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Introduction: People with opioid use disorder (OUD) on buprenorphine smoke at high rates and have low cessation rates, even with evidence-based medications. Electronic cigarettes (EC) are a promising harm reduction strategy for combusted cigarette (CC) smokers unable to quit. Unfortunately, people with OUD are underrepresented in EC research., Methods: A pilot study assessed the feasibility, acceptability, and preliminary effectiveness of EC as a harm reduction tool among CC smokers with OUD on buprenorphine (N=30). Participants were provided with an EC and freebase nicotine liquid (6mg/mL) with a choice of flavor, and a brief training session. Research visits were scheduled in-person at baseline, week 4, and week 8 (follow-up). Daily diary assessments were completed during the 4-week EC period., Results: Most visits (>74%) and 61.4% of daily diary assessments were completed. During the 4-week study period, 90% of participants used the EC at least one day, 66.7% used the EC for at least 16 days, and 43.3% used the EC every day. Significant reductions were observed between baseline and both weeks 4 and 8 in cigarettes smoked per day (CPDbaseline=16.2(8.3), CPDweek4=9.6(9.3), CPDweek8=8.4(8.3)) carbon monoxide (CO) levels (CObaseline=21.5(15.0), COweek4=16.9(9.6), COweek8=15.7(10.0)), and nicotine dependence measured using the Fagerström Test for Nicotine Dependence (FTNDbaseline=5.4(2.5), FTNDweek4=4.2(2.6), FTNDweek8=4.4(2.6))), with all p-values<.05., Conclusions: Implementing an EC protocol in outpatient maintenance treatment programs is feasible and acceptable. Preliminary results suggest that ECs may facilitate reductions in CPD, CO levels, and nicotine dependence. Future research should explore the effect of prolonged EC use on harm reduction and cessation milestones., Implications: EC are a potentially promising harm reduction strategy for adult CC smokers with OUD on buprenorphine who are unable to quit using evidence-based medications. However, previous studies have largely overlooked people with OUD on buprenorphine with recent drug use. This study addresses this gap through a pilot trial investigating the feasibility, acceptability, and preliminary effects of EC on CC behavior. The brief and standardized nature of the protocol and its implementation in outpatient settings highlights its potential for widespread implementation in facilities providing care to people with OUD on buprenorphine., (© 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.)

Background: Questions remain on the relationship between pain and hepatitis C virus cure among persons who inject drugs (PWID). This study aimed to explore whether achieving hepatitis C virus cure reduced pain severity., Methods: Prespecified secondary analysis utilized data from a pragmatic clinical trial of care delivery models that enrolled PWIDs between 2016 and 2018 and treated with sofosbuvir/velpatasvir. Current pain severity (0-100) was assessed before and after treatment and 5-point Likert pain scales were used to determine moderate or greater current pain at baseline; the duration and etiology of current pain were not assessed. We used generalized mixed-effects linear models to test whether achieving sustained virologic response (SVR), that is, cure, was associated with lower numeric pain scores (primary outcome) posttreatment, adjusting for potential confounders (age, sex, intervention assignment, time/visit, and baseline pain severity category) and to examine changes in pain over time. Adjusted means estimated from a fitted model for pain severity at each visit were compared between participants who did and did not achieve SVR, both for the sample overall and for the subsample of participants who reported moderate or greater pain at baseline., Results: Of the 501 participants who were randomized, treated with DAAs and had SVR data, moderate or greater pain was reported at baseline in 174 (34.7%) of participants. Numeric pain severity did not significantly differ by SVR status at any study visit except for the week 48 visit from baseline, when the estimated pain score was significantly higher for those who failed treatment (38.0 vs 26.3, P = 0.033). Among the subsample with baseline moderate or greater pain, pain severity scores were significantly lower in subsequent visits compared to the baseline visit, with the exception of week 48 among participants who did not achieve SVR., Conclusions: Among PWID, achieving SVR did not improve pain severity. However, participants who failed treatment had significantly greater pain at the visit immediately following visit for SVR, which may relate to adverse psychological effects of treatment failure. Among those with baseline moderate or greater pain, pain scores declined post treatment, suggesting that treatment itself (irrespective of SVR) may be associated with improved pain., Competing Interests: Conflicts of interest: JF has received research grant support from Gilead Sciences. AYK has served on advisory boards for Biomarin. AYK has a DSMB relationship with Kintor Pharmaceuticals, Inc. AHL has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. SHM has received speaker fees from Gilead Sciences. OFN has received research grants paid to her institution from AbbVie Inc. All other authors had nothing to disclose., (Copyright © 2024 American Society of Addiction Medicine.)

Background: We investigated whether nutritional intake is associated with physical activity (PA) and handgrip strength (HGS) in individuals with airflow limitation., Methods: This study analyzed data from the 2014 to 2016 Korean National Health and Nutrition Examination Survey. We assessed total protein intake (g/day), caloric intake (kcal/day), and other nutritional intakes using a 24-hour dietary recall questionnaire. HGS was measured three times for each hand using a digital grip strength dynamometer, and PA was assessed as health-enhancing PA. Airflow limitation was defined as a forced expiratory volume/forced vital capacity ratio of 0.7 in individuals over 40 years of age. Participants were categorized into groups based on their PA levels and HGS measurements: active aerobic PA vs. non-active aerobic PA, and normal HGS vs. low HGS., Results: Among the 622 individuals with airflow limitation, those involved in active aerobic PA and those with higher HGS had notably higher total food, calorie, water, protein, and lipid intake. The correlations between protein and caloric intake with HGS were strong (correlation coefficients = 0.344 and 0.346, respectively). The forest plots show that higher intakes of food, water, calories, protein, and lipids are positively associated with active aerobic PA, while higher intakes of these nutrients are inversely associated with low HGS. However, in the multivariate logistic regression analysis, no significant associations were observed between nutritional intake and active aerobic PA or HGS., Conclusion: Nutritional intake was not found to be an independent factor associated with PA and HGS. However, the observed correlations suggest potential indirect effects that warrant further investigation.

A footnote in Adolphe Quetelet's classic 1835 Treatise on Man described his algebraic analysis of how body weight ( W $$ W $$ ) varies with height ( H $$ H $$ ) in adult males and females. Using data on 12 short and 12 tall subjects of each sex, Quetelet established the rule that W $$ W $$ is approximately proportional ( ∝ $$ \propto $$ ) to H 2 in adults; that is, W ∝ H 2 $$ W\propto {H}^2 $$ when W ≈ α H 2 $$ W\approx \alpha {H}^2 $$ for some constant α $$ \alpha $$ . Quetelet's Rule ( W ∝ H 2 $$ W\propto {H}^2 $$ ), transformed and renamed in the twentieth century to body mass index ( BMI = W / H 2 $$ \mathrm{BMI}=W/{H}^2 $$ ), is now a globally applied phenotypic descriptor of adiposity at the individual and population level. The journey from footnote to ubiquitous adiposity measure traveled through hundreds of scientific reports and many more lay publications. The recent introduction of highly effective pharmacologic weight loss treatments has heightened scrutiny of BMI's origins and appropriateness as a gateway marker for diagnosing and monitoring people with obesity. This contemporary context prompted the current report that delves into the biological and mathematical paradigms that underlie the simple index BMI = W / H 2 $$ \mathrm{BMI}=W/{H}^2 $$ . Students and practitioners can improve or gain new insights into their understanding of BMI's historical origins and quantitative underpinning from the provided overview, facilitating informed use of BMI and related indices in research and clinical settings., (© 2024 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Despite decades of extensive research on thermoelectric materials, Bi 2 Te 3 alloys have dominated room-temperature applications. However, recent advancements have highlighted the potential of alternative candidates, notably Mg 3 Sb 2 -Mg 3 Bi 2 alloys, for low- to mid-temperature ranges. This study optimizes the low-temperature composition of this alloy system through Nb addition (Mg 3.2- x Nb x (Sb 0.3 Bi 0.7 ) 1.996 Te 0.004 ), characterizing composition, microstructure, and transport properties. A high Mg 3 Bi 2 content improves the band structure by increasing weighted mobility while enhancing the microstructure. Crucially, it suppresses detrimental grain boundary scattering effects for room-temperature applications. While grain boundary scattering suppression is typically achieved through grain growth, our study reveals that Nb addition significantly reduces grain boundary resistance without increasing grain size. This phenomenon is attributed to a grain boundary complexion transition, where Nb addition transforms the highly resistive Mg 3 Bi 2 -rich boundary complexion into a less resistive, metal-like interfacial phase. This marks the rare demonstration of chemistry noticeably affecting grain boundary interfacial electrical resistance in Mg 3 Sb 2 -Mg 3 Bi 2 . The results culminate in a remarkable advancement in zT , reaching 1.14 at 330 K. The device ZT is found to be 1.03 at 350 K, which further increases to 1.24 at 523 K and reaches a theoretical maximum device efficiency (η max ) of 10.5% at 623 K, underscoring its competitive performance. These findings showcase the outstanding low-temperature performance of n -type Mg 3 Bi 2 -Mg 3 Sb 2 alloys, rivaling Bi 2 Te 3 , and emphasize the critical need for continued exploration of complexion phase engineering to advance thermoelectric materials further.

Objective: To compare and analyze professional (P chart) and simple (S chart) clinical image evaluation charts for evaluating panoramic radiograph image quality., Methods: Ten evaluators assessed 285 clinical panoramic radiograph images. The evaluators were divided into oral and maxillofacial radiologists (OMFR, n = 5) and general dentist (dentists not specializing in oral and maxillofacial radiology, G, n = 5) groups. For image evaluation, P and S charts provided by the Korean Academy of Oral and Maxillofacial Radiology were used. Scores of items for each evaluation chart were used to compare the reliability, correlation, evaluation scores, evaluation time, and preference, and statistical analyses were performed using IBM SPSS Statistics., Results: The S chart showed similar levels of evaluation scores at shorter evaluation time, as compared to the P chart. In the results for each evaluation chart, all analyzed correlations were statistically significant. Total score, image density/contrast/sharpness, and overall image quality items showed a very high positive correlation in the P chart. While the overall range of correlation coefficients was relatively lower in the S chart than the P chart, the same items showed high correlation coefficients. In the preference evaluation, both the professional and generalist groups preferred the S chart., Conclusions: A comparative analysis with the P chart, revisions, and upgrades are needed for the S chart items that showed low correlations in this study, such as artifacts, coverage area, and patient movement., (© 2024. The Author(s).)

Background: Endothelial activation and stress index (EASIX) reflects endothelial dysfunction or damage. Because endothelial dysfunction is one of the key mechanisms, a few studies have shown the clinical usefulness of original and age-adjusted EASIX (age-EASIX) in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical utility of age-EASIX in predicting intensive care unit (ICU) mortality in critically ill patients with COVID-19 in South Korea., Methods: Secondary analysis was performed using clinical data retrospectively collected from 22 nationwide hospitals in South Korea between January 1, 2020, and August 31, 2021. Patients were at least 19 years old and admitted to the ICU for severe COVID-19, demanding at least high-flow nasal cannula oxygen therapy. EASIX [lactate dehydrogenase (U/L)×creatinine (mg/dL)/platelet count (109 cells/L)] and age-EASIX (EASIX×age) were calculated and log2-transformed., Results: The mean age of 908 critically ill patients with COVID-19 was 67.4 years with 59.7% male sex. The mean log2 age-EASIX was 7.38±1.45. Non-survivors (n=222, 24.4%) in the ICU had a significantly higher log2 age-EASIX than of survivors (8.2±1.52 vs. 7.1±1.32, p&lt;0.001). log2 age-EASIX was significantly associated with ICU mortality (odds ratio, 1.541; 95% confidence interval, 1.322 to 1.796; p&lt;0.001) and had a better area under the receiver operating characteristic curve than of the sequential organ failure assessment (SOFA) score in predicting ICU mortality (0.730 vs. 0.660, p=0.001)., Conclusion: Age-EASIX is significantly associated with ICU mortality and has better discriminatory ability than the SOFA score in predicting ICU mortality.

Heterogeneity of outcomes across different clinical trial study sites is often inevitable. Understanding how outcomes differ by site is important for planning future programs and studies. We examined the extent of heterogeneity of hepatitis C virus (HCV) treatment cascade outcomes among persons who inject drugs (PWIDs) across sixteen clinical sites utilized in the HERO Study-a pragmatic randomized trial of HCV treatment support. Treatment cascade outcomes included averages of overall treatment adherence and proportions of treatment initiation, treatment completion, sustained virologic response (SVR) test completion, and SVR achievement. The HERO study utilized 16 clinical sites across the United States (US): eight opioid treatment programs (OTPs) and eight community health centers (CHCs). Variability of the outcomes across the 16 clinical sites was assessed using ranges and intraclass correlation coefficients (ICC) estimated from mixed-effects linear or logistic regression models. Treatment initiation was analyzed in the intention-to-treat (ITT) sample (N = 755); treatment completion, adherence, and SVR test completion in the modified ITT (mITT) sample, which is the sample that initiated treatment (N = 623); and SVR achievement in the mITT and per-protocol (PP, N = 501) samples. Across the 16 clinical sites, the range observed in the averages of overall treatment adherence was from 68% to 81% [ICC = 0.026 (0.005, 0.054)], and the ranges of proportions observed were from 68% to 96% for treatment initiation [ICC (95% CI) = 0.086 (0.051, 0.155)], 60% to 100% for treatment completion [ICC = 0.049 (0.008, 0.215)], 54% to 95% for SVR test completion [ICC = 0.096 (0.006, 0.177)], 46% to 90% for SVR achievement in the mITT sample [ICC = 0.070 (0.014, 0.122)], and 76% to 100% for SVR achievement in the PP sample [ICC = 0.143 (0.021, 0.422)]. The variability of the outcomes across 16 US sites treating HCV among PWIDs appears to be substantial in view of the ranges and ICC values of the outcomes. It is imperative to develop tailored interventions to target the sources of variability and reduce barriers at the patient, provider, clinic, and state policy levels to facilitate more equitable access to HCV treatment and reduce heterogeneity in treatment outcomes.

Background: Self-efficacy, a patient-level factor, has been shown to facilitate patient engagement in treatment and optimize treatment-related outcomes in various health contexts. Research on interventions supporting hepatitis C virus (HCV) direct-acting antiviral (DAA) treatment uptake and adherence among persons who inject drugs (PWID) is needed, but whether self-efficacy factors influence DAA treatment cascade outcomes in this population has been less studied., Methods: Using the HERO study data, we analyzed a subset of participants with any general health self-efficacy data (n=708) measured at baseline and end-of-treatment time points using a 5-items instrument (facets: 'goal setting', 'goal attainment', 'having a positive effect', 'being in control', and 'working to improve'). The cascade outcomes included DAA treatment initiation, duration, adherence, completion, and sustained virologic response (SVR). The effect of baseline and change (Δ) scores for composite and item-level self-efficacy on the cascade outcomes was assessed using logistic regression and generalized linear models., Results: Higher baseline composite self-efficacy [adjusted odds ratio (95 % confidence interval) =1.57 (1.07, 2.29)], 'goal attainment' [1.31 (1.03, 1.67)] and 'having a positive effect' [1.33 (1.03, 1.74)] were associated with greater likelihood of treatment initiation. 'Δ Goal attainment' was significantly associated with SVR [1.63 (1.04, 2.53)]. 'Δ Being in control' and 'Δ working to improve' were associated with treatment adherence and duration, respectively., Conclusions: General health self-efficacy positively influences DAA treatment initiation among PWID. 'Goal attainment' facilitates the achievement of DAA treatment-related outcomes. Further studies should assess the effect of self-efficacy related to performing healthcare tasks specific to DAAs on the treatment-related outcomes., Competing Interests: Declaration of Competing Interest JF has received research grant support from Gilead Sciences. AYK has served on advisory boards for BioMarin. AHL has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. SHM has received speaker fees from Gilead Sciences. All other authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

This study is a secondary analysis of a randomized clinical trial (October 2013-April 2017) involving 150 People Who Inject Drugs (PWIDs) with hepatitis C virus (HCV) seen in opioid agonist treatment programs in the Bronx, New York, and investigates the impact of distrust in the healthcare system on adherence to Direct-Acting Antivirals (DAAs) HCV treatment therapy among PWIDs. The distrust was scaled on a 9-item instrument and the adherence to DAA medications was measured using electronic blister packs. This study demonstrated a significant inverse relationship between levels of distrust and medication adherence: 71.8 ± 2.2% (se) vs. 77.9 ± 1.8%, p = 0.024 between participants with higher and lower distrust levels. Despite the absence of significant association of distrust with sociodemographic or substance use characteristics, these findings suggest that building trust within the healthcare system is paramount for improving adherence to DAAs among PWIDs. The results call for a healthcare approach that emphasizes trust-building through patient-centered care, sensitivity training, peer support, and health system reform to effectively address the treatment needs of this marginalized population.

Importance: Hepatitis C virus (HCV) reinfection after curative treatment remains a concern for people who inject drugs., Objective: To assess the incidence of HCV reinfection and associated risk factors., Design, Setting, and Participants: This cohort study is a secondary analysis of a randomized clinical trial that was conducted across opioid treatment programs and community health centers in the US between September 2016 and August 2018. The current analyses were performed in March 2022. People who inject drugs who achieved sustained virologic response (SVR) were followed for up to 42 months., Exposure: Patients were randomly assigned to receive modified directly observed therapy or patient navigation., Main Outcomes and Measures: The primary outcome was rate of HCV reinfection. Change in reinfection rates over time was assessed using a Poisson regression model., Results: A total of 415 participants (mean [SD] age, 44.7 [11.5] years; 302 male [72.8%]) achieved a SVR and had 1 or more post-SVR assessments for HCV RNA. Overall, 302 (72.8%) reported recent injection drug use, 192 (46.3%) were living in unstable housing, and 313 (75.4%) had received recent methadone or buprenorphine for opioid use disorder. The overall reinfection rate was 11.4 per 100 person-years at risk (95% CI, 8.7-14.7 per 100 person-years at risk) over 518 person-years of follow-up. Reinfection rates varied significantly across sites, ranging from 2.9 per 100 person-years at risk (95% CI, 0.1-16.3 per 100 person-years) to 25.2 per 100 person-years at risk (95% CI, 15.6-38.5 per 100 person-years at risk) (P = .006). There was a significant decrease in incident reinfection with increasing post-SVR follow-up (weeks 0-24, 15.5 per 100 person-years; 95% CI, 10.3-22.3 per 100 person-years; weeks 73-144, 4.3 per 100 person-years; 95% CI, 0.9-12.5 per 100 person-years; P = .008). Reinfection rates were lower for participants aged 40 years or older than for younger participants (adjusted incidence rate ratio, 0.32; 95% CI, 0.18-0.57) and for participants for whom methamphetamine was not detected in urinary drug screening compared with participants for whom methamphetamine was detected (adjusted incidence rate ratio, 0.41; 95% CI, 0.21-0.82). Participants who reported injection drug use within the preceding 3 months had higher risk of reinfection than those who did not have recent injection drug use (adjusted incidence rate ratio, 3.33; 95% CI, 1.86-5.97)., Conclusions and Relevance: In this cohort study of people who injected drugs and were treated for HCV infection in community settings, reinfection was high in the period immediately after SVR but decreased significantly over time. These findings highlight the importance of early intervention to prevent reinfection., Trial Registration: ClinicalTrials.gov Identifier: NCT02824640.

Rationale: Immune-mediated vasculitis with 2 or more autoantibodies, for example, anti-proteinase-3, combined with anti-myeloperoxidase (MPO) or anti-glomerular basement membrane (GBM) antibodies, is extremely unusual. Furthermore, the coexistence of autoimmune vasculitis and hematological malignancies is uncommon. Herein, we describe a case of double-seropositive anti-neutrophil cytoplasmic antibody (ANCA) vasculitis with multiple myeloma., Patient Concerns: A 79-year-old Asian man presented with persistent leg edema and kidney dysfunction. His kidney function rapidly decreased, and serologic test results showed higher titers of the anti-MPO antibody (54.7 IU/mL) and anti-GBM antibodies (>200 IU/mL). Additionally, the clinical features showed the possibility of monoclonal gammopathy with anemia and hyperglobulinemia. We performed kidney and bone marrow biopsy. Serum protein electrophoresis and immunofixation revealed no significant differences, but the results of the bone marrow smear were compatible with those of myeloma with 15% plasmacytosis. However, kidney biopsy showed diffuse crescentic glomerulonephritis without deposition of the immune complex or kappa/lambda chain., Diagnoses and Interventions: Finally, the patient was diagnosed with double-seropositive ANCA-associated glomerulonephritis and multiple myeloma. Given the patient's performance status, we initiated low-dose steroid pulse therapy, followed by conservative management., Outcomes: While the pulmonary lesions showed improvement, the kidney function did not regain its previous state, prompting the initiation of kidney replacement therapy by hemodialysis. There has been a decrease in the levels of anti-GBM and anti-MPO antibodies since the initial diagnosis., Lessons: This case elucidates the complex interplay between ANCA-associated glomerulonephritis and hematologic malignancy and emphasizes the need for a nuanced treatment strategy considering its multifaceted clinical presentation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study assesses the clinical performance of BTXBrain-Amyloid, an artificial intelligence-powered software for quantifying amyloid uptake in brain PET images., Methods: 150 amyloid brain PET images were visually assessed by experts and categorized as negative and positive. Standardized uptake value ratio (SUVR) was calculated with cerebellum grey matter as the reference region, and receiver operating characteristic (ROC) and precision-recall (PR) analysis for BTXBrain-Amyloid were conducted. For comparison, same image processing and analysis was performed using Statistical Parametric Mapping (SPM) program. In addition, to evaluate the spatial normalization (SN) performance, mutual information (MI) between MRI template and spatially normalized PET images was calculated and SPM group analysis was conducted., Results: Both BTXBrain and SPM methods discriminated between negative and positive groups. However, BTXBrain exhibited lower SUVR standard deviation (0.06 and 0.21 for negative and positive, respectively) than SPM method (0.11 and 0.25). In ROC analysis, BTXBrain had an AUC of 0.979, compared to 0.959 for SPM, while PR curves showed an AUC of 0.983 for BTXBrain and 0.949 for SPM. At the optimal cut-off, the sensitivity and specificity were 0.983 and 0.921 for BTXBrain and 0.917 and 0.921 for SPM12, respectively. MI evaluation also favored BTXBrain (0.848 vs. 0.823), indicating improved SN. In SPM group analysis, BTXBrain exhibited higher sensitivity in detecting basal ganglia differences between negative and positive groups., Conclusion: BTXBrain-Amyloid outperformed SPM in clinical performance evaluation, also demonstrating superior SN and improved detection of deep brain differences. These results suggest the potential of BTXBrain-Amyloid as a valuable tool for clinical amyloid PET image evaluation., Competing Interests: Conflict of InterestSeung Kwan Kang, Seong A Shin, and Jae Sung Lee are Brightonix Imaging Inc.’s employees. Mina Heo, Ji Yeon Chung, Daewoon Kim, Hongyoon Choi, Ari Chong, Jung-Min Ha, and Hoowon Kim declare that they have no conflict of interest., (© The Author(s) 2024.)

Background & Aims: Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR., Methods: Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined., Results: The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04-1.16; p <0.001) even among participants with ≥14 consecutive missed days., Conclusions: High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR., Impact and Implications: People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers., Clinical Trial Number: NCT02824640., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6-phosphate, phosphoenolpyruvate, lactate, and inosine monophosphate, in those inhabiting polluted areas. An investigation of the associations between metabolites and blood clinical parameters through meet-in-the-middle analysis indicated that female residents were more affected by heavy metal exposure, resulting in more metabolomic alterations. For women, inhabiting the abandoned mine area, metabolites in the glycolysis and pentose phosphate pathways, such as ribose-5-phosphate and 3-phosphoglycerate, have shown a negative correlation with albumin and calcium. Finally, Mendelian randomization(MR) was used to determine the causal effects of these heavy metal exposure-related metabolites on heavy metal exposure-related clinical parameters. Metabolite biomarkers could provide insights into altered metabolic pathways related to exposure to toxic heavy metals and improve our understanding of the molecular mechanisms underlying the health effects of toxic heavy metal exposure., 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 Ltd.. All rights reserved.)

Background: This study evaluates a novel multidisciplinary program providing expanded access to hepatitis C virus (HCV) treatment for rural Appalachian patients in South Carolina. This program identified patients via an opt-out emergency department screening program, and it aimed to achieve HCV cure by using community paramedics (CPs) to link and monitor patients from treatment initiation through 12-week sustained virologic response (SVR)., Methods: Patients aged ≥18 years who were HCV RNA positive were eligible for enrollment if they failed to appear for a scheduled HCV appointment or reported barriers to accessing office-based treatment. CPs provided home visits (initial and 4, 12, and 24 weeks) using a mobile Wi-Fi hotspot to support telemedicine appointments (compliant with the Health Insurance Portability and Accountability Act) and perform focused physical assessments, venipuncture, and coordinated home delivery of medications. Statistics described participant characteristics, prevalence of SVR, and patient satisfaction results at 12 weeks posttreatment., Results: Thirty-four patients were eligible for SVR laboratory tests by 31 August 2023; the majority were male (61.7%) and White (64.7%) with an average age of 56 years (SD, 11.7). Twenty-eight (82.4%) completed treatment and achieved 12-week SVR. Six (17.6%) were lost to follow-up. Two-thirds strongly agreed that they were satisfied with the overall care that they received, and half strongly agreed that their overall health had improved., Conclusions: This CP-augmented treatment program demonstrated success curing HCV for rural patients who lacked access to office-based treatment. Other health care systems may consider this novel delivery model to treat hard-to-reach individuals who are HCV positive., Competing Interests: Potential conflicts of interest. A. H. L. has served on advisory board for Merck Pharmaceuticals, AbbVie and Gilead Sciences. A. H. L. has received research grants from Merck Pharmaceuticals and Gilead Sciences. P. M. has received research grants from Gilead Sciences. No other authors declared any conflict of interest related to this work., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The Mini-Mental State Examination (MMSE) is a widely employed screening tool for the severity of cognitive impairment. Among the MMSE items, the pentagon copying test (PCT) requires participants to accurately replicate a sample of two interlocking pentagons. While the PCT is traditionally scored on a binary scale, there have been limited developments of granular scoring scale to assess task performance. In this paper, we present a novel three-stage algorithm, called Quantification of Interlocking Pentagons (QIP) which quantifies PCT performance by computing the areas of individual pentagons and their intersection areas, and a balance ratio between the areas of the two individual pentagons. The three stages of the QIP algorithm include: (1) detection of line segments, (2) unraveling of the interlocking pentagons, and (3) quantification of areas. A set of 497 PCTs from 84 participants including their baseline and follow-up PCTs from the Rush Memory and Aging Project was selected blinded about their cognitive and clinical status. Analysis of the quantified data revealed a significant inverse relationship between age and balance ratio (beta = - 0.49, p = 0.0033), indicating that older age was associated with a smaller balance ratio. In addition, balance ratio was associated with perceptual speed (r = 0.71, p = 0.0135), vascular risk factors (beta = - 3.96, p = 0.0269), and medical conditions (beta = - 2.78, p = 0.0389). The QIP algorithm can serve as a useful tool for enhancing the scoring of performance in the PCT., (© 2024. The Author(s).)

Galectins play a pivotal role in lung cancer oncogenic pathways, influencing apoptosis, angiogenesis, and tumor metastasis. Biomarkers that diagnose, prognose, and guide cancer treatment are crucial, with galectins having the biomarker potential for non-small cell lung cancer (NSCLC). Using enzyme-linked immunosorbent assay (ELISA), we assessed serum galectin-1, -3, and -9 levels in NSCLC patients. A retrospective chart review was performed to examine patient demographics, cancer stage, tumor biology, cancer treatment, and patient outcomes. Galectin levels were then compared across these factors. In this exploratory analysis, galectin-3 levels were significantly lower in patients with squamous cell lung cancer ( p = 0.0019) and in patients exposed to chemotherapy ( p = 0.0375). Galectin-1 levels were significantly lower in patients with previous metastasis but had no correlation with future metastasis. Abnormal galectin-1 levels were significantly correlated with decreased overall survival (OS) in NSCLC ( p = 0.0357) and specifically in patients with surgically resectable NSCLC ( p = 0.0112). However, abnormal galectin-1 levels were not found to correlate with decreased OS in multivariable analysis ( p = 0.0513). These findings may have clinical implications as galectin-3 inhibitors are in trials for NSCLC. Additionally, they suggest that galectin-1 has potential as a prognostic marker for surgically resectable NSCLC.

SnSe 2 with its layered structure is a promising thermoelectric material with intrinsically low lattice thermal conductivity. However, its poor electronic transport properties have motivated extensive doping studies. Br doping effectively improves the power factor and converts the dimorphic SnSe 2 to a fully hexagonal structure. To understand the mechanisms underlying the power factor improvement of Br-doped SnSe 2 , the electronic band parameters of Br-doped dimorphic and hexagonal SnSe 2 should be evaluated separately. Using the single parabolic band model, we estimate the intrinsic mobility and effective mass of the Br-doped dimorphic and hexagonal SnSe 2 . While Br doping significantly improves the mobility of dimorphic SnSe 2 (with the dominant hexagonal phase), it results in a combination of band convergence and band flattening in fully hexagonal SnSe 2 . Br-doped dimorphic SnSe 2 is predicted to exhibit higher thermoelectric performance ( zT ∼0.23 at 300 K) than Br-doped fully hexagonal SnSe 2 ( zT ∼0.19 at 300 K). Characterisation of the other, currently unidentified, structural phases of dimorphic SnSe 2 will enable us to tailor the thermoelectric properties of Br-doped SnSe 2 ., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Self-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold., Methods: This study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold., Results: The self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis., Conclusions: Self-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence., (© 2024. The Author(s).)

Rationale: Epiglottic retroversion is the abnormal movement of the epiglottis to the rima glottis, resulting in blockage of inspiratory airflow. Acute upper airway obstruction caused by epiglottic retroversion can lead to sudden respiratory failure. Epiglottic retroversion has occasionally been reported in horses and dogs; however it is extremely rare in humans. Herein, we report a case of epiglottic retroversion causing recurrent upper airway obstruction in human., Patient Concerns: We present the case of a 74-year-old man who was diagnosed with epiglottic retroversion without evidence of epiglottis. The patient presented with recurrent episodes of abnormal breathing sounds and dyspnea. Inspiratory stridor was evident whenever the patient experienced dyspnea., Diagnosis: Epiglottic retroversion was diagnosed as the cause of upper airway obstruction using fiber-optic bronchoscopy., Interventions: The patient underwent tracheostomy to prevent acute respiratory failure because the recurrent episodes of stridor and dyspnea did not improve., Outcomes: The episodic dyspnea and oxygen desaturation did not relapse after tracheostomy and he could be discharged home., Lessons: This case highlights the importance of considering epiglottic retroversion as a cause of acute upper airway obstruction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Treating hepatitis C virus (HCV) in people who inject drugs (PWID) has been associated with increased health-related quality of life (HRQOL). Polysubstance use (PSU) is common among PWID, but no studies have investigated PSU influence on PWID's HRQOL HCV treatment., Methods: Participants included 150 PWID receiving HCV treatment at opioid agonist treatment clinics in Bronx, NY. The EQ-5D-3L measurement tool assessed five health dimensions producing an index of HRQOL measured at baseline, 4-, 8-, and 12-weeks during treatment and 12- and 24-weeks post-treatment. PSU was determined at baseline. Generalized estimating equations assessed the influence of baseline PSU on changes in mean EQ-5D-3L index over time., Results: Of the 150 participants, 46 (30.7%) reported PSU and mean HRQOL overall was 0.655, indicating moderate HRQOL. Mean HRQOL was lower at all time-points for the PSU group compared to the non-PSU group. Though PSU group showed improvements in mean HRQOL from baseline (0.614) to 4-, 12- and follow-up week 24 (0.765, 0.768, and 0.731, respectively), the mean change of HRQOL scores was not significantly associated with PSU (p-value=0.956)., Conclusions: For individuals with PWID, our study showed no difference in HRQOL between those who did and did not engage in PSU following HCV treatment., Competing Interests: AHL has served on advisory board for Merck Pharmaceuticals, AbbVie and Gilead Sciences. He has received research grants from Merck Pharmaceuticals and Gilead Sciences. No other authors declared any conflict of interest related to this work.

Introduction: Behavioral and mental health conditions present significant challenges in the United States where access to care is limited. Family medicine physicians play a crucial role in addressing these challenges, often serving as frontline clinicians for behavioral and mental health conditions., Methods: This study examined the current behavioral and mental health system in a predominantly rural 10-county region in the Southeastern United States through gap analysis in addition to a survey of preparedness and barriers among family medicine physicians in the region., Results: Gap analysis results indicated that (1) stigma and lack of accessible education about behavioral and mental health, (2) fragmented resources, (3) inaccessible care, and (4) workforce shortage and burnout were primary drivers of poor outcomes in the region. Survey results indicated that physicians feel prepared to treat anxiety and depression but feel less prepared to manage bipolar disorder, schizophrenia, and substance use disorders. Respondents disagreed that there are adequate local resources and referral options for patients with behavioral and mental health conditions. Lack of timely access, distance, cost/insurance status, were all cited by respondents as barriers to appropriate care., Conclusion and Recommendations: Findings underscore the importance of supporting family medicine physicians to enhance behavioral and mental healthcare outcomes. Behavioral health integration in primary care settings is a promising strategy to improve care accessibility and clinician preparedness. Bridging gaps in health care outcomes requires collaborative efforts, enhanced training, and policy advocacy within the family medicine community to ensure comprehensive and equitable behavioral and mental healthcare delivery., 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.

Background: Objective adherence measures, such as electronic blister pack (BP), for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment have high accuracy, but their use is limited in real practice settings. We examined the association of self-reported adherence using a visual analogue scale (VAS) with objective BP adherence and sustained virologic response (SVR) among people who inject drugs., Methods: We conducted secondary analyses using a subset of participants (N = 493) from the per-protocol sample of the HERO study, a pragmatic randomized trial of HCV treatment interventions that used both VAS and BP to measure adherence to a 12-week sofosbuvir/velpatasvir DAA regimen. Multivariable mixed-effects regression models tested the association of self-report adherence level with longitudinal weekly objective adherence. Multivariable logistic regression tested the association of self-report adherence with SVR., Results: The average VAS and BP adherences were 95.1 % (SD = 8.9 %) and 76.0 % (16.0 %), respectively, and the proportion of the participants achieving SVR was 92.9 %. The estimated adjusted mean objective adherence was significantly different (-16 %; 95 % CI: -22 %, -11 %, p < .001) between participants with 100 % and <80 % VAS adherence. The likelihood of SVR was significantly lower for those with <80 % VAS adherence [adjusted OR = 0.07; 95 % CI: 0.02, 0.24; p < .001] compared to those with 100 %., Conclusion: Self-reported adherence overestimated objective adherence. However, higher self-report adherence was significantly associated with higher objective adherence. Also, self-reported adherence ≥80 % was significantly associated with SVR. Thus, the self-report measure has utility as a monitoring tool for adherence during DAA treatment., 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 © 2023. Published by Elsevier B.V.)

Transitional care programs (TCPs), where hospital care team members repeatedly follow up with discharged patients, aim to reduce post-discharge hospital or emergency department (ED) utilization and healthcare costs. We examined the effectiveness of TCPs at reducing healthcare costs, hospital readmissions, and ED visits. Centers for Medicare and Medicaid Services Bundled Payments for Care Improvement (BPCI) program adjudicated claims files and electronic health records from Greenville Memorial Hospital, Greenville, SC, were accessed. Data on post-discharge 30- and 90-day ED visits and readmissions, total costs, and episodes with costs over BPCI target prices were extracted from November 2017 to July 2020 and compared between the "TCP-Graduates" (N = 85) and "Did Not Graduate" (DNG) (N = 1310) groups. As compared to the DNG group, the TCP-Graduates group had significantly fewer 30-day (7.1% vs. 14.9%, p = 0.046) and 90-day (15.5% vs. 26.3%, p = 0.025) readmissions, episodes with total costs over target prices (25.9% vs. 36.6%, p = 0.031), and lower total cost/episode (USD 22,439 vs. USD 28,633, p = 0.018), but differences in 30-day (9.4% vs. 11.2%, p = 0.607) and 90-day (20.0% vs. 21.9%, p = 0.680) ED visits were not significant. TCP was associated with reduced post-discharge hospital readmissions, total care costs, and episodes exceeding target prices. Further studies with rigorous designs and individual-level data should test these findings.

Background: Psycho-social experiences including shame and experienced and internalized stigma have been associated with substance use, HCV infection, and reluctance to disclose HCV status and pursue treatment. These psycho-social barriers have been examined independently for many chronic diseases, including HCV, but to our knowledge have not been quantitatively explored in a large multi-site US-based sample of people who inject drugs (PWID) in HCV treatment., Methods: We examine baseline relationships with HCV-stigma and engagement across the HCV treatment cascade as well as baseline and longitudinal relationships between shame and engagement across the HCV treatment cascade including treatment initiation, adherence, completion, and sustained virologic response (SVR) among a multi-site sample of PWID with HCV, where N=755 were randomized to the pragmatic trial comparing HCV treatment outcomes in modified directly observed treatment (mDOT) or patient navigation, and N=623 initiated treatment., Results: While cross-sectional assessments of shame and HCV-stigma were not associated with engagement across the HCV treatment cascade, those whose shame scores decreased compared to those who reported consistently high and increasing levels of shame were significantly more likely to complete HCV treatment (aOR=5.29; 95%CI: 1.56,18.00) and achieve SVR (aOR=6.32; 95%CI: 1.61, 24.87)., Conclusion: Results underscore the relationships between lower levels of shame and health-related behavior and treatment outcomes among PWID and suggest SVR achievement may contribute to reductions in shame or that reductions in shame may contribute to continued treatment and thus SVR., Competing Interests: Declaration of Competing Interest A.H.L. is a consultant/advisor and has received research grants from AbbVie, Gilead Sciences, and Merck Pharmaceuticals., (Copyright © 2023. Published by Elsevier B.V.)

We conducted a critical review of the article "Effects on Children's Physical and Mental Well-Being of a Physical-Activity-Based School Intervention Program: A Randomized Study", published in the International Journal of Environmental Research and Public Health in 2023 as part of the Special Issue "Psychomotricity and Physical Education in School Health". We identified multiple mistakes in the statistical analyses applied. First, the authors claim to have found a statistically significant association between the proposed intervention and change in body composition (body mass index (BMI) percentiles, relative fat mass, and BMI classes) by way of exhibiting differences in nominal significance between the pre- and post-intervention changes within the control and intervention groups, instead of exhibiting a significant difference between groups. Furthermore, the analysis described fails to account for clustering and nesting in the data. The reporting of the statistical methods and results include multiple elements that are variously incorrect, incoherent, or impossible. Revised statistical analyses are proposed which can render the study's methods valid and its results substantiated, whereas the current methods and results are invalid and unsubstantiated, respectively.

Introduction: An intersectionality framework recognizes individuals as simultaneously inhabiting multiple intersecting social identities embedded within systems of disadvantage and privilege. Previous research links perceived discrimination with worsened health outcomes yet is limited by a focus on racial discrimination in isolation. We applied an intersectional approach to the study of discrimination to examine the association with adverse perinatal health outcomes., Methods: We analyzed data from a cohort of 2,286 pregnant participants (Black, n = 933; Hispanic, n = 471; White, n = 853; and Other, n = 29) from the Centering and Racial Disparities trial. Perceived discrimination was assessed via the Everyday Discrimination Scale (EDS) and perinatal health outcomes collected via electronic medical record review. Latent class analysis was used to identify subgroups of discrimination based on EDS item response and the rate of adverse perinatal health outcomes compared between subgroups using a Bolck, Croon and Hagenaars 3-step approach., Results: Four discrimination subgroups were identified: no discrimination, general discrimination, discrimination attributed to one or several social identities, and discrimination attributed to most or all social identities. Experiencing general discrimination was associated with postpartum depression symptoms when compared with experiencing no discrimination among Black (9% vs 5%, P = .04) and White participants (18% vs 9%, P = .01). White participants experiencing general discrimination gave birth to low birthweight infants at a higher rate than those experiencing no discrimination (11% vs 6%, P = .04). No significant subgroup differences were observed among Hispanic participants., Conclusion: Perceived discrimination may play an influential role in shaping perinatal health. More research applying an intersectional lens to the study of discrimination and perinatal health outcomes is needed.

Background: Depressive symptoms are prevalent among people who inject drugs (PWID) and people with hepatitis C virus (HCV). We examined changes in depressive symptoms among HCV-infected PWID following direct-acting antiviral treatments to evaluate whether these changes differed by history of depressive symptoms, substance use, or HCV treatment outcome., Methods: We conducted a secondary analysis of the HERO Study (NCT02824640), a pragmatic randomized clinical trial among PWID, to test the effectiveness of HCV care models. Depressive symptoms (primary outcome) were measured using the Patient Health Questionnaire (PHQ-9) at baseline, end of treatment (EOT), and at follow-up 12 and 24 weeks after EOT. Sustained virologic response (SVR) was defined as undetectable HCV RNA at ≥12 weeks following EOT. Baseline drug use was defined as having a positive urine screening test for amphetamine, methamphetamine, benzodiazepine, cocaine, cannabis, opiate, or oxycodone., Results: The sample (n = 498) was 72.3% male, 64.2% White, and on average 43.9 years old. In patients who achieved SVR (F(3432) = 4.58; P = .004) and those with drug use at baseline (F(3478) = 5.11; P < .01), PHQ-9 scores significantly declined over time, with scores lower at EOT and both follow-ups as compared with baseline. Mean PHQ-9 scores at EOT and follow-ups were significantly lower than at baseline, except for those with no depression or mild depression at baseline., Conclusions: This study showed that HCV treatment in PWID is associated with sustained declines in depression up to 24 weeks post-treatment among those who achieve SVR and that drug use does not interfere with improvement in depressive symptoms., Competing Interests: Potential conflicts of interest. J.F. has received research grant support from Gilead Sciences. A.Y.K. has served on advisory boards for Biomarin. A.F.L. has received research grant support from Gilead and Merck. The Task Force for Global Health receives funds for the general support of the Coalition for Global Hepatitis Elimination from Abbott, Gilead, AbbVie, Merck, Siemens, Roche, Pharco, Zydus-Cadila, governmental agencies, and philanthropic organizations. A.H.L. has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. S.H.M. has received speaker fees from Gilead Sciences. All other authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Purpose: Chondrosarcoma and synovial chondromatosis of the temporomandibular joint share overlapping clinical and histopathologic features. We aimed to identify CT and MR imaging features to differentiate chondrosarcoma from synovial chondromatosis of the temporomandibular joint., Materials and Methods: The CT and MR images of 12 and 35 patients with histopathologically confirmed chondrosarcoma and synovial chondromatosis of the temporomandibular joint, respectively, were retrospectively reviewed. Imaging features including lesion size, center, enhancement, destruction/sclerosis of surrounding bone, infiltration into the tendon of the lateral pterygoid muscle, calcification, periosteal reaction, and osteophyte formation were assessed. A comparison between chondrosarcoma and synovial chondromatosis was performed with a Student t test for quantitative variables and the Fisher exact test or linear-by-linear association test for qualitative variables. Receiver operating characteristic analysis was performed to determine the diagnostic performance for differentiation of chondrosarcoma and synovial chondromatosis based on a composite score obtained by assigning 1 point for each of 9 imaging features., Results: High-risk imaging features for chondrosarcoma were the following: lesion centered on the mandibular condyle, destruction of the mandibular condyle, no destruction/sclerosis of the articular eminence/glenoid fossa, infiltration into the tendon of the lateral pterygoid muscle, absent or stippled calcification, periosteal reaction, internal enhancement, and size of ≥30.5 mm. The best cutoff value to discriminate chondrosarcoma from synovial chondromatosis was the presence of any 4 of these high-risk imaging features, with an area under the curve of 0.986 and an accuracy of 95.8%., Conclusions: CT and MR imaging features can distinguish chondrosarcoma from synovial chondromatosis of the temporomandibular joint with improved diagnostic performance when a subcombination of 9 imaging features is used., (© 2023 by American Journal of Neuroradiology.)

People on buprenorphine maintenance treatment (BMT) commonly present cognitive deficits that have been associated with illicit drug use and dropout from buprenorphine treatment. This study has compared cognitive responses to the Stroop Task and the Continuous Performance Task (CPT) among individuals on BMT, with recent drug use, and healthy controls and explored the associations between cognitive responses and drug use, craving, and buprenorphine use among participants on BMT. The participants were 16 individuals on BMT and 23 healthy controls. All participants completed a 60 min laboratory session in which they completed the Stroop Task and the CPT, a saliva drug test, a brief clinical history that collected substance-use- and treatment-related information, and the Opioid Craving Scale. The results showed that the BMT participants presented more commission errors (MBMT participants = 2.49; Mhealthy controls = 1.38; p = 0.048) and longer reaction times (MBMT participants = 798.09; Mhealthy controls = 699.09; p = 0.047) in the Stroop Task than did the healthy controls. More days on buprenorphine were negatively associated with reaction time in the CPT (-0.52) and the number of commission errors (-0.53), simple reaction time (-0.54), and reaction time correct (-0.57) in the Stroop Task. Neither drug use nor craving was significantly associated with the results for the cognitive tasks. Relative to the control participants, the BMT individuals performed worse in terms of longer reaction times and more commission errors in the Stroop Task. Within the BMT participants, longer times on buprenorphine were associated with better cognitive results in terms of faster reaction times for both tasks and lower commission errors for the Stroop Task.

Background: Genome-wide dysregulation of CpG methylation accompanies tumor progression and characteristic states of cancer cells, prompting a rationale for biomarker development. Understanding how the archetypic epigenetic modification determines systemic contributions of immune cell types is the key to further clinical benefits., Results: In this study, we characterized the differential DNA methylome landscapes of peripheral blood mononuclear cells (PBMCs) from 76 canines using methylated CpG-binding domain sequencing (MBD-seq). Through gene set enrichment analysis, we discovered that genes involved in the growth and differentiation of T- and B-cells are highly methylated in tumor PBMCs. We also revealed the increased methylation at single CpG resolution and reversed expression in representative marker genes regulating immune cell proliferation (BACH2, SH2D1A, TXK, UHRF1). Furthermore, we utilized the PBMC methylome to effectively differentiate between benign and malignant tumors and the presence of mammary gland tumors through a machine-learning approach., Conclusions: This research contributes to a better knowledge of the comprehensive epigenetic regulation of circulating immune cells responding to tumors and suggests a new framework for identifying benign and malignant cancers using genome-wide methylome., (© 2023. The Author(s).)

Background: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy., Methods: A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model., Results: In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL-COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL-COL ball., Conclusion: Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

Delay discounting describes how rapidly delayed rewards lose value as a function of delay and serves as one measure of impulsive decision-making. Nicotine deprivation among combustible cigarette smokers can increase delay discounting. We aimed to explore changes in discounting following nicotine deprivation among electronic nicotine delivery systems (ENDS) users. Thirty young adults (aged 18-24 years) that exclusively used ENDS participated in two laboratory sessions: one with vaping as usual and another after 16 hr of nicotine deprivation (biochemically assessed). At each session, participants completed a craving measure and three hypothetical delay discounting tasks presenting choices between small, immediate rewards and large, delayed ones (money-money; e-liquid-e-liquid; e-liquid-money). Craving for ENDS significantly increased during short-term nicotine deprivation relative to normal vaping. Delay discounting rates in the e-liquid now versus money later task increased (indicating a shift in preference for smaller, immediate rewards) following short-term nicotine deprivation relative to vaping as usual, but no changes were observed in the other two discounting tasks. Short-term nicotine deprivation increased the preference for smaller amounts of e-liquid delivered immediately over larger, monetary awards available after a delay in this first study of its kind. As similar preference shifts for drug now versus money later have been shown to be indicative of increased desire to use drug as well as relapse risk, the findings support the utility of the current model as a platform to explore interventions that can mitigate these preference shifts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Persons who inject drugs (PWID) are a key population for hepatitis C virus (HCV) treatment. Study aims were to describe injection practices of PWID during HCV treatment with direct-acting antivirals (DAAs) and assess whether injection practices were associated with not achieving a sustained virologic response (SVR)., Methods: Secondary analysis of the HERO Study (ClinicalTrials.gov, NCT02824640), a pragmatic randomized trial in 8 U.S. states to evaluate the effectiveness of HCV care models among active PWID seen in opioid treatment programs and community clinics. Frequency, sharing and reuse of injecting equipment were assessed at baseline, end-of-treatment (EOT) and quarterly visits up to 60 weeks post-treatment. Generalized Estimating Equations logistic regression models with linear spline were used to compare trends in injecting behaviors during vs. post-treatment. Multivariable logistic regression models explored associations between injecting behaviors during treatment and lack of SVR., Results: Among 501 participants, 27% were female, 35% were non-white, mean age was 44 (SD 11.5) years and nearly half (49%) were unhoused. At baseline, 41% reported receptive sharing of injecting equipment, declining to 16% at EOT visit. Receptive sharing of cookers, rinses, or needles/syringes during treatment was associated with a nearly 5-fold increase in not achieving SVR (adjusted odds ratio (aOR)=4.83; 95% CI: 2.26, 10.28) as was reuse of one's own needles/syringes (aOR=2.37; 95% CI: 1.11, 4.92)., Conclusions: PWID in the HERO study adopted safer injecting behaviors during DAA treatment; receptive sharing of injecting equipment and reuse of one's own equipment during treatment were associated with not achieving cure., Competing Interests: Declaration of Competing Interest FN has served on advisory panels for Gilead Sciences and reports research funds from AbbVie paid to Johns Hopkins University. JF has received research grant support from Gilead Sciences. AYK has served on advisory boards for Biomarin. AFL received research grant support from Gilead and Merck. The Task Force for Global Health receives funds for the general support of the Coalition for Global Hepatitis Elimination from Abbott, Gilead, AbbVie, Merck, Siemens, Roche, Pharco, Zydus-Cadila, governmental agencies, and philanthropic organizations. AHL has served on advisory boards for Gilead Sciences and Merck Pharmaceuticals and received research funding from Gilead Sciences. Dr. Mehta has received speaker fees from Gilead Sciences. LT has received UpToDate Royalties for peer review of viral hepatitis topics. All other authors had nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Complete surgical excision is the only curative treatment for primary cardiac tumors. For wide excision, interatrial septal reconstruction (ISR) is commonly performed. We hypothesized that ISR may increase the risk of postoperative atrial tachyarrhythmia (AT) after surgical resection of cardiac myxoma., Methods: After excluding patients with a history of cardiac surgery and concomitant procedures unrelated to tumor resection and those with AT or permanent pacemakers, we finally enrolled 272 adult patients who underwent benign cardiac tumor surgery from 1995 to 2021 at our institution. They were divided into the ISR (n=184) and non-ISR (n=88) groups. The primary outcome was postoperative new-onset AT., Results: The study cohort predominantly consisted of women (66.2%), with a mean age of 57.2±13.6 years. The incidence of postoperative new-onset AT was 15.4%. No 30-day mortality or recurrence was observed. The cardiopulmonary bypass time and aortic cross-clamping time were significantly longer in the ISR group than in the non-ISR group (p<0.001). The median duration of hospital stay of all patients was 6.0 days (interquartile range, 5.0-7.0 days), and no significant difference was observed between the 2 groups (p=0.329). ISR was not an independent predictor of new-onset AT (p=0.248). Male sex and hypertension were found to be independent predictors of new-onset AT., Conclusion: ISR was not a significant predictor of postoperative new-onset AT. ISR might be a feasible and safe procedure for surgical resection of cardiac myxoma and should be considered if needed.

Background: The survival benefit of coronary artery bypass grafting (CABG) using the bilateral internal thoracic arteries (BITA) is well known; however, the role of BITA in concomitant aortic valve replacement (AVR) and CABG has not been studied., Methods: We retrospectively reviewed patients who underwent concomitant AVR and CABG. Cases not using an internal thoracic artery and less than 2 bypass grafts were excluded. We enrolled 114 patients in this study. The mean follow-up duration was 61.5±43.5 months., Results: Forty patients (35.1%) underwent CABG with a single internal thoracic artery (SITA) and 74 patients (64.9%) underwent CABG with BITA. The preoperative clinical characteristics were not significantly different between the 2 groups, with the exception of a higher prevalence of atrial fibrillation in the SITA group. Postoperative mortality and morbidity were not significantly higher in the BITA group than in the SITA group. In the univariable analysis, the survival of the BITA group was similar to that of the SITA group (p=0.157). Multivariable analysis showed that only mean age was a predictor of death (p=0.042), but using BITA was not an independent predictor (p=0.094). In low-risk patients whose preoperative ejection fraction was >45%, the survival of the BITA group was significantly better than that of the SITA group (p=0.043)., Conclusion: BITA use in concomitant AVR and CABG showed no difference in mortality compared to using SITA. Although its impact on long-term survival was inconclusive, BITA use can be considered for low-risk patients.

Background/objectives: Fat-free mass (FFM) often serves as a body composition outcome variable in weight loss studies. An important assumption is that the proportions of components that make up FFM remain stable following weight loss; some body composition models rely on these "constants". This exploratory study examined key FFM component proportions before and following weight loss in two studies of participants with overweight and obesity., Subjects/methods: 201 men and women consumed calorie-restricted moderate- or very-low carbohydrate diets leading to 10-18% weight loss in 9-15 weeks. Measured total body fat, lean mass, bone mineral, total body water (TBW), and body weight at baseline and follow-up were used to derive FFM and its chemical proportions using a four-component model., Results: A consistent finding in both studies was a non-significant reduction in bone mineral and a corresponding increase (p < 0.001) in bone mineral/FFM; FFM density increased significantly in one group of women and in all four participant groups combined (both, p < 0.05). FFM hydration (TBW/FFM) increased in all groups of men and women, one significantly (p < 0.01), and in the combined sample (borderline, p < 0.10). The proportion of FFM as protein decreased across all groups, two significantly (p < 0.05-0.01) and in the combined sample (p < 0.05)., Conclusion: FFM relative proportions of chemical components may not be identical before and after short-term weight loss, an observation impacting some widely used body composition models and methods. Caution is thus needed when applying FFM as a safety signal or to index metabolic evaluations in clinical trials when these body composition approaches are used., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objectives: Cognitive benefits of longitudinal curricula and interleaving have been demonstrated in several disciplines. However, most residency curricula are structured in a block format. There is no consensus definition as to what constitutes a longitudinal program, making comparative research on curricular efficacy a challenge. The objective of our study was to arrive at a consensus definition of Longitudinal Interleaved Residency Training (LIRT) in family medicine., Methods: A national workgroup was convened and utilized a Delphi method between October 2021 and March 2022 to arrive at a consensus definition., Results: Twenty-four invitations were sent, and 18 participants initially accepted. The final workgroup (n=13) was representative of the nationwide diversity of family medicine residency programs in terms of geographic location (P=.977) and population density (P=.123). The following definition was approved: "LIRT is a curricular design and program structure that offers graduated, concurrent clinical experiences in the core competencies of the specialty. LIRT models the comprehensive scope of practice and continuity that defines the specialty; applies training methods that enhance long-term retention of knowledge, skills, and attitudes across all dimensions and locations of care delivery; and accomplishes program objectives through employment of longitudinal curricular scheduling and interleaving with spaced repetition." Additional technical criteria and definitions of terms are elucidated in the body of this article., Conclusions: A representative national workgroup crafted a consensus definition of Longitudinal Interleaved Residency Training (LIRT) in family medicine, a program structure with a basis in emerging evidence-based cognitive science.

Background: Rural areas in the United States (US) are ravaged by the opioid overdose epidemic. Oconee County, an entirely rural county in northwest South Carolina, is likewise severely affected. Lack of harm reduction and recovery resources (e.g., social capital) that could mitigate the worst outcomes may be exacerbating the problem. We aimed to identify demographic and other factors associated with support for harm reduction and recovery services in the community., Methods: The Oconee County Opioid Response Taskforce conducted a 46-item survey targeting a general population between May and June in 2022, which was mainly distributed through social media networks. The survey included demographic factors and assessed attitudes and beliefs toward individuals with opioid use disorder (OUD) and medications for OUD, and support for harm reduction and recovery services, such as syringe services programs and safe consumption sites. We developed a Harm Reduction and Recovery Support Score (HRRSS), a composite score of nine items ranging from 0 to 9 to measure level of support for placement of naloxone in public places and harm reduction and recovery service sites. Primary statistical analysis using general linear regression models tested significance of differences in HRRSS between groups defined by item responses adjusting for demographic factors., Results: There were 338 survey responses: 67.5% were females, 52.1% were 55 years old or older, 87.3% were Whites, 83.1% were non-Hispanic, 53.0% were employed, and 53.8% had household income greater than US$50,000. The overall HRRSS was relatively low at a mean of 4.1 (SD = 2.3). Younger and employed respondents had significantly greater HRRSS. Among nine significant factors associated with HRRSS after adjusting for demographic factors, agreement that OUD is a disease had the greatest adjusted mean difference in HRSSS (adjusted diff = 1.22, 95% CI=(0.64, 1.80), p < 0.001), followed by effectiveness of medications for OUD (adjusted diff = 1.11, 95%CI=(0.50, 1.71), p < 0.001)., Conclusions: Low HRRSS indicates low levels of acceptance of harm reduction potentially impacting both intangible and tangible social capital as it relates to mitigation of the opioid overdose epidemic. Increasing community awareness of the disease model of OUD and the effectiveness of medications for OUD, especially among older and unemployed populations, could be a step toward improving community uptake of the harm reduction and recovery service resources critical to individual recovery efforts., (© 2023. The Author(s).)

Background: The objective of this study was to investigate whether alcohol consumption might affect the quality of life (QOL), depressive mood, and metabolic syndrome in patients with obstructive lung disease (OLD)., Methods: Data were obtained from the Korean National Health and Nutrition Examination Survey from 2014 and 2016. OLD was defined as spirometry of forced expiratory volume in 1 second/forced vital capacity &lt;0.7 in those aged more than 40 years. QOL was evaluated using the European Quality of Life Questionnaire-5D (EQ-5D) index. Patient Health Questionnaire-9 (PHQ-9) was used to assess the severity of depressive mood. Alcohol consumption was based on a history of alcohol ingestion during the previous month., Results: A total of 984 participants with OLD (695 males, 289 females, age 65.8±9.7 years) were enrolled. The EQ-5D index was significantly higher in alcohol drinkers (n=525) than in non-alcohol drinkers (n=459) (0.94±0.11 vs. 0.91±0.13, p=0.002). PHQ- 9 scores were considerably lower in alcohol drinkers than in non-alcohol drinkers (2.15±3.57 vs. 2.78±4.13, p=0.013). However, multiple logistic regression analysis showed that alcohol consumption was not associated with EQ-5D index or PHQ-9 score. Body mass index ≥25 kg/m2, triglyceride ≥150 mg/dL, high-density lipoprotein &lt;40 mg/dL in men and &lt;50 mg/dL in women, and blood pressure ≥130/85 mm Hg were significantly more common in alcohol drinkers than in non-alcohol drinkers (all p&lt;0.05)., Conclusion: Alcohol consumption did not change the QOL or depressive mood of OLD patients. However, metabolic syndrome-related factors were more common in alcohol drinkers than in non-alcohol drinkers.

Background: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Totally thoracoscopic ablation (TTA) is a surgical treatment showing a high success rate as a hybrid procedure with radiofrequency catheter ablation to control AF. This study compared the early complications of warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) in patients who underwent TTA., Methods: This single-center retrospective cohort study enrolled patients who underwent planned TTA for AF from February 2012 to October 2020. All patients received postoperative anticoagulation, either with warfarin or a NOAC (apixaban, rivaroxaban, dabigatran, or edoxaban). Propensity score matching was performed for both groups. Early complications were assessed at 12 weeks after TTA and were divided into efficacy and safety outcomes. Both efficacy and safety outcomes were compared in the propensity score-matched groups., Results: Early complications involving efficacy outcomes, such as stroke and transient ischemic attack, were seen in 5 patients in the warfarin group and none in the NOAC group. Although the 2 groups differed in the incidence of efficacy outcomes, it was not statistically significant. In safety outcomes, 11 patients in the warfarin group and 24 patients in the NOAC group had complications, but likewise, the between-group difference was not statistically significant., Conclusion: Among patients who underwent TTA, those who received NOACs had a lower incidence of thromboembolic complications than those who received warfarin; however, both groups showed a similar bleeding complication rate. Using a NOAC after TTA does not reduce efficacy and safety when compared to warfarin.

Purpose: Addressing lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin-7 (IL-7) is necessary for proliferation of lymphocytes and to increase total lymphocyte count (TLC), IL-7 therapy has been attempted in various cancers. Here, we describe the clinical results of treatment of recurrent glioblastoma (GBM) with a long-acting engineered version of recombinant human IL-7 (rhIL-7-hyFc)., Methods: This prospective case series based on compassionate use was approved by the Ministry of Food and Drug Safety in South Korea. Primary outcomes were safety profile and TLC. Secondary outcomes were overall survival (OS) and progression-free survival (PFS)., Results: Among the 18 patients enrolled, 10 received rhIL-7-hyFc with temozolomide, 5 received rhIL-7-hyFc with bevacizumab, 1 received rhIL-7-hyFc with PCV chemotherapy, and 2 received rhIL-7-hyFc alone. Mean TLC of the enrolled patients after the first rhIL-7-hyFc treatment increased significantly from 1131 cells/mm 3 (330-2989) at baseline to 4356 cells/mm 3 (661-22,661). Higher TLCs were maintained while rhIL-7-hyFc was repeatedly administered. Median OS and PFS were 378 days (107-864 days) and 231 days (55-726 days), respectively., Conclusion: Our study reports that IL-7 immunotherapy can restore and maintain TLC during treatment with various salvage chemotherapies in recurrent GBM patients without serious toxicity., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Lipocalin-2 (LCN2) is an acute-phase protein that regulates inflammatory responses to bacteria or lipopolysaccharide (LPS). Although the bacteriostatic role of LCN2 is well studied, the function of LCN2 in acute lung damage remains unclear. Here, LCN2 knockout (KO) mice were used to investigate the role of LCN2 in LPS-treated mice with or without recombinant LCN2 (rLCN2). In addition, we employed patients with pneumonia. RAW264.7 cells were given LCN2 inhibition or rLCN2 with or without iron chelator deferiprone. LCN2 KO mice had a higher survival rate than wild-type (WT) mice after LPS treatment. In addition to elevated LCN2 levels in serum and bronchoalveolar lavage fluid (BALF), LPS treatment also increased LCN2 protein in alveolar macrophage lysates of BALF. LCN2 deletion attenuated neutrophil and macrophage infiltration in the lungs of LPS-treated mice as well as serum and BALF interleukin-6 (IL-6). Circulating proinflammatory cytokines and LCN2-positive macrophages were prominently increased in the BALF of pneumonia patients. In addition to increase of iron-stained macrophages in pneumonia patients, increased iron-stained macrophages and oxidative stress in LPS-treated mice were inhibited by LCN2 deletion. In contrast, rLCN2 pretreatment aggravated lung inflammation and oxidative stress in LPS-treated WT mice and then resulted in higher mortality. In RAW264.7 cells, exogenous LCN2 treatment also increased inflammation and oxidative stress, whereas LCN2 knockdown markedly diminished these effects. Furthermore, deferiprone inhibited inflammation, oxidative stress, and phagocytosis in RAW264.7 cells with high LCN2 levels, as well as LPS-induced acute lung injury in WT and LCN2 KO mice. Thus, these findings suggest that LCN2 plays a key role in inflammation and oxidative stress following acute lung injury and that LCN2 is a potential therapeutic target for pneumonia or acute lung injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)