Instrumental variable and colocalization analyses identify endotrophin and HTRA1 as potential therapeutic targets for coronary artery disease.

Coronary artery disease (CAD) remains a leading cause of disease burden globally, and there is a persistent need for new therapeutic targets. Instrumental variable (IV) and genetic colocalization analyses can help identify novel therapeutic targets for human disease by nominating causal genes in genome-wide association study (GWAS) loci. We conducted cis-IV analyses for 20,125 genes and 1,746 plasma proteins with CAD using molecular trait quantitative trait loci variant (QTLs) data from three different studies. 19 proteins and 119 genes were significantly associated with CAD risk by IV analyses and demonstrated evidence of genetic colocalization. Notably, our analyses validated well-established targets such as PCSK9 and ANGPTL4 while also identifying HTRA1 and endotrophin (a cleavage product of COL6A3) as proteins whose levels are causally associated with CAD risk. Further experimental studies are needed to confirm the causal role of the genes and proteins identified through our multiomic cis-IV analyses on human disease.

Development and validation of a health literacy scale for family caregivers of older people with chronic illness.

BACKGROUND: Family caregivers (FCs) encounter a variety of health problems in older people with chronic illness, necessitating a certain level of health literacy to access, understand, appraise and apply health information and services. This study aimed to develop and validate a scale for measuring health literacy among FCs of older people with chronic illness. METHODS: Concept mapping was first employed to develop a conceptual model of health literacy of FCs. Scale domains were derived from the conceptual model, and item generation was performed using deductive and inductive methods. Quantitative methods, including merging scale dimensions and items, expert reviews, cognitive interviews, and item reduction analysis, were used to refine the scale. Confirmatory factor analysis was employed to validate the scale's structure. Concurrent validity, internal consistency, and test-retest reliability were also examined. RESULTS: A 20-dimension conceptual model was developed, and 60 items were generated for the scale. Expert review (content validity index > 0.85) and cognitive interview with FCs confirmed the relevance and clarity of the majority of the generated scale items. Confirmatory factor analysis with 451 FCs of older people with chronic illness supported a 5-factor structure (symptom management, daily personal care and household tasks, care coordination, communication and relationship with the care recipient, and self-care of caregivers) with 42 finalized scale items, including four levels of health literacy skills (accessing, understanding, appraising and applying health information). Concurrent validity with the European Health Literacy Questionnaire (HLS-EU-Q47) was satisfactory (r = 0.67, p < 0.01). The Cronbach's α coefficient of the scale was 0.96, with subscales ranging from 0.84 to 0.91. The two-week test-retest reliability was 0.77 (p < 0.01). CONCLUSION: This study developed a conceptual model explaining the concept and factors of health literacy among FCs of older people with chronic illness that could provide the groundwork for future studies in developing relevant evidence-based interventions. A new Health Literacy Scale-Family Caregiver (HLS-FC) with satisfactory psychometric properties was developed in this study, which can be utilized to identify caregivers with insufficient health literacy and facilitate timely interventions by healthcare professionals.

The Efficacy of Buprenorphine in Preoperative and Postoperative Patients: A Literature Review.

Although research suggests that less than half of individuals who have surgical procedures report effective postoperative pain alleviation, the majority of patients endure acute postoperative discomfort. To lessen and manage postoperative pain, a variety of preoperative, intraoperative, and postoperative treatments and management methods are available. For several years an opioid called buprenorphine has become an effective tool to treat opioid use disorder (OUD) in patients across many different demographics. It has however endured barriers to its usage which can be seen when treating patients with chronic pain or postoperative pain, who also have an OUD. While buprenorphine may be underutilized within the clinical setting, the significantly low rates of chronic abuse when using the drug allow it to be an attractive treatment option for patients. This paper aims to explore a wide range of studies that examine buprenorphine as an analgesic and how it can be used for preoperative pain and postoperative pain. This paper will give an in-depth analysis of buprenorphine and its use in patients with chronic pain as well as OUD. A systematic literature review was performed by identifying studies through the database PubMed. The data from various publications were gathered with preference being given to publications within the last three years. We reviewed studies that examined the pain level of the patients after having buprenorphine. Despite long-available pharmacologic evidence and clinical research, buprenorphine has maintained a mystique as an analgesic. Its usage in the treatment of OUD was further influenced by its well-known safety benefits and relative lack of psychomimetic side effects compared to other opioids. For patients accustomed to long-term, high-dose opioids who may be experiencing hyperalgesia but have not been informed about this phenomenon by their doctors or the potential for buprenorphine to resolve it, buprenorphine's pronounced antihyperalgesic effect is a compelling pharmacologic characteristic that makes it particularly attractive as an option. When used in pre-, peri-, and postoperative circumstances, buprenorphine provides various pain-management benefits and patients can still benefit from effective pain management from mu-opioid agonists while remaining on buprenorphine. Buprenorphine can be continued at a reduced dose as needed to avoid withdrawal symptoms and to improve the analgesic efficiency of mu-opioid agonists used in combination with acute postoperative pain in light of the evidence at hand. Buprenorphine administration needs a patient-centered, multidisciplinary strategy that considers the benefits and drawbacks of the many perioperative therapy options to have the best chance of success.

Evaluating ChatGPT Responses on Atrial Fibrillation for Patient Education.

Background ChatGPT is a language model that has gained widespread popularity for its fine-tuned conversational abilities. However, a known drawback to the artificial intelligence (AI) chatbot is its tendency to confidently present users with inaccurate information. We evaluated the quality of ChatGPT responses to questions pertaining to atrial fibrillation for patient education. Our analysis included the accuracy and estimated grade level of answers and whether references were provided for the answers. Methodology ChatGPT was prompted four times and 16 frequently asked questions on atrial fibrillation from the American Heart Association were asked. Prompts included Form 1 (no prompt), Form 2 (patient-friendly prompt), Form 3 (physician-level prompt), and Form 4 (prompting for statistics/references). Responses were scored as incorrect, partially correct, or correct with references (perfect). Flesch-Kincaid grade-level unique words and response lengths were recorded for answers. Proportions of the responses at differing scores were compared using the chi-square analysis. The relationship between form and grade level was assessed using the analysis of variance. Results Across all forms, scoring frequencies were one (1.6%) incorrect, five (7.8%) partially correct, 55 (85.9%) correct, and three (4.7%) perfect. Proportions of responses that were at least correct did not differ by form (p = 0.350), but perfect responses did (p = 0.001). Form 2 answers had a lower mean grade level (12.80 ± 3.38) than Forms 1 (14.23 ± 2.34), 3 (16.73 ± 2.65), and 4 (14.85 ± 2.76) (p < 0.05). Across all forms, references were provided in only three (4.7%) answers. Notably, when additionally prompted for sources or references, ChatGPT still only provided sources on three responses out of 16 (18.8%). Conclusions ChatGPT holds significant potential for enhancing patient education through accurate, adaptive responses. Its ability to alter response complexity based on user input, combined with high accuracy rates, supports its use as an informational resource in healthcare settings. Future advancements and continuous monitoring of AI capabilities will be crucial in maximizing the benefits while mitigating the risks associated with AI-driven patient education.

Health Care Use for Eye Pain.

Importance: National estimates regarding the frequency of presentations and patterns of care for eye pain are unknown. This information could guide research and clinical efforts to optimize outcomes. Objective: To estimate eye pain visits in the US in the outpatient and emergency department (ED) settings. Design, Setting, and Participants: This retrospective cross-sectional study of National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey data (2008-2019) analyzed a population-based sample of visits to outpatient clinics and EDs. The sample consisted of patients presenting with eye pain. Data were analyzed from September 2023 to April 2024. Main Outcomes and Measures: Weighted sample data estimated outpatient and ED eye pain presentations including patient and clinician characteristics, diagnoses (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10]), and disposition. Results: From 2008 through 2019, 4.6 million (95% CI, 3.9 million to 5.3 million) outpatient and 1.0 million (95% CI, 0.8 million to 1.1 million) ED eye pain visits occurred annually. Patients were predominantly women (63.2% [95% CI, 59.4%-67.0%]) and older than 60 years (46.6% [95% CI, 42.4%-51.0%]) in the outpatient setting. Patients presenting to the ED were more often men (51.8% [95% CI, 48.7%-55.0%]) and aged younger than 45 years (aged <15 years: 16.4% [95% CI, 13.9%-18.8%]; 15-24 years: 19.2% [95% CI, 16.6%-21.7%]; and 25-44 years: 35.6% [95% CI, 32.7%-38.5%]). In nearly half of outpatient eye pain visits, the major problem was classified as nonacute (2.0 million [95% CI, 1.6 million to 2.3 million]). Eye pain was the primary reason for the visit (RFV) in 42.0% (95% CI, 37.8%-46.2%) of outpatient visits and 66.9% (95% CI, 62.9%-70.9%) of ED eye pain visits. It was the only RFV in 18.3% (95% CI, 15.0%-21.7%) of outpatient and 32.7% (95% CI, 29.0%-36.4%) of ED eye pain encounters. Ophthalmologists evaluated the largest number of outpatient visits (45.3% [95% CI, 38.8%-51.7%). The primary diagnosis was non-vision threatening for most outpatient (78.5% [95% CI, 56.8%-100%]) and ED (69.9% [95% CI, 62.1%-77.7%]) visits when eye pain was the primary RFV. Additional follow-up was scheduled in 89.4% (95% CI, 86.2%-92.6%) of visits. Conclusions and Relevance: More than 5 million eye pain visits occur annually; the largest percentage are outpatient with ophthalmologists. Most diagnoses were non-vision threatening in both the outpatient and ED setting and resulted in additional care. Expanding therapeutic approaches to treat the causes of eye pain may reduce the burden on the health care system and optimize outcomes.

The mediating effect of dispositional mindfulness on the association between UPPS-P impulsivity traits and gaming disorder among Asia-Pacific young adults.

BACKGROUND: Little evidence is available to verify the mediating effect of dispositional mindfulness on the association between gaming disorder and various impulsivity traits. The present study aimed to investigate the mediating effect of dispositional mindfulness on the association between the five UPPS-P impulsivity traits and the risk of gaming disorder among young adults. METHODS: It was an inter-regional cross-sectional study using online survey in Australia, Japan, The Philippines and China. Impulsivity measured by the UPPS-P Impulsive Behavior Scale-Short version; dispositional mindfulness measured by the Mindfulness Attention Awareness Scale; and the risk of gaming disorder measured by the Internet Gaming Disorder Scale were collected in the focal regions. Structural equation modeling was performed by SPSS AMOS version 26 to verify the study hypotheses. Bootstrapped 95% confidence interval was reported. Statistical significance was indicated by the p-value below 0.05. RESULTS: Among the 1,134 returned questionnaires, about 40% of them aged 18-20 years and 21-23 years, respectively. 53.8% were male. 40.7% had been playing digital and video games for over 10 years. The prevalence of gaming disorder was 4.32%. The model fitness indices reflected that the constructed model had an acceptable model fit (χ2(118) = 558.994, p < 0.001; χ2/df = 4.737; CFI = 0.924; TLI = 0.890; GFI = 0.948; RMSEA = 0.058; SRMR = 0.0487). Dispositional mindfulness fully mediated the effect of positive urgency and negative urgency on the risk of gaming disorder. The effect of lack of premeditation on the risk of gaming disorder was partially mediated by dispositional mindfulness. However, dispositional mindfulness did not mediate the effect of sensation seeking on the risk of gaming disorder. CONCLUSIONS: The varied associations between dispositional mindfulness and the five impulsivity traits hints that improving some impulsive traits may increase dispositional mindfulness and so lower the risk of gaming disorder. Despite further studies are needed to verify the present findings, it sheds light on the need to apply interventions on gamers based on their impulsivity profile. Interventions targeting at emotion regulation and self-control such as mindfulness-based interventions seem to be effective to help gamers with dominant features of urgency and lack of premeditation only. Other interventions shall be considered for gamers with high sensation seeking tendency to enhance the effectiveness of gaming disorder prevention.

Acceptability of virtual psychiatric consultations for routine follow-ups post COVID-19 pandemic for people with intellectual disabilities: cross-sectional study.

BACKGROUND: After the rapid implementation of digital health services during the COVID-19 pandemic, a paucity of research exists about the suitability of remote consulting in people with intellectual disabilities and their carers, particularly for neuropsychiatric reviews. AIM: This study examines when remote neuropsychiatric routine consulting is suitable for this population. METHOD: A survey was conducted of people with intellectual disabilities and their carers, examining their preference between face-to-face and video consultations for ongoing neuropsychiatric reviews within a rural countywide intellectual disability service in Cornwall, England (population: 538 000). The survey was sent to all adults with intellectual disabilities open to the service on 30 July 2022, closing on 30 September 2022. Participants were asked to provide responses on 11 items predesigned and co-produced between clinicians and experts by experience. The entire service caseload of people had White ethnicity, reflecting the ethnic demographics of Cornwall. Responses received without consent were excluded from the study dataset. RESULTS: Of 271 eligible participants, 119 responses were received, 104 of whom consented to having their anonymised data used for research analysis. There were no significant differences between preferences and age and gender variables. There was no statistically significant difference regarding preference for the reintroduction of face-to-face appointments (52.0%) compared with video consultations (48.0%). Travel distance (>10 miles) to the clinical setting was important but did not outweigh benefits for those preferring a face-to-face appointment. CONCLUSIONS: This study offers insights into the factors that influence preferences about what type of neuropsychiatric appointment is most suitable for people with intellectual disabilities.

Ultralow-Dose Dynamic Expiratory CT and Repeated Imaging Enhance Evaluation for Tracheomalacia.

OBJECTIVE: This study aims to determine if a novel imaging protocol (ultralow-dose dynamic expiratory computed tomography [CT] with repeated imaging) identifies tracheomalacia (TM) more reliably than traditional dynamic tracheal CT. METHODS: We performed a retrospective evaluation of 184 consecutive ultralow-dose dynamic CTs for TM during 2017. The protocol obtains images during 1 inspiration and 2 forced expirations. Tracheal narrowing during both expirations (airway narrowing [percentage] during first dynamic expiration CT [DE1], airway narrowing [percentage] during second dynamic expiration CT [DE2]) was reported as a percentage of inspiratory area. We identified maximum narrowing of each patient's sequence (maximum narrowing [percentage] on either dynamic expiration CT [DEmax] = greatest narrowing of DE1 or DE2) and compared DE1, DE2, and DEmax in individual studies and between patients. Outcomes included frequency of TM, tracheal narrowing, and severity. Reliability was assessed by comparing tracheal area narrowing and TM grade. RESULTS: There was significantly more airway narrowing using 2 expiratory image acquisitions. Average DEmax tracheal area was 12% narrower than DE1 alone and 21% worse than DE2 alone (both P < 0.001). Using DEmax, TM was diagnosed 35% more often than DE1 alone and 31% more often than DE2 alone ( P < 0.001). DEmax identified more severe distribution of TM compared with DE1 or DE2 alone ( P < 0.001). Reliability between DE1 and DE2 was good for tracheal narrowing and moderate for TM grade. The mean effective radiation dose was 2.41 millisievert (mSv) for routine inspiration CT and 0.07 mSv for each dynamic expiration CT (total effective radiation, 2.55 mSv). CONCLUSIONS: Dynamic expiration CT with 2 expiratory image acquisitions enhanced evaluation of TM, minimally increased radiation dose, and should be considered as a noninvasive screening option.

Talking in primary care (TIP): protocol for a cluster-randomised controlled trial in UK primary care to assess clinical and cost-effectiveness of communication skills e-learning for practitioners on patients' musculoskeletal pain and enablement.

INTRODUCTION: Effective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain. METHODS AND ANALYSIS: A cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews. ETHICS APPROVAL AND DISSEMINATION: Approved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country. TRIAL REGISTRATION NUMBER: ISRCTN18010240.

Federated learning for multi-omics: A performance evaluation in Parkinson's disease.

While machine learning (ML) research has recently grown more in popularity, its application in the omics domain is constrained by access to sufficiently large, high-quality datasets needed to train ML models. Federated learning (FL) represents an opportunity to enable collaborative curation of such datasets among participating institutions. We compare the simulated performance of several models trained using FL against classically trained ML models on the task of multi-omics Parkinson's disease prediction. We find that FL model performance tracks centrally trained ML models, where the most performant FL model achieves an AUC-PR of 0.876 ± 0.009, 0.014 ± 0.003 less than its centrally trained variation. We also determine that the dispersion of samples within a federation plays a meaningful role in model performance. Our study implements several open-source FL frameworks and aims to highlight some of the challenges and opportunities when applying these collaborative methods in multi-omics studies.

Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions.

While previous studies suggest that many mRNAs contain more than one translation initiation site (TIS), the biological significance of most alternative TISs and their corresponding protein isoforms (proteoforms) remains undetermined. Here we show that alternative translation initiation at a CUG and an AUG TIS in neuronal pentraxin receptor (NPR) mRNA produces two proteoforms, and their relative abundance is regulated by both neuronal activity as well as an adjacent RNA secondary structure. Downstream AUG initiation transforms the N-terminal transmembrane domain into a signal peptide, thereby converting NPR to a secreted factor sufficient to promote synaptic clustering of AMPA-type glutamate receptors. Changing the relative proteoform ratio, but not the overall NPR abundance reduces AMPA receptor in parvalbumin (PV)-positive interneurons and induces changes in learning behaviors in mice. In addition to NPR, N-terminal extensions of C1q-like synaptic organizers, mediated by upstream AUU start codons, anchor these otherwise secreted factors to the membrane. Thus, our results uncovered the plasticity of N-terminal signal sequences regulated by alternative TIS usage as a widespread mechanism to diversify protein localization and functions.

Robotic hiatal hernia repair without mesh.

Background: Newer minimally invasive techniques have supplanted laparotomy and thoracotomy for management of hiatal hernias. Limited data exists on outcomes after robotic hiatal hernia repair without mesh despite the increasing popularity of this approach. We report our high-volume experience with durable robotic hiatal hernia repair with gastric fundoplication without mesh. Methods: A retrospective review was conducted on patients with type I-IV hiatal hernias who underwent an elective robotic-assisted repair from 2016 to 2019 using a novel technique of approximating the hiatus with running barbed absorbable (V-locTM) suture and securing it with interrupted silk sutures. Main outcomes included length of stay, readmission rate, and recurrence rate. Results: A total of 144 patients were reviewed. The average age of the patient was 61 years. Most of the patients were female [95 females (66%) to 49 males], and the average body mass index (BMI) was 29.96 kg/m2. The average operating time was 173 minutes (standard deviation 62 minutes). The average length of stay in the hospital was 2 days, and 89% of patients went home within the first 3 days. Ten patients (6.9%) were readmitted within 30 days, there were no mortalities in 30 days, and there were 6 (4.2%) recurrences on follow up requiring reoperation. Conclusions: Elective robotic hiatal hernia repair with fundoplication and primary closure of the hiatus with V-locTM and nonabsorbable suture without mesh is safe and effective. The robotic approach has similar operative times, lengths of stay, and complications compared to nationally published data on laparoscopic hiatal hernia repairs.

Corrigendum: Evaluation of N95 respirators on fit rate, real-time leakage, and usability among Chinese healthcare workers: study protocol of a randomized crossover trial.

[This corrects the article DOI: 10.3389/fpubh.2023.1266607.].

A marker-less human motion analysis system for motion-based biomarker identification and quantification in knee disorders.

In recent years the healthcare industry has had increased difficulty seeing all low-risk patients, including but not limited to suspected osteoarthritis (OA) patients. To help address the increased waiting lists and shortages of staff, we propose a novel method of automated biomarker identification and quantification for the monitoring of treatment or disease progression through the analysis of clinical motion data captured from a standard RGB video camera. The proposed method allows for the measurement of biomechanics information and analysis of their clinical significance, in both a cheap and sensitive alternative to the traditional motion capture techniques. These methods and results validate the capabilities of standard RGB cameras in clinical environments to capture clinically relevant motion data. Our method focuses on generating 3D human shape and pose from 2D video data via adversarial training in a deep neural network with a self-attention mechanism to encode both spatial and temporal information. Biomarker identification using Principal Component Analysis (PCA) allows the production of representative features from motion data and uses these to generate a clinical report automatically. These new biomarkers can then be used to assess the success of treatment and track the progress of rehabilitation or to monitor the progression of the disease. These methods have been validated with a small clinical study, by administering a local anaesthetic to a small population with knee pain, this allows these new representative biomarkers to be validated as statistically significant (p-value <0.05). These significant biomarkers include the cumulative acceleration of elbow flexion/extension in a sit-to-stand, as well as the smoothness of the knee and elbow flexion/extension in both a squat and sit-to-stand.

Number of days required to reliably measure weekday and weekend total sleeping time with accelerometer: A secondary data analysis with National Health and Nutritional Survey (NHANES) 2011-2014 data.

The current standard practice for measuring sleeping time with accelerometer is to ask the participants to wear it for 7 consecutive days and analysing data from participants who have provided at least 4 days of valid data. However, this standard lacks supporting evidence. This study aims to evaluate this standard of practice by examining the reliability of measuring total sleeping time in a representative sample of US adults using accelerometer data from the National Health and Nutritional Survey (NHANES) waves 2011-2012 and 2013-2014. The sample included a total of 14,676 participants, out of which only those who provided data for seven days (n = 9510) were included in the analysis. The results revealed that the intra-class correlation coefficient (ICC) for a single day of measurement was 0.38 for weekdays and 0.27 for weekends. To achieve a reliability of 0.7, measurements for 4 and 7 nights were necessary for weekdays and weekends, respectively. Our simulation study found that the randomly-selected 3-day average of weekday sleeping time strongly correlated with the actual mean (ρ = 0.92), capturing at least 80 % of the variance. However, the randomly-selected 1-day average of weekend sleeping time only captured about 60 % of the variance. In conclusion, we recommend that future accelerometer research adopts a 9-day continuous measurement period, covering four weekend days, to reliably estimate both weekday and weekend sleeping time.

ANGPTL3 deficiency impairs lipoprotein production and produces adaptive changes in hepatic lipid metabolism.

Angiopoietin-like protein 3 (ANGPTL3) is a hepatically secreted protein and therapeutic target for reducing plasma triglyceride-rich lipoproteins and low-density lipoprotein (LDL) cholesterol. Although ANGPTL3 modulates the metabolism of circulating lipoproteins, its role in triglyceride-rich lipoprotein assembly and secretion remains unknown. CRISPR-associated protein 9 (CRISPR/Cas9) was used to target ANGPTL3 in HepG2 cells (ANGPTL3-/-) whereupon we observed ∼50% reduction of apolipoprotein B100 (ApoB100) secretion, accompanied by an increase in ApoB100 early presecretory degradation via a predominantly lysosomal mechanism. Despite defective particle secretion in ANGPTL3-/- cells, targeted lipidomic analysis did not reveal neutral lipid accumulation in ANGPTL3-/- cells; rather ANGPTL3-/- cells demonstrated decreased secretion of newly synthesized triglycerides and increased fatty acid oxidation. Furthermore, RNA sequencing demonstrated significantly altered expression of key lipid metabolism genes, including targets of peroxisome proliferator-activated receptor α, consistent with decreased lipid anabolism and increased lipid catabolism. In contrast, CRISPR/Cas9 LDL receptor (LDLR) deletion in ANGPTL3-/- cells did not result in a secretion defect at baseline, but proteasomal inhibition strongly induced compensatory late presecretory degradation of ApoB100 and impaired its secretion. Additionally, these ANGPTL3-/-;LDLR-/- cells rescued the deficient LDL clearance of LDLR-/- cells. In summary, ANGPTL3 deficiency in the presence of functional LDLR leads to the production of fewer lipoprotein particles due to early presecretory defects in particle assembly that are associated with adaptive changes in intrahepatic lipid metabolism. In contrast, when LDLR is absent, ANGPTL3 deficiency is associated with late presecretory regulation of ApoB100 degradation without impaired secretion. Our findings therefore suggest an unanticipated intrahepatic role for ANGPTL3, whose function varies with LDLR status.

The relationships among executive functions, self-regulation, and physical exercise in children with autism spectrum disorder.

LAY ABSTRACT: This study examined the impacts of two types of physical exercises (two-wheel cycling vs stationary cycling) on cognition and self-regulation among 64 children with autism spectrum disorder. It also explored the role of social, emotional, and physical needs of an individual in the relationship between exercise, cognition, and self-regulation. Results showed that participants in the two-wheel cycling group showed significant improvements in their cognition and that the two exercise groups also enhanced their self-regulation. Moreover, this study also revealed that the social need is crucial in mediating the relationship between exercise and self-regulation. This study strengthens the notion that cognitively engaging exercise is more beneficial than the non-cognitively engaging exercise in enhancing cognition in children with autism spectrum disorder.

Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a-b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery.

INTRODUCTION: We aimed to compare outcomes of patients with first primary clinical T1a-bN0M0 NSCLC treated with surgery or stereotactic body radiation therapy (SBRT). METHODS: We identified patients with first primary clinical T1a-bN0M0 NSCLCs on last pretreatment computed tomography treated by surgery or SBRT in the following two prospective cohorts: International Early Lung Cancer Action Program (I-ELCAP) and Initiative for Early Lung Cancer Research on Treatment (IELCART). Lung cancer-specific survival and all-cause survival after diagnosis were compared using Kaplan-Meier analysis. Propensity score matching was used to balance baseline demographics and comorbidities and analyzed using Cox proportional hazards regression. RESULTS: Of 1115 patients with NSCLC, 1003 had surgery and 112 had SBRT; 525 in I-ELCAP in 1992 to 2021 and 590 in IELCART in 2016 to 2021. Median follow-up was 57.6 months. Ten-year lung cancer-specific survival was not significantly different: 90% (95% confidence interval: 87%-92%) for surgery versus 88% (95% confidence interval: 77%-99%) for SBRT, p = 0.55. Cox regression revealed no significant difference in lung cancer-specific survival for the combined cohorts (p = 0.48) or separately for I-ELCAP (p = 1.00) and IELCART (p = 1.00). Although 10-year all-cause survival was significantly different (75% versus 45%, p < 0.0001), after propensity score matching, all-cause survival using Cox regression was no longer different for the combined cohorts (p = 0.74) or separately for I-ELCAP (p = 1.00) and IELCART (p = 0.62). CONCLUSIONS: This first prospectively collected cohort analysis of long-term survival of small, early NSCLCs revealed that lung cancer-specific survival was high for both treatments and not significantly different (p = 0.48) and that all-cause survival after propensity matching was not significantly different (p = 0.74). This supports SBRT as an alternative treatment option for small, early NSCLCs which is especially important with their increasing frequency owing to low-dose computed tomography screening. Furthermore, treatment decisions are influenced by many different factors and should be personalized on the basis of the unique circumstances of each patient.

Giant fronto-spheno-orbitary juvenile psammomatoid ossifying fibroma: Case report and literature review.

Juvenile psammomatoid ossifying fibroma (JPOF) is an osteofibrous neoplasm that originates in the craniofacial skeleton typically during the first three decades of life. JPOFs usually involve the orbit, paranasal sinuses or the jaws. Extensive involvement of the anterior cranial base with compromised visual function is a rare phenomenon. In such clinical context, a definite diagnosis can only be made on the basis of histopathological findings, given the absence of pathognomonic radiological features. Despite being considered a benign entity, JPOFs present a locally aggressive behavior. Therefore, these neoplasms must be included in the differential diagnosis in every patient harboring a skull base osteofibrous lesion, and, once diagnosed, gross total surgical removal should be attempted. In this study, we present our experience in the diagnosis and treatment of a patient diagnosed with a giant JPOF involving the cranial base.