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Background: Robust and well-defined data collection is important when using electronic patient-reported outcome measures (ePROMs) in clinical studies. Questions have been raised as to whether older age may be a barrier to data collection due to patients' unfamiliarity with electronic devices. Older adults may also have underlying health conditions that affect their ability to fill out patient-reported outcome measures (PROMs) on electronic devices. The aim of this observational, qualitative research study was to evaluate the usability of electronic PROMs (ePROMs) on a tablet and smartphone in older participants with and without bullous pemphigoid (BP)., Methods: Older people with and without BP were recruited in the US and France. They participated in 60-min in-person interviews, with moderators observing their completion of various tasks, including ePROMs, using a tablet and smartphone. Participants were scored on ease of task completion using a scale from 1 to 5., Results: A total of 12 participants were recruited (≥65 years old; six each with and without BP [all participants without BP were ≥75 years old]). Most participants (83%) could easily and confidently perform most assigned tasks on both the tablet and smartphone. Although select tasks required assistance, all participants were eventually able to complete all tasks. Overall, ePROM usability did not correlate with age, sex, country, or disease state. Feedback on the general usability of both electronic devices was largely positive, and most participants (n = 11; 92%) were willing to use them. Participants were generally pleased with the training modules offered on both devices, describing the training as sufficient, straightforward, and helpful. In total, 25 usability issues were identified, which fell into three categories: incomplete instructions, unclear language, and insufficient technical/visual design. Participants provided feedback on how to enhance device usability., Conclusions: The results suggest that older people can confidently use a tablet or smartphone for ePROM completion, particularly with appropriate training. ePROMs should be designed with the needs of the target patient population in mind. These results can be leveraged to improve clinical data recording, optimize device usability, and enhance the user experience for older people and those with functional or physical limitations., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice and applicable regulatory requirements. Independent institutional review for this study was provided by WCG (WIRB-Copernicus Group) IRB (Tracking Number: 20230164), and all participants consented to participate in this research via signed informed consent. Consent for publication: No patient-identifiable data have been presented. Informed consent stipulated that if the results of this study are published, no patient will be identified. Competing interests: CNH, LB, and AK are employees of AstraZeneca and may own stock/stock options. KR, KK, RB, and CPG are employees of IQVIA, which received funding from AstraZeneca to conduct this study. TM is an employee of Clario, which received funding from AstraZeneca to (1) create the electronic build for the study and (2) supply the devices., (© 2024. The Author(s).)

In the face of growing health challenges, nontraditional sources of data, such as open data, have the potential to transform how decisions are made and used to inform public health policies. Focusing on the COVID-19 pandemic, this article presents a case study employing sentiment analysis on unstructured social media data from Twitter (now X) to gauge public sentiment regarding pandemic-related restrictions. Our study aims to uncover and analyze Jamaican citizens' emotions and opinions surrounding COVID-19 restrictions following an outbreak at a call center in April 2020. Machine learning sentiment analysis was used to analyze tweets from Twitter related to the lockdown. A total of 1 609 tweets were retrieved and analyzed, 76% of which expressed negative sentiments, suggesting that the majority of citizens were not in favor of the restrictions. The low compliance with the government-mandated policy may be related to the high percentage of negative sentiments expressed. Insights from citizens' sentiments derived from open data sources such as Twitter can serve as valuable indicators for public health policymakers, providing critical input that will aid in tailoring interventions that align with public sentiments, thereby enhancing the effectiveness of and compliance with public health policies. This type of analysis can be useful to the health community and more generally to governments, as it allows for a more scientific assessment of public response to public health intervention techniques in real time. This study contributes to the emerging discourse on the integration of nontraditional data into public health policy-making, highlighting the growing potential for the use of these novel analytic techniques in addressing complex public health challenges., Competing Interests: Conflict of interest. None declared.

Background: Human immunodeficiency virus type 1 (HIV-1) acquired drug resistance (ADR) compromises antiretroviral therapy (ART)., Methods: We aggregated all HIV-1 protease-reverse transcriptase-integrase sequences over 2004-2021 at the largest HIV center in Rhode Island and evaluated ADR extent, trends, and impact using Stanford Database tools. Trends were measured with Mann-Kendall statistic, and multivariable regressions evaluated resistance predictors., Results: Sequences were available for 914 ART-experienced persons. Overall ADR to any drug decreased from 77% to 49% (-0.66 Mann-Kendall statistic); nucleoside reverse transcriptase inhibitors 65% to 32%, nonnucleoside reverse transcriptase inhibitors 53% to 43%, and protease inhibitors 28% to 7% (2004-2021), and integrase strand transfer inhibitors 16% to 13% (2017-2021). Multiclass resistance decreased from 44% to 12% (2-class) and 12% to 6% (3-class). In 2021, 94% had at least one 3-drug or 2-drug one-pill-once-daily (OPOD) option. Males and those exposed to more ART regimens were more likely to have ≥2-class resistance, and higher regimen exposure was also associated with fewer OPOD options., Conclusions: Comprehensive analyses within a densely-sampled HIV epidemic over 2004-2021 demonstrated decreasing ADR. Continued ADR monitoring is important to maintain ART success, particularly with rising INSTI use in all lines of therapy and 2-drug and long-acting formulations., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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.)

Excessive aldosterone production increases the risk of heart disease, stroke, dementia, and death. Aldosterone increases both sodium retention and sodium consumption, and increased sodium consumption may worsen end-organ damage in patients with aldosteronism. Preventing this increase could improve outcomes, but the behavioral mechanisms of aldosterone-induced sodium appetite remain unclear. In rodents, we previously identified aldosterone-sensitive neurons, which express the mineralocorticoid receptor and its prereceptor regulator, 11-β-hydroxysteroid dehydrogenase 2 (HSD2). In the present study, we identified HSD2 neurons in the human brain and then used a mouse model to evaluate their role in aldosterone-induced salt intake. First, we confirmed that dietary sodium deprivation increases aldosterone production, salt intake, and HSD2 neuron activity. Next, we showed that continuous chemogenetic stimulation of HSD2 neurons causes a large and specific increase in salt intake. Finally, we used dose-response studies and genetically targeted ablation of HSD2 neurons to show that these neurons are necessary for aldosterone-induced salt intake. Identifying HSD2 neurons in the human brain and establishing their necessity for aldosterone-induced salt intake in mice improves our understanding of appetitive circuits and highlights this small cell population as a therapeutic target for moderating dietary sodium.

Background: The identification of a heterozygous exonic GGC repeat expansion in ZFHX3 underlying spinocerebellar ataxia type 4 (SCA4) has solved a 25-year diagnostic conundrum. We used adaptive long-read sequencing to decipher the pathogenic expansion in the index Utah family and an unrelated family from Iowa of Swedish ancestry. Contemporaneous to our discovery, other groups identified the same repeat expansion in affected individuals from Utah, Sweden, and Germany, highlighting the current pivotal time for detection of novel repeat expansion disorders., Methods: Given that the pathogenic repeat expansion is rare on a population level, we proposed a common ancestor across all families. Here, we employed targeted long-read sequencing through adaptive sampling, enriching for the chr16q22 region of interest., Results: Using phased sequencing results from individuals from Utah, Iowa, and Southern Sweden, we confirmed a common ~2000-year-old ancestral haplotype harbouring the repeat expansion., Conclusion: This study provides further insight into the genetic architecture of SCA4. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: The current study attempted to replicate the original findings regarding the effects of power posing on testosterone and cortisol levels, risk-taking behavior, and perceived power. We further extended the investigation by testing the effect of power posing on estradiol and progesterone levels., Methods: A sample of 92 young adults (30 males; 32 females taking oral contraceptives; and 30 females not taking oral contraceptives who were in their midluteal phase) were randomly assigned to high-power-pose or low-power-pose conditions and asked about their feelings of power. They completed a risk-taking task, and their neuroendocrine levels were measured both at baseline and following the power manipulation., Results: Power posing was not found to replicate the original results regarding effects on testosterone levels or feelings of power; however, our findings partially supported the original results regarding effects on cortisol levels and risk-taking. Among high-power posers, a decrease in cortisol levels was associated with risk tolerance. Power posing was not found to influence progesterone levels. However, among females taking oral contraceptives, high-power posing increased estradiol levels., Conclusions: These preliminary findings suggest that estradiol is influenced by short-term exposure to social cues under specific hormonal profiles., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the institutional review boards (IRBs) of the Max Stern Academic College of Emek Yezreel. "All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards". Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Macroscopic and structural properties of one-dimensional (1D) dipolar fluids are investigated theoretically. The equation of state is fully explored by means of analytical limiting laws, integral equations and corroborating Monte Carlo simulations. An interesting mapping with the Tonks gas (i.e. hard rods) is established at strong coupling. Crucially, we report a novel solid phase characterized by a universal algebraic decay of the pair distribution function whose range extends with increasing coupling. This discovery provides a clarified view in 1D systems and open new routes to explore theoretically as well as experimentally., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Sarcopenia is associated with various geriatric diseases, such as gait disorders, falls, malnutrition, and osteoporosis. Accordingly, interest in the prevention and treatment of sarcopenia has grown over the years. The human milk oligosaccharide (HMO) 6'-sialyllactose (6'-SL) is known to improve exercise performance, reduce muscle fatigue, and improve GNE myopathy; however, its effect on sarcopenia has not yet been reported. In this study, we aimed to investigate the efficacy of 6'-SL in dexamethasone-induced muscle atrophy, which is a widely used model for the study of sarcopenia. The effects of 6'-SL on differentiated C2C12 skeletal muscle cells and on mice were examined by treatment with 6'-SL in the presence or absence of dexamethasone. 6'-SL was found to inhibit the dexamethasone-induced decrease of MHC expression, as well as to prevent reduction in the number, length, and width of myotubes. Furthermore, the dexamethasone-induced upregulation of myostatin, muscle RING-finger protein-1 (MuRF1), and atrogin-1 were also inhibited by 6'-SL treatment. In mice, intraperitoneal administration of dexamethasone caused decreases in muscle fiber diameter, muscle weight, and exercise performance, most of which were significantly inhibited by oral treatment with 6'-SL. Therefore, utilization of 6'-SL could contribute to the prevention and treatment of muscle atrophy and sarcopenia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiroe Go, Nam Ji Sung, Lila Kim, and Eun Jung Park are employed by GeneChem, Inc. Jaeil Choi declares no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications., Methods: Results for the phase 3 LIBERTY EoE TREET study co-primary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses., Results: A steep initial relationship then plateau was observed between higher dupilumab steady state trough concentrations (Ctrough) and decreased eosinophilic infiltration at Week 24, while a graded exposure-response relationship was observed for symptomatic improvement at Week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation., Conclusions: The dupilumab 300 mg qw regimen approved for adults and adolescents with EoE weighing ≥40 kg is supported by dose- and exposure-response relationships., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Over the past 10 years, sexually transmitted infections (STIs) have seen a significant resurgence in the United States despite the availability of effective treatments and reliable prevention methods. Rhode Island has experienced a similar uptick in the incidence of syphilis, chlamydia and gonorrhea, with many cases occurring among gay, bisexual, men who have sex with men (GBMSM), which coincides with a recent concerning rise in congenital syphilis cases. We reviewed the most recent STI trends for the state of Rhode Island in 2022. During this year, 6,883 cases of STIs were reported to the Department of Health (N=5,199 chlamydia, 1,444 gonorrhea, and 240 infectious syphilis cases). Compared to 2012, this represented a 21%, 185%, and 253% increase in chlamydia, gonorrhea, and syphilis infections, respectively. Since 2020, eight cases of congenital syphilis have been reported. Prior to 2020, no cases of congenital syphilis were reported since 2009. This resurgence is mainly attributed to shifting social and behavioral trends, particularly among younger individuals and shared sexual networks across diverse groups.1 Further efforts and resources are needed to effectively address these concerning trends in STIs.

Background: Malaysia currently faces significant challenges in controlling the spread of dog-mediated human rabies, as evidenced by recurrent outbreaks in newly affected areas and increasing human fatalities., Materials and Methods: A cross-sectional study was conducted to analyse surveillance data from 2015 to 2023 to examine the epidemiological characteristics of rabies in Malaysia. Data from multiple sources were used, and descriptive statistics, incidence rates, and reproductive numbers were calculated. QGIS software was used to map the distribution of rabies cases, and statistical methods were employed to evaluate associations between rabies incidence, vaccination coverage, and risk factors. We further explored the effectiveness of vaccination campaigns and public health interventions in reducing rabies transmission., Results: Our findings revealed 995 confirmed rabies cases in animals. Sarawak reported the highest proportion of rabies cases at 97.99 %, showing a significant correlation between location and rabies cases (p < .001). Dogs comprised 89.35 % of confirmed cases, while the average annual vaccination rate was only 16.66 %, far below the 59.05 % needed for herd immunity. Moreover, human rabies cases reported in Sarawak had an alarmingly high fatality rate of 90.28 %, highlighting the urgent need for improved public health measures and surveillance., Conclusion: This research provides critical insights for policymakers and health officials to improve rabies control strategies in Malaysia., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The 78 Nord Porte de Normandie territorial professional health communities (CPTS), created in 2020 in the Yvelines department, aims to improve care coordination and access to healthcare services for a population of 170,000 inhabitants spread over 57 communes. Driven by the Odyssée association, the project has been designed to meet the challenges of a region marked by social inequalities, unfavorable medical demographics and difficulties in accessing care. It stands out for its inclusive governance, bringing together healthcare professionals, users and local players, enabling decisions to be taken in line with the realities on the ground. Thanks to its collaborative approach and the commitment of its members, the CPTS has established itself as an essential pillar in the reorganization of care in its area., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: This study aimed to describe the prevalence of lymphatic filariasis (LF), soil-transmitted helminthiasis (STH) and schistosomiasis (SC) in Indonesia before and after PC implementation through a systematic review and meta-analysis., Methods: Embase, MEDLINE, PubMed, Scopus, Web of Science and Google Scholar were searched for articles published between 1 January 1992 and 31 December 2022, reporting LF, STH and SC in Indonesia. Using the Ministry of Health lists of districts receiving PC programs, we identified whether data collection was conducted before or after PC implementation in that particular district. A meta-analysis was performed with a random-effects model applied to pool pre- and post-PC prevalence of LF, STH and SC., Results: Overall, 195 studies were included. The pooled prevalence of LF was 9.72% (95% CI, 5.56%-13.87%). The pre-PC pooled prevalence of LF was 11.48% (95% CI, 5.52%-17.45%). The prevalence decreased after PC implementation, and the pooled prevalence was 7.12% (95% CI, 1.79%-12.44%). The overall prevalence of STH was 35.16% (95% CI, 30.36%-39.96%). The pre-PC prevalence of STH was 36.29% (95% CI, 30.37%-42.20%). The post-PC prevalence of STH decreased at 31.93% (95% CI, 24.25%-39.62%), although the difference between before and after PC was not significant (p = 0.379). Only nine studies investigated the prevalence of SC; based on the random-effects model, the pooled prevalence was 21.90% (95% CI, 4.88%-38.92%). Owing to the scarcity of studies, we could not perform the funnel tests for publication bias and moderating variables of the pooled prevalence for SC., Conclusions: The prevalence of LF and STH decreased after PC implementation, although it was not significant. The difference for SC could not be assessed because of limited post-PC data. The uneven distribution of research and the lack of standardised sampling methods may not fully capture the situation., (© 2024 John Wiley & Sons Ltd.)

Objective: This retrospective, real-world claims database analysis described the clinical burden and healthcare resource utilization (HCRU) among patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in France., Methods: The French National Health Data System database (système national des données de santé) was used to identify eligible patients from 1 January 2012 to 1 March 2019. Inclusion criteria were a SCD diagnosis, ≥2 VOCs/year for ≥2 consecutive years following the diagnosis, and ≥1 year of follow-up data to 1 March 2020. Patients with hereditary persistence of fetal hemoglobin or hematopoietic stem cell transplant in their medical records were excluded. Clinical complications, mortality, treatment use, and HCRU were evaluated during follow-up., Results: Overall, 4602 patients with SCD with recurrent VOCs were eligible; their mean (standard deviation [ SD ]) age was 19.8 (13.5) years, and 51.8% were female. Patients experienced a mean (SD) of 3.82 (3.57) VOCs per patient per year (PPPY). Prevalent complications were anemia or leukocytosis (44.1%), infections (42.0%), and organ failure (38.2%). In total, 101 (2.2%) patients died during follow-up (mean age of death [SD]: 39.3 [17.5] years; mortality rate: 0.64 deaths per 100 person-years). Most patients received opioids (89.1%) and hydroxycarbamide (72.8%). Patients had a mean of 5.7 inpatient hospitalizations, 6.0 emergency room visits, 6.6 outpatient visits, and 13.4 outpatient prescriptions PPPY., Conclusions: Patients with SCD with recurrent VOCs in France have substantial clinical complications, mortality, and HCRU despite currently available treatment options. Innovative treatments that reduce frequency of or eliminate VOCs are needed to alleviate the burden associated with SCD.

Here we test the hypothesis that continuous nicotine exposure throughout pre- and postnatal development (developmental nicotine exposure, DNE) alters the cardiovascular structure and function in neonatal and juvenile rats. Echocardiography showed that DNE reduced left ventricular mass, left ventricular outflow tract (LVOT) diameter, and posterior wall thickness, but only in females. Both male and female DNE rats had a lower end-systolic volume, higher ejection fraction, and increased fractional shortening, with unchanged stroke volume and cardiac output. Left ventricular single cardiac myocytes from male and female DNE animals exhibited increased calcium-evoked maximal tension with no effect on EC 50 . Tail-cuff plethysmography in awake rats showed that DNE males had lower systolic blood pressure and higher heart rate than control males. No significant changes in preload, afterload, or the in vitro renal artery response to vasodilators were observed. The results suggest that DNE enhances myocyte tension-generating capacity, possibly compensating for an unknown developmental insult, which may differ in males and females. Although this adaptation maintains normal resting cardiac function, it may lead to reduced cardiac reserve, increased energy demand, and elevated oxidative stress, potentially compromising both short- and long-term cardiovascular health in developing neonates. NEW & NOTEWORTHY Developmental nicotine exposure (DNE) induced cardiovascular changes in neonatal/juvenile rats. Relative to controls, females had reduced left ventricular mass and dimensions, while both sexes had increased ejection fraction and fractional shortening. DNE increased calcium-evoked tension in cardiac myocytes, suggesting an adaptive mechanism as resting cardiac output was preserved. Despite normal resting function, these changes may reduce cardiac reserve, potentially compromising long-term cardiovascular health. These novel findings highlight how DNE disrupts cardiovascular development and function.

Abstract: A 34-year-old woman who presented with severe psychosis and clinical features of Cushing syndrome underwent 18 F-FDG PET/CT that revealed hypermetabolic lung lesion along with predominantly increased metabolism of bilateral basal ganglia, a scintigraphic correlate of acute psychosis. The lesion was surgically excised and histopathologically proven to be adrenocorticotropic hormone-producing lung carcinoid. Posttreatment 18 F-FDG PET scan showed restoration of normal brain metabolism with complete reversal of psychosis. Even though rare, one should be aware of psychosis as an initial presentation of Cushing syndrome and use of 18 F-FDG PET/CT for mapping brain metabolism as shown in this case., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: A 53-year-old woman of primary hyperparathyroidism with both ultrasound neck examination and planar 99m Tc-MIBI scan being negative revealed a tracer-avid focus in the left submandibular region in early (15 minutes postinjection) 99m Tc-MIBI SPECT/CT views, raising a suspicion of rare ectopic parathyroid adenoma. This finding was correlated on 4D-CT and confirmed on histopathology following surgical excision. Submandibular region is an unusual location for ectopic parathyroid adenoma. Nevertheless, high degree of suspicion with utilization of multimodality imaging including 99m Tc MIBI-SPECT/CT and 4D-CT improves preoperative detection of parathyroid adenoma at rare ectopic sites as seen in this case of persistent hyperparathyroidism., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to compare oncologic and perioperative outcomes of robot-assisted laparoscopy (RA) and conventional laparoscopy (LSC) in apparent clinically uterine-confined, high-grade adenocarcinoma., Methods: A retrospective review was conducted to identify patients with newly diagnosed high-grade uterine adenocarcinoma treated at our institution between 1 January 2009 and 30 June 2021. Exclusion criteria included bulky extrauterine disease, no lymph node assessment, or synchronous tumors. Clinicopathologic details were obtained from medical records. Postoperative complications were classified using the Memorial Sloan Kettering Cancer Center Surgical Secondary Events system, and statistical analysis was performed using appropriate tests., Results: Of 901 patients identified, 748 (83%) underwent RA and 153 (17%) underwent LSC. Median age was 65 years (range 25-92) and median body mass index was 30 kg/m 2 (range 15-60). Overall, 650 patients (72%) had 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I disease. Forty-one patients (4.6%) converted to laparotomy-26 (3.5%) from RA versus 15 (9.8%) from LSC (p = 0.02). Postoperative complications occurred in 81 patients (9.0%), with no significant differences in type or rate between groups. Median operative time was 192 mins (range 88-936) for RA versus 168 mins (range 90-372) for LSC (p = 0.002). Median follow-up was 52 months (range 1-163) for RA and 66 months (range 7-165) for LSC. Four-year progression-free survival (PFS) and disease-specific survival (DSS) were similar between groups. Multivariate analysis showed stage, histology, peritoneal cytology, and lymphovascular invasion predicated a decrease in PFS and DSS., Conclusions: RA demonstrated comparable oncologic outcomes to LSC in patients with high-grade endometrial carcinoma, with no significant difference in postoperative complications or long-term survival., (© 2024. Society of Surgical Oncology.)

Analyses of health care data can reveal utilization of treatment options that comprise a multidisciplinary approach to chronic pain management. This retrospective cohort study aimed to characterize treatments among commercially versus Medicaid-insured adults with incident episodes of chronic pain. We used MarketScan data to identify patients with diagnoses for conditions associated with chronic pain, assess procedure codes that align with broad categories of treatment options, and compare receipt of treatments by insurance type. Among enrollees aged ≥18 years, 4,254,818 adults with commercial insurance and 583,369 with Medicaid met continuous enrollment criteria and had no chronic pain episodes in 2017. Among patients with incident chronic pain episodes during 2018 to 2020, we determined the proportions receiving different categories of treatment options during the year following diagnosis. Cohen's h determined meaningful differences by insurance. Study cohorts included 1,095,358 commercial (mean [standard deviation] age, 47.3 [13.3] years; 54.3% women) and 176,607 Medicaid adults (38.1 [12.7] years; 70.6% women) with incident chronic pain episodes during 2018 to 2020. More commercial than Medicaid patients received restorative therapies such as physical therapy (38.6% vs 19.2%), complementary or integrative care such as chiropractic treatment (31.1% vs 9.0%), and 2 or more different types of nonmedication treatment procedures (34.1% vs 16.3%). Median days to treatments were shorter for commercial patients. Disparities in the provision, patterns, and timing of treatments by insurance suggest differential access to the full range of treatment options early during the course of care and identify opportunities to align coverage and reimbursement policies with current practice guidelines. PERSPECTIVE: This analysis of medical claims for patients with incident chronic pain episodes found disparities in the provision, patterns, and timing of treatments by insurance type. These results suggest differential access to evidence-based treatment options early during care and identify opportunities to align coverage and reimbursement policies with current practice guidelines., (Published by Elsevier Inc.)

Dating violence (DV) is a social problem that affects adolescents worldwide. Prevalence figures show that this type of violence is starting at an increasingly younger age, which is why it is important to study attitudes toward DV, as they are an important risk factor. Victim-blaming attitudes justify this type of violence by excusing perpetrators and blaming victims. The present study aimed to validate an instrument developed to assess victim-blaming attitudes in DV cases among the adolescent population: The Adolescent Dating Violence Victim-Blaming Attitudes Scale (ADV-VBA). Two samples of high school students were recruited using a two-stage stratified sampling by conglomerates, one consisting of 758 adolescents (48% females) and the other of 160 (50% females), whose ages ranged from 12 to 18 years. We found that this instrument presented good reliability and validity evidence, showing good internal consistency, a clear one-factor latent structure, and a close relation to other related constructs, such as ambivalent sexism and perpetration and victimization of DV. We also found that items did not present differential item functioning across gender and the instrument was especially informative for assessing moderate to high levels of victim-blaming attitudes. A short five-item version is also presented for use when time and space constraints exist. Our results indicate that the ADV-VBA scale is a psychometrically sound measure to assess victim-blaming attitudes in cases of adolescent DV., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background: To elucidate the role of various imaging modalities for tumor localization in ectopic ACTH Cushing's syndrome (EAS)., Design and Method: Systematic review of the literature published between January 2015-2024 was performed. Patients (290 EAS patients, 23.8% Occult) who underwent contrast enhanced CT (CECT) and at least one PET/CT-scan ( 68 Ga-SSTR, FDG and/or F-DOPA) were included., Results: The sensitivity for identifying EAS tumor was comparable across CECT (63.1%, n=290), SSTR-PET/CT (58.2%, n=187), and FDG-PET/CT (57.6%, n=191), but was poor for DOPA-PET/CT (30.8%, n=26). Sensitivity for detecting metastasis was also comparable across CECT (78%, n=73), SSTR-PET/CT (85.3%, n=41), and FDG-PET (73.7%, n=38). For localised lesions, sensitivity as per etiology and grade of NET were similar for three scans, with exception of Thymic NET and grade 1 NET where CECT was better than FDG PET/CT. In patients not localised on CECT, sensitivity of SSTR PET/CT was 33.3% (vs. 18.9% FDG-PET/CT) whereas for patients negative on CECT and FDG-PET, sensitivity of SSTR-PET/CT was 15%. In cases where CECT and SSTR-PET/CT failed to localize, the sensitivities of FDG-PET/CT and DOPA-PET/CT were only 5.7% (2/35) and 0% (0/9), respectively. SSTR-PET/CT has a distinct advantage with significantly lesser false positive (FP) lesions (2.6%, mostly in thyroid/or pancreas). In comparison, CECT and FDG-PET/CT had FP ∼11% (mostly in lung and/or mediastinum), most of which were negative on SSTR-PET/CT., Conclusions: As per the current evidence, SSTR-PET/CT can be considered as the scan of choice in EAS evaluation, and further research is needed as one-fourth of the lesions remain occult., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objectives: Primary human papillomavirus (HPV) testing by clinician-collection is endorsed by U.S. guideline organizations for cervical cancer screening, but uptake remains low and insights into patients' understanding are limited. This study aims to primarily address patient awareness of primary HPV screening by clinician-collection and acceptance of primary HPV screening by clinician- and self-collection, and secondarily assess factors associated with awareness and acceptance., Setting: Primary care practices affiliated with an academic medical center., Methods: A cross-sectional survey study of screening-eligible women aged 30-65 years was conducted to assess awareness and acceptability of primary HPV screening. We analyzed bivariate associations of respondent characteristics with awareness of primary HPV screening by clinician-collection, willingness to have clinician- or self-collected primary HPV testing, and reasons for self-collection preference., Results: Respondents (n = 351; response rate = 23.4%) reported cervical cancer screening adherence of 82.8% but awareness of clinician-collected primary HPV as an option was low (18.9%) and only associated with HPV testing with recent screening ( p  = 0.003). After reviewing a description of primary HPV screening, willingness for clinician-collected (81.8%) or home self-collected (76.1%) HPV testing was high, if recommended by a provider. Acceptability of clinician-collected HPV testing was associated with higher income ( p  = 0.009) and for self-collection was associated with higher income ( p  = 0.002) and higher education ( p  = 0.02). Higher education was associated with reporting self-collection as easier than clinic-collection ( p  = 0.02). Women expected self-collection to be more convenient (94%), less embarrassing (85%), easier (85%), and less painful (81%) than clinician-collection., Conclusions: Educational interventions are needed to address low awareness about the current clinician-collected primary HPV screening option and to prepare for anticipated federal licensure of self-collection kits. Informing women about self-collection allows them to recognize benefits which could address screening barriers., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Improvements in outcomes for adolescent and young adult (AYA) oncology patients have lagged behind those of other age-specific cancer populations. Research has indicated that low availability of clinical trials, biological differences of this age-group, and several psychosocial factors including higher emotional distress impact outcomes. To improve care and survival rates for these patients, hospitals have implemented AYA oncology programs. The current study evaluated documentation of care in an AYA program housed in an academic medical center based on three areas emphasized in the National Comprehensive Cancer Network's Clinical Practice Guidelines in Oncology for AYAs: clinical trial enrollment, fertility, and psychosocial care. Methods: Retrospective chart reviews were conducted for 45 patients treated before the start of the AYA oncology program and 45 patients treated after program initiation. Patients aged 15-39 years with a diagnosis of a malignant tumor were included. Variables evaluated included documentation of clinical trial enrollment, fertility preservation and sexual health considerations, and behavioral health referrals. Results: Documentation of most clinical trial and fertility variables did not significantly improve from pre- to post-program, although a higher number of patients had these variables documented post-program. Behavioral health referrals increased significantly from 52.8% pre-program to 95.4% post-program. Conclusion: Access to behavioral health care improved the most following implementation of our AYA program, which is likely because of the integration of a dedicated psychologist for AYAs when the program began. The practice of guideline-based care for this population can be better assessed and improved with designated behavioral health providers and more systematic documentation processes.

Introduction: Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in parts A and B of the LIBERTY EoE TREET (NCT03633617) study., Methods: The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of nondysphagia symptoms), EoE Impact Questionnaire (impact of EoE on HRQoL), and Patient Global Impression of Severity and Patient Global Impression of Change of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo., Results: At week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] part A -1.7 [-2.9, -0.5], part B -1.4 [-2.3, -0.5]; both P < 0.01) and EoE-SQ Severity (part A -2.0 [-3.9, 0.0], P < 0.05, part B -1.5 [-3.0, 0.1], P = 0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE Impact Questionnaire average scores and improved individual item scores at week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the Patient Global Impression of Change of dysphagia vs placebo or reported having no symptoms per the Patient Global Impression of Severity of dysphagia at week 24., Discussion: Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

GNE myopathy is a rare genetic muscle disorder characterized by initial ankle dorsiflexor weakness and the presence of rimmed vacuoles in muscle histopathology. Biallelic mutations in the GNE gene are causative, leading to reduced production of sialic acid. In our previous clinical trial, we used 6'-sialyllactose (6SL) as a supplement to increase sialic acid levels and compared the effects of 6SL at doses of 3 g and 6 g. The findings from the trial revealed superior outcomes in muscle strength, attenuation of muscle degeneration, and bioavailability in the 6 g group. This trial was planned to complement the lack of placebo arm from the previous trial and to provide more conclusive evidence for therapeutic value of 6SL in GNE myopathy. Of the 11 participants, five were allocated to the 6SL and six to the placebo group after undergoing 12 weeks of pre-study observation and stratified randomization. At every visit with an interval of 12 weeks for 48 weeks, all participants underwent muscle strength measurement, muscle MRI, biochemical evaluations, 6-min-walk test, and completed a questionnaire. No safety concerns arose during the trial period. Muscle strength, excluding hand grip power, did not show a significant difference between the two groups, which is attributed to the lack of pronounced muscle strength decline in both groups. Hand grip power tended to decrease in both groups, and this decline was statistically significant in the placebo group (p = 0.0004). The fat fraction measured by MRI showed the most significant results in the posterior thigh. The increase in fat fraction, indicating muscle degeneration, was statistically significant between the two groups (p = 0.0004). Although no statistically significant differences were observed between the groups in anterior thigh and both anterior and posterior lower leg, a trend of slowed increase in fat fraction was noted in the 6SL group compared to the placebo group starting from 24 or 36 weeks. Resialylation of cell surface glycoconjugate was demonstrated in 6SL group by measuring lectin bindings on peripheral blood monocytes. The GNEM-FAS, used to assess patient-reported outcomes, did not show statistical significance in the total score or any of the three domains. However, the tendency for scores in the self-care and upper extremity domains to rebound after 24 weeks in the 6SL group suggests the potential for long-term benefits. The effect of 6SL on muscle strength appeared to be minimal compared to our previous clinical trial, likely due to the short duration of the study and the inclusion of relatively early-stage patients. However, the changes in fat fraction measured by muscle MRI and the results of biochemical assays are more promising, suggesting potential benefits with long-term administration in the future., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Use of serum procalcitonin (PCT), an inflammatory biomarker for bacterial infections, has shown promising results for early stopping antibiotic treatment among patients with respiratory infections and sepsis. There is need for additional data regarding effectiveness and safety of this concept among patients with cancer., Methods: Individual data of patients with a documented diagnosis of cancer and proven or suspected respiratory infection and/or sepsis were extracted from previous trials where adult patients were randomized to receive antibiotic treatment based on a PCT protocol or usual care (control group). The primary efficacy and safety endpoints were antibiotic exposure and 28-day all-cause mortality., Results: This individual-patient data meta-analysis included 777 patients with a diagnosis of cancer from 15 randomized-controlled trials. Regarding efficacy, there was a 18% reduction in antibiotic exposure in patients randomized to PCT-guided care compared to usual care ([days] 8.2 ± 6.6 vs. 9.8 ± 7.3; adjusted difference, - 1.77 [95% CI, - 2.74 to - 0.80]; p < 0.001). Regarding safety, there were 72 deaths in 379 patients in the PCT-guided group (19.0%) compared to 91 deaths in 398 participants in the usual care group (22.9%) resulting in an adjusted OR of 0.78 (95% CI, 0.60 to 1.02). A subgroup analysis showed a significant reduction in mortality in patients younger than 70 years (adjusted OR, 0.58 [95% CI, 0.40 to 0.86])., Conclusion: Result of this individual patient meta-analysis from 15 previous trials suggests that among patients with cancer and suspected or proven respiratory infection or sepsis, use of PCT to guide antibiotic treatment decisions results in reduced antibiotic exposure with a possible reduction in mortality, particularly among younger patients., Competing Interests: Declarations. Human ethics and consent to participate: Not applicable due to the meta-analysis design. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Food delivery riders (FDRs) play a crucial role in the food delivery industry but face considerable challenges, including a rising number of traffic accidents. This study aimed to examine the incidence of traffic accidents and develop a decision tree model to predict the likelihood of traffic accidents among FDRs., Methods: A cross-sectional study was conducted with 257 FDRs in Chiang Mai and Lampang Province, Thailand. Participants were interviewed using questionnaires and provided self-reports of accidents over the previous 6 months. Univariable logistic regression was used to identify factors influencing traffic accidents. Subsequently, a decision tree model was developed to predict traffic accidents using a training and validation dataset split in a 70:30 ratio., Results: The results indicated that 45.14% of FDRs had been involved in a traffic accident. The decision tree model identified several significant predictors of traffic accidents, including delivering food in the rain, job stress, fatigue, inadequate sleep, and the use of a modified motorcycle, achieving a prediction accuracy of 66.54%., Conclusion: Based on this model, we recommend several measures to minimize accidents among FDRs: ensuring adequate sleep, implementing work-rest schedules to mitigate fatigue, managing job-related stress effectively, inspecting motorcycle conditions before use, and exercising increased caution when delivering food during rainy conditions.

Objectives: In line with the widespread acknowledgement of the harms which can be caused to healthcare staff through their role in adverse events and unexpected patient outcomes, so is there now acceptance of the role of staff peer support programs to support these 'second victims' in a non-clinical way. Here, we share reproduceable steps that any service might take in creating their own staff peer support program., Methods: We outline the establishment of a program in a NSW health-service encompassing several hospitals and services, from initiation of the program, customising it to our local needs, engaging the broader health service, launching the program, and the ongoing maintenance required., Results: Dedicated resourcing and strong executive support have been essential to launch and maintain the program. Reaching all staff in a large organisation and building trust in the program's confidentiality have been the main challenges., Conclusions: Staff peer support programs, whilst early in their evidence, offer a way to provide practical, non-clinical support to staff harmed through adverse events in healthcare. Here, we offer methodology and learnings for all services to consider when implementing a localised program., Competing Interests: DisclosureThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The unprecedented speed of developing vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has propelled mRNA technologies into the public eye. The versatility of mRNA technology, often referred to as "plug and play," offers immense promise for rapidly updating vaccines to address newer variants of respiratory diseases and combat emerging infectious diseases and lethal pathogens, such as the Ebolavirus. However, the potential applications of mRNA technology extend well beyond prophylactic vaccines. This session explored the two primary mRNA platforms: nonreplicating mRNA and self-amplifying mRNA (variably referred to as saRNA, samRNA, or SAM). Presentation topics were on current research efforts aimed at broadening the applications of mRNA modalities beyond vaccines. Topics included opportunities for delivering mRNA via intra-tumoral and inhalational routes, immunological and systemic inflammatory responses elicited by these modalities, and regulatory considerations involved in the development and licensing of these technologies., 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.

Introduction: Increased salience of drug-related cues over nondrug reinforcers can drive drug use and contribute to tobacco use disorder (TUD). An important scientific and clinical goal is to effectively measure this elevated drug-seeking behavior in TUD. However, most TUD assessments rely on self-reported cravings and cigarette consumption, not providing an objective measure of the impact of drug cues on biasing behavior toward drugs. The probabilistic image choice (PIC) task investigates the choice of viewing drug-related pictures as compared to other salient pictures (eg, pleasant and unpleasant). This study aimed to develop and validate the PIC task for TUD and evaluate the associations between behavioral choice and tobacco craving, daily cigarette consumption, quit attempts and motivation to quit, and nicotine dependence (the Fagerström score)., Methods: We recruited 468 smokers and 121 nonsmokers using the Prolific online platform. Participants performed the PIC task twice (at a 1-month interval) and completed other measures relevant to TUD., Results: Compared to nonsmokers, tobacco smokers selected to view significantly more tobacco images and less pleasant (nondrug reinforcer) images, a profile that remained stable at retest. Individual differences in choice of tobacco as compared to pleasant images on the PIC task were associated with craving but not with the other tobacco dependence measures, suggesting that the task may serve as a behavioral proxy measure of drug "wanting" rather than of cumulative nicotine exposure or physical dependence., Conclusions: These results suggest that the PIC task can be a valuable tool for objectively assessing craving-associated tobacco seeking in TUD., Implications: Most of the current measures of TUD rely on self-reports of consumption, dependence, and craving, and do not take into consideration the role of drug-related cues in driving tobacco seeking. This study shows that the PIC task provides an objective, reliable proxy measure of tobacco image-seeking behavior in people who smoke cigarettes that is linked to craving (desire) for smoking but not to other measures of TUD. Therefore, the PIC task may be a useful complementary tool for the classification, diagnosis, and prognosis of TUD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. 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.)

Contamination of water by oil-based pollutants is a major environmental problem because of its harmful impact on human life, marine life, and the environment. As a result, a wide range of materials are being investigated for the effective separation of oil from water. Among these materials, metal-organic frameworks (MOFs) and their composites have emerged as excellent candidates due to their ultraporous structures with high surface areas that can be engineered to achieve high selectivity for one of the phases in an oil/water mixture for efficient water filtration. However, the often nanocrystalline/microcrystalline form of MOFs combined with challenges of processability and poor stability in water has largely limited their use in industrial and environmental applications. Hence, considerable efforts have recently been made to improve the performance and stability of MOFs by introducing hydrophobic functional groups into the organic linkers and fabricating polymer-MOF composites to increase their stability and recyclability. In addition, the use of biobased or biodegradable MOF composites can be particularly useful for applications in natural environments. This Review presents recent advances in the field of hydrophobic MOFs and MOF-based composites studied for the separation of oil from oil/water mixtures, with an account of future challenges in this area., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on the cardiovascular system in RA patients remains poorly understood, especially with its long-term use. This study investigates the effect of therapy with IL-6 receptor blocker tocilizumab (TCZ) on the dynamics of cardiovascular risk (CVR), modifiable risk factors (RFs), carotid artery (CA) structural changes, and the incidence of cardiovascular complications (CVCs) in RA patients during a 265-week follow-up period. Forty-five patients with active RA (DAS28-ESR 6.2 (5.5;6.8) with ineffectiveness and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included in this study. During long-term therapy with TCZ in RA patients, no increase in CVR and no significant structural changes in CA were observed. No significant changes in the blood lipid spectrum were observed in patients without statin therapy. In the group of patients receiving statins, there was a 43% increase in high-density lipoprotein cholesterol (HDL-C), a 15% reduction in total cholesterol levels, and a 56% decrease in the atherogenicity index ( p < 0.01 in all cases). Associations were found between ∆ total cholesterol and ∆ C-reactive protein (CRP) (R = 0.36, p = 0.04), ∆ low-density lipoprotein cholesterol (LDL-C), and ∆-CRP (R = 0.42, p = 0.03) in RA patients receiving statins. Initially, the thickness of the intima-media complex of carotid arteries (cIMT) positively moderately correlated with age (R = 0.7; p < 0.01), BMI (R = 0.37; p < 0.01), and systolic blood pressure (R = 0.64; p < 0.01); however, it weakly correlated with the lipid spectrum parameters: total cholesterol (R = 0.29; p < 0.01) and LDL-C (R = 0.33; p < 0.01). No new associations of cIMT by the end of the follow-up period, as well as the relationship of cIMT value with RA activity and therapy, were revealed. Patients with carotid ASPs showed an oppositely directed relationship between total cholesterol and sVCAM-1 at baseline (R = -0.25, p = 0.01) and at the end of this study (R = 0.29, p < 0.01). The incidence of cardiovascular events was 0.53 per 100 patient-years during the 265-week period of TCZ therapy.

Spatial navigation allows animals to understand their environment position and is crucial to survival. An animal's primary mode of spatial navigation (horizontal or vertical) is dependent on how they naturally move in space. Observations of the domestic dog ( Canis familiaris ) have shown that they, like other terrestrial animals, navigate poorly in vertical space. This deficit is visible in their use of multi-story buildings. To date, no research has been conducted to determine if dogs can learn how to navigate in an anthropogenic vertical environment with the help of a landmark. As such, we herein investigate the effect of the addition of a visual or olfactory landmark on dogs' ability to identify when they are on their home floor. Subject behaviors toward their home door and a contrasting floor door were compared before and after exposure to a landmark outside of their home door. While subjects initially showed no difference in latency to approach an apartment door on their home or a wrong floor, we found a significant difference in latency to approach the doors in the test trials for subjects who approached the doors in every trial. Other findings are equivocal, but this result is consistent with the hypothesis that dogs can learn to navigate in vertical space., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

A complete understanding of RNA biology requires methods for tracking transcripts in vivo. Common strategies rely on fluorogenic probes that are limited in sensitivity, dynamic range, and depth of interrogation, owing to their need for excitation light and tissue autofluorescence. To overcome these challenges, we report a bioluminescent platform for serial imaging of RNAs. The RNA tags are engineered to recruit light-emitting luciferase fragments (termed RNA lanterns) upon transcription. Robust photon production is observed for RNA targets both in cells and in live animals. Importantly, only a single copy of the tag is necessary for sensitive detection, in sharp contrast to fluorescent platforms requiring multiple repeats. Overall, this work provides a foundational platform for visualizing RNA dynamics from the micro to the macro scale., Competing Interests: Competing interests A.L., J.A.P., O.S., K.K.N., K.H.C., L.P.H., and C.C.C. are on a provisional patent application, filed through UCI, based on the results described here. The remaining authors declare no competing interests., (© 2024. The Author(s).)

The complex mechanism of synaptic vesicle fusion with the plasma membrane for neurotransmitter release is initiated by the formation of the SNARE complex at the presynaptic terminal of the neuron. The SNARE complex is composed of four helices contributed by three proteins: one from syntaxin (localized at the plasma membrane), one from synaptobrevin (localized at the synaptic vesicle), and two from the intrinsically disordered and aggregation-prone synaptosomal-associated 25 kDa protein (SNAP-25), which is localized to the plasma membrane by virtue of palmitoylation of cysteine residues. The fusion process is tightly regulated and requires the constitutively expressed Hsp70 chaperone (Hsc70) and its J-protein co-chaperone CSPα. We hypothesize that Hsc70 and CSPα cooperate to chaperone SNAP-25, disfavoring its aggregation and keeping it in a folding state competent for SNARE complex formation. To test this hypothesis, we used a bottom-up approach and studied the interaction between Hsc70 and CSPα with SNAP-25 in vitro. We showed that the aggregation of SNAP-25 is delayed in the presence of Hsc70 and CSPα. Using a peptide array that spans the sequence of SNAP-25, we identified three potential Hsc70-interacting sequences and designed peptides containing these sequences to test binding in solution. We characterized the interaction of SNAP-25-derived peptides with Hsc70 and CSPα using a combination of biochemical and biophysical techniques, including native-PAGE, binding affinity by fluorescence anisotropy, ATPase-activity of Hsc70, and NMR. We have identified an Hsc70 binding site within SNAP-25 that is likely to represent the site used in the cell to facilitate SNARE complex formation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systems consolidation theories propose two mechanisms that enable the behavioral integration of related memories: coordinated reactivation between hippocampus and cortex, and the emergence of cortical traces that reflect overlap across memories. However, there is limited empirical evidence that links these mechanisms to the emergence of behavioral integration over time. In two experiments, participants implicitly encoded sequences of objects with overlapping structure. Assessment of behavioral integration showed that response times during a recognition task reflected behavioral priming between objects that never occurred together in time but belonged to overlapping sequences. This priming was consolidation-dependent and only emerged for sequences learned 24 hr prior to the test. Critically, behavioral integration was related to changes in neural pattern similarity in the medial prefrontal cortex and increases in post-learning rest connectivity between the posterior hippocampus and lateral occipital cortex. These findings suggest that memories with a shared predictive structure become behaviorally integrated through a consolidation-related restructuring of the learned sequences, providing insight into the relationship between different consolidation mechanisms that support behavioral integration., Competing Interests: AT No competing interests declared, LD Reviewing editor, eLife, (© 2024, Tompary and Davachi.)

This study was conducted to monitor and evaluate the health risks of multiple organophosphorus pesticide residues in three characteristic fruits of Maragheh district, East Azerbaijan province. The Monte Carlo method was used to quantify the possible non-carcinogenic health risks associated with pesticide residues in adults and children. The residues of 17 pesticides in 36 samples were analysed using the QuEChERS extraction method coupled with gas chromatography-mass spectrometry (GC/MS). Residues of 13 pesticides (76.47%) were detected in grape samples and 15 pesticides (88.23%) in apricot and plum samples. The maximum level found in grape samples was due to chlorpyrifos with 1.2 mg/kg, and in apricot and plum samples to diazinon with 1.6 and 1.3 mg/kg, respectively. All grape, apricot and plum samples contained at least ten pesticides with levels exceeding the Iranian and EU Maximum Residue Limits (MRLs). The processing factor for washing treatment in grape, apricot and plum samples was less than 1, ranging from 0.53 to 0.69. Chlorpyrifos with values of 0.064 and 0.256 in the grape samples and diazinon with values of 0.0443 and 0.177 in the apricot samples and values of 0.0263 and 0.105 in the plum samples contain the highest hazard quotients (HQ) for adults and children, respectively. The cumulative risk assessment due to exposure to several pesticide residues suggests that there is no significant health risk for adults (HI < 1). However, consumption of unwashed grapes may cause adverse effects in children (HI = 1.48). However, for further research, a comprehensive longitudinal study is suggested to assess the long-term effects of exposure to pesticides especially for children.

Purpose: A cancer diagnosis in adolescence and young adulthood significantly impacts a person's quality of life, particularly concerning identity, self-esteem, and subsequently, body image. This study aims to develop a psychometrically-sound patient-reported outcome measure of body image for adolescent and young adult (AYA) oncology patients that was guided by the National Institutes of Health's Patient-Reported Outcomes Measurement Information System® (PROMIS) Scientific Standards and our past concept elicitation interviews with AYAs. Methods: We conducted a multi-step approach involving item identification, refinement, generation; translatability and reading level review; and cognitive interviews. A purposive sample of 25 AYA patients participated, ensuring representation across educational levels, gender, treatment status, and cancer type. Results: Translatability and reading level reviews facilitated language adjustments. Cognitive interviews revealed that 76% of AYAs found the 50 candidate items assessing body image concerns to be easy to answer. AYAs reported that the body image items captured their lived experiences. Three items were excluded due to comprehension difficulties. Conclusion: This study addresses the critical gap in validated measures for assessing body image in AYA oncology patients. Interview findings provided evidence for the content validity and comprehensibility for 47 items assessing body image. The next steps involve large-scale psychometric testing to evaluate the reliability and validity of the body image items to form an item bank allowing the design of short forms or use of computerized-adaptive testing. Ultimately, this work lays the foundation for developing interventions to mitigate the impact of cancer on AYAs' body image during diagnosis, treatment, and recovery.

Repeat expansions in the C9orf72 gene are the most common genetic cause of (ALS) and frontotemporal dementia (FTD). Like other genetic forms of neurodegeneration, pinpointing the precise mechanism(s) by which this mutation leads to neuronal death remains elusive, and this lack of knowledge hampers the development of therapy for C9orf72-related disease. We used an agnostic approach based on genomic data (n = 41,273 ALS and healthy samples, and n = 1,516 C9orf72 carriers) to overcome these bottlenecks. Our drug-repurposing screen, based on gene- and expression-pattern matching and information about the genetic variants influencing onset age among C9orf72 carriers, identified acamprosate, a γ-aminobutyric acid analog, as a potentially repurposable treatment for patients carrying C9orf72 repeat expansions. We validated its neuroprotective effect in cell models and showed comparable efficacy to riluzole, the current standard of care. Our work highlights the potential value of genomics in repurposing drugs in situations where the underlying pathomechanisms are inherently complex. VIDEO ABSTRACT., Competing Interests: Declaration of interests B.J.T. holds patents on clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72., (Published by Elsevier Inc.)

Introduction: Differentiating pheochromocytomas from other adrenal masses based on computed tomography (CT) characteristics remains challenging, particularly in lipid-poor lesions with variable washout patterns. This study evaluated CT features for distinguishing pheochromocytomas in good and poor washout subcohorts., Methods: We prospectively analyzed 72 patients with unilateral lipid-poor adrenal masses. CT protocol included basal, bolus-tracked arterial, early venous (45 seconds postarterial), and delayed (15 minutes postarterial) phases. Masses were categorized into good and poor washout groups. Histopathology provided the final diagnosis. CT characteristics and calculated indices were compared between pheochromocytomas and other masses in each washout category., Results: The cohort included pheochromocytomas (n = 35), adrenocortical carcinoma (ACC; n = 15), lipid-poor adenomas (n = 13), and metastatic infiltration/infection (n = 9). In the good washout group, pheochromocytomas (n = 15) showed larger diameters (6.00 vs 3.45 cm, P = .001), higher necrosis frequency (73.3% vs 30%, P = .049), and greater arterial attenuation (173.2 vs 74.5 HU, P < .001) compared to adenomas (n = 9). Arterial attenuation provided a high discriminatory value [area under the curve (AUC): 0.967], with 100% sensitivity at 87.6 Hounsfield unit (HU) and 100% specificity at 139.9 HU. In the poor washout group, pheochromocytomas (n = 20) exhibited higher arterial attenuation (99.2 vs 59.2 HU, P < .001; AUC: 0.844) compared to ACC (n = 14), metastatic infiltration (n = 9), and adenomas (n = 4), with 85% sensitivity and 78% specificity at 73.3 HU. Normetanephrine-secreting/nonsecretory pheochromocytomas showed higher arterial enhancement than metanephrine-secreting ones (132.0 vs 90.5 HU, P = .020) within the poor washout group., Conclusion: Arterial phase attenuation on CT has good diagnostic accuracy for differentiating pheochromocytomas from other adrenal masses in both good and poor washout categories, potentially guiding hormonal workup., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Intimate partner violence against women (IPVAW) is a global problem, and suicidal behaviour is one of its most serious consequences. However, no study has investigated the spatial overlap between the two. The aim of this paper is to analyse whether there is spatial overlap between IPVAW and suicide-related calls in the same neighbourhoods, and to identify common risk factors. Geocoded data on IPVAW (N = 2060) and suicide-related calls (N = 4916) from the city of Valencia, Spain, between 2019 and 2021 were collected from the 112 emergency service and the Spanish National Police Corps. We used two analytical approaches: (i) a Bayesian spatial Poisson regression modelling analysis to identify the risk factors associated with IPVAW and suicide-related calls; (ii) Bayesian joint spatial modelling to examine the common spatial distribution of these outcomes. Relative risk maps are also displayed and analysed. The study revealed a higher incidence of IPVAW and suicide-related calls in neighbourhoods with lower income and population density, and greater residential instability and immigrant concentration. There was a 70% similarity between high- and low-risk areas for these incidents, with a moderate positive correlation of 0.43. Notably, 98% of IPVAW risk variance was explained by shared factors, while 30% applied to suicide-related calls; high IPVAW risk was also found in peripheral areas, while suicide-related calls were concentrated in the city centre. The findings highlight the need to identify areas with shared risk and neighbourhood characteristics for the development of more effective intervention strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: : Characterizing HIV clustering rates and their trends over time can improve understanding a local epidemic and enhance its control., Methods: Leveraging an academic-public health partnership in Rhode-Island, we explored longitudinal dynamics of statewide clustering rates among key populations from 1991 to 2023. Partial HIV-1 pol sequences were grouped by year of HIV-1 diagnosis. Molecular clusters were identified in cumulative annual phylogenies. Overall clustering rates, and clustering rates of newly-diagnosed and prevalent infections, and of specific socio-demographic characteristics of key populations over time were determined. Mann-Kendall statistics were used to estimate clustering rate trends and relationships among groups., Results: By the end of 2023, 2,630 individuals with sequences represented the statewide epidemic in Rhode Island. Overall clustering rates increased from 7% in 1991 to 46% in 2023, correlating with cumulative sequence increase. Clustering rates of newly-diagnosed and prevalent infections significantly increased over time, higher in newly-diagnosed individuals since the early 2000 s. Increases were also observed among groups defined by gender, age, transmission risks, race, mental illness, HIV-1 subtypes, and country of birth, with some crossovers and divergence patterns over time., Conclusions: Exploring dynamics of HIV clustering rates over three decades in a statewide HIV-1 epidemic expanded its characterization and provided insight into its evolving changes. These dynamics may indicate a gradual shift towards a more concentrated and localized HIV-1 epidemic, highlighting important opportunities for targeted interventions to effectively prevent new HIV transmissions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Despite significant advancements in COVID-19 vaccine research and development, hesitancy in its acceptance, particularly among pregnant women, is recognized as a health threat. Based on the Health Belief Model, this study aimed to identify the factors influencing vaccine nonacceptance among pregnant women in the cities of Zahedan and Tabriz, Iran., Methods: The present research was a multicenter cross-sectional study conducted among pregnant women in two Iranian provinces, Zahedan and Tabriz, covering both high and low fertility regions. The study was conducted from February 2022 to August 2022. The sample size comprised 650 pregnant women attending selected healthcare centers. Data collection tools included questionnaires on sociodemographic characteristics, awareness, vaccine acceptance, and health beliefs related to vaccination. Data were analyzed using descriptive and analytical methods, including Analysis of variance (ANOVA), Independent t -test, and multivariable logistic regression., Results: Among the 650 pregnant women, the vaccine acceptance rate was 47.4% and 52.6% of pregnant women reported vaccine nonacceptance during pregnancy. The logistic regression model indicated that the odds of vaccine acceptance increase with maternal employment (OR = 11.53, 95% CI: 4.81-27.63), higher maternal education levels (OR = 6.97, 95% CI: 3.11-15.63), higher income (OR = 1.60, 95% CI: 1.07-2.55), and increased awareness levels (OR = 1.37, 95% CI: 1.03-1.52). Additionally, the odds of vaccine acceptance increase with increased perceived susceptibility (OR = 2.55, 95% CI: 0.47-3.76), increased perceived benefits (OR = 2.22, 95% CI: 1.06-4.61), increased perceived barriers (OR = 0.42, 95% CI: 0.18-1.12), and increased cues to action (OR = 2.01, 95% CI: 1.03-3.92)., Conclusion: Our study underscores the multifaceted nature of COVID-19 vaccine acceptance among pregnant women, with socioeconomic, awareness-related, and psychological factors all playing pivotal roles. These findings can inform targeted interventions and strategies aimed at increasing vaccine acceptance in this vulnerable population, ultimately contributing to enhanced maternal and fetal health during the ongoing pandemic., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

(1) Background: Intimate partner violence (IPV) remains a pervasive issue, particularly among adolescents. Its prevalence is still high despite intervention efforts, especially for younger generations. Empathy and sexism are factors linked with IPV that have shown gender differences. This study focuses on how gender moderates the association of empathy and sexist attitudes among adolescents in Spain; (2) Methods: A two-stage stratified cluster sampling method for collecting data from 516 adolescents (219 boys, 297 girls) aged 12-18 years was used. Participants completed the Ambivalent Sexism Inventory and the Interpersonal Reactivity Index. Hierarchical multiple regression analyzed the moderating role of gender in the relation between empathy and ambivalent sexism; (3) Results: Boys exhibited higher sexism levels than girls. Perspective taking negatively predicted hostile sexism. Empathic concern positively predicted hostile and benevolent sexism. Significant gender-specific patterns emerged: more empathic concern was linked with increased hostile sexism in boys; higher perspective taking was linked with increased benevolent sexism in boys, but was lower in girls; (4) Conclusions: There is a complex interplay among empathy, gender, and sexism, suggesting that IPV prevention programs should be tailored differently for boys and girls by considering broader socio-political contexts, addressing traditional gender norms, and promoting gender equality.

Post-traumatic stress disorder (PTSD) is a multifactorial psychological disorder that affects different neurotransmitter systems, including the central CRH system. CRH acts via the CRHR1 and CRHR2 receptors, which exert opposite effects, i.e., anxiogenic or anxiolytic. The aim of this work was to investigate how intranasal administration of the CRHR2-specific agonist urocortin 2 (Ucn2) or urocortin 3 (Ucn3) affects manifestations of PTSD in a single prolonged stress (SPS) animal model of PTSD. Elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behavior. Changes in the gene expressions of CRH , CRHR1 , CRHR2 , glucocorticoid receptor ( GR ), and FKBP5 were measured in brain regions (BNST, amygdala, and PVN) responsible for modulating the stress response. The SPS animals spent less time in the OF central zone and were less mobile than the controls; however, the Ucn3 treatment reversed this effect. SPS decreased the GR and FKPB5 mRNA levels in the PVN. Ucn3 suppressed the effect of SPS on FKBP5 mRNA expression in the PVN and increased FKBP5 mRNA in the BNST and PVN compared to the stressed animals. We demonstrate that Ucn3 has the potential to ameliorate anxiety-like behavior in SPS animals and also to affect the neuroendocrine system in the BNST and PVN. In addition, we confirm the important role of CRHR2 signaling in mediating the stress response.

In the United States, individuals with disabilities and those aged ≥65 can supplement their Medicare with so-called stand-alone Medicare Part D prescription drug plans. Beneficiaries can switch their stand-alone prescription drug plans annually, but most do not. Indirect evidence has raised concerns that non-switchers do not even make plan comparisons (labeled "inattention"), but direct evidence is scarce. Therefore, we surveyed 439 beneficiaries of Medicare Part D plans from a nationally representative adult sample after the 2024 open-enrollment period. Overall, 53% self-reported making no comparisons. Of those who did not compare, 98% did not switch (vs 67% of those who did compare). Multinomial regressions revealed that beneficiaries who neither compared nor switched were more likely than switchers to report difficulties with comparing and switching, experiencing no plan-related discontinuation, changes, or dissatisfaction, not using advisors or the plan-finder website, and receiving potentially confusing mailings. Non-switchers who did compare were similar to switchers in reporting few difficulties and relying on advisors and the plan-finder website, but they were less likely than switchers to report plan-related changes, discontinuation, or dissatisfaction, while being more likely to report receiving mailings and having no college degree. We discuss insights for policy-making., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Introduction: The clinicopathological characteristics and efficacy of perioperative treatment of Epstein-Barr virus-associated gastric cancer (EBVaGC) were investigated., Methods: The clinicopathological characteristics and perioperative treatment outcomes of patients with EBVaGC who underwent radical gastrectomy in Tianjin Medical University Cancer Hospital from September 2016 to May 2022 were retrospectively reviewed. Disease-free survival (DFS) was analyzed, and Cox regression analysis was performed to identify risk factors., Results: The study cohort included 128 patients with EBVaGC. Histologically, 126 (98.4%) patients had adenocarcinoma and only 2 (1.6%) had adenosquamous carcinoma. In addition, 18 (14.1%) had nerve invasion and 29 (22.7%) had vascular invasion. Notably, 41 (32.0%) patients had tumors in the proximal stomach and 69 (53.9%) had no lymph node metastasis. Proficient mismatch repair was confirmed in all 104 patients with available results. Overall, 16 (12.5%) patients received neoadjuvant therapy, 81 (63.3%) received adjuvant therapy, and 10 (7.8%) received perioperative immunotherapy combined with chemotherapy. In total, 22 patients experienced disease progression or had died. The 3-year DFS rate was 75.0%. DFS was relatively poorer for patients with advanced tumor (T) stage, lymph node (N) stage, disease stage, and vascular invasion., Conclusion: EBVaGC had unique clinicopathological characteristics and prognosis. Advanced T, N, and disease stages, in addition to vascular invasion, were predictive of poorer DFS. However, the efficacy of perioperative treatment of EBVaGC remains uncertain., (© 2024 S. Karger AG, Basel.)

Background and Objectives: Cerebellopontine angle (CPA) meningiomas present challenges given their proximity to neurovascular structures. Postoperative complications and persistent symptoms can debilitate patients, and our ability to predict recovery course remains variable. Here, we examine the presentation, management, and outcomes of patients with CPA meningiomas., Methods: We retrospectively reviewed CPA meningiomas resected at Mass General Brigham, using descriptive statistics and logistic regression to identify predictors of progression or recurrence., Results: In total, 95 patients were identified (median age 59.1 years, 82.1% female) who presented most commonly with hearing loss (49.5%), ataxia (42.1%), and headaches (29.5%). The retrosigmoid (78.9%) or transmastoid retrosigmoid (17.9%) approaches were most frequently used for resection, with gross total resection (GTR) achieved in 62.1% of patients: Simpson grade 1 (32.6%), grade 2 (17.9%), and grade 3 (11.6%). Smaller tumor size (t = 3.17, P = .002) is associated with GTR. For tumors with intracanalicular invasion, drilling the internal auditory canal (IAC) was also associated with GTR (χ2 = 21.8, P < .001). Among cases with invasion, GTR was achieved in 88.5% of cases when the IAC was drilled vs 11.8% of cases when the IAC was not drilled. The cranial nerve VII/VIII complex was frequently inferior (45.6%) or superior (19.1%) to the meningioma. Postoperative hearing loss was stable (38.7%) or improved (54.8%) in most of patients at the final clinical follow-up (median: 39.4 months). 25.3% of patients had progression/recurrence, with some difference between World Health Organization grade 1 (median: 3.0 years, IQR: 2.9 years) and World Health Organization grade 2 (median: 1.6 years, IQR: 2.8 years) tumors. After multivariate adjustment, Simpson grade I (P = .02), Simpson grade II (P = .01), or being of older age (P = .003) were associated with lower odds of progression/recurrence., Conclusion: GTR remains critical to achieve optimal symptom control and reduce progression/recurrence rates for CPA meningiomas. Drilling the IAC is an important predictor of GTR in tumors with intracanalicular invasion., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Macrophages play a central role in cardiovascular diseases, like atherosclerosis, by accumulating in vessel walls and inducing sustained local inflammation marked by the release of chemokines, cytokines, and matrix-degrading enzymes. Recent studies indicate that 6'-sialyllactose (6'-SL) may mitigate inflammation by modulating the immune system. Here, we examined the impact of 6'-SL on lipopolysaccharide (LPS)-induced acute inflammation using RAW 264.7 cells and a mouse model. In vivo , ICR mice received pretreatment with 100 mg/kg 6'-SL for 2 h, followed by intraperitoneal LPS injection (10 mg/kg) for 6 h. In vitro , RAW 264.7 cells were preincubated with 6'-SL before LPS stimulation. Mechanistic insights were gained though Western blotting, qRT-PCR, and immunofluorescence analysis, while reactive oxygen species (ROS) production was assessed via DHE assay. 6'-SL effectively attenuated LPS-induced p38 MAPK and Akt phosphorylation, as well as p65 nuclear translocation. Additionally, 6'-SL inhibited LPS-induced expression of tissue damage marker MMP9, IL-1β, and MCP-1 by modulating NF-κB activation. It also reduced ROS levels, mediated by p38 MAPK and Akt pathways. Moreover, 6'-SL restored LPS-suppressed Nrf2 and HO-1 akin to specific inhibitors SB203580 and LY294002. Consistent with in vitro results, 6'-SL decreased oxidative stress, MMP9, and MCP-1 expression in mouse endothelium following LPS-induced macrophage activation. In summary, our findings suggest that 6'-SL holds promise in mitigating atherosclerosis by dampening LPS-induced acute macrophage inflammation.