in study I were as follows: HDL-SPE, 0.68; apolipoprotein A-I (apoA-I), 0.62; HDL-C, 0.63; and CEC, 0.52. The AUCs in study II were as follows: HDL-SPE, 0.83; apoA-I, 0.64; and HDL-C, 0.53. Also longitudinally, HDL-SPE was significantly associated with incident CVD events independent of traditional risk factors with ORs below 0.2 per SD increment in the PREVEND study (P < 0.001).CONCLUSIONHDL-SPE could serve as a routine clinical assay for improving CVD risk assessment and drug discovery.TRIAL REGISTRATIONClinicalTrials.gov NCT01621594.FUNDINGNHLBI Intramural Research Program, NIH (HL006095-06).

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease leading to continuous mucosal inflammation in the rectum extending proximally towards the colon. Chronic and/or recurrent UC is one of the critical predisposing mediators of the oncogenesis of human colorectal carcinoma (CRC). Perturbations of the differential expression of the UC-critical genes exert an intense impact on the neoplastic transformation of the affected tissue(s). Herein, a comprehensive exploration of the UC-critical genes from the transcriptomic profiles of UC patients was conducted to study the differential expression, functional enrichment, genomic alterations, signal transduction pathways, and immune infiltration level encountered by these genes concerning the oncogenesis of CRC. The study reveals that WFDC2, TTLL12, THRA, and EPHB3 play crucial roles as UC-CRC critical genes and are positively correlated with the molecular transformation of UC to CRC. Taken together, these genes can be used as potential biomarkers and therapeutic targets for combating UC-induced human CRC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Patra 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.)

Objectives: To better understand the relationship between high-quality contraceptive counseling and met family planning needs, we examined the association between quality of counseling and selection of a method postvisit among women requesting contraception in Ethiopia., Study Design: We used post-counseling survey data from women receiving care in public health centers and nongovernmental clinics in three regions in Ethiopia. Among women whose reason for visit was requesting a contraceptive method, we examined the association between scores on the validated quality of contraceptive counseling (QCC) scale and subscales and selection of a method post-counseling (primary analysis) and type of method selected (secondary analysis). We conducted mixed-effects multivariable logistic regression for the primary analysis and multinomial regression for the secondary analysis., Results: There was a nonsignificant increase in odds of selecting contraception with increasing total QCC scale scores (adjusted odds ratio [aOR] 2.35, 0.43-12.95). However, among women experiencing no disrespect and abuse, there was increasing odds of selecting contraception (aOR 3.46, 95% CI 1.09-10.99) and likelihood of selecting injectable contraception (adjusted relative risk ratio 4.27, 95% CI 1.34-13.60) compared to women experiencing disrespect and abuse. Additionally, 168 (32.1%) of women felt pressured by their provider to use a certain method of which>50% selected long-acting reversible contraception., Conclusions: Increasing QCC is associated with selecting contraception among women requesting contraception. Additionally, probing for negative experiences can reveal feelings of disrespect and abuse that could lead women to avoid selecting contraception or feeling pressured to use methods heavily promoted by providers., Implications: Our study assesses contraceptive counseling quality using a validated tool with items on provider pressure and other forms of disrespect and abuse; findings highlight the importance of respectful treatment in meeting women's needs and the potential influence of disrespect on decision to select contraception and type of method selected., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study addresses mental health concerns among university students, examining cumulative stress exposure as well as resilience resources. Participants : Participants were 253 first- and second-year undergraduate students (age = 18.76; 49.80% male, 69% students of color) enrolled at a large western US university. Methods : Data were obtained from a cross-sectional online survey examining marginalized statuses and multiple stressors alongside coping responses, adaptive self-concept, and social support as predictors of stress, anxiety, and depression. Results : Multivariate regressions demonstrated significant associations between stress exposures and lower levels of resilience resources with each mental health indicator (with substantial R 2 of.49-.60). Although stressor exposures accounted for significant increases in mental health concerns, their exploratory power was attenuated by resilience resources (e.g., beta decreases from.25 to.16). Conclusions : Better understanding cumulative adversity/resilience resource profiles, particularly among marginalized students, can help universities in prioritizing institutional support responses toward prevention and mitigating psychological distress.

Background: In Bangladesh, labour migration is a source of employment and workers' remittances are critical to poverty mitigation. The aim of this study was to assess the prevalence of hepatitis B, C, HIV, tuberculosis, syphilis, kidney and liver diseases along with presence of infections among aspirant migrant workers of Bangladesh., Method: This study was carried out from September-December 2019. We analysed data collected on screening tests of specific diseases of aspirant workers. For each test, the prevalence was computed with 95% confidence interval. Association between categorical data was determined by the Chi-square test., Results: A total of 2385 aspirants, 1988 (83.35%) males, aged between 18 and 65 years (29.76±6.578) were studied. Positive results for screening tests of HBsAg were 38 (1.6%,), anti-HCV were 2 (0.08%), TPHA were 25 (1.05%) and VDRL were 5 (0.21%) though no individual was positive for HIV and TB. Elevated level of SGOT (n=99, 4.2%), SGPT (n=322, 13.5%), RBS (n=57, 2.4%), bilirubin (n=46, 1.92%), creatinine (n=7, 0.3%) and ESR (n=19, 0.8%) were found in the workers., Conclusion: Diagnosis of diseases of workers is obligatory before going abroad to safeguard the health of the workers and residents of destination country. Consequently, it will contribute to reducing the global burden of infectious diseases., Competing Interests: None., (© 2023 Afroz J et al.)

Background: Digital just-in-time adaptive interventions can reduce binge-drinking events (BDEs; consuming ≥4 drinks for women and ≥5 drinks for men per occasion) in young adults but need to be optimized for timing and content. Delivering just-in-time support messages in the hours prior to BDEs could improve intervention impact., Objective: We aimed to determine the feasibility of developing a machine learning (ML) model to accurately predict future, that is, same-day BDEs 1 to 6 hours prior BDEs, using smartphone sensor data and to identify the most informative phone sensor features associated with BDEs on weekends and weekdays to determine the key features that explain prediction model performance., Methods: We collected phone sensor data from 75 young adults (aged 21 to 25 years; mean 22.4, SD 1.9 years) with risky drinking behavior who reported their drinking behavior over 14 weeks. The participants in this secondary analysis were enrolled in a clinical trial. We developed ML models testing different algorithms (eg, extreme gradient boosting [XGBoost] and decision tree) to predict same-day BDEs (vs low-risk drinking events and non-drinking periods) using smartphone sensor data (eg, accelerometer and GPS). We tested various "prediction distance" time windows (more proximal: 1 hour; distant: 6 hours) from drinking onset. We also tested various analysis time windows (ie, the amount of data to be analyzed), ranging from 1 to 12 hours prior to drinking onset, because this determines the amount of data that needs to be stored on the phone to compute the model. Explainable artificial intelligence was used to explore interactions among the most informative phone sensor features contributing to the prediction of BDEs., Results: The XGBoost model performed the best in predicting imminent same-day BDEs, with 95% accuracy on weekends and 94.3% accuracy on weekdays (F 1 -score=0.95 and 0.94, respectively). This XGBoost model needed 12 and 9 hours of phone sensor data at 3- and 6-hour prediction distance from the onset of drinking on weekends and weekdays, respectively, prior to predicting same-day BDEs. The most informative phone sensor features for BDE prediction were time (eg, time of day) and GPS-derived features, such as the radius of gyration (an indicator of travel). Interactions among key features (eg, time of day and GPS-derived features) contributed to the prediction of same-day BDEs., Conclusions: We demonstrated the feasibility and potential use of smartphone sensor data and ML for accurately predicting imminent (same-day) BDEs in young adults. The prediction model provides "windows of opportunity," and with the adoption of explainable artificial intelligence, we identified "key contributing features" to trigger just-in-time adaptive intervention prior to the onset of BDEs, which has the potential to reduce the likelihood of BDEs in young adults., Trial Registration: ClinicalTrials.gov NCT02918565; https://clinicaltrials.gov/ct2/show/NCT02918565., (©Sang Won Bae, Brian Suffoletto, Tongze Zhang, Tammy Chung, Melik Ozolcer, Mohammad Rahul Islam, Anind K Dey. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.05.2023.)

Competing Interests: Conflict of interestThe authors declare no competing interests.

Herein, a novel nanocomposite, namely, Zn-modified CeO 2 @biochar (Zn/CeO 2 @BC), is synthesized via facile one-step sol-precipitation to study its photocatalytic activity towards the removal of methylene blue dye. Firstly, Zn/Ce(OH) 4 @biochar was precipitated by adding sodium hydroxide to cerium salt precursor; then, the composite was calcined in a muffle furnace to convert Ce(OH) 4 into CeO 2 . The crystallite structure, topographical and morphological properties, chemical compositions, and specific surface area of the synthesized nanocomposite are characterized by XRD, SEM, TEM, XPS, EDS, and BET analysis. The nearly spherical Zn/CeO 2 @BC nanocomposite has an average particle size of 27.05 nm and a specific surface area of 141.59 m 2 /g. All the tests showed the agglomeration of Zn nanoparticles over the CeO 2 @biochar matrix. The synthesized nanocomposite showed remarkable photocatalytic activity towards removing methylene blue, an organic dye commonly found in industrial effluents. The kinetics and mechanism of Fenton-activated dye degradation were studied. The nanocomposite exhibited the highest degradation efficiency of 98.24% under direct solar irradiation of 90 min, at an optimum dosage of 0.2 g l -1 catalyst and 10 ppm dye concentration, in the presence of 25% (V/V) 0.2 ml (4 µl/ml) hydrogen peroxide. The hydroxyl radical generated from H 2 O 2 during the photo-Fenton reaction process was attributed to the nanocomposite's improved photodegradation performance. The degradation process followed pseudo-first-order kinetics having a rate constant (k) value of 0.0274 min -1 ., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Academic achievement in the first year of college is critical for setting students on a pathway toward long-term academic and life success, yet little is known about the factors that shape early college academic achievement. Given the important role sleep plays in learning and memory, here we extend this work to evaluate whether nightly sleep duration predicts change in end-of-semester grade point average (GPA). First-year college students from three independent universities provided sleep actigraphy for a month early in their winter/spring academic term across five studies. Findings showed that greater early-term total nightly sleep duration predicted higher end-of-term GPA, an effect that persisted even after controlling for previous-term GPA and daytime sleep. Specifically, every additional hour of average nightly sleep duration early in the semester was associated with an 0.07 increase in end-of-term GPA. Sensitivity analyses using sleep thresholds also indicated that sleeping less than 6 h each night was a period where sleep shifted from helpful to harmful for end-of-term GPA, relative to previous-term GPA. Notably, predictive relationships with GPA were specific to total nightly sleep duration, and not other markers of sleep, such as the midpoint of a student's nightly sleep window or bedtime timing variability. These findings across five studies establish nightly sleep duration as an important factor in academic success and highlight the potential value of testing early academic term total sleep time interventions during the formative first year of college.

Research on discrimination and risks for violence and mental health issues under the pandemic is notably absent. We examined the relative effects of perceived everyday discrimination (e.g., poorer service, disrespectful treatment in a typical week) and major experiences of race-based discrimination (e.g., racial/ethnic discrimination in housing or employment at any point in the lifetime) on experiences of violence and the PHQ-4 assessment of symptoms of depression and anxiety under the pandemic. We analyzed state-representative cross-sectional survey data from California adults (N = 2114) collected in March 2021. We conducted multivariate regression models adjusting for age, race/ethnicity, gender, sexual identity, income, and disability. One in four Californians (26.1%) experienced everyday discrimination in public spaces, due most often to race/ethnicity and gender. We found that everyday discrimination was significantly associated with past year physical violence (single form Adjusted Odds Ratio [AOR] 5.0, 95% CI 2.5-10.3; multiple forms AOR 2.6, 95% CI 1.1-5.8), past year sexual violence (multiple forms AOR 2.5, 95% CI 1.4-4.4), and mental health symptoms (e.g., severe symptoms, multiple forms AOR 3.3, 95% CI 1.6-6.7). Major experiences of race-based discrimination (reported by 10.0% of Californians) were associated with past year sexual violence (AOR 2.0, 95% CI 1.1-3.8) and severe mental health symptoms (AOR 2.7, 95% CI 1.2-6.2). Non-race-based major discrimination (reported by 23.9% of Californians) was also associated with violence and mental health outcomes Everyday discrimination, more than major experiences of discrimination, was associated with higher risk for violence and poor mental health outcomes during the pandemic. Non-race-based forms of major discrimination independently were also associated with these negative outcomes. Findings indicate that efforts to reduce and ultimately eliminate discrimination should be a focus of public health and COVID-19 rebuilding efforts., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Sedentary behavior (SB) is prevalent after abdominal cancer surgery, and interventions targeting perioperative SB could improve postoperative recovery and outcomes. We conducted a pilot study to evaluate the feasibility and preliminary effects of a real-time mobile intervention that detects and disrupts prolonged SB before and after cancer surgery, relative to a monitoring-only control condition., Objective: Our aim was to evaluate the feasibility and preliminary effects of a perioperative SB intervention on objective activity behavior, patient-reported quality of life and symptoms, and 30-day readmissions., Methods: Patients scheduled for surgery for metastatic gastrointestinal cancer (n=26) were enrolled and randomized to receive either the SB intervention or activity monitoring only. Both groups used a Fitbit smartwatch and companion smartphone app to rate daily symptoms and collect continuous objective activity behavior data starting from at least 10 days before surgery through 30 days post discharge. Participants in the intervention group also received prompts to walk after any SB bout that exceeded a prespecified threshold, with less frequent prompts on days that patients reported more severe symptoms. Participants completed end-of-study ratings of acceptability, and we also examined adherence to assessments and to walking prompts. In addition, we examined effects of the intervention on objective SB and step counts, patient-reported quality of life and depressive and physical symptoms, as well as readmissions., Results: Accrual (74%), retention (88%), and acceptability ratings (mean overall satisfaction 88.5/100, SD 9.1) were relatively high. However, adherence to assessments and engagement with the SB intervention decreased significantly after surgery and did not recover to preoperative levels after postoperative discharge. All participants exhibited significant increases in SB and symptoms and decreases in steps and quality of life after surgery, and participants randomized to the SB intervention unexpectedly had longer maximum SB bouts relative to the control group. No significant benefits of the intervention with regard to activity, quality of life, symptoms, or readmission were observed., Conclusions: Perioperative patients with metastatic gastrointestinal cancer were interested in a real-time SB intervention and rated the intervention as highly acceptable, but engagement with the intervention and with daily symptom and activity monitoring decreased significantly after surgery. There were no significant effects of the intervention on step counts, patient-reported quality of life or symptoms, and postoperative readmissions, and there was an apparent adverse effect on maximum SB. Results highlight the need for additional work to modify the intervention to make reducing SB and engaging with mobile health technology after abdominal cancer surgery more feasible and beneficial., Trial Registration: ClinicalTrials.gov NCT03211806; https://tinyurl.com/3napwkkt., (©Carissa A Low, Michaela Danko, Krina C Durica, Julio Vega, Meng Li, Abhineeth Reddy Kunta, Raghu Mulukutla, Yiyi Ren, Susan M Sereika, David L Bartlett, Dana H Bovbjerg, Anind K Dey, John M Jakicic. Originally published in JMIR Perioperative Medicine (http://periop.jmir.org), 12.01.2023.)

Polymeric nanoparticles (NPs) are extremely promising for theranostic applications. However, their interest depends largely on their interactions with immune system, including the capacity to activate inflammation after their capture by macrophages. In the present study, we generated monodisperse poly(ethyl methacrylate) (PEMA) NPs loaded with hydrophobic photoluminescent gold nanoclusters (Au NCs) emitting in the NIR-II optical windows and studied their interaction in vitro with J774.1A macrophages. PEMA NPs showed an efficient time and dose dependent cellular uptake with up to 70 % of macrophages labelled in 24 h without detectable cell death. Interestingly, PEMA and Au-PEMA NPs induced an anti-inflammatory response and a strong down-regulation of nitric oxide level on lipopolysacharides (LPS) activated macrophages, but without influence on the levels of reactive oxygen species (ROS). These polymeric NPs may thus present a potential interest for the treatment of inflammatory diseases., 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 B.V. All rights reserved.)

Background: Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown., Methods: Leveraging two large U.S.-based registries, the National Inpatient Sample (NIS) and the Food and Drug Administration Adverse Event Reporting System (FAERS) databases, we assessed the incidence, factors, and outcomes of hypertensive events among BC patients from 2007 to 2015. Differences in baseline characteristics, hypertension-related discharges, and complications were examined over time. Further, we performed a disproportionality analysis using reporting-odds-ratios (ROR) to determine the association between individual BC drugs and hypertensive events. Utilizing an ROR cutoff of >1.0, we quantified associations by drug-class, and individual drugs with the likelihood of excess hypertension., Results: Overall, there were 5,464,401 BC-admissions, of which 46,989 (0.8%) presented with hypertension. Hypertensive BC patients were older, and saw initially increased in-hospital mortality, which equilibrated over time. The mean incidence of hypertension-related admissions was 732 per 100,000 among BC patients, versus 96 per 100,000 among non-cancer patients (RR 7.71, p < 0.001). Moreover, in FAERS, those with hypertension versus other BC-treatment side-effects were more frequently hospitalized (40.1% vs. 36.7%, p < 0.001), and were most commonly associated with chemotherapy (45.9%). Outside of Eribulin (ROR 3.36; 95% CI 1.37-8.22), no specific drug was associated with a higher reporting of hypertension; however, collectively BC drugs were associated with a higher odds of hypertension (ROR 1.66; 95% CI 1.09-2.53)., Conclusions: BC therapies are associated with a substantial increase in limiting hypertension., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

This study evaluated the association between impulsivity and linkage to HIV care among Russians living with HIV recruited from an inpatient narcology hospital. Linking Infectious and Narcology Care (LINC) study participants who completed the Barratt Impulsiveness Scale (BIS) were included in these analyses. The primary independent variable was impulsivity score which was categorized as high impulsivity (BIS score > 71) vs. low impulsivity (BIS score < = 71). The primary outcome, linkage to care post recruitment, was defined as one or more HIV medical care visits at 12-month follow-up. Multiple logistic regression models were used to evaluate the association between high impulsivity and linkage to HIV care controlling for potential confounders. Participants (N = 227) were adults with a mean age of 34 years (SD = 5), and the majority were male (74%). We did not detect a significant association between impulsivity and linkage to HIV care after adjusting for respondents' age, gender, CD4 cell count, and depression score. We also found that substance use and hazardous drinking did not appear to confound the relationship. Although our study was unable to detect an association between impulsivity and linkage to HIV care, it may provide direction for future research exploring the associations between impulsivity and HIV care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pathways to low healthcare utilisation under the COVID-19 pandemic are not well understood. This study aims to understand women's concerns about the health system's priorities and their increased burden of domestic responsibilities during COVID-19 as predictors of delayed or non-receipt of needed care for themselves or their children., Methods: We surveyed married women in rural Maharashtra, India (N = 1021) on their health and economic concerns between Feb 1 and March 26, 2021. This study period was when India emerged from the first wave of the pandemic, which had severely impacted the health systems, and before the second-even more devastating wave had started. We captured if women were concerned about access to non-COVID health services due to healthcare being directed solely to COVID-19) (exposure 1) and whether their domestic responsibilities increased during the pandemic (exposure 2). Our outcomes included women's reports on whether they delayed healthcare seeking (secondary outcome and mediator) and whether they received healthcare for themselves or their children when needed (primary outcome). We conducted adjusted regression models on our predictor variables with each outcome and assessed the mediation effects of delayed healthcare seeking for each of the exposure variables., Findings: We found that women who were concerned that healthcare was directed solely towards COVID-19 were more likely not to receive healthcare when needed (Adjusted Risk Ratio [ARR] = 1.49, 95% CI = 1.14, 1.95). We also found that women whose domestic care burden increased under the pandemic were more likely to delay healthcare seeking (ARR = 1.84, 95% CI = 1.05, 3.21). Delayed healthcare seeking mediated the associations between each of our exposure variables with our outcome variable, non-receipt of needed healthcare., Interpretation: Our findings suggested that women's perceptions of healthcare systems and their domestic labour burdens affected healthcare seeking during the pandemic in India, even before the second wave of COVID-19 incapacitated the health system. Support for women and health systems is needed to ensure healthcare uptake during crises., Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA (grant numbers: R01HD084453- 01A1 and RO1HD61115); Department of Biotechnology, Government of India (grant #BT/IN/US/01/BD/2010); the EMERGE project (Bill and Melinda Gates Foundation Grants: OPP1163682 and INV018007; PI Anita Raj), and Bill and Melinda Gates Foundation Grant number INV-002967., Competing Interests: All authors declare that they have no conflicts of interest., (© 2022 The Author(s).)