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N-Nitrosamines (NAs) pose a threat to food safety due to their carcinogenic and mutagenic properties. In this study, we developed and validated a QuEChERS-based LC-MS/MS method for the simultaneous analysis of 11 NAs in 74 processed fish meat, processed meat, and salted fish products. Sample preparation was optimized by screening two versions of QuEChERS buffer, four extraction methods, and eight purification methods. The optimal analytical approach was validated for three product categories in terms of linearity, matrix effects, accuracy, and precision. Satisfactory precision and accuracy were demonstrated, with relative recoveries of 70-120% for the 11 NAs. The limits of detection for fish meat, processed meat, and salted fish products were 0.12-7.50, 0.12-4.14, and 0.10-7.81 ng·g -1 , respectively. Among the 11 NAs, nine were detected in all 74 samples. This methodology could be applied to monitor NA levels to ensure the safety and quality of food products., 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. Published by Elsevier Ltd.)

Background: Glyceryl trinitrate (GTN), also known as nitroglycerin, is predominantly recognized as a vasodilator for ischemic heart disease, and its potential neuroprotective properties in acute ischemic stroke remain under exploration. We sought to discover the therapeutic advantages and mechanisms of post-recanalization GTN administration in acute ischemic stroke., Methods and Results: A total of 118 male Sprague-Dawley rats were divided into groups: sham, transient/permanent middle cerebral artery occlusion (MCAO) with or without GTN treatment, and transient/permanent MCAO treated with both GTN and KT5823, an inhibitor of PKG. Acute ischemic stroke was induced by transient MCAO for 2 hours followed by 6 or 24 hours of reperfusion and permanent MCAO (28-hour MCAO without reperfusion). The study assessed infarct volumes, neurological deficits, glucose metabolism metrics, NO, and cGMP levels via ELISA. mRNA and protein expression of key molecules of hyperglycolysis, gluconeogenesis, endoplasmic reticulum stress as well as signaling molecules (PKG, AMPK) were conducted via reverse transcription polymerase chain reaction and Western blotting, and cell death was assessed with TUNEL and ELISA. GTN significantly reduced cerebral infarct volumes, neurological deficits, and cell death only after transient MCAO. GTN led to a significant reduction in the expression of NO and cGMP levels, key glucose metabolism, endoplasmic reticulum stress-related genes and proteins, and phosphorylated AMPK while boosting PKG expression, in transient MCAO but not permanent MCAO. The GTN-induced reduction in glucose metabolites, lactate, and reactive oxygen species was exclusive to transient MCAO groups. Coadministration of GTN and PKG inhibitors reversed the observed GTN benefits., Conclusions: GTN induced neuroprotection in transient MCAO by improving glucose metabolism and potentially controlling endoplasmic reticulum stress through the NO-cGMP-PKG signaling cascade to inhibit AMPK phosphorylation.

Studying fundamental aspects of eukaryotic biology through genetic information can face numerous challenges, including contamination and intricate biotic interactions, which are particularly pronounced when working with uncultured eukaryotes. However, existing tools for predicting open reading frames (ORFs) from transcriptomes are limited in these scenarios. Here we introduce Transcript Identification and Selection (TIdeS), a framework designed to address these non-trivial challenges associated with current 'omics approaches. Using transcriptomes from 32 taxa, representing the breadth of eukaryotic diversity, TIdeS outperforms most conventional ORF-prediction methods (i.e., TransDecoder), identifying a greater proportion of complete and in-frame ORFs. Additionally, TIdeS accurately classifies ORFs using minimal input data, even in the presence of 'heavy contamination'. This built-in flexibility extends to previously unexplored biological interactions, offering a robust single-stop solution for precise ORF predictions and subsequent decontamination. Beyond applications in phylogenomic-based studies, TIdeS provides a robust means to explore biotic interactions in eukaryotes (e.g., host-symbiont, prey-predator) and for reproducible dataset curation from transcriptomes and genomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Background: During the COVID-19 pandemic, the provision of quality care for behavioral and psychological symptoms in older adults with dementia may have been impeded due to physical distancing and infection control measures. Of particular concern is whether psychotropic medication use has increased despite its limited efficacy and adverse effects. This systematic review described the trajectory of psychotropic use for older adults with dementia across various settings, from community living to healthcare settings during the pandemic. Also, psychotropic use was explored in relation to patients, caregivers, and environment-related factors along with the occurrence of the pandemic., Methods: We conducted a comprehensive search across five databases: Embase, PubMed, PsycINFO, CINAHL, and Cochrane Library. Methodological quality was assessed using Joanna Briggs Institute Critical Appraisal tools. A random-effects model was used to estimate the pooled risk ratios (RRs) of psychotropic use in older adults with dementia, comparing the pandemic period to the pre-pandemic period. Subgroup analyses based on the class of psychotropics and sensitivity analyses also were conducted. A funnel plot and Egger's regression test were used to detect potential publication bias., Results: Of the 3,123 screened articles, 15 studies were included in this systematic review, with 10 of them being part of the meta-analysis. Our meta-analysis yielded an RR of 1.16 (95% CI = 1.05-1.26) for overall psychotropic medication use. Further subgroup analysis based on the type of psychotropic medication revealed a significantly greater prevalence in the use of antipsychotics (RR = 1.19, 95% CI = 1.08-1.30). However, no significant differences were observed in the use of anxiolytics and/or hypnotics (including benzodiazepines), antidepressants, and mood stabilizers. Among psychotropics, some studies on antipsychotic use additionally explored patients, caregivers, and environmental-related factors during the pandemic., Conclusions: The review indicates a higher risk of psychotropic use, especially antipsychotics, during the pandemic. Nonetheless, underlying reasons for the increased psychotropic use are not fully available from the reviewed studies. Therefore, further research is needed to identify the factors driving psychotropic use during the pandemic and facilitate the development of quality improvement interventions that can be implemented to minimize inappropriate psychotropic prescribing in future pandemics., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Remote learning during the COVID-19 pandemic caused behavioural changes such as increased screen time and decreased outdoor time. This study aimed to investigate myopia progression in children during the COVID-19 pandemic., Methods: This was a retrospective observational study performed among 2064 patients ages 2-17 with cycloplegic refractions in the months of January 2019-March 2021 at a tertiary children's hospital. Exclusion criteria were a medical history of relevant connective tissue diseases, myopia control treatment, pseudophakia and aphakia., Results: The overall cohort (n=2064) had a mean spherical equivalent (SE) of 0.12±3.70 D in 2019, -0.07±3.95 D in 2020 and -0.49±3.85 D in 2021. The change in mean SE (0.42 D) from 2020 to 2021 was 2.2 times greater than the change (0.19 D) from 2019 to 2020 at baseline. In the cohort of return patients, there was a significant difference in myopic shift between years (F-ratio=14.4, p<0.00001), and a significant change from 2020 to 2021 (p=0.00008) but not from 2019 to 2020. When observing the prevalence of myopia grouped by age, 8-year-old and 17-year-old patients had the greatest increase compared with baseline. When grouped by refractive error, low myopia children (-0.5 D to -3.00 D) displayed the greatest change in mean SE 2020-2021., Conclusions: There was a substantial increase in myopia progression for children in the Chicagoland area after the period of COVID-19 changes. The behavioural changes of home confinement and online learning during the pandemic may explain these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

With the continued increase in the number of pieces of diagnostic medical radiography equipment being used, radiation shielding in radiology departments is becoming increasingly important. Lead is the most commonly used material for radiation protection; however, there are numerous disadvantages associated with the use of lead, including environmental hazards and harm to the human body. Alternative shielding materials that can be used as replacements include barium sulfate, tungsten, or bismuth. Among alternative materials, barium sulfate appears to be the most cost-effective and easiest to process. In the present study, before constructing shielding barriers, a barrier thickness program for lead-free barrier materials based on National Council on Radiation Protection and Measurements (NCRP) Report No. 147 was used to determine the appropriate barrier thickness. The required thickness for lead-free boards for each type of diagnostic radiography room was calculated based on a tertiary general hospital in the Republic of Korea., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Crystal structure and morphology dictate the mechanical, thermal, and degradation properties of poly l-lactide (PLLA), the structural polymer of the first clinically approved bioresorbable vascular scaffolds (BVS). New experimental methods are developed to reveal the underlying mechanisms governing structure formation during the crimping step of the BVS manufacturing process. Our research specifically examines the "U-bends" - the region where the curvature is highest and stress is maximised during crimping, which can potentially lead to failure of the device with dramatic consequences on patient life. A custom-made crimping rig operated at a synchrotron beamline enabled collection of wide- and small-angle X-ray scattering (WAXS/SAXS) to probe local variations of the polymer morphology as a function of position in the crest of multiple U-bends with 5 μm resolution in situ after crimping and expansion. Additionally, polarised light microscopy (PLM) images of these deformed U-bends revealed areas with varying stress distribution developed during crimping and expansion. These variations were dependant on the initial biaxial stretching processing step. The integrated X-ray scattering-microscopy approach offered a comprehensive work-flow for uncovering the intricate relationship between processing conditions and the corresponding spatially-resolved semicrystalline morphology of a BVS. STATEMENT OF SIGNIFICANCE: This research introduces a new method for gaining critical insights into the structural changes that occur during the manufacturing process of bioresorbable vascular scaffolds (BVS). The crimping and expansion of poly l-lactide (PLLA) - the structural material of BVS - are sequential manufacturing steps characterised by highly non-linear deformations at temperature conditions that remain unexplored. By utilising synchrotron X-ray scattering techniques alongside polarised light microscopy, we have developed new experimental methods to uncover the mechanisms governing structure formation during processing. This innovative approach not only deepens our understanding of the relationship between processing conditions and polymer morphology but also establishes the foundation for real-time observation methods during crimping and expansion. By improving the design and performance of BVS, this study has the potential to advance cardiovascular treatments and improve patient safety, making it highly relevant and impactful to both scientific research and clinical applications., 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. Published by Elsevier Ltd.)

Traditional phase I dose finding cancer clinical trial designs aim to determine the maximum tolerated dose (MTD) of the investigational cytotoxic agent based on a single toxicity outcome, assuming a monotone dose-response relationship. However, this assumption might not always hold for newly emerging therapies such as immuno-oncology therapies and molecularly targeted therapies, making conventional dose finding trial designs based on toxicity no longer appropriate. To tackle this issue, numerous early-phase dose finding clinical trial designs have been developed to identify the optimal biological dose (OBD), which takes both toxicity and efficacy outcomes into account. In this article, we review the current model-assisted dose finding designs, BOIN-ET, BOIN12, UBI, TEPI-2, PRINTE, STEIN, and uTPI to identify the OBD and compare their operating characteristics. Extensive simulation studies and a case study using a CAR T-cell therapy phase I trial have been conducted to compare the performance of the aforementioned designs under different possible dose-response relationship scenarios. The simulation results demonstrate that the performance of different designs varies depending on the particular dose-response relationship and the specific metric considered. Based on our simulation results and practical considerations, STEIN, PRINTE, and BOIN12 outperform the other designs from different perspectives.

Delivering nanoparticles to deep tumor tissues while maintaining high therapeutic efficacy and minimizing damage to surrounding tissues has long posed a significant challenge. To address this, we have developed innovative self-propelling bowl-shaped nanomotors MSLA@GOx-PDA composed of mesoporous silica loaded with l-arginine and polydopamine, along with glucose oxidase (GOx). These nanomotors facilitate the generation of hydrogen peroxide through GOx-catalyzed glucose oxidation, thereby initiating nitric oxide production from l-arginine. This dual mechanism equips MSLA@GOx-PDA with the robust motility required for deep tumor tissue penetration while depleting essential nutrients necessary for tumor growth, consequently impeding tumor progression. In addition, near-infrared lasers have the significant advantage of being depth-penetrating and non-invasive, allowing real-time fluorescence imaging and guiding dopamine-mediated mild photothermal therapy. Notably, starvation therapy depletes intracellular adenosine triphosphate and inhibits the synthesis of heat shock proteins, thus overcoming the Achilles' heel of mild photothermal therapy and significantly enhancing the efficacy of this therapy with encouraging synergistic anti-tumour effects. Overall, the integration of biochemical and optics strategies in this nanomotor platform represents a significant advancement in deep-tissue tumor therapy. It has substantial clinical translational value and is expected to have a transformative impact on future cancer treatments., 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 Ltd. All rights reserved.)

Background: There are legal protections for nurse researchers at public universities who employ community-based participatory research (CBPR) in research about social or health inequities. Dissemination of CBPR research data by researchers or participants may divulge unjust laws and create an imperative for university involvement., Research Question: What are United States-based legal dissemination protections for CBPR health equity nurse researchers?, Research Design: Three case examples employing CBPR are examined: 1) a mixed methods study with participants reporting illegal discrimination in a municipal initiative about capacity building in community-based organizations serving children; 2) a visual methods study exposing potential clean air law violations in environmental justice research; and 3) a study examining workload violations and illegal discrimination among hotel workers., Participants and Research Context: The cases involved participants from protected social class backgrounds. The research is described with respect to: background, funding, research purpose, and research team; research participants' power and legal vulnerability; dissemination of relevant research information balancing vulnerability and power; research dissemination issues; potential legal issues involved; and laws researchers may use., Ethical Considerations: IRB approval was obtained for the studies. Using a social justice ethical framework, studies highlight actual or potential legal aspects of data dissemination in the context of gathering data about injustice., Findings: Legal protections for research data dissemination, whistleblower protection, research advancement protection, anti-harassment protection, false claims, defamation, and visual data liabilities are described., Conclusion: Knowledge of legal research data dissemination protections is an essential competency for nurse researchers invested in uplifting social justice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Genomic instability disorders are characterized by DNA or chromosomal instability, resulting in various clinical manifestations, including developmental anomalies, immunodeficiency, and increased risk of developing cancers beginning in childhood. Many of these genomic instability disorders also present with exquisite sensitivity to anticancer treatments such as ionizing radiation and chemotherapy, which may further increase the risk of second cancers. In July 2023, the American Association for Cancer Research held the second Childhood Cancer Predisposition Workshop, where multidisciplinary international experts discussed, reviewed, and updated recommendations for children with cancer predisposition syndromes. This article discusses childhood cancer risks and surveillance recommendations for the group of genomic instability disorders with predominantly recessive inheritance, including the DNA repair disorders ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi anemia, xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome, as well as the telomere biology disorders and mosaic variegated aneuploidy. Recognition of children with genomic instability disorders is important in order to make the proper diagnosis, enable genetic counseling, and inform cancer screening, cancer risk reduction, and choice of anticancer therapy., (©2024 American Association for Cancer Research.)

Background: Evidence has indicated that nocturia is a clinical manifestation of adverse health conditions, including cardiovascular diseases and metabolic disorders. However, previous studies are less available for the clinical implication of nocturia on the development of hypertension., Methods: Study participants were 32,420 working-aged Koreans (21,355 men and 11,065 women) who periodically received health checkups. They were categorized into 4 groups by the frequency of nocturia (never, <1, 1-2, and ≥3/week). We used Cox proportional hazards models to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CIs) for incident hypertension (multivariable-adjusted HR [95% CI]) in relation to the frequency of nocturia. Subgroup analysis was conducted by gender and sleep quality (good and poor sleep quality)., Results: In women, nocturia was associated with an increased risk of hypertension, compared with never nocturia (HR [95% CI]; never: reference, <1/week: 1.33 [1.10-1.60], 1-2/week: 1.26 [1.00-1.58], and ≥3/week: 1.34 [1.05-1.72]). This association was not observed in men (HR [95% CI]; never: reference, <1/week: 1.00 [0.93-1.08], 1-2/week: 1.00 [0.88-1.12], and ≥3/week: 1.06 [0.94-1.23]). In subgroup analysis by sleep quality, only women with good sleep quality showed an association between nocturia and the risk of hypertension. However, women with poor sleep quality and men did not show an association between the frequency of nocturia and the risk of hypertension., Conclusions: Nocturia is a potential risk factor for incident hypertension in working-aged women with good sleep quality., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In biological systems, electrons, energy, and information "flow" through the redox modality, and we ask, does biology have redox capacitor capabilities for storing electrons? We describe emerging evidence indicating that biological phenolic/catecholic materials possess such redox capacitor properties. We further describe results that show biomimetic catecholic materials are reversibly redox-active with redox potentials in the midphysiological range and can repeatedly accept electrons (from various reductants), store electrons, and donate electrons (to various oxidants). Importantly, catechol-containing films that are assembled onto electrode surfaces can enhance the flow of electrons, energy, and information. Further, catechol-containing films can serve as redox-based interactive materials capable of actuating biological responses by turning on gene expression from redox-responsive genetic circuits. Looking forward, we envision that the emerging capabilities for measuring dynamic redox processes and reversible redox states will provide new insights into redox biology and will also catalyze new technological opportunities for information processing and energy harvesting.

Ammonia (NH 3 ) is a major cause of odor emissions from swine farms, and exposure to high concentrations of NH 3 in short-term periods has been reported to cause respiratory and systemic disorders in pigs. However, the impact of long-term NH 3 exposure on pig health and productivity remain unknown. This study aimed to assess the impact of long-term NH 3 exposure on growth performance and pathological outcomes in pigs. Pigs were reared in the treatment room [34.8 mg/m 3 NH 3 concentration (50 ppm); TRT group, n = 40] and the control room [5.6 mg/m 3 (8 ppm); CON, n = 40]. The experimental period was 107 days (from weaning piglets to market age). Our findings revealed that long-term NH 3 exposure results in severe respiratory and systemic pathological lesions, including chronic tracheitis, epithelial metaplasia of the trachea, severe interstitial pneumonia, myocarditis, and interstitial nephritis. In addition, the TRT group exhibited reduced productivity, with two deaths, indicating that uncontrolled NH 3 concentrations on pig farms could be linked to a decline in growth performance and even death. Transcriptomic analysis revealed significant changes in immune and inflammatory pathways in lung from TRT pigs, including dysregulated cytokine signaling and incomplete inflammatory responses. The enrichment of DEGs in pathways, such as Cytokine-cytokine receptor interaction, JAK-STAT, and Toll-like receptor signaling, indicated chronic NH 3 exposure disrupted immune homeostasis, contributing to chronic inflammation and impaired tissue repair. In conclusion, this study provides valuable insights into the detrimental effects of NH 3 exposure on pig health and productivity under farm conditions., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Clonal hematopoiesis (CH) increases inflammasome-linked atherosclerosis but the mechanisms by which CH mutant cells transmit inflammatory signals to non-mutant cells are largely unknown. To address this question we transplanted 1.5% Jak2VF bone marrow (BM) cells with 98.5% WT BM cells into hyperlipidemic Ldlr-/- mice. Low allele burden (LAB) mice showed accelerated atherosclerosis with increased features of plaque instability, decreased levels of macrophage phagocytic receptors MERTK and TREM2, and increased neutrophil extracellular traps (NETs). These changes were reversed when Jak2VF BM was transplanted with Il1r1-/- BM. LAB mice with non-cleavable MERTK in WT BM showed improvements in necrotic core and fibrous cap formation and reduced NETs. An agonistic TREM2 antibody (4D9) markedly increased fibrous caps in both control and LAB mice eliminating the difference between groups. Mechanistically, 4D9 increased TREM2+PDGFB+ macrophages and PDGF receptor-α positive fibroblast-like cells in the cap region. TREM2 and PDGFB mRNA levels were positively correlated in human carotid plaques and co-expressed in macrophages. In summary, low frequency Jak2VF mutations promote atherosclerosis via IL-1 signaling from Jak2VF to WT macrophages and neutrophils promoting cleavage of phagocytic receptors and features of plaque instability. Therapeutic approaches that stabilize MERTK or TREM2 could promote plaque stabilization especially in CH- and inflammasome-driven atherosclerosis.

Background: The US faces a maternal health crisis and struggles to deliver recommended postpartum care. In some populations, less than half of mothers attend a postpartum visit., Objective: To determine if a two-generation (Two-Gen) model of interdisciplinary, postpartum primary care was associated with increased visit attendance for postpartum care, primary care, and behavioral health., Design: Retrospective study of care delivered at a single, urban, academic, safety-net medical center between 2020 and 2023., Participants: Mothers who received postpartum care in Two-Gen and a comparison group who received usual postpartum care., Main Measures: Adjusted logistic regression to estimate the effect of Two-Gen participation on the odds of attending an early (birth-to-3 weeks) postpartum visit, later (4-to-12 weeks) postpartum visit, OB/GYN visit, and primary care visit., Key Results: A total of 247 mothers (98 Two-Gen and 149 usual care) were included for analysis. Most identified as Non-Hispanic Black (55%) or Hispanic (34%) and had Medicaid insurance (74%). On average, Two-Gen mothers were younger and more likely to be primiparous. Compared to usual care, Two-Gen mothers had similar rates of early postpartum visits (79% vs 64%; adjusted odds ratio (aOR) 1.70; 95% confidence interval (CI) 0.92-3.14) and were significantly more likely to have a later postpartum visit (92% vs 79%; aOR 2.46; 95%CI 1.06-5.74) in adjusted analyses. Almost all Two-Gen mothers (97%) had a visit with a primary care doctor in the first postpartum year, compared to 19% of mothers receiving usual care (aOR 12.95; 95%CI 6.80-24.68). Of those with behavioral health diagnoses, Two-Gen mothers had higher rates of psychiatrist visits than usual care mothers (49% vs 13%; p = 0.001)., Conclusions: Two-Gen clinic participation was associated with high rates of timely postpartum care in a group of predominantly young, publicly insured, racial, and ethnic minority mothers and compared favorably to usual care across multiple metrics, notably utilization of primary and behavioral health care., Competing Interests: Declarations: Conflict of Interest: The authors declare that they do not have a conflict of interest. Ethics Approval and Consent to Participate: All experimental protocols were approved by the University of Illinois at Chicago Institutional Review Board (protocol # 2022–1621) with a waiver of informed consent as a review of routine clinical care. All methods were carried out in accordance with relevant guidelines and regulations. Disclaimer: The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement, by HRSA/HHS, or the U.S. Government., (© 2024. The Author(s).)

Introduction: Little is known about how pharmacists' attitudes and stigma toward naloxone and Medication for opioid use disorder (MOUD) influence effective linkage to treatment. We examine the psychometrics of a new Pharmacist Opioid Use Disorder Perceptions Questionnaire (P-OUDP-Q), a multidimensional measure to examine pharmacists' stigma and perceptions related to MOUD in the New York State (NYS) site of the HEALing Communities Study., Methods: The study recruited a sample of 324 pharmacists from 16 counties in NYS between January and June 2022. A 74-item questionnaire assessed pharmacists' familiarity with opioid-related medications, protocols, policies and attitudes regarding their role, confidence, and beliefs centered around delivery of MOUD and naloxone in the community. Exploratory factor analysis assessed individual and community-level factors associated with four underlying constructs. Factor scores were compared across the demographic predictors. Variables factor loadings <0.4 were eliminated from the factor analysis and the process was reiterated., Results: Eighty-six percent (n = 280) of the pharmacists were white. A little over half, 57 % (n = 186), were female, 35 % (n = 113) were 30-35 years old. The mean number of years practicing (SD) was 18 (SD: 13). Exploratory factor analysis identified four underlying constructs: (1) practice confidence, (2) practice familiarity, (3) practice attitudes, and (4) methadone attitudes. Statistically significant (p < .05) mean factor scale score differences by race were observed for practice familiarity (white reporting higher than non-white); by pharmacy size for practice familiarity (across all groups; non-significant Tukey post-hoc) and practice attitudes (hospital/clinic greater than big chain pharmacies); by gender (males greater than females) for practice familiarity and methadone attitudes; by poverty quartile for practice attitudes (lowest less than highest quartile); and urban versus rural pharmacist county setting for practice familiarity (rural greater than urban)., Conclusions: Findings show the P-OUDP-Q is a concise measure of pharmacists' perceptions of their role in dispensing MOUD and naloxone, including distinct "stigma" dimensions, which is valuable for use with pharmacists in communities highly impacted by the opioid epidemic. The development and validation of a reliable measure to assess pharmacists' perceptions of stigma and barriers represents a valuable contribution to the field, to inform the design/implementation of targeted interventions and support systems., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cleft repair remains a contentious issue in craniofacial surgery, especially regarding the optimal timing and techniques. This study aims to present our institutions' current protocol for cleft lip and palate repair, including alveolar bone grafting (ABG)., Methods: A total of 17 patients (20 clefts) treated with the latest protocol from 2016 to 2023 were evaluated. Demographic and clinical data were obtained from electronic charts. The protocol includes lip repair at 3 months, soft palate repair at 1 year, and hard palate closure with concurrent ABG at 2 years., Results: Mean graft height and thickness scores were 2.3 and 2.2, respectively. Three clefts showed scores marginally below the threshold for thickness, potentially requiring regrafting. Malocclusion was minimal with no significant crossbites or velopharyngeal insufficiency., Conclusions: Our modified protocol, emphasizing early hard palate closure with ABG, yields satisfactory outcomes in terms of graft height and thickness. Although long-term follow-up is warranted, our approach seems safe and efficient, potentially improving outcomes compared with traditional methods., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The human interleukin-1 receptor I (IL-1R1) is a cytokine receptor recognized by interleukin 1β (IL-1β), among other cytokines. Over activation of IL-1R1 has been implicated in various inflammatory conditions. This research aims to identify small-molecule inhibitors targeting the hIL1R1/IL1β interaction, employing a multi-task transfer learning approach for quantitative structure-activity relationship (QSAR) modelling. A comprehensive bioactivity dataset from functionally related proteins was utilised to build a robust ensemble machine learning model for predicting IC 50 values against the target protein. Despite the availability of antibody-based therapies, the absence of orally available small-molecule inhibitors necessitates their development. By combining model predictions with docking and simulation approaches, the interleukin-1 receptor inhibitor (IRI-1) emerged as a lead compound. It potently inhibited human IL1-R1 with micromolar activity in THP-1 and Saos-2 cells and demonstrated good biocompatibility. Western blot analysis revealed that IRI-1 inhibits IL-1β-mediated phosphorylation of IL1-R1, JNK, IRAK-4, and ERK in THP-1 cells. Furthermore, molecular dynamics simulations confirmed the structural stability of the protein-ligand complexes. This study highlights the effectiveness of multi-task transfer learning approaches for building robust QSAR models against novel proteins or those with limited bioactivity data, such as hIL-1β/IL-1R1 protein., 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.)

A PHD (prolyl hydroxylase) inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), is a drug that can artificially promote tissue regeneration by enhancing metabolic activity through the upregulation of hypoxia inducible factor 1 subunit alpha (Hif-1α) under normoxic conditions. This study presents a novel design methodology for a drug delivery system to maximize the regenerative effect of 1,4-DPCA. Specifically, by encapsulating 1,4-DPCA in polydopamine (PDA) that generates reactive oxygen species (ROS), the combined effects of Hif-1α upregulation and the induction of cellular antioxidant defense mechanisms by localized ROS can significantly enhance tissue regeneration. The study confirmed that each material (PDA and 1,4-DPCA) triggers a positive synergistic effect on the regenerative mechanisms. As a result, the use of a PDA drug delivery system loaded with 1,4-DPCA showed approximately six times greater bone regeneration compared to the control (no treatment) in a mouse calvarial defect model.

Calcific aortic valve disease (CAVD) is a considerable health burden with a lack of effective therapeutic options. There is an urgent need to develop interventions that inhibit the osteogenic transformation of valvular interstitial cells (VICs) and delay the calcification process. Niclosamide, an FDA-approved anti-helminthic drug, has emerged as a promising candidate that demonstrates a negative regulatory effect on porcine VICs calcification. However, its molecular mechanism in human VICs (hVICs) remains to be investigated. In this study, high-resolution mass spectrometry-based proteomics and phosphoproteomics were employed, and 8373 proteins and 3697 phosphosites were identified in hVICs treated with a pro-calcifying medium and niclosamide. The quantitative proteomic and phosphoproteomic analysis resulted in the identification of calcification markers and osteogenesis-associated proteins. Bioinformatic analysis of the protein-protein interaction network and affected kinase prediction revealed that the AMPK/mTOR/p70S6K signaling cascade was altered upon calcific induction and niclosamide treatment. Further validation indicated that niclosamide inhibited the calcification of hVICs by targeting the mammalian target of the rapamycin (mTOR) signaling pathway. This study provides the first evidence that niclosamide could prevent osteoblastic differentiation in hVICs partially through the inhibition of the AMPK/mTOR/p70S6k signaling pathway, thereby mitigating hVICs calcification. These findings present a foundation for potential therapeutic strategies to impede the progression of CAVD and provide valuable insights into the pharmacological effects of niclosamide on human VICs., 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 Inc. All rights reserved.)

Background: Prioritization strategy during gait significantly influences gait performance and successful gait relies on interactions between cognitive and motor functions. This study aimed to examine the within- and between-network connectivities of cognitive and motor networks associated with dual-task priority during gait. Methods: Twenty-nine healthy individuals (66.86 ± 8.53 years) underwent the timed-up-and-go (TUG) test alone, TUG with a cognitive task, and the cognitive task alone. The cognitive task involved sequentially subtracting three from a random number between 50 and 100. The resting-state functional magnetic resonance imaging was acquired on the same day. Using independent component analysis, the dorsal attention network (DAN), frontoparietal network (FPN), primary motor network (PM), and lateral motor network were assessed. The participants were divided into cognitive and motor priority groups based on the modified attention allocation index (mAAI). Group comparisons of within- and between-network connectivity were conducted using permutation tests. Additionally, correlation analysis was employed to investigate the association between-network connectivity and task priority. Results: The cognitive priority group showed cognitive dual-task facilitation. In comparison to the motor priority group, they also showed comparable motor dual-task costs and lower combined dual-task costs. They exhibited increased within-network connectivity in the left FPN and enhanced between-network connectivity between the right FPN and both the DAN and PM. These between-network connectivities were negatively correlated with mAAI scores. Conclusion: The results suggest distinct neural mechanisms across cognitive and motor networks based on individuals' dual-task strategies. This may have implications for understanding gait performance in complex contexts.

Photodynamic therapy (PDT) - which combines light, oxygen and photosensitizers (PS) to generate reactive oxygen species - has emerged as an effective approach for targeted ablation of pathogenic cells with reduced risk of inducing resistance. Some organic PS are now being applied for PDT in the clinic or undergoing evaluation in clinical trials. A limitation of the first-generation organic PS was their potential off-target toxicity. This shortcoming prompted the design of constructs that can be activated by the presence of specific biomolecules - from small biomolecules to large enzymes - in the target cells. Here, we review advances in the design and synthesis of activatable organic PS and their contribution to PDT in the past decade. Important areas of research include novel synthetic methodologies to engineer smart PS with tuneable singlet oxygen generation, their integration into larger constructs such as bioconjugates, and finally, representative examples of their translational potential as antimicrobial and anticancer therapies., (© 2024. Springer Nature Limited.)

The incorporation of photoresponsive groups into porous materials is attractive as it offers potential advantages in controlling the pore size and selectivity to guest molecules. A combination of computational modeling and experiment resulted in the synthesis of two azobenzene-derived organic cages based on building blocks identified in a computational screen. Both cages incorporate three azobenzene moieties, and are therefore capable of 3-fold isomerization, using either ditopic or tetratopic aldehydes containing diazene functionality. The ditopic aldehyde forms a Tri 2 Di 3 cage via a 6-fold imine condensation and the tritopic aldehyde forms a Tet 3 Di 6 cage via a 12-fold imine condensation. The relative energies and corresponding intrinsic cavities of each isomeric state were computed, and the photoswitching behavior of both cages was studied by UV-Vis and 1 H NMR spectroscopy, including a detailed kinetic analysis of the thermal isomerization for each of the EEZ , EZZ and ZZZ metastable isomers of the Tet 3 Di 6 cage. Both cages underwent photoisomerization, where a photostationary state of up to 77% of the cis -isomer and overall thermal half-life of 110 h was identified for the Tet 3 Di 6 species. Overall, this work demonstrates the potential of computational modeling to inform the design of photoresponsive materials and highlights the contrasting effects on the photoswitching properties of the azobenzene moieties on incorporation into the different cage species.

Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8 + T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection., Competing Interests: Declaration of interests A.-C.V. has a financial interest in 10X Genomics. The company designs and manufactures gene-sequencing technology for use in research, and such technology is being used in this research. A.-C.V.’s interests were reviewed by The Massachusetts General Hospital and Mass General Brigham in accordance with their institutional policies. J.R.H. consults for CJ CheilJedang and Interon Laboratories. A.G.E. consults for Mirvie, Inc. outside of this work and receives research funding from Merck Pharmaceuticals outside of this work. K.J.G. has served as a consultant for BillionToOne, Aetion, Roche, and Janssen Global Services outside of this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background Context: Lumbar decompression and short-segment lumbar fusion are standard procedures for short-segment lumbar canal stenosis, even in patients with moderate Cobb angles. Adult degenerative scoliosis is diagnosed at a threshold of 10 degrees, and patients with coronal Cobb angles over 30 degrees are recommended for long fusion due to global spinal deformity. However, there is a lack of research on clinical outcomes in patients with moderate coronal deformity, such as Cobb angles between 20 and 30 degrees., Purpose: This study aims to investigate the radiographic and clinical outcome differences between isolated decompression and short-segment interbody fusion for lumbar spinal canal stenosis in patients with moderate coronal deformity., Study Design: A retrospective analysis of a prospectively collected registry PATIENT SAMPLE: Patients with Cobb angle exceeding 20 degrees who underwent 1- or 2- levels of lumbar surgery for lumbar canal stenosis. Patients diagnosed as spinal deformity were excluded., Outcome Measures: Patient-reported outcomes included Oswestry Disability Index (ODI), VAS back, VAS leg, Short Form 12 Physical Component Score (SF-12 PCS) and Mental Component Score (SF-12 MCS), and Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF) at preoperative, 12-week postoperative, and 1-year postoperative timepoints. Preoperative and postoperative spinopelvic alignment was assessed using Cobb angle, pelvic tilt, sacral slope, pelvic incidence, lumbar lordosis and PI minus LL., Methods: A propensity score-matched analysis with the overlap weighting was utilized to investigate patient-reported outcomes at 12-week and 1-year postoperatively between the surgery groups. Spinopelvic alignments were compared between preoperative and 1-year postoperative timepoint using a linear mixed-effect model., Results: Before overlap weighting, the two surgery groups showed significant differences in age and diagnosis. No obvious sagittal malalignment was observed (decompression, 7.4° vs. fusion, 11.5°). After propensity score weighting, the fusion groups exhibited significantly better ODI and VAS back at the 1-year timepoint (ODI: fusion, 16.6 vs. decompression, 28.1, P=0.013; VAS back: fusion, 1.5 ± 2.1 vs. decompression, 3.7 ± 1.9, P<0.001). Radiographic assessment showed that the fusion group achieved better PI minus LL compared to decompression group (15° vs. 10°, P=0.008) CONCLUSION: In patients with degenerative scoliosis and a Cobb angle greater than 20 degrees, short-segment lumbar fusion surgery may result in enhanced improvement for short-segment lumbar pathology compared to isolated decompression., Competing Interests: Conflicts of Interest Sheeraz Qureshi has the following disclosures: AMOpportunities: Other financial or material support; Globus Medical: IP royalties; Paid consultant; Paid presenter or speaker; HS2, LLC: Stock or stock Options; Lifelink.com: Other financial or material support; SpineGuard, Inc.: Paid consultant; Stryker: IP royalties; Paid consultant; Surgalign: Paid consultant; Tissue Differentiation Intelligence: Stock or stock Options; Viseon, Inc.: Paid consultant; Research support; Annals of Translational Medicine: Editorial or governing board; Association of Bone and Joint Surgeons: Board or committee member; Cervical Spine Research Society: Board or committee member; Contemporary Spine Surgery: Editorial or governing board; International Society for the Advancement of Spine Surgery (ISASS) - Program Committee member: Board or committee member; Lumbar Spine Research Society: Board or committee member; Minimally Invasive Spine Study Group: Board or committee member; North American Spine Society: Board or committee member; Simplify Medical, Inc.: Other financial or material support; Society of Minimally Invasive Spine Surgery (SMISS) - Program Committee member: Board or committee member; Spinal Simplicity: Other financial or material support; Clinical Spine Surgery: Editorial or governing board; Hospital Special Surgery Journal: Editorial or governing board; Sravisht Iyer has the following disclosures: Globus Medical: Paid presenter or speaker; Stryker: Paid presenter or speaker; Vertebral Columns/International Society for the Advancement of Spine Surgery (ISASS): Editorial or governing board, (Copyright © 2024. Published by Elsevier Inc.)

Background: Survivors of breast and prostate cancer, especially those that are Black and/or Hispanic, are at high risk for cardiovascular events. Physical activity can reduce the risk of cardiovascular events in cancer survivors, but Black and Hispanic people are less likely to engage in routine physical activity. Concepts from behavioral economics have been used to design scalable, low-touch, gamification interventions that increase physical activity in individuals at high risk for cardiovascular events, but the effectiveness of these strategies in Black and Hispanic survivors of breast and prostate cancer is uncertain., Study Design and Objectives: ALLSTAR (NCT05176756) is a pragmatic, virtual, randomized controlled trial designed to evaluate the effectiveness of a gamification intervention informed by behavioral economic concepts to increase daily physical activity in Black and Hispanic breast and prostate cancer survivors who received cardiotoxic therapies and have additional risk factors for cardiovascular disease. Patients were either referred by their cancer care team or identified by electronic health record searches; contacted by letter, email, text message and/or phone; and complete enrollment and informed consent on the Penn Way to Health online platform. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 1500-3000 steps from baseline, and are randomized 1:1 to control or gamification. Interventions continue for 6 months, with follow-up for an additional 3 months to evaluate the durability of behavior change. The trial has met its enrollment goal of 150 participants, with a primary endpoint of change from baseline in daily steps over the 6-month intervention period. Key secondary endpoints include change from baseline in daily steps over the 3-month post-intervention follow-up period, change in moderate to vigorous physical activity over the intervention and follow-up periods, and change in patient-reported measures of physical function, fatigue, and overall quality of life., Conclusions: ALLSTAR is a virtual, pragmatic randomized clinical trial powered to demonstrate whether gamification is superior to control in increasing physical activity in Black and Hispanic breast and prostate cancer survivors. Its results will have important implications for strategies to promote physical activity in survivors of breast and prostate cancer, specifically among minority populations., Clinical Trial Registration: clinicaltrials.gov; https://clinicaltrials.gov/study/NCT05176756., Competing Interests: Declaration of competing interest Dr. Volpp is a co-owner of a behavioral economics consulting firm, VAL Health, and a member of the Scientific Advisory Board of THRIVE Global. Neither organization has any involvement in this study. All other authors report no relevant conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Aim: Despite the high success rate of endodontic microsurgery (EMS), it is difficult to suggest EMS as a general treatment option considering the difficulty of the procedure. A surgical guide has been proposed to overcome this problem. This study aimed to evaluate the stability of the surgical guide of a new design concept, as well as the accuracy of root resection, and to introduce the manufacturing method of the newly designed surgical guide., Methodology: The experiment was conducted on 59 roots (9 in the maxillary and 50 in the mandibular region) of adult human cadavers. The surgical guide was designed using CAD/CAM design software based on cone-beam computed tomography (CBCT) images and optical scan files. Unlike conventional surgical guides, the surgical guide proposed herein was designed to act as a tooth-bone-supported removable appliance. Two different types of guides were prepared: the osteotomy guide (O guide) for separation of the cortical bone above the root tip with a trephine bur with an outer diameter of 6 mm and the root resection guide (R guide) for resection of the root tip with a trephine bur with an outer diameter of 4 mm. For stability evaluation, the guides were pressed at five predetermined locations after installation and checked for the presence of any movement. For accuracy evaluation, the length at which the root tip was cut was measured and examined by overlapping the preoperative and postoperative CBCT images., Results: Of the 15 R guides, 14 were stably installed without mobility. For the R guide group, the root tip was resected with an average of 3.2 mm, showing better results than the no-guide group with an average of 4.0 mm., Conclusions: The newly designed surgical guide of this study can be applied more stably, enabling root resection to be performed more accurately and simply according to the preoperative plan than when performed without a guide., (© 2024 The Author(s). International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Background: Heart-Smile Training (HST) is an interoceptive compassion-based behavioral intervention that in case reports has been beneficial for depression. Interoception refers to the awareness and regulation of physiological signals from inside the body. Depressed patients often have diminished interoceptive awareness and often experience disconnection from bodily needs and sensations. In addition to interoceptive dysfunction, depression often involves negative self-evaluation and self-critical rumination. HST is a compassion-based meditation training program that explicitly cultivates interoceptive awareness of the heart area. This study aims to investigate the possible neurocardiac mechanisms engaged through HST for depression patients., Methods: We plan to enroll 50 subjects to be randomized into a 4-week HST intervention group and a waitlist group. A battery of psychological questionnaires will be administered at baseline and post-intervention timepoints, and electroencephalography (EEG) will be collected during compassion meditation guided by pre-recorded audio. The primary clinical outcome measures are on the feasibility of the intervention and research procedures, the primary mechanistic outcome measure is the post-intervention change in Heartbeat Evoked Potential (HEP) amplitude. Secondary outcome measures include changes in depression severity and EEG gamma spectral activity. Exploratory outcome measures include effects of HST on skin conductance response, heart rate variability, EEG spectral properties in other frequency bands, as well as a list of psychological questionnaires that measure depression and anxiety symptoms, emotion regulation, mindfulness, interoceptive awareness, self-compassion, gratitude, sleep quality, quality of life and social connectedness., Results: Results not yet available., Conclusion: This is the first study on the feasibility and interoceptive neurocardiac mechanism of HST. Our findings will provide frontier knowledge on the physiological working mechanism of behavioral interventions with an interoception-based meditative approach. https://clinicaltrials.gov/study/NCT05564533., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Misan W. D. Kim is the developer of the Heart Smile Training program and will not be involved in data analyses and interpretation., (© The Author(s) 2024.)

This study investigates a micro light-emitting diode (µLED) pixel circuit using the heterogeneous integration of complementary field-effect transistors (CFETs). The CFETs are fabricated using a semiconductor layer composed of tellurium (Te) and indium-gallium-zinc oxide (IGZO) layers. Te and IGZO layers in the heterostructure IGZO/Te film exhibit hexagonal and amorphous phases, respectively, indicating that each layer maintains independent material characteristics. The fabricated IGZO/Te CFETs exhibit ambipolar behavior with a turn-on voltage of 2.0 V and field-effect mobility of 0.74 and 1.42 cm 2 V -1 s -1 for p-type and n-type channels, respectively. Inverters comprising IGZO/Te CFET and IGZO TFT exhibit inverting behavior. A µLED pixel circuit is designed using IGZO/Te CFETs based on pulse width modulation (PWM). The proposed circuit uses an inverter structure with IGZO/Te and IGZO to control the emission time, suppressing the wavelength shift of µLEDs depending on the µLED current levels. The operation of the proposed pixel circuit is investigated through simulation and measurement of the fabricated circuit. The fabricated µLED pixel circuit successfully exhibits PWM operation, controlling the emission time and luminance. Consequently, IGZO/Te CFETs show promise as devices for high-quality µLED displays., (© 2024 Wiley‐VCH GmbH.)

Chronic hepatitis B (CHB) is a condition that disproportionately affects Asian Americans in the United States. Knowledge of transmission is crucial for CHB patients to practice prevention methods to limit the spread of the hepatitis B virus (HBV), but also live their lives free from unwarranted fears or restrictions. Among Asian CHB patients, several misperceptions about HBV transmission have been identified. This analysis aims to assess the current state of HBV knowledge among a cohort of Korean-American CHB patients. This mixed-methods study includes 363 respondents who completed a survey in either Korean (N = 298) or English (N = 65) at two clinical care settings in Philadelphia (N = 161) and Los Angeles (N = 202); 30 participants also completed in-depth interviews. Knowledge was measured on a 10-point scale, asking patients yes or no transmission questions (n = 10, alpha = 0.87). The average knowledge score was 6.3. In multivariate analyses, older age was associated with lower knowledge (β=-0.25, p < 0.001). More years of formal education (β = 0.09, p = 0.076) and utilizing more sources for health information (β = 0.12, p = 0.023) were both independently associated with higher knowledge scores. Qualitative findings show that misperceptions about transmission through shared food still exist and that provider communication is an important part of knowledge acquisition. These results suggest that despite receiving specialized, culturally concordant medical care for their disease, some Korean-American CHB patients have an inadequate understanding of transmission and that opportunities exist to improve education in this population. Identifying additional factors that influence knowledge acquisition and retention is key to developing culturally effective education interventions for this population., (© 2024. The Author(s).)

Guidelines encouraging social distancing, limited outings, and remote work due to COVID-19 have increased sedentary periods and reduced levels of physical activity. These habits increase the risk of metabolic diseases, obesity, cardiovascular disease, and diabetes mellitus. The World Health Organization recommends muscle-strengthening exercises as well as regular physical activity to promote overall health. This study investigates the effect of a wearable hip exoskeleton on muscle activity and heart rate during anaerobic exercise in 40 healthy adults (mean age of 40.00 ± 11.51 years; n = 20 females). Bot Fit, a wearable hip-type robotic exoskeleton, was developed by Samsung Electronics Co., Ltd. (Suwon, Republic of Korea) to enhance the effects of both aerobic and anaerobic exercise. All study participants performed a fitness exercise protocol, including knee-ups, good mornings, squats, mountain climbs, kick-backs, reverse lunges, and split jacks, with and without a Bot Fit. To evaluate the effect of anaerobic exercise with the Bot Fit, muscle activity and heart rate were measured during fitness exercises with and without a Bot Fit. Measured muscles were the rectus abdominis (RA), erector spinae (ES), rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), tibialis anterior (TA), gastrocnemius medialis (GCM), and gluteus maximus (GM). During anaerobic exercises with the Bot Fit, there was a significant increase in muscle activity compared to exercising without the Bot Fit. Muscle activity increased significantly in the RA, RF, VL, BF and TA muscles during knee-ups; in the ES, BF, and GM during good mornings; in the RF, VL, VM, BF, and GM during squats; in RA, RF, VL, VM, and GM during mountain climbs; in the RA and BF during kick-backs; in the RF, BF, and GCM during reverse lunges; and in the RF and VL during split jacks (p < 0.05). Heart rates showed a statistically significant increase during good mornings, mountain climbs, and reverse lunge exercises while wearing the Bot Fit (p < 0.05). This study demonstrated that anaerobic exercises by healthy adults using a Bot Fit led to enhanced activation of abdominal and lower-limb muscles as well as an improved heart rate, maximizing the effect of anaerobic exercise compared with the same exercise protocol without a Bot Fit. This suggests that use of a Bot Fit can increase the effectiveness of anaerobic exercise in healthy adults., (© 2024. The Author(s).)

The mitochondrial DNA (mtDNA) can trigger immune responses and directly entrap pathogens, but it is not known to encode for active immune factors. The immune system is traditionally thought to be exclusively nuclear-encoded. Here, we report the identification of a mitochondrial-encoded host defense peptide (HDP) that presumably derives from the primordial proto-mitochondrial bacteria. We demonstrate that MOTS-c (mitochondrial open reading frame from the twelve S rRNA type-c) is a mitochondrial-encoded amphipathic and cationic peptide with direct antibacterial and immunomodulatory functions, consistent with the peptide chemistry and functions of known HDPs. MOTS-c targeted E. coli and methicillin-resistant S. aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains. In monocytes, IFNγ, LPS, and differentiation signals each induced the expression of endogenous MOTS-c. Notably, MOTS-c translocated to the nucleus to regulate gene expression during monocyte differentiation and programmed them into macrophages with unique transcriptomic signatures related to antigen presentation and IFN signaling. MOTS-c-programmed macrophages exhibited enhanced bacterial clearance and shifted metabolism. Our findings support MOTS-c as a first-in-class mitochondrial-encoded HDP and indicates that our immune system is not only encoded by the nuclear genome, but also by the co-evolved mitochondrial genome.

Purpose: Over the past decade, significant surges in cancer data of all types have happened. To promote sharing and use of these rich data, the National Cancer Institute's Cancer Research Data Commons (CRDC) was developed as a cloud-based infrastructure that provides a large, comprehensive, and expanding collection of cancer data with tools for analysis. We conducted this scoping review of articles to provide an overview of how CRDC resources are being used by cancer researchers., Methods: A thorough literature search was conducted to identify all relevant publications. We included publications that directly cited CRDC resources to specifically examine the impact and contributions of CRDC by itself. We summarized the distributions and trends of how CRDC components were used by the research community and discussed current research gaps and future opportunities., Results: In terms of CRDC resources used by the research community, encouraging trends in utilization were observed, suggesting that CRDC has become an important building block for fostering a wide range of cancer research. We also noted a few areas where current applications are rather lacking and provided insights on how improvements can be made by CRDC and research community., Conclusion: CRDC, as the foundation of a National Cancer Data Ecosystem, will continue empowering the research community to effectively leverage cancer-related data, uncover novel strategies, and address the needs of patients with cancer, ultimately combatting this disease more effectively.

Background: Depression and anxiety have a complex association with opioid dependence, though their impact on acute postoperative pain is unclear. The present study investigated the impact of depression and anxiety on acute postoperative pain and opioid requirements following deep inferior epigastric perforator (DIEP) flap breast reconstruction., Methods: Patients receiving DIEP flap breast reconstruction were retrospectively identified from 2019 to 2023. Patients were classified into the psychiatric comorbidity (PC) group based on a history of depression or anxiety diagnoses, or the control group. Pain (0-10 Numerical Rating Scale [NRS]) scores and cumulative inpatient opioid requirements (in morphine milli-equivalents [MMEs]) were compared between groups. Linear regression analysis assessed the association of psychiatric comorbidities with pain outcomes., Results: In total, 557 patients were included, of which 11.4% reported a psychiatric history. The PC group was younger (50.0 vs. 52.7 years, p = 0.032) and more frequently reported current marijuana use (15.6% vs. 4.3%, p = 0.001) and former smoking (51.6% vs. 24.5%, p < 0.001). The PC group had higher mean (2.5 vs. 2.0, p < 0.001) and maximum pain scores (8.6 vs. 7.8, p = 0.003) than the control group, which corresponded to higher opioid requirements (256 vs. 223 MMEs, p = 0.041). Psychiatric comorbidities were associated with higher average and maximum pain scores (p < 0.01) while current marijuana use was associated with higher opioid requirements (p = 0.033)., Conclusion: Patients with depression or anxiety comorbidities tended to have greater acute postoperative pain and opioid consumption. Marijuana use was also more prevalent, potentially exacerbating pain outcomes, and risk of opioid dependence. These findings will inform patient discussions and targeted interventions to mitigate opioid misuse., (© 2024 Wiley Periodicals LLC.)

Background: Enfortumab vedotin, a fully human monoclonal antibody-drug conjugate (ADC) directed to Nectin-4, prolonged overall survival (OS) versus standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC) previously receiving a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor and platinum-based chemotherapy in the pivotal, phase 3 EV-301 clinical trial, supporting global approvals of enfortumab vedotin monotherapy. This bridging study was the first to evaluate enfortumab vedotin monotherapy in previously treated Chinese patients with locally advanced or mUC., Methods: EV-203 was a multicenter, open-label, phase 2 study (NCT04995419) assessing efficacy, safety/tolerability, pharmacokinetics (PK), and immunogenicity of enfortumab vedotin in 40 Chinese patients (PK analysis set, n = 13) with previously treated locally advanced or mUC. Patients received enfortumab vedotin 1.25 mg/kg (Days 1, 8, and 15). Primary endpoints included confirmed objective response rate (ORR) by the independent review committee (IRC) and PK parameters of ADC, total antibody (TAb), and free monomethyl auristatin E (MMAE). Secondary endpoints included investigator-assessed confirmed ORR; investigator-/IRC-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS); OS; immunogenicity; and safety/tolerability., Results: As of May 13, 2022, the median follow-up was 6.5 months. Confirmed ORR was 37.5% (n/N = 15/40; 95% CI: 22.7%-54.2%) by IRC and 42.5% (n/N = 17/40; 95% CI: 27.0%-59.1%) by investigator assessment. By IRC, DCR was 72.5% (n = 29), median DOR was not reached, and median PFS was 4.7 months. Median OS was not reached. Endpoints assessed by investigators were consistent with IRC assessments. Two patients discontinued treatment for treatment-related adverse events. No new safety signals were identified. ADC, TAb, and free MMAE were characterized in Chinese patients and consistent with previously characterized populations. The incidence of positive antitherapeutic antibodies postbaseline was 0%., Conclusion: Enfortumab vedotin demonstrated meaningful clinical activity with a manageable safety profile in Chinese patients with previously treated locally advanced or mUC., Trial Registration: ClinicalTrials.gov identifier: NCT04995419., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

With the rising incidence of hepatocellular carcinoma, there has been increasing use of local-regional therapy (LRT) to downstage or bridge to transplant, for definitive treatment, and for palliation. The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Assessment (TRA) algorithm provides guidance for step-by-step tumor assessment after LRT and standardized reporting. Current evidence suggests that the algorithm performs well in the assessment of tumor response to arterial embolic and loco-ablative therapies and fair when assessing response to radiation-based therapies, with limited data to validate the latter. Both evidence-based and expert-based refinements of the algorithm are needed to improve its diagnostic accuracy after varying types of LRT. This review provides an overview of the challenges and limitations of the LI-RADS TRA algorithm version 2017 and discusses the refinements introduced in the updated 2024 LI-RADS algorithm for CT/MRI., (© RSNA, 2024.)

Ion-conducting polymer membranes are essential in many separation processes and electrochemical devices, including electrodialysis 1 , redox flow batteries 2 , fuel cells 3 and electrolysers 4,5 . Controlling ion transport and selectivity in these membranes largely hinges on the manipulation of pore size. Although membrane pore structures can be designed in the dry state 6 , they are redefined upon hydration owing to swelling in electrolyte solutions. Strategies to control pore hydration and a deeper understanding of pore structure evolution are vital for accurate pore size tuning. Here we report polymer membranes containing pendant groups of varying hydrophobicity, strategically positioned near charged groups to regulate their hydration capacity and pore swelling. Modulation of the hydrated micropore size (less than two nanometres) enables direct control over water and ion transport across broad length scales, as quantified by spectroscopic and computational methods. Ion selectivity improves in hydration-restrained pores created by more hydrophobic pendant groups. These highly interconnected ion transport channels, with tuned pore gate sizes, show higher ionic conductivity and orders-of-magnitude lower permeation rates of redox-active species compared with conventional membranes, enabling stable cycling of energy-dense aqueous organic redox flow batteries. This pore size tailoring approach provides a promising avenue to membranes with precisely controlled ionic and molecular transport functions., Competing Interests: Competing interests A.W. and Q.S. are inventors on UK patent application no. PCT/EP2024/075338 submitted by Imperial College London, which covers the cPIM polymers and aspects of their use., (© 2024. The Author(s).)

The application of environmentally friendly and sustainable catalysts requires efficient and safe preparation methods using cheap and renewable materials. Although many metal nanoparticles (NPs) have low colloidal stability, they are still very effective as catalysts. Using a straightforward method, we developed a bacterial cellulose-glycol chitosan-silver (BC-GCS-Ag) nanocomposite, by introducing both AgNPs and self-crosslinked GCS within the BC network. Self-crosslinking of GCS occurred during the formation of AgNPs by employing the glycol moieties for reduction to produce aldehyde functionalities, thereby forming Schiff's base bonds within the GCS structure. Using GCS, well-defined AgNPs within the BC matrix. The formation of AgNPs and the self-crosslinking of GCS were characterized using UV-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results showed that spherical AgNPs with a mean diameter of 10 nm exhibited a well-organized structure within the BC-GCS matrix. The BC-GCS-Ag nanocomposite was applied as dip catalyst for the reduction of 4-nitrophenol (4NP) to 4-aminophenol (4AP), chosen as a model reaction. The results showed that the catalytic reaction was completed within 4 min, with high reusability (10 times) and without loss of catalyst. The reaction followed pseudo-first-order kinetics with a high rate constant of 0.582 min -1 . Therefore, the BC-GCS-Ag dip catalyst is an attractive alternative for environmentally friendly and sustainable catalysis, owing to its exceptional catalytic performance, high recyclability, and stability, as well as the minimal environmental footprint of the supporting materials., 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.)

The objective of this study was to optimize the microbial and ingredient composition of kombucha for enhanced production of gluconic acid (GA). Fourteen strains of Komagataeibacter spp. and one yeast strain of Dekkera sp. were isolated from kombucha. Among them, Komagataeibacter swingsii SS1 (SS1) and Komagataeibacter saccharivorans SS11 (SS11) were selected for their high GA production. A rapid reduction of pH, high GA content relative to acetic acid, and high cellulose production were observed in the tea infusion fermented by the microbial consortium (SS1 + SS11 + Dekkera bruxellensis Y24). From the correlation between the materials composition and quality indicators of kombucha, the decrease in pH was the most critical quality indicator of kombucha and the most closely related to GA content. Maximal GA production (11.7 mg/mL) was obtained under the conditions of 1% (w/v) tea extract, 8.5% (w/v) glucose, and 1.5% (v/v) ethanol through the optimization of materials composition by response surface methodology. The GA content of kombucha was enhanced threefold in comparison to general kombucha by fermentation with Komagataeibacter spp. and optimization of the composition of the ingredients. Overall, this study showed that a specific microbial consortium and materials composition could be established by correlation analysis among the ingredients, which results in increased GA levels in kombucha. These findings offer valuable foundational data for both commercial production and quality control of kombucha., (© 2024 Institute of Food Technologists.)

Fibroblast Growth Factor (FGF) receptor signalling is important for skeletal development. The FGF19 subfamily which includes FGF19 and FGF21 are involved in bone metabolism, although their effects on bone mineral density (BMD) and bone strength remain unclear. To further characterise the influence of these two factors on the skeleton, we studied the association between circulating concentrations of FGF19 and 21 with BMD and parameters of hip geometry and strength in post-menopausal osteoporosis (PMO). The study cohort consisted of 374 women aged (mean [SD]) 68.7[12.3] years with PMO. FGF19 and FGF21 were measured in serum by ELISA. BMD was measured at the lumbar spine (LS), total hip (TH) and femoral neck (FN) (n = 277) by dual energy X-ray absorptiometry (DXA) and hip structural analysis (HSA) parameters (n = 263) at the narrow neck of the femur (NN), Intertrochanter (IT) and Femoral shaft (FS) were derived from DXA scans. FGF19 and 21 were not associated with prevalent fractures or BMD when corrected for covariates; age, BMI, smoking habits and alcohol intake. Log-transformed FGF 21 was negatively associated with HSA parameters including Outer Diameter (OD) (p = 0.019), Cross-sectional area (CSA) (p = 0.01), cross-sectional moment of inertia (CSMI) (p = 0.011), Section modulus (Z) (p = 0.002) and cortical thickness (Co Th) (p = 0.026) at the IT only. CSA, CSMI, Z and Co Th were significantly lower (p < 0.05) in women with FGF21 concentrations greater than the median (> 103.5 pg/ml). Our data suggest that FGF 21 may have potentially adverse effects on the skeleton. Further characterisation is needed, particularly as FGF 21 analogues or agonists may be used to treat obesity-related metabolic disorders., (© 2024. Crown.)

Objectives: Antimicrobial stewardship programmes (ASPs) have gained prominence, with increased awareness regarding the importance of appropriate antibiotic use. However, ASP implementation for outpatient antibiotic prescription is uncommon, particularly in South Korea. This study aimed to analyse the patterns and appropriateness of outpatient antibiotic prescription at a tertiary care hospital in Korea., Methods: This study analysed the patterns of oral antibiotic prescription between 1 st June 2018 and 31 st May 2023 at the outpatient department of Seoul National University Bundang Hospital. The appropriateness of prescriptions issued between 15 th and 19 th May 2023 was assessed. The assessment criteria included: indication for antibiotic use; antibiotic choice; duration; and dose/frequency. Pharmacists and infectious diseases specialists performed evaluations., Results: In total, 7,282,407 outpatient visits were recorded over the 5-year study period, and oral antibiotics were prescribed in 243,967 (3.4%) cases. The frequency of antibiotic prescription was highest in dentistry, dermatology and urology departments. The most commonly prescribed antibiotics were cephalosporins, penicillins and sulphonamides. Of the 423 prescriptions evaluated, 289 (68.3%) and 134 (31.7%) were for treatment and prophylaxis, respectively. Prescriptions were classified as inappropriate in 28.4% (82/289) and 70.9% (95/134) of treatment and prophylaxis cases, respectively. The primary reason for inappropriateness in both treatment and prophylaxis cases was inappropriate indication, accounting for 46.3% (38/82) of treatment prescriptions and 96.8% (92/95) of prophylaxis prescriptions., Conclusions: Antibiotics were prescribed at 3.4% of all outpatient visits. The prescription was inappropriate in 28.4% of treatment cases and 70.9% of prophylactic cases. Proactive and expansive ASP activities by pharmacists should be considered in outpatient settings., Competing Interests: Conflict of interest statement None declared., (Copyright © 2024. Published by Elsevier Ltd.)

Gastric cancer (GC) is recognized as the fifth most prevalent malignant tumor worldwide. It is characterized by diverse clinical symptoms, treatment responses, and prognoses. In GC prognosis, the promotion of epithelial-mesenchymal transition (EMT) fosters cancer cell invasion and metastasis, thereby triggering the dissemination of tumor cells. This study proposes a nucleic acid amplification circuit-based hydrogel (NACH) assay for identifying exosomal miRNA derived from metastatic GC. The NACH assay employs the rolling circle amplification method and targets miRNA-21, a tumor-related oncogene, and miRNA-99a, which promotes EMT. Specific amplification probes for each target are immobilized within the hydrogel, enabling a streamlined, one-step amplification reaction. The NACH assay exhibits a detection limit of 1 fm for miRNA-21 and miRNA-99a, thereby enabling rapid and highly sensitive on-site detection. Performance evaluation using exosomal miRNA extracted from cell culture media, mouse plasma, and human plasma revealed fluorescence intensity patterns similar to those obtained in qRT-PCR. Furthermore, deploying a custom-developed portable fluorometer for the NACH assay allows for diagnostic performance assessment and point-of-care testing using clinical samples from GC patients. These findings emphasize the potential of the NACH assay to be used as a robust tool for the genetic diagnosis of GC based on exosome detection., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Germline genomic sequencing is increasingly integrated into pediatric cancer care, with pathogenic cancer-predisposing variants identified among 5-18% of affected children and variants of uncertain significance (VUS) in up to 70%. Given the potential medical implications for children and their families, parents' psychosocial responses to learning results are important to understand. Parents of children with cancer who learned their children's germline pathogenic or VUS results following paired tumor and germline genomic sequencing described their cognitive and affective responses to results in an open-ended write-in question after disclosure (M = 10 months post-disclosure; range = 1-28). Responses were coded and categorized using content analysis, then compared across results using chi-square and Fisher's exact test. Parents of children with pathogenic (n = 9), VUS (n = 52), and pathogenic plus VUS results (n = 9) described negative emotions, positive reactions, mixed emotions (i.e., positive and negative emotions), and neutral reactions. Negative emotions were described significantly more frequently with pathogenic results than VUS only (χ 2  = 5.19; p = .02), with peace of mind and empowerment only described for those with VUS. Parents also described approach(es) to coping (e.g., faith, plan of action) and reactions specific to the uncertainty of VUS (e.g., disappointment at no explanation for cancer etiology). A subset with VUS described decreasing worry/distress with increased understanding of results, whereas others displayed misconceptions regarding VUS. Screening for emotional adjustment is warranted for parents of children with cancer receiving pathogenic germline results, and screening for understanding is warranted with VUS. Findings highlight the importance of pre-and posttest genetic counseling., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The relationship between perioperative temperatures and postoperative pain is unknown. The present study investigated the relationship of intraoperative hypothermia and perioperative opioid requirements after immediate implant-based breast reconstruction., Methods: A retrospective chart review was conducted on patients undergoing immediate implant-based breast reconstruction from 2019-2023. Patients were classified into the hypothermic group (majority of procedure <36.0 °C) or normothermic group (majority of procedure ≥36.0 °C). Cumulative inpatient opioid requirements (morphine milli-equivalents [MMEs]) and frequency of patients requiring "high-dose opioids" (≥100 MMEs) were collected and compared between the groups., Results: In total, 536 patients (835 breasts) were included, among whom 135 (25.1%) were hypothermic. The hypothermic group had lower mean intraoperative (88.4 vs. 99.1 MMEs, P = 0.007) and postoperative (45.6 vs. 56.8 MMEs, P = 0.006) than the normothermic group. Mean (B = 14.6, P = 0.004) and nadir (B = 10.4, P = 0.038) intraoperative temperatures directly predicted higher opioid requirements while higher percentages of the procedure time spent under 36 °C (B = -27.6, P = 0.004) predicted lower opioid requirements. The hypothermic group was associated with 66% decreased odds of requiring high-dose opioids after adjusting for differences in patient and operative characteristics (P = 0.007)., Conclusion: Hypothermia is associated with decreased perioperative opioid requirements. Future studies should further investigate ideal temperature thresholds for warming protocols to minimize postoperative pain., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Problematic mealtime behaviors and inadequate diet quality are pressing concerns for children with autism spectrum disorder (ASD). This study aimed to evaluate recruitment feasibility and baseline outcomes of the Autism Eats program for children under 3 years with ASD., Methods: Recruitment feasibility was assessed through reach and participation rates. The Healthy Eating Index (HEI-2015) scores were calculated from 3-day food records. Problematic mealtime behaviors were assessed with the Brief Autism Mealtime Behavior Inventory. Parental feeding practices were assessed using the Child Feeding Questionnaire. Anthropometric measurements of children and parents were taken. Weight-for-length percentiles were calculated based on the CDC growth charts. Descriptive statistics, one-sample t-tests, and Spearman's rho correlations were used for data analysis., Results: Of the contacted dyads, 74 % agreed to participate. All 51 enrolled dyads completed baseline survey (100 %), and 98 % completed 3-day food records and anthropometric measurements. Significantly higher problematic mealtime behaviors were observed, compared to the reference (e.g., Total score 55.7 vs. 32.5; p < .001). Children with ASD exhibited lower HEI-2015 scores than national data (e.g., Total score 59 vs. 62). A large proportion of the children (29 %) had a weight-for-length ≥ 95th percentile. Several significant associations were found among mealtime behaviors, diet quality, parental feeding practices, and weight status., Conclusion: Recruitment was highly feasible, and the findings suggest that early nutrition intervention may hold promise in addressing problematic mealtime behaviors and promoting healthier dietary habits in young children with ASD., Clinical Trial Registration: This trial has been registered at www., Clinicaltrials: gov (NCT05194345)., 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 Inc. All rights reserved.)