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Abstract Background As cancer centers have increased focus on patient-centered, evidenced-based care, implementing efficient programs that facilitate effective patient-clinician communication remains critical. We implemented an electronic health record-integrated patient-reported symptom and needs monitoring program (‘cPRO’ for cancer patient-reported outcomes). To aid evaluation of cPRO implementation, we asked patients receiving care in one of three geographical regions of an academic healthcare system about their experiences. Methods Using a sequential mixed-methods approach, we collected feedback in two waves. Wave 1 included virtual focus groups and interviews with patients who had completed cPRO. In Wave 2, we administered a structured survey to systematically examine Wave 1 themes. All participants had a diagnosed malignancy and received at least 2 invitations to complete cPRO. We used rapid and traditional qualitative methods to analyze Wave 1 data and focused on identifying facilitators and barriers to cPRO implementation. Wave 2 data were analyzed descriptively. Results Participants (n = 180) were on average 62.9 years old; were majority female, White, non-Hispanic, and married; and represented various cancer types and phases of treatment. Wave 1 participants (n = 37) identified facilitators, including cPRO’s perceived value and favorable usability, and barriers, including confusion about cPRO’s purpose and various considerations for responding. High levels of clinician engagement with, and patient education on, cPRO were described as facilitators while low levels were described as barriers. Wave 2 (n = 143) data demonstrated high endorsement rates of cPRO’s usability on domains such as navigability (91.6%), comprehensibility (98.7%), and relevance (82.4%). Wave 2 data also indicated low rates of understanding cPRO’s purpose (56.7%), education from care teams about cPRO (22.5%), and discussing results of cPRO with care teams (16.3%). Conclusions While patients reported high value and ease of use when completing cPRO, they also reported areas of confusion, emphasizing the importance of patient education on the purpose and use of cPRO and clinician engagement to sustain participation. These results guided successful implementation changes and will inform future improvements.

Abstract Background Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain. Methods We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005–2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models. Results Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90–1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96–1.41] vs 0.92 [0.70–1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04–1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose. Conclusions In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.

Abstract Background Drinking water at U.S. Marine Corps Base (MCB) Camp Lejeune, North Carolina was contaminated with trichloroethylene and other industrial solvents from 1953 to 1985. Methods A cohort mortality study was conducted of Marines/Navy personnel who, between 1975 and 1985, began service and were stationed at Camp Lejeune (N = 159,128) or MCB Camp Pendleton, California (N = 168,406), and civilian workers employed at Camp Lejeune (N = 7,332) or Camp Pendleton (N = 6,677) between October 1972 and December 1985. Camp Pendleton’s drinking water was not contaminated with industrial solvents. Mortality follow-up was between 1979 and 2018. Proportional hazards regression was used to calculate adjusted hazard ratios (aHRs) comparing mortality rates between Camp Lejeune and Camp Pendleton cohorts. The ratio of upper and lower 95% confidence interval (CI) limits, or CIR, was used to evaluate the precision of aHRs. The study focused on underlying causes of death with aHRs ≥ 1.20 and CIRs ≤ 3. Results Deaths among Camp Lejeune and Camp Pendleton Marines/Navy personnel totaled 19,250 and 21,134, respectively. Deaths among Camp Lejeune and Camp Pendleton civilian workers totaled 3,055 and 3,280, respectively. Compared to Camp Pendleton Marines/Navy personnel, Camp Lejeune had aHRs ≥ 1.20 with CIRs ≤ 3 for cancers of the kidney (aHR = 1.21, 95% CI: 0.95, 1.54), esophagus (aHR = 1.24, 95% CI: 1.00, 1.54) and female breast (aHR = 1.20, 95% CI: 0.73, 1.98). Causes of death with aHRs ≥ 1.20 and CIR > 3, included Parkinson disease, myelodysplastic syndrome and cancers of the testes, cervix and ovary. Compared to Camp Pendleton civilian workers, Camp Lejeune had aHRs ≥ 1.20 with CIRs ≤ 3 for chronic kidney disease (aHR = 1.88, 95% CI: 1.13, 3.11) and Parkinson disease (aHR = 1.21, 95% CI: 0.72, 2.04). Female breast cancer had an aHR of 1.19 (95% CI: 0.76, 1.88), and aHRs ≥ 1.20 with CIRs > 3 were observed for kidney and pharyngeal cancers, melanoma, Hodgkin lymphoma, and chronic myeloid leukemia. Quantitative bias analyses indicated that confounding due to smoking and alcohol consumption would not appreciably impact the findings. Conclusion Marines/Navy personnel and civilian workers likely exposed to contaminated drinking water at Camp Lejeune had increased hazard ratios for several causes of death compared to Camp Pendleton.

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPARα. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and transcriptional activity of the YAP–TEAD complex. Pharmacological inhibition of YAP–TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly. Other factors, such as MYC, KRT23, RAS, and RHOA, might also participate in fenofibrate-promoted hepatomegaly and liver regeneration. These studies demonstrate that fenofibrate-promoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling, with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

Abstract Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here, we generate and characterize a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to aminopeptidase N (APN), the entry receptor for PDCoV. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen.

Abstract Background Three-dimensional (3D) printing technology has impacted many clinical applications across medicine. However, 3D printing for Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) has not yet been reported in the peer-reviewed literature. The current observational cohort study aimed to evaluate the impact of half scaled (50% scale) 3D printed (3DP) anatomic models in the pre-procedural planning of MIDCAB. Methods Retrospective analysis included 12 patients who underwent MIDCAB using 50% scale 3D printing between March and July 2020 (10 males, 2 females). Distances measured from CT scans and 3DP anatomic models were correlated with Operating Room (OR) measurements. The measurements were compared statistically using Tukey’s test. The correspondence between the predicted (3DP & CT) and observed best InterCostal Space (ICS) in the OR was recorded. Likert surveys from the 3D printing registry were provided to the surgeon to assess the utility of the model. The OR time saved by planning the procedure using 3DP anatomic models was estimated subjectively by the cardiothoracic surgeon. Results All 12 patients were successfully grafted. The 3DP model predicted the optimal ICS in all cases (100%). The distances measured on the 3DP model corresponded well to the distances measured in the OR. The measurements were significantly different between the CT and 3DP (p

The aim of this study was to expand knowledge about endocrine disorders in individuals with Cornelia de Lange syndrome (CdLS), a rare developmental genetic disorder with anomalies in multiple organs and systems. Hormone levels, clinical scores, anthropometric measurements, and molecular analysis were assessed in 24 individuals with CdLS. Hyperprolactinemia was the most common endocrine disorder. Three patients showed subclinical hypothyroidism. Concerning the gonadotropic axis, mildly delayed puberty was observed, as well as genital anomalies, such as cryptorchidism. Despite short stature, levels of insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 tended to be normal. Three prepubertal individuals without risk factors had higher than normal values for the homeostatic model assessment of insulin resistance (HOMA-IR) and for insulinemia, suggesting insulin resistance. Furthermore, two adults had elevated body mass indexes associated with HOMA-IR values over the cut-off values. CdLS may lead to dysregulation of the endocrine system, particularly in patients with high HOMA-IR values and insulinemia who are at risk of insulin resistance. Therefore, clinical follow-up with comprehensive hormonal assessment appears warranted in individuals with CdLS.

Abstract The landscape of non-coding mutations in cancer progression and immune evasion is largely unexplored. Here, we identify transcrptome-wide somatic and germline 3′ untranslated region (3′-UTR) variants from 375 gastric cancer patients from The Cancer Genome Atlas. By performing gene expression quantitative trait loci (eQTL) and immune landscape QTL (ilQTL) analysis, we discover 3′-UTR variants with cis effects on expression and immune landscape phenotypes, such as immune cell infiltration and T cell receptor diversity. Using a massively parallel reporter assay, we distinguish between causal and correlative effects of 3′-UTR eQTLs in immune-related genes. Our approach identifies numerous 3′-UTR eQTLs and ilQTLs, providing a unique resource for the identification of immunotherapeutic targets and biomarkers. A prioritized ilQTL variant signature predicts response to immunotherapy better than standard-of-care PD-L1 expression in independent patient cohorts, showcasing the untapped potential of non-coding mutations in cancer.

Abstract Background Greenness exposure has been associated with many health benefits, for example through the pathway of providing opportunities for physical activity (PA). Beside the limited body of longitudinal research, most studies overlook to what extent different types of greenness exposures may be associated with varying levels of PA and sedentary behavior (SB). In this study, we investigated associations of greenness characterized by density, diversity and vegetation type with self-reported PA and SB over a 9-year period, using data from the ORISCAV-LUX study (2007–2017, n = 628). Methods The International Physical Activity Questionnaire (IPAQ) short form was used to collect PA and SB outcomes. PA was expressed as MET-minutes/week and log-transformed, and SB was expressed as sitting time in minutes/day. Geographic Information Systems (ArcGIS Pro, ArcMap) were used to collect the following exposure variables: Tree Cover Density (TCD), Soil-adjusted Vegetation Index (SAVI), and Green Land Use Mix (GLUM). The exposure variables were derived from publicly available sources using remote sensing and cartographic resources. Greenness exposure was calculated within 1000m street network buffers around participants’ exact residential address. Results Using Random Effects Within-Between (REWB) models, we found evidence of negative within-individual associations of TCD with PA (β = − 2.60, 95% CI − 4.75; − 0.44), and negative between-individual associations of GLUM and PA (β = − 2.02, 95% CI − 3.73; − 0.32). There was no evidence for significant associations between greenness exposure and SB. Significant interaction effects by sex were present for the associations between TCD and both PA and SB. Neighborhood socioeconomic status (NSES) did not modify the effect of greenness exposure on PA and SB in the 1000 m buffer. Discussion Our results showed that the relationship between greenness exposure and PA depended on the type of greenness measure used, which stresses the need for the use of more diverse and complementary greenness measures in future research. Tree vegetation and greenness diversity, and changes therein, appeared to relate to PA, with distinct effects among men and women. Replication studies are needed to confirm the relevance of using different greenness measures to understand its’ different associations with PA and SB.

Abstract Objective Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. Methods This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. Results and conclusions The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.

Background: Management of acromioclavicular (AC) joint injuries has been an ongoing source of debate, with over 150 variations of surgery described in the literature. Without a consensus on surgical technique, patients are seeking answers to common questions through internet resources. This study investigates the most common online patient questions pertaining to AC joint injuries and the quality of the websites providing information. Hypothesis: 1) Question topics will pertain to surgical indications, pain management, and success of surgery and 2) the quality and transparency of online information are largely heterogenous. Methods: Three AC joint search queries were entered into the Google Web Search. Questions under the “People also ask” tab were expanded in order and 100 results for each query were included (300 total). Questions were categorized based on Rothwell’s classification. Websites were categorized by source. Website quality was evaluated by the Journal of the American Medical Association (JAMA) Benchmark Criteria. Results: Most questions fell into the Rothwell Fact category (48.0%). The most common question topics were surgical indications (28.0%), timeline of recovery (13.0%), and diagnosis/evaluation (12.0%). The least common question topics were anatomy/function (3.3%), evaluation of surgery (3.3%), injury comparison (1.0%), and cost (1.0%). The most common websites were medical practice (44.0%), academic (22.3%), and single surgeon personal (12.3%). The average JAMA score for all websites was 1.0 ± 1.3. Government websites had the highest JAMA score (4.0 ± 0.0) and constituted 45.8% of all websites with a score of 4/4. PubMed articles constituted 63.6% (7/11) of government website. Comparatively, medical practice websites had the lowest JAMA score (0.3 ± 0.7, range [0-3]). Conclusion: Online patient AC joint injury questions pertain to surgical indications, timeline of recovery, and diagnosis/evaluation. Government websites and PubMed articles provide the highest-quality sources of reliable, up-to-date information but constitute the smallest proportion of resources. In contrast, medical practice represents the most visited websites, however, recorded the lowest quality score. Physicians should utilize this information to answer frequently asked questions, guide patient expectations, and help provide and identify reliable online resources.

A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP  80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.

BackgroundCancer patients and survivors often experience acute cognitive impairments; however, the long-term cognitive impact remains unclear particularly among Hispanics/Latinos. We examined the association between cancer history and neurocognitive test performance among middle-aged and older Hispanic/Latinos.MethodsParticipants included 9639 Hispanic/Latino adults from the community-based and prospective Hispanic Community Health Study/Study of Latinos. At baseline (2008-2011; V1), participants self-reported their cancer history. At V1 and again at a 7-year follow-up (2015-2018; V2), trained technicians administered neurocognitive tests including the Brief-Spanish English Verbal Learning Test (B-SEVLT), Word Fluency Test (WF), and Digit Symbol Substitution Test (DSS). We used survey linear regression to estimate the overall, sex-specific, and cancer site-specific [i.e., cervix, breast, uterus, and prostate] adjusted associations between cancer history and neurocognitive test performance at V1 and changes from V1 to V2.ResultsAt V1, a history of cancer (6.4%) versus no history of cancer (93.6%) was associated with higher WF scores (β = 0.14, SE = 0.06; p = 0.03) and global cognition (β = 0.09, SE = 0.04; p = 0.04). Among women, a history of cervical cancer predicted decreases in SEVLT-Recall scores (β = -0.31, SE = 0.13; p = 0.02) from V1 to V2, and among men, a history of prostate cancer was associated with higher V1 WF scores (β = 0.29, SE = 0.12; p = 0.02) and predicted increases in SEVLT-Sum (β = 0.46, SE = 0.22; p = 0.04) from V1 to V2.ConclusionAmong women, a history of cervical cancer was associated with 7-year memory decline, which may reflect the impacts of systemic cancer therapies. Among men, however, a history of prostate cancer was associated with improvements in cognitive performance, perhaps due in part to engaging in health promoting behaviors following cancer.

Study designComparative cohort study.ObjectiveFactors that influence the lower instrumented vertebra (LIV) selection in adult cervical deformity (ACD) are less reported, and outcomes in the cervicothoracic junction (CTJ) and proximal thoracic (PT) spine are unclear.MethodsA prospective ACD database was analyzed using the following inclusion criteria: LIV between C7 and T5, upper instrumented vertebra at C2, and at least a 1-year follow-up. Patients were divided into CTJ (LIV C7-T2) and PT groups (LIV T3-T5) based on LIV levels. Demographics, operative details, radiographic parameters, and the health-related quality of life (HRQOL) scores were compared.ResultsForty-six patients were included (mean age, 62 years), with 22 and 24 patients in the CTJ and PT groups, respectively. Demographics and surgical parameters were comparable between the groups. The PT group had a significantly higher preoperative C2-C7 sagittal vertical axis (cSVA) (46.9 mm vs 32.6 mm, P = 0.002) and T1 slope minus cervical lordosis (45.9° vs 36.0°, P = 0.042) than the CTJ group and was more likely treated with pedicle-subtraction osteotomy (33.3% vs 0%, P = 0.004). The PT group had a larger correction of cSVA (-7.7 vs 0.7 mm, P = 0.037) and reciprocal change of increased T4-T12 kyphosis (8.6° vs 0.0°, P = 0.001). Complications and reoperations were comparable. The HRQOL scores were not different preoperatively and at 1-year follow-up.ConclusionsThe selection of PT LIV in cervical deformities was more common in patients with larger baseline deformities, who were more likely to undergo pedicle-subtraction osteotomy. Despite this, the complications and HRQOL outcomes were comparable at 1-year follow-up.

Introduction Inadequate treatment of enlarged lateral lymph nodes (LLNs) in rectal cancer patients is associated with an increased lateral local recurrence (LLR) risk, despite neoadjuvant treatment and total mesorectal excision (TME) surgery. There is a promising role for LLN dissection (LLND) to lower this risk, but this challenging procedure requires appropriate training. This study protocol describes a prospective evaluation of oncological outcomes after standardised treatment based on multidisciplinary training, thereby aiming for a 50% reduction in LLR rate.Methods and analysis A prospective registration study will be opened in hospitals in which the involved multidisciplinary team members (radiologists, radiation oncologists, surgeons and pathologists) have received dedicated training to enhance knowledge and awareness of LLNs and in which standardised treatment including LLND has been implemented. Patients with rectal cancer and at least one enlarged LLN (short-axis ≥7.0 mm), or intermediate LLN (short-axis 5.0–6.9 mm) with at least one malignant feature on primary MRI, evaluated by a trained radiologist, are eligible. Patients will undergo neoadjuvant treatment by trained radiation oncologists, followed by TME surgery in combination with a minimally invasive, nerve-sparing LLND performed by trained surgeons. LLND specimens are evaluated by trained pathologists or grossing assistants. The primary outcome is LLR rate 3 years postoperatively. Secondary outcomes are morbidity, disease-free survival, overall survival and quality of life. To demonstrate a significant reduction in LLR rate from 13% (based on historical control data) to 6% after optimised treatment, 200 patients with enlarged LLNs are required.Ethics and dissemination The medical ethics board of the Vrije Universiteit Medical Centre (VUMC), the Netherlands, approved the study on 23 November 2022 (reference: 2021.0524). Participating centres must obtain local approval and participants are required to provide written informed consent. Results obtained from this study will be communicated via peer-reviewed medical journals and presentations at conferences.Trail registration number NCT04486131, 24 July 2020, https://clinicaltrials.gov/ct2/show/NCT04486131.

BackgroundIn the past 2 decades, melanoma incidence among Hispanic individuals has risen by 20%. The mortality rate of Hispanic individuals is higher than that for non-Hispanic White individuals. Skin cancer can largely be prevented with regular sun protection, and skin cancer outcomes can be improved through early detection, for example, by skin self-examination. Alarmingly, Hispanic individuals are less aware of the symptoms and harms of skin cancers, tend to have misperceptions regarding the risks and benefits of skin cancer prevention behaviors, and engage in less sun protection behaviors than non-Hispanic White individuals. ObjectiveThis study aimed to use a community-engaged approach and conduct both group and individual interviews among Hispanic individuals and relevant key stakeholders to explore the potential design of a mobile-based skin cancer prevention intervention for Hispanic individuals. MethodsThis study used a qualitative design (focus groups and individual interviews). Participants were recruited from local community organizations’ social media, local events, and contact lists (eg, email). Zoom interviews were conducted to examine whether Hispanic individuals would be interested in a mobile-based skin cancer intervention and to explore their preferences and suggestions to inform skin cancer prevention intervention design. ResultsFive focus groups (2 in Spanish and 3 in English) among self-identified Hispanic individuals (n=34) and 15 semistructured, in-depth individual interviews among key stakeholders (health care providers and community leaders; eg, dermatologist, nurse practitioner, licensed social worker, and church leader) were conducted. The main themes and subthemes emerging from the group discussions and individual interviews were organized into the following categories: intervention platform, delivery frequency and format, message design, engagement plan, and activities. WhatsApp and Facebook were identified as suitable platforms for the intervention. Messages including short videos, visuals (eg, images and photographs), and simple texts messages were preferred. Recommendations for message design included personalized messages, personal stories and narratives, culturally relevant design (eg, incorporating family values), and community-trusted sources. Potential engagement and retention recommendations were also discussed. Additional details and exemplar quotes of each theme and subtheme are described. ConclusionsThis study provides important insights and directions for the design of a mobile, digital skin cancer intervention to modify Hispanic individuals’ sun protection and skin self-examination behaviors to help improve skin cancer outcomes. Insights gathered from community leaders and health care providers provided valuable additions to the community-derived data. Leveraging popular digital platforms among Hispanic individuals such as WhatsApp or Facebook could be a promising approach to skin cancer prevention. Recommendations from the community included the use of concise videos, illustrative images, clear text messages, tailored communications, narratives featuring personal experiences, designs that reflect cultural significance, and information from sources that are trusted by the community, which provided useful strategies for future intervention design among Hispanic individuals.

IntroductionCancer survivors experienced poorer health-related quality of life (HRQoL) and greater psychological distress during the COVID-19 pandemic than those without cancer. However, the underlying mechanisms that may explain how negative experiences during the pandemic are associated with distress and HRQoL remain unknown. We examined whether psychosocial risk factors (i.e., healthcare disruption, disruption to daily activities and social interaction [DDASI], and financial hardship) mediated the relationship between negative COVID-19-related experiences and cancer survivors’ HRQoL and psychological distress (i.e., depressive symptoms, and anxiety) and whether the mediating effects were moderated by psychosocial protective factors (i.e., stress management ability and social support).MethodsA total of 9,651 cancer survivors completed a questionnaire assessing negative COVID-19-related experiences, psychosocial and practical experiences, and HRQoL. Conditional process analysis was used to evaluate the proposed moderated mediation models.ResultsParticipants had a mean age of 63.8 years (SD = 12.3) and were mostly non-Hispanic White (82.3%). DDASI and financial hardship mediated the relationship between negative COVID-19-related experiences and cancer survivor’s HRQoL and psychological distress. Stress management ability buffered the indirect effect of DDASI on cancer survivors’ HRQoL and psychological distress. Social support buffered the indirect effect of financial hardship on HRQoL and depressive symptoms.ConclusionFinancial resources and social interactions may buffer negative effects of major disruptions such as the COVID-19 pandemic. Future studies should assess the longitudinal impact of these associations.

Background: There is increasing evidence that air pollution and noise may have detrimental psychological impacts, but there are few studies evaluating adolescents, ground-level ozone exposure, multi-exposure models, or metrics beyond outdoor residential exposure. This study aimed to address these gaps. Methods: Annual air pollution and traffic noise exposure at home and school were modelled for adolescents in the Greater London SCAMP cohort (N=7555). Indoor, outdoor and hybrid environments were modelled for air pollution. Cognitive and mental health measures were self-completed at two timepoints (baseline aged 11–12 and follow-up aged 13–15). Associations were modelled using multi-level multivariate linear or ordinal logistic regression. Results: This is the first study to investigate ground-level ozone exposure in relation to adolescent executive functioning, finding that a 1 interquartile range increase in outdoor ozone corresponded to −0.06 (p

Background: Buprenorphine maintenance treatment remains unavailable in most jails in the US. We provide data on a four-day rapid sublingual buprenorphine (SL-B) induction strategy followed by a weekly dose of extended-release injectable buprenorphine (XR-B) with incarcerated individuals with opioid use disorder (OUD) who were not opioid tolerant. Methods: Between October 2020 to April 2024, N = 65 individuals with an opioid use disorder in jails participating in a larger randomized, controlled trial received SL-B and XR-B prior to release. Primary outcomes included completing the proposed dose induction and any reported adverse events (AEs). Results: Sixty-five individuals received SL-B dose induction from our team’s medical staff, 53 (81.5 %) completed the four-day SL-B dose induction and received their first weekly XR‑B injection on day 5. Of the 65 individuals, 10 (15.38 %) participants reported AEs during the dosing period and/or in the week following the dosing period. All but one of the AEs were rated as mild. One participant experienced a serious adverse event in the week following dose induction. The study medical team determined that this was unlikely to be related to the intervention. Discussion: Overall, our study findings demonstrate the feasibility of implementing a four-day sublingual dose induction followed by a weekly XR-B injection with incarcerated individuals who are not opioid tolerant. This study provides important data to illustrate a dose induction strategy that might assist in reducing illicit diversion in jails, which is a main barrier to buprenorphine delivery cited by correctional administrators.

Background and Aim: The prevalence of depressive symptoms and major depressive disorder is high among adults living with HIV. Depressive symptoms are associated with increased cardiovascular disease risk. This study examined the association between depressive symptoms and echocardiographic indices of left ventricular diastolic dysfunction (LVDD) among men and women living with and without HIV. Methods: Cross-sectional analysis included individuals in the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS) who participated in transthoracic echocardiogram substudies and completed measures of depressive symptoms at the same visit as, or up to 6 months prior to, the transthoracic echocardiogram visit. Participants had helper T cells (CD4) >350 cells/mm3 and HIV RNA viral load less than 499 copies/mL. The presence of LVDD was defined according to the Characterizing Heart Function on Antiretroviral Therapy (CHART) criteria. Secondary outcomes were continuous values of each component of the CHART criteria: left ventricular ejection fraction >50%, septal e’ velocity, lateral e’ velocity, left atrial volume index, left ventricular mass index, and relative wall thickness. Logistic and linear regression were used to adjust for sociodemographic, behavioural, cardiometabolic, and HIV-related factors. Results: Among 874 men (51% with HIV) and 1,191 women (76% with HIV), in whom the overall prevalence of LVDD was 22.5% and depressive symptoms 30.8%, depressive symptoms were not significantly associated with LVDD. The associations between individual LVDD components and depression were in the small to medium range, though generally not significant. Conclusion: Findings warrant further research regarding the association between LVDD and depressive symptoms in the era of combination antiretroviral therapy.

Abstract Ferroptosis is a form of regulated cell death that can be modulated by small molecules and has the potential for the development of therapeutics for oncology. Although excessive lipid peroxidation is the defining hallmark of ferroptosis, DNA damage may also play a significant role. In this study, a potential mechanistic role for MIF in homologous recombination (HR) DNA repair is identified. The inhibition or genetic depletion of MIF or other HR proteins, such as breast cancer type 1 susceptibility protein (BRCA1), is demonstrated to significantly enhance the sensitivity of cells to ferroptosis. The interference with HR results in the translocation of the tumor suppressor protein p53 to the mitochondria, which in turn stimulates the production of reactive oxygen species. Taken together, the findings demonstrate that MIF‐directed small molecules enhance ferroptosis via a putative MIF‐BRCA1‐RAD51 axis in HR, which causes resistance to ferroptosis. This suggests a potential novel druggable route to enhance ferroptosis by targeted anticancer therapeutics in the future.

Summary: Background: Longitudinal changes in vaccination-induced immune response remain inadequately characterized in adolescents. We present long-term safety, immunogenicity, and COVID-19 incidence following a 2-dose mRNA-1273 100-μg primary series, and immunogenicity following a single dose of mRNA-1273 50 μg in vaccine-naïve adolescents. Methods: TeenCOVE (NCT04649151) Part 1 randomized adolescents (12–17 years) to 2-dose mRNA-1273 100 μg (n = 2490) or placebo (n = 1243) 28 days apart. Subsequently, placebo recipients (n = 91) could receive open-label mRNA-1273. Primary objectives included prespecified adverse events through 12 months; secondary objectives were COVID-19 incidence and neutralizing and spike-binding antibodies (nAbs/bAbs) against SARS-CoV-2 (ancestral/variants) through 12 months (study period: December 2020–January 2022). In Part 2, vaccine-naïve adolescents (n = 52) received up to 2 doses of mRNA-1273 50 μg; interim analysis included Day 28 (D28) nAbs post-injection 1 in SARS-CoV-2-baseline-positive participants (serologic/virologic evidence of prior infection). Findings: In SARS-CoV-2-baseline-negative adolescents (N = 369), mRNA-1273 induced robust nAb responses versus baseline (geometric mean concentration [GMC] = 11; 95% CI, 11–12) at D28 (1868 [1759–1985]), 6 months (625 [583–670]) and 12 months (550 [490–618]) post-injection 2. Similar bAb responses were observed to alpha/beta/delta/gamma variants; nAb/bAb responses were similar in SARS-CoV-2-baseline-positive adolescents. The 2-dose mRNA-1273 100-μg primary series was generally well-tolerated; one case of nonserious, moderate, probable acute myocarditis resolved by 8 days from symptom onset. A single dose of mRNA-1273 50 μg in SARS-CoV-2-baseline-positive adolescents induced higher D28 nAb GMCs against ancestral SARS-CoV-2 than 2-dose mRNA-1273 100 μg in young adults (geometric mean ratio = 4.322 [3.274-5.707]). Interpretation: The overall risk–benefit profile of mRNA-1273 remains favorable in adolescents, with durable 12-month immune responses against SARS-CoV-2 (ancestral/variants). A single mRNA-1273 50-μg injection in vaccine-naïve adolescents elicited robust immune responses against SARS-CoV-2. Funding: This project has been funded in whole or in part with federal funds by the Department of Health and Human Services, United States; Administration for Strategic Preparedness and Response, United States; Biomedical Advanced Research and Development Authority, United States, under Contract No. 75A50120C00034. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Department of Health and Human Services or its components.

The androgen receptor is a key regulator of prostate cancer and the principal target of current prostate cancer therapies collectively termed androgen deprivation therapies. Insensitivity to these drugs is a hallmark of progression to a terminal disease state termed castration-resistant prostate cancer. Therefore, novel therapeutic options that slow progression of castration-resistant prostate cancer and combine effectively with existing agents are in urgent need. We show that JG-98, an allosteric inhibitor of HSP70, re-sensitizes castration-resistant prostate cancer to androgen deprivation drugs by targeting mitochondrial HSP70 (HSPA9) to suppress aerobic respiration. Rather than impacting androgen receptor stability as previously described, JG-98's primary effect is inhibition of mitochondrial translation, leading to disruption of electron transport chain activity. Although functionally distinct from HSPA9 inhibition, direct inhibition of the electron transport chain with a complex I or II inhibitor creates a similar physiological state capable of re-sensitizing castration-resistant prostate cancer to androgen deprivation therapies. These data identify a significant role for HspA9 in mitochondrial ribosome function and highlight an actionable metabolic vulnerability of castration-resistant prostate cancer.