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The world population is aging. Comprehensive Geriatric assessment (CGA) has been proven to improve the well-being of older adults. However, evidence suggests not all clinicians implement these recommendations in their practice; nor do all patients adhere to them. Currently, there is no up-to-date review of interventions that can improve older adults' adherence to CGA recommendations and health care provider/clinician implementation of those recommendations. The objective of this scoping review protocol is to describe the methodology of the scoping review with the aim to identify interventions that have been tested to improve adherence to CGA recommendations. We will use the Arksey and O'Malley framework and subsequent extension by Levac and colleagues to complete the scoping review. We searched OVID MEDLINE, OVID Embase, EBSCO CINAHL, APA PsychInfo, and Cochrane CENTRAL databases from inception to November 14, 2024, and will include a review of reference lists of included studies. Studies eligible for inclusion are studies of any design that examined one or more interventions aiming to improve clinician implementation of and patient adherence to CGA in any clinical setting. We will use standard methods for study selection, data abstraction, assessment of methodological quality of individual studies, and data synthesis. Results will be analyzed and reported using descriptive numerical summaries and narrative analysis. Findings from the scoping review will be published in a manuscript and presented at scientific conferences.

Background:. Obesity is widely recognized as a significant risk factor for postoperative complications of breast reconstruction. Despite extensive research, there remains a lack of consensus regarding the specific complications and outcomes experienced by patients with obesity who undergo deep inferior epigastric perforator (DIEP) flap reconstruction. To provide a clearer understanding of the challenges faced by patients with obesity, we present a single-center outcome analysis of individuals who underwent DIEP flap reconstruction. Methods:. A cohort of 194 patients who underwent at least 1 DIEP flap was retrospectively analyzed at the University of Nebraska Medical Center utilizing electronic medical records. Patients who underwent DIEP flap breast reconstruction were organized into 5 categories using World Health Organization weight status by body mass index (BMI) obtained from the day of surgery. Surgical complications within 120 days and postsurgical complication-related procedural interventions were also evaluated and compared. Comparisons of variables of interest between weight groups were assessed using Mantel–Haenszel chi-square tests or Spearman correlations. Results:. Increases in patient weight category were associated with increased length of operation (P = 0.003), increased rates of breast fat necrosis (P = 0.04), breast wound dehiscence (P = 0.01), abdominal wound dehiscence (P = 0.02), numbers of abdominal complications (P = 0.001), and rates of requiring an intervention (P = 0.03). Conclusions:. The findings imply that higher BMI values may lead to a higher likelihood of postoperative complications and the need for intervention. It is crucial for patients with obesity to be aware of the elevated risk associated with rising BMI values.

IntroductionPeripheral neuropathy (PN) is the most common neurodegenerative disorder, and the primary causes are chemotherapy-induced peripheral neuropathy (CIPN) and diabetic neuropathy (DN). Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-pharmacological and non-invasive intervention that targets key pathways involved with PN. However, research is needed to determine the feasibility, acceptability, and effects of taVNS in people with PN. It is also critical that this research on taVNS include the perspectives of Black and Hispanic/Latino patients, who are often underrepresented in research.MethodsThis research was comprised of two consecutive studies: a survey and a pilot randomized sham-controlled trial (RCT). The survey assessed symptom burden, management strategies, and interest in taVNS among CIPN patients. The pilot RCT evaluated the feasibility, acceptability, and preliminary effects of taVNS in Black and Hispanic/Latino patients with CIPN or diabetic neuropathy. Participants were recruited from the University of Miami medical system, with culturally sensitive approaches to enhance minority participation.ResultsThe survey included 62 respondents, 78% Black or Hispanic/Latino, revealing high symptom burden and significant interest in taVNS (82% expressed moderate to high interest). The pilot RCT enrolled 28 participants, achieving a 42% recruitment rate and 86% retention. taVNS was well tolerated, with no significant adverse effects. Preliminary data indicated a decrease in neuropathic symptoms and an increased heart rate variability (HRV) during active taVNS, suggesting autonomic modulation. Tingling sensation and pain decreased by median values of 2.0 and 1.5, respectively. Additionally, the median values for standard deviation of the RR interval increased from 34.9 (CI = 21.6–44.8) at baseline to 44.8 (CI = 26.5–50.3) during intervention. Exit interviews highlighted positive participant experiences and identified potential barriers, such as protocol length and distrust in medical research.ConclusionThe findings underscore the need for novel CIPN treatments and demonstrate the feasibility of conducting taVNS research in historically underrepresented populations. High interest in taVNS and successful recruitment and retention rates suggest that culturally sensitive approaches can enhance minority participation in clinical trials. These findings will be used to develop a large clinical trial to determine the efficacy of repeated taVNS in a diverse cohort. Clinical Trial Registrationhttps://clinicaltrials.gov, identifier (NCT05896202).

Abstract Background Lumbar degenerative spondylolisthesis (LDS), characterized as degeneration of the intervertebral disc and structural changes of the facet joints, is a condition with varying degrees of instability that may lead to pain, canal stenosis, and subsequent surgical intervention. However, the etiology of LDS remains inconclusive. Gut microbiome dysbiosis may stimulate systemic inflammation in various disorders. However, the role of such dysbiosis upon spine health remains under‐studied. The current study assessed the association of gut microbiome dysbiosis in symptomatic patients with or without LDS. Methods A cross‐sectional analysis within the framework of a prospective study was performed. DNA was extracted from fecal samples collected from adult symptomatic patients with (n = 21) and without LDS (n = 12). Alpha and beta diversity assessed differences in fecal microbial community between groups. Taxon‐by‐taxon analysis identified microbial features with differential relative abundance between groups. Subject demographics and imaging parameters were also assessed. Results There was no significant group differences in age, sex, race, body mass index, smoking/alcohol history, pain profiles, spinopelvic alignment, and Modic changes (p >0.05). LDS subjects had significantly higher disc degeneration severity (p = 0.018) and alpha diversity levels compared to non‐LDS subjects (p = 0.002–0.003). Significant differences in gut microbial community structure were observed between groups (p = 0.046). Subjects with LDS exhibited distinct differences at the phylum level, with a significantly higher Firmicutes to Bacteroidota ratio compared to non‐LDS (p = 0.003). Differential relative abundance analysis identified six taxa with significant differences between the two groups, with LDS demonstrating an increase in putative pro‐inflammatory bacteria (Dialister, CAG‐352) and a decrease in anti‐inflammatory bacteria (Slackia, Escherichia‐Shigella). Conclusion This study is the first to report a significant association of gut microbiome dysbiosis and LDS in symptomatic patients, noting pro‐inflammatory bacterial taxa. This work provides a foundation for future studies addressing the role of the gut microbiome in association with spine health and disease.

ObjectiveTo examine the social determinants of early childhood caries (ECC), one of the greatest public health risks affecting children, and examine alternative pathways of influence.MethodsA physically healthy, socio-demographically high-risk sample of initially caries-free children, aged 1–4 years, was prospectively studied for 2 years. At 6-month intervals, assessments were made of caries presence from a standard dental exam; oral microbiology was assayed from saliva samples; oral hygiene behaviors and psychological and psychosocial risk exposure were derived from interviews and questionnaires.Results189 children were enrolled; ECC onset occurred in 48 children over the 2-year study period. A composite measure of psychosocial risk was significantly associated with ECC onset over the course of the study (1.57, 95% CI 1.12–2.20, p

IntroductionLes effets de l’utilisation des médias sociaux sur la santé des adolescents soulèvent de plus en plus de préoccupations en matière de santé publique. Nous avons exploré la relation entre cette utilisation et la santé du sommeil chez les adolescents du Canada de 11 à 17 ans. MéthodologieDes données de l’Enquête sur les comportements de santé des jeunes d’âge scolaire de 2017-2018 étaient disponibles pour 12 557 participants (dont 55,2 % de sexe féminin). Des catégories d’utilisation des médias sociaux ont été établies en fonction de la fréquence (utilisation non active, active ou intensive) et de la présence de symptômes évoquant une dépendance (utilisation problématique). Des modèles de régression logistique à effets mixtes ont révélé des associations entre l’utilisation des médias sociaux et sept indicateurs de la santé du sommeil (symptômes d’insomnie, somnolence diurne, utilisation d’un écran avant de se coucher, respect des recommandations sur la durée du sommeil, variabilité du sommeil, heure de coucher tardive les jours d’école et heure de coucher tardive les jours de repos). RésultatsComparativement à une utilisation active des médias sociaux, une utilisation non active a été associée à de meilleurs résultats des indicateurs de la santé du sommeil, sauf en ce qui concerne les symptômes d’insomnie. Une utilisation intensive des médias sociaux a été associée à un risque accru d’indicateurs défavorables de la santé du sommeil (rapport de cotes ajusté [RCa] de 1,09 à 2,24) et une utilisation problématique a été associée au RCa le plus élevé (1,67 à 3,24). Les associations avec une utilisation problématique des médias sociaux étaient plus marquées chez les filles que chez les garçons, en particulier en ce qui concerne l’heure de coucher tardive les jours d’école (RCa = 3,74 vs 1,84) et les jours de repos (RCa = 4,13 vs 2,18). Les associations entre l’utilisation des médias sociaux et les résultats en matière de sommeil ne variaient pas selon la tranche d’âge. ConclusionUne utilisation intensive et une utilisation problématique des médias sociaux ont été associées à un risque accru de troubles du sommeil chez les adolescents du Canada, avec des associations plus marquées chez les filles que chez les garçons. D’autres recherches doivent être menées pour éclaircir les mécanismes à l’origine des associations entre l’utilisation des médias sociaux et le sommeil, de manière à orienter les recommandations en matière de santé publique.

IntroductionPublic health concerns over the impact of social media use (SMU) on adolescent health are growing. We investigated the relationship between SMU and sleep health in adolescents in Canada aged 11 to 17 years. MethodsData from the 2017–2018 Health Behaviour in School-aged Children study were available for 12 557 participants (55.2% female). SMU was categorized by frequency of use (non-active, active and intense) and the presence of addiction-like symptoms (problematic). Mixed effects logistic regression models identified associations between SMU and seven sleep health indicators (insomnia symptoms, daytime wakefulness problems, screen time before bed, meeting sleep duration recommendations, sleep variability and late bedtime on school and non-school days). ResultsCompared to active SMU, non-active SMU was associated with better sleep indicators, except for insomnia symptoms. Intense SMU was associated with greater odds of having poor sleep health indicators (adjusted odds ratio [aORs] from 1.09 to 2.24) and problematic SMU with the highest odds (aORs from 1.67 to 3.24). Associations with problematic SMU were greater among girls than boys, including having a later bedtime on school days (aOR = 3.74 vs. 1.84) and on non-school days (aOR = 4.13 vs. 2.18). Associations between SMU and sleep outcomes did not differ by age group. ConclusionCompared to active SMU, non-active SMU was associated with better sleep indicators, except for insomnia symptoms. Intense SMU was associated with greater odds of having poor sleep health indicators (adjusted odds ratio [aORs] from 1.09 to 2.24) and problematic SMU with the highest odds (aORs from 1.67 to 3.24). Associations with problematic SMU were greater among girls than boys, including having a later bedtime on school days (aOR = 3.74 vs. 1.84) and on non-school days (aOR = 4.13 vs. 2.18). Associations between SMU and sleep outcomes did not differ by age group.

Abstract Depressive and anxiety symptoms are prevalent among patients with various clinical conditions, resulting in diminished emotional well-being and impaired daily functioning. The neural mechanisms underlying these symptoms, particularly across different disorders, remain unclear, limiting the effectiveness of conventional treatments. Therefore, it is crucial to elucidate the neural underpinnings of depressive and anxiety symptoms and investigate novel, effective treatments across clinical conditions. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that can help understand the neural underpinnings of symptoms and facilitate the development of interventions, addressing the two research gaps at both neural and clinical levels. Thus, this systematic review and meta-analysis aims to evaluate the existing evidence regarding the therapeutic efficacy of tDCS in reducing depressive and anxiety symptoms among individuals with diverse clinical diagnoses. This review evaluated evidence from fifty-six randomized, sham-controlled trials that administered repeated tDCS sessions with a parallel design, applying a three-level meta-analytic model. tDCS targeting the left dorsolateral prefrontal cortex (DLPFC) at 2-mA intensity demonstrates moderate efficacy in alleviating depressive symptoms, identifying the left DLPFC as a transdiagnostic neural mechanism of depressive symptoms across clinical conditions. In comparison, the findings on anxiety symptoms demonstrate greater heterogeneity. tDCS over the left DLPFC is effective in reducing depressive symptoms and shows promising effects in alleviating anxiety symptoms among individuals with diverse diagnoses. These findings enhance our understanding of the neuropsychological basis of depressive and anxiety symptoms, laying the groundwork for the development of more effective tDCS interventions applicable across clinical conditions.

Abstract Background Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). Methods Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. Results At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25–5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48–9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03–8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02–5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57–5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23–5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46–9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76–7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07–3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10–4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15–8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. Conclusion Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.

Background The comparison of coronary computed tomography angiography plaques and perivascular adipose tissue (PVAT) between patients with acute myocardial infarction (AMI) posttreatment and patients with stable coronary artery disease is poorly understood. Our objective was to evaluate the differences in coronary computed tomography angiography–quantified plaque and PVAT characteristics in patients post‐AMI and identify signs of residual inflammation. Methods and Results We analyzed 205 patients (age, 59.77±9.24 years; 92.20% men) with AMI ≤1 month and matched them with 205 patients with stable coronary artery disease (age, 60.52±10.04 years; 90.24% men) based on age, sex, and cardiovascular risk factors. Coronary computed tomography angiography scans were assessed for nonculprit plaque and vessel characteristics, plaque volumes by composition, high‐risk plaques, and PVAT mean attenuation. Both patient groups exhibited similar noncalcified plaque volumes (383.35±313.23 versus 378.63±426.25 mm3, P=0.899). However, multivariable analysis revealed that patients post‐AMI had a greater patient‐wise noncalcified plaque volume ratio (estimate, 0.089 [95% CI, 0.053–0.125], P

BackgroundEffective post-stroke mobility, recovery, performance, and participation are key goals for stroke survivors. However, these outcomes may be hindered by post-stroke fatigue (PSF), which can affect numerous aspects of post-stroke mobility, recovery, performance, functioning, community participation, and return to work. This review aimed to assess the scientific evidence on the relationship between PSF and mobility function, functional recovery, functional performance, and participation-related outcomes among stroke survivors.MethodA comprehensive search of Cochrane Central, PubMed, Embase, and Web of Science (WoS) databases was conducted from inception to December 2023. Observational, cross-sectional, and longitudinal studies were included. The methodological quality of the included studies was assessed using the National Institute of Health’s quality assessment tool, while the risk of bias was assessed using the Quality in Prognostic Studies tool. A total of 28 studies (n = 2,495 participants, 1,626 men, mean age ranging from 52.5 ± 9.5 to 71.1 ± 9.9 years) were included. The data analysis was conducted using narrative and quantitative synthesis. Fixed and random effects meta-analyses were conducted to explore the relationships between PSF and relevant outcomes.ResultsChronic PSF was found to have significant negative correlations with mobility (meta r = −0.106, p

Abstract Background Cancer is the fourth leading cause of death in adolescents and young adults (AYA) worldwide. Although successful treatment of cancer in AYA has increased in recent years in most of the world, this is not true for many low‐ and middle‐income countries (LMIC) where over 80% of all AYA live. This study investigated the needs of AYA with cancer in parts of Latin America (LATAM) through the perspectives of non‐physician health care providers and partners. Methods Semi‐structured interviews (in Spanish) were conducted with non‐physician partners from Mexico, Peru, Central America, and the Caribbean over Zoom. Participants were recruited through previously identified local physicians and international non‐physician professionals working in these countries. Transcripts were coded and key themes identified until thematic saturation was reached (Atlas.ti). Findings Thirty participants representing eight countries were interviewed, providing 1202 min of transcript data. Data were organized into barriers, facilitators, and strategies to improve the delivery of health care for AYA with cancer in LATAM at the patient‐ (e.g., financial barriers, continued schooling), parent‐ (e.g., limited medical literacy, advocacy), and hospital‐level (e.g., structural barriers, increasing funding). Interpretation There are many similarities in the barriers and facilitators to AYA care between LATAM and high‐income countries (HIC); however, some characteristics are more unique to LATAM, for example, strict age restrictions for pediatric care and abandonment of therapy. As LATAM countries continue to build cancer control programs, there is an opportunity to consider our identified barriers, facilitators, and strategies to address the unique needs of AYA with cancer.

Abstract Background The application of artificial intelligence (AI) in academic writing has raised concerns regarding accuracy, ethics, and scientific rigour. Some AI content detectors may not accurately identify AI-generated texts, especially those that have undergone paraphrasing. Therefore, there is a pressing need for efficacious approaches or guidelines to govern AI usage in specific disciplines. Objective Our study aims to compare the accuracy of mainstream AI content detectors and human reviewers in detecting AI-generated rehabilitation-related articles with or without paraphrasing. Study design This cross-sectional study purposively chose 50 rehabilitation-related articles from four peer-reviewed journals, and then fabricated another 50 articles using ChatGPT. Specifically, ChatGPT was used to generate the introduction, discussion, and conclusion sections based on the original titles, methods, and results. Wordtune was then used to rephrase the ChatGPT-generated articles. Six common AI content detectors (Originality.ai, Turnitin, ZeroGPT, GPTZero, Content at Scale, and GPT-2 Output Detector) were employed to identify AI content for the original, ChatGPT-generated and AI-rephrased articles. Four human reviewers (two student reviewers and two professorial reviewers) were recruited to differentiate between the original articles and AI-rephrased articles, which were expected to be more difficult to detect. They were instructed to give reasons for their judgements. Results Originality.ai correctly detected 100% of ChatGPT-generated and AI-rephrased texts. ZeroGPT accurately detected 96% of ChatGPT-generated and 88% of AI-rephrased articles. The areas under the receiver operating characteristic curve (AUROC) of ZeroGPT were 0.98 for identifying human-written and AI articles. Turnitin showed a 0% misclassification rate for human-written articles, although it only identified 30% of AI-rephrased articles. Professorial reviewers accurately discriminated at least 96% of AI-rephrased articles, but they misclassified 12% of human-written articles as AI-generated. On average, students only identified 76% of AI-rephrased articles. Reviewers identified AI-rephrased articles based on ‘incoherent content’ (34.36%), followed by ‘grammatical errors’ (20.26%), and ‘insufficient evidence’ (16.15%). Conclusions and relevance This study directly compared the accuracy of advanced AI detectors and human reviewers in detecting AI-generated medical writing after paraphrasing. Our findings demonstrate that specific detectors and experienced reviewers can accurately identify articles generated by Large Language Models, even after paraphrasing. The rationale employed by our reviewers in their assessments can inform future evaluation strategies for monitoring AI usage in medical education or publications. AI content detectors may be incorporated as an additional screening tool in the peer-review process of academic journals.

Abstract Insect activity powers ecosystems and food production globally. Although insect activity is known to vary with the rise and setting of the sun, there is surprisingly limited empirical information on how insect abundance and richness varies across the 24-hour day–night (diel) cycle. Moreover, commonly used methods for sampling insects such as light traps do not provide suitable comparisons of community properties between diel periods. We present a dataset of 1512 observations of abundance and richness during diurnal and nocturnal periods in insect communities worldwide. The data were collected from 99 studies that systematically sampled insect communities during day and night, using sampling methods minimally influenced by diel variation, such as movement-based interception traps. Spanning six continents, 41 countries and 16 insect orders, the data can support investigations into the factors influencing insect diel preferences as well as the causes and consequences of temporal changes in insect biodiversity. The data also provides key baseline information on the diel activity patterns of insect communities for long-term ecological monitoring. These pursuits take on added significance considering contemporary ‘insect declines’ and increasing anthropogenic impacts on diurnal and nocturnal biodiversity.

The genus Leptanilla Emery, 1870 of the family Formicidae, subfamily Leptanillinae, comprises miniscule, pale, blind ants that are rarely collected and poorly understood due to their hypogaeic (i.e. underground) lifestyles. Here we describe a new Leptanilla species from two workers collected via subterranean scraping in the arid Pilbara region of Western Australia. Leptanilla voldemort sp. nov. is the second leptanilline species documented in Australia after the elusive Leptanilla swani Wheeler, 1932. Workers of L. voldemort sp. nov. display a remarkably gracile morphology characterised by elongated legs, antennae, and mandibles, and they are easily differentiated from other Leptanilla species. We also provide new measurements for L. swani from two workers found proximally to the type locality of L. voldemort sp. nov. A key to the worker caste of Leptanilla species of the Australian continent is presented.

Abstract Insects sustain key ecosystem functions, but how their activity varies across the day–night cycle and the underlying drivers are poorly understood. Although entomologists generally expect that more insects are active at night, this notion has not been tested with empirical data at the global scale. Here, we assemble 331 quantitative comparisons of the abundances of insects between day and night periods from 78 studies worldwide and use multi-level meta-analytical models to show that insect activity is on average 31.4% (CI: −6.3%–84.3%) higher at night than in the day. We reveal diel preferences of major insect taxa, and observe higher nocturnal activity in aquatic taxa than in terrestrial ones, as well as in warmer environments. In a separate analysis of the small subset of studies quantifying diel patterns in taxonomic richness (31 comparisons from 13 studies), we detect preliminary evidence of higher nocturnal richness in tropical than temperate communities. The higher overall (but variable) nocturnal activity in insect communities underscores the need to address threats such as light pollution and climate warming that may disproportionately impact nocturnal insects.

Abstract Digital ocular massage has been reported to temporarily lower intraocular pressure (IOP). This could be related to an enhanced aqueous humor outflow; however, the mechanism is not clearly understood. Using anterior segment optical coherence tomography, the Schlemm’s canal (SC) and trabecular meshwork (TM) can be imaged and measured. Here, 66 healthy adults underwent digital ocular massage for 10 min in their right eyes. The IOP and dimensions of the SC and TM were measured before and after ocular massage. All subjects demonstrated IOP reduction from 15.7 ± 2.5 mmHg at baseline to 9.6 ± 2.2 mmHg immediately after, and median of 11.6 mmHg 5-min after ocular massage (Friedman’s test, p

Aims: This systematic review aims to identify 3D predictors derived from biplanar reconstruction, and to describe current methods for improving curve prediction in patients with mild adolescent idiopathic scoliosis. Methods: A comprehensive search was conducted by three independent investigators on MEDLINE, PubMed, Web of Science, and Cochrane Library. Search terms included “adolescent idiopathic scoliosis”,“3D”, and “progression”. The inclusion and exclusion criteria were carefully defined to include clinical studies. Risk of bias was assessed with the Quality in Prognostic Studies tool (QUIPS) and Appraisal tool for Cross-Sectional Studies (AXIS), and level of evidence for each predictor was rated with the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. In all, 915 publications were identified, with 377 articles subjected to full-text screening; overall, 31 articles were included. Results: Torsion index (TI) and apical vertebral rotation (AVR) were identified as accurate predictors of curve progression in early visits. Initial TI > 3.7° and AVR > 5.8° were predictive of curve progression. Thoracic hypokyphosis was inconsistently observed in progressive curves with weak evidence. While sagittal wedging was observed in mild curves, there is insufficient evidence for its correlation with curve progression. In curves with initial Cobb angle < 25°, Cobb angle was a poor predictor for future curve progression. Prediction accuracy was improved by incorporating serial reconstructions in stepwise layers. However, a lack of post-hoc analysis was identified in studies involving geometrical models. Conclusion: For patients with mild curves, TI and AVR were identified as predictors of curve progression, with TI > 3.7° and AVR > 5.8° found to be important thresholds. Cobb angle acts as a poor predictor in mild curves, and more investigations are required to assess thoracic kyphosis and wedging as predictors. Cumulative reconstruction of radiographs improves prediction accuracy. Comprehensive analysis between progressive and non-progressive curves is recommended to extract meaningful thresholds for clinical prognostication. Cite this article: Bone Jt Open 2024;5(3):243–251.

The treatment landscape for patients with advanced ALK-positive NSCLC has rapidly evolved following the approval of several ALK TKIs in Canada. However, public funding of ALK TKIs is mostly limited to the first line treatment setting. Using linked provincial health administrative databases, we examined real-world outcomes of patients with advanced ALK-positive NSCLC receiving ALK TKIs in Ontario between 1 January 2012 and 31 December 2021. Demographic, clinical characteristics and treatment patterns were summarized using descriptive statistics. Kaplan–Meier analysis was performed to evaluate progression-free survival (PFS) and overall survival (OS) among the treatment groups. A total of 413 patients were identified. Patients were administered alectinib (n = 154), crizotinib (n = 80), or palliative-intent chemotherapy (n = 55) in the first-line treatment. There was a significant difference in first-line PFS between the treatment groups. The median PFS (mPFS) was not reached for alectinib (95% CI, 568 days—not reached), compared to 8.2 months (95% CI, 171–294 days) for crizotinib (HR = 0.34, p < 0.0001) and 2.4 months (95% CI, 65–100 days) for chemotherapy (HR = 0.14, p < 0.0001). There was no significant difference in first-line OS between the treatment groups. In patients who received more than one line of treatment, there was a significant difference in mOS between patients who received two or more lines of ALK TKIs compared to those who received one line of ALK TKI (mOS = 55 months (95% CI, 400–987 days) and 26 months (95% CI, 1448–2644 days), respectively, HR = 4.64, p < 0.0001). This study confirms the effectiveness of ALK TKIs in real-world practice and supports the potential benefit of multiple lines of ALK TKI on overall survival in patients with ALK-positive NSCLC.

Breast cancer stem cells (CSCs) are resistant to most cancer therapeutics and contribute to tumor recurrence and metastasis. Two breast CSC-promoting transcription factors, truncated glioma-associated oncogene homolog 1 (tGLI1) and signal transducer and activator of transcription 3 (STAT3), have been reported to be frequently co-expressed in HER2-enriched breast cancer and triple-negative breast cancer (TNBC), undergo protein-protein interactions for gene regulation and activation, and functionally cooperate to promote breast CSCs. STAT3 can be activated by activated interleukin-6 receptor/glycoprotein-130 (IL-6R/GP130). Co-targeting of tGLI1 and IL-6R/GP130 has not been investigated in breast cancer or any tumor type. Here, we report that tGLI1 and GP130 are co-overexpressed in the majority of HER2-enriched breast cancers and TNBCs at 53.8% and 44.4%, respectively. tGLI1+IL-6/IL-6R/GP130 signaling is frequently co-enriched and co-activated in HER2-enriched breast cancer and TNBC when compared to luminal subtypes. tGLI1+GP130 co-overexpression strongly promotes CSCs of HER2-enriched breast cancer and TNBC. FDA-approved tGLI1 inhibitor Ketoconazole and GP130 inhibitor Bazedoxifene synergize against breast cancer proliferation and CSC phenotypes in vitro and reduce TNBC tumor growth and metastatic burden in vivo. Our study demonstrates, for the first time, that co-targeting tGLI1 and IL-6R/GP130/STAT3 signaling pathways is synergistic against HER2-enriched breast cancer and TNBC, warranting future clinical investigations.

Breast cancer is the most frequent malignancy in women, constituting 15.2% of all new cancers diagnosed in the United States. Distant breast cancer metastasis accounts for the majority of breast cancer-related deaths; brain metastasis is the third most common site for metastatic breast cancer but is associated with worst prognosis of approximately eight months of survival. Current treatment options for breast cancer brain metastasis (BCBM) are limited and ineffective. To help identify new and effective therapies for BCBM, it is important to investigate the mechanisms by which breast cancer cells metastasize to the brain and thrive in the brain microenvironment. To this end, studies have reported that primary breast tumor cells can prime brain microenvironmental cells, including, astrocytes and microglia, to promote the formation of BCBM through the release of extracellular vesicle-microRNAs (miRNAs). Breast tumor-derived miRNAs can also promote breast cancer cell invasion through the blood-brain barrier by disrupting the integrity of the brain microvascular endothelial cells. In this review, we summarize current literature on breast cancer-derived BCBM-promoting miRNAs, cover their roles in the complex steps of BCBM particularly their interactions with microenvironmental cells within the brain metastatic niche, and finally discuss their therapeutic applications in the management of BCBM.

PURPOSEThis study aimed to identify, evaluate, and rank suitable safety innovations developed during the COVID-19 pandemic in Latin American and Caribbean (LAC) radiation oncology centers.METHODSWe conducted a multimodal participatory engagement collaboration with the Latin-American and Caribbean Society of Medical Oncology. The study consisted of four phases. Innovations were collected from a panel of radiotherapy experts representing a diverse group of 11 countries from LAC (Phase I). Next, a medical scientific team compared the innovations against international standards regarding their potential impact on risk of infection, clinical operation, and continuity of quality cancer care (Phase II). Their findings were supplied to the country representatives who rated the innovations for acceptability in their cancer centers (Phase III), resulting in a final report of the panel's recommendations (Phase IV).RESULTSA total of 81 innovations were reported by the country representatives and merged by the medical scientific team into 24 innovations that combined similar innovations. The 24 innovations were grouped into six categories including practices aimed at (1) reducing clinic crowding (n = 3), (2) increasing screening and vaccinations for COVID-19 disease (n = 5), (3) implementing social distancing (n = 6), (4) strengthening personal infection equipment and disinfection (n = 6), (5) avoiding delaying or shortening treatment protocols (n = 2), and (6) mixed procedures (n = 2). The medical scientific team found nearly all innovations were supported by international recommendations and rated as safe, efficient, and acceptable.CONCLUSIONBy using the lessons learned from the Community-Led Action Research in Oncology: Pandemic-Appropriate Radiotherapy Innovations Evaluated study, a manual of scalable practices in radiation oncology clinics may be developed to guide actions during future large-scale public health crises in low- and middle-income countries of LAC.

ObjectiveTo investigate the psychometric properties of the Lift and Carry Test (LCT) time in people with stroke.DesignCross-sectional design.SettingUniversity based neurorehabilitation laboratory.ParticipantsTwenty-four people with stroke and 24 healthy controls.Outcome measuresLift and Carry Test (LCT), Fugl-Meyer Assessment of upper extremity and lower extremity, ankle dorsiflexor and plantarflexor muscle strength, Berg Balance Scale (BBS), Timed Up and Go (TUG) and Community Integration Measure.ResultsThe mean LCT time (29.70s) in people with stroke was more than double of that in healthy controls (13.70s). The LCT showed excellent intra-rater, inter-rater and test–retest reliability [intraclass correlation coefficient (ICC) = 0.943–1.000]. The LCT times demonstrated a significant negative correlation with the BBS score (rs = −0.771) and significant positive correlations with the TUG times (rs = 0.933). There was no significant correlation between LCT times and FMA score (p > 0.05). An optimal cut-off LCT time of 15.48 s (sensitivity = 95.8%, specificity = 87.5%) was identified to differentiate between people with stroke and healthy controls (area under the curve = 0.957).ConclusionLCT is an excellent clinical test for examining advanced functional ability in people with stroke and distinguishing people with stroke from healthy controls.

AimTo assess the effects of SDF and SDF+KI treatment on enamel and dentin carious lesions in primary teeth using x-ray Microtomography (XMT) and back scattered scanning electron microscopy (BSE-SEM).MethodsArtificial enamel caries of 3 caries free primary teeth were created by immersion of the samples in 50 ml demineralization solution for 72 h. Three other teeth with natural dentin caries were selected. Both groups were divided into 3 subgroups: EC–Enamel Control; ES–Enamel with SDF application; ESK–Enamel with SDF followed by KI application; DC–Dentin Control; DS–Dentin with SDF application; DSK–Dentin with SDF followed by KI application. Each tooth was imaged using XMT at 3 time points: (1) Pretreatment; (2) after immersion in remineralization solution for 120 h, with or without SDF or SDF+KI; (3) after subsequent immersion in demineralization solution for 72 h. The change of radiopacities of the lesions in these time points were assessed from the XMT images. After the XMT scans, all teeth were investigated microscopically using BSE-SEM.ResultsIn EC, no change in linear attenuation coefficient (LAC) was observed after remineralization, but LAC reduction was observed after subsequent demineralization. For ES, thin layer of high LAC material was deposited on the enamel surface after remineralization, and further reduction of LAC was observed after demineralization. In ESK, the surface layer was lost after SDF+KI, and small reduction of LAC was observed after demineralization. In DC, no LAC change was observed after remineralization, but reduction of LAC was detected after demineralization. In DS, high LAC material was formed on the carious dentin surface and randomly inside the lesion. No further LAC change was found after demineralization. In DSK, thick layer of high LAC material was deposited on the carious surface and inside the dentinal tubules. No further LAC reduction was found after subsequent demineralization.ConclusionSDF and SDF+KI did not protect artificial enamel under acid attack even though Ag products were deposited in the porous enamel. However, SDF and SDF+KI shows protective properties against acid challenges and Ag products are deposited in carious dentin lesion without tubular structure randomly; and within dentinal tubules when these structures are retained.

Abstract Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, the accuracy and applicability of routine PGT is confounded by uneven genome coverage and high allele drop‐out rate from existing single‐cell whole genome amplification methods. Here, a method to diagnose genetic mutations and concurrently evaluate embryo competence by leveraging the abundant mRNA transcript copies present in trophectoderm cells is developed. The feasibility of the method is confirmed with 19 donated blastocysts. Next, the method is applied to 82 embryos from 26 families with monogenic defects for simultaneous mutation detection and competence assessment. The accuracy rate of direct mutation detection is up to 95%, which is significantly higher than DNA‐based method. Meanwhile, this approach correctly predicted seven out of eight (87.5%) embryos that failed to implant. Of six embryos that are predicted to implant successfully, four met such expectations (66.7%). Notably, this method is superior at conditions for mutation detection that are challenging when using DNA‐based PGT, such as when detecting pathogenic genes with a high de novo rate, multiple pseudogenes, or an abnormal expansion of CAG trinucleotide repeats. Taken together, this study establishes the feasibility of an RNA‐based PGT that is also informative for assessing implantation competence.

PurposeCurrent evidence supports the use of integrative oncology (IO) interventions in cancer supportive care. The demand for outpatient IO services in Hong Kong is expected to soar following the surge in cancer incidence due to population ageing. This study identified the factors influencing the delivery and utilisation of outpatient IO from local stakeholders’ perspectives and developed corresponding implementation strategies.MethodsThis study involved two sequential stages. First, with individual semi-structured interviews guided by the Theoretical Domains Framework (TDF), we explored stakeholders’ views on the barriers to and facilitators for implementing IO. Second, guided by a TDF-based qualitative data analysis of interview transcripts, we performed intervention mapping to develop Behaviour Change Wheel-based implementation strategies that may overcome the barriers and strengthen the facilitators.ResultsWe interviewed 31 stakeholders, including traditional Chinese medicine (TCM) practitioners (n = 8), biomedically-trained doctors (n = 7), nurses (n = 6), administrators (n = 4), caregivers (n = 4), and pharmacists (n = 2). The key local factors influencing outpatient IO are (1) lacking nursing and administrative workforce supporting IO service delivery, (2) lacking awareness of IO services among healthcare professionals, administrators, patients, and caregivers, and (3) lacking knowledge among healthcare professionals of herb–drug interaction and herbal toxicities.ConclusionWe recommended a multi-faceted implementation strategies package that included arranging funding to train, recruit, and retain nursing and administrative staff, devolving resources into promoting interprofessional collaborations and evidence on IO effectiveness and safety, integrating evidence on herb–drug interactions and herbal toxicities into automated electronic health record systems monitored by pharmacists with dual qualifications in TCM and conventional pharmacy.

ABSTRACT Background N7‐methylguanosine (m7G) modification is one of the most prevalent RNA modifications in humans. Dysregulated m7G modifications caused by aberrant expression of m7G writers contribute to cancer progression and result in worse patient survival in several human cancers. However, studies that systematically assess the frequency and clinical relevance of aberrant m7G writer expression in a pan‐cancer cohort remain to be performed. Aims This study aims to systematically investigate the molecular alteration and clinical relevance of m7G methyltransferase in human cancers. Methods We analysed genome, transcriptome and clinical data from the Cancer Genome Atlas Research Network spanning 33 types of human cancers for aberrant changes in genes encoding m7G writers. Result We demonstrate that m7G writers are dysregulated in human cancers and are associated predominantly with poorer survival. By dividing patients into those with high and low m7G scores, we show that a lower m7G score is generally associated with immune infiltration and better response to immunotherapy. Conclusion Our analyses indicate the genetic alterations, expression patterns and clinical relevance of m7G writers across various cancers. This study provides insights into the potential utility of m7G writer expression as a cancer biomarker and proposes the possibility of targeting m7G writers for cancer therapy.

Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in vertebrates. In fish models, GnRH can also induce prolactin (PRL) release, but little is known for the corresponding effect on PRL gene expression as well as the post-receptor signalling involved. Using grass carp as a model, the functional role of GnRH and its underlying signal transduction for PRL regulation were examined at the pituitary level. Using laser capture microdissection coupled with RT-PCR, GnRH receptor expression could be located in carp lactotrophs. In primary cell culture prepared from grass carp pituitaries, the native forms of GnRH, GnRH2 and GnRH3, as well as the GnRH agonist [D-Arg6, Pro9, NEt]-sGnRH were all effective in elevating PRL secretion, PRL mRNA level, PRL cell content and total production. In pituitary cells prepared from the rostral pars distalis, the region in the carp pituitary enriched with lactotrophs, GnRH not only increased cAMP synthesis with parallel CREB phosphorylation and nuclear translocation but also induced a rapid rise in cytosolic Ca2+ by Ca2+ influx via L-type voltage-sensitive Ca2+ channel (VSCC) with subsequent CaM expression and NFAT2 dephosphorylation. In carp pituitary cells prepared from whole pituitaries, GnRH-induced PRL secretion was reduced/negated by inhibiting cAMP/PKA, PLC/PKC and Ca2+/CaM/CaMK-II pathways but not the signalling events via IP3 and CaN/NFAT. The corresponding effect on PRL mRNA expression, however, was blocked by inhibiting cAMP/PKA/CREB/CBP and Ca2+/CaM/CaN/NFAT2 signalling but not PLC/IP3/PKC pathway. At the pituitary cell level, activation of cAMP/PKA pathway could also induce CaM expression and Ca2+ influx via VSCC with parallel rises in PRL release and gene expression in a Ca2+/CaM-dependent manner. These findings, as a whole, suggest that the cAMP/PKA-, PLC/PKC- and Ca2+/CaM-dependent cascades are differentially involved in GnRH-induced PRL secretion and PRL transcript expression in carp lactotrophs. During the process, a functional crosstalk between the cAMP/PKA- and Ca2+/CaM-dependent pathways may occur with PRL release linked with CaMK-II and PKC activation and PRL gene transcription caused by nuclear action of CREB/CBP and CaN/NFAT2 signalling.

Background and aimsEndovascular thrombectomy (EVT) is the current standard of care for large vessel occlusion (LVO) acute ischemic stroke (AIS); however, up to two-thirds of EVT patients have poor functional outcomes despite successful reperfusion. Many radiological markers have been studied as predictive biomarkers for patient outcomes in AIS. This study seeks to determine which clinico-radiological factors are associated with outcomes of interest to aid selection of patients for EVT for LVO AIS.MethodsA retrospective study of patients who underwent EVT from 2016 to 2020 was performed. Data on various radiological variables, such as anatomical parameters, clot characteristics, collateral status, and infarct size, were collected alongside traditional demographic and clinical variables. Univariate and multivariate analysis was performed for the primary outcomes of functional independence at 3 months post-stroke (modified Rankin Scale 0–2) and secondary outcomes of in-hospital mortality and symptomatic intracranial hemorrhage.ResultsThe study cohort comprised 325 consecutive patients with anterior circulation LVO AIS (54.5% male) with a median age of 68 years (interquartile range 57–76). The median NIHSS was 19. Age, hypertension, hyperlipidaemia, National Institutes of Health Stroke Scale (NIHSS), Alberta mCTA score, ASPECTS, clot length, thrombus HU and mTICI score and the angle between ICA and CCA were associated with functional outcomes at 3 months on univariate analysis. On multivariate analysis, age, Alberta mCTA collaterals and NIHSS were significantly associated with functional outcomes, while ASPECTS approached significance.ConclusionAmong the many proposed radiological markers for patients in the hyperacute setting undergoing EVT, the existing well-validated clinico-radiological measures remain strongly associated with functional status.

Summary: Continuous assessment of the impact of SARS-CoV-2 on the host at the cell-type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral-strain and Alpha-variant SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from younger adults (26–32 Y) and older children (12–14 Y) using single-cell RNA-sequencing. Ciliated and secretory-ciliated cells formed the majority of highly infected cell-types, with the latter derived from ciliated lineages. Strong innate immune responses were observed across lowly infected and uninfected bystander cells and heightened in Alpha-infection. Alpha highly infected cells showed increased expression of protein-refolding genes compared with ancestral-strain-infected cells in children. Furthermore, oxidative phosphorylation-related genes were down-regulated in bystander cells versus infected and mock-control cells, underscoring the importance of these biological functions for viral replication. Overall, this study highlights the complexity of cell-type-, age- and viral strain-dependent host epithelial responses to SARS-CoV-2.

Abstract RNA modifications have emerged as central regulators of gene expression programs. Amongst RNA modifications are N6-methyladenosine (m6A) and RNA 5-hydroxymethylcytosine (5hmC). While m6A is established as a versatile regulator of RNA metabolism, the functions of RNA 5hmC are unclear. Despite some evidence linking RNA modifications to immunity, their implications in gene expression control in macrophage development and functions remain unclear. Here we present a multi-omics dataset capturing different layers of the gene expression programs driving macrophage differentiation and polarisation. We obtained mRNA-Seq, m6A-IP-Seq, 5hmC-IP-Seq, Polyribo-Seq and LC-MS/MS data from monocytes and resting-, pro- and anti-inflammatory-like macrophages. We present technical validation showing high quality and correlation between samples for all datasets, and evidence of biological consistency of modelled macrophages at the transcriptomic, epitranscriptomic, translational and proteomic levels. This multi-omics dataset provides a resource for the study of RNA m6A and 5hmC in the context of macrophage biology and spans the gene expression process from transcripts to proteins.

Abstract Pseudomonas aeruginosa is a major nosocomial pathogen that causes severe disease including sepsis. Carbapenem-resistant P. aeruginosa is recognised by the World Health Organisation as a priority 1 pathogen, with urgent need for new therapeutics. As such, there is renewed interest in using bacteriophages as a therapeutic. However, the dynamics of treating pan-resistant P. aeruginosa with phage in vivo are poorly understood. Using a pan-resistant P. aeruginosa in vivo infection model, phage therapy displays strong therapeutic potential, clearing infection from the blood, kidneys, and spleen. Remaining bacteria in the lungs and liver displays phage resistance due to limiting phage adsorption. Yet, resistance to phage results in re-sensitisation to a wide range of antibiotics. In this work, we use phage steering in vivo, pre-exposing a pan resistant P. aeruginosa infection with a phage cocktail to re-sensitise bacteria to antibiotics, clearing the infection from all organs.

Abstract Many machine learning applications in bioinformatics currently rely on matching gene identities when analyzing input gene signatures and fail to take advantage of preexisting knowledge about gene functions. To further enable comparative analysis of OMICS datasets, including target deconvolution and mechanism of action studies, we develop an approach that represents gene signatures projected onto their biological functions, instead of their identities, similar to how the word2vec technique works in natural language processing. We develop the Functional Representation of Gene Signatures (FRoGS) approach by training a deep learning model and demonstrate that its application to the Broad Institute’s L1000 datasets results in more effective compound-target predictions than models based on gene identities alone. By integrating additional pharmacological activity data sources, FRoGS significantly increases the number of high-quality compound-target predictions relative to existing approaches, many of which are supported by in silico and/or experimental evidence. These results underscore the general utility of FRoGS in machine learning-based bioinformatics applications. Prediction networks pre-equipped with the knowledge of gene functions may help uncover new relationships among gene signatures acquired by large-scale OMICs studies on compounds, cell types, disease models, and patient cohorts.

Abstract Background By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients’ symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (

Abstract Introduction Duchenne muscular dystrophy (DMD) is a genetic muscle disorder that manifests during early childhood and is ultimately fatal. Recently approved treatments targeting the genetic cause of DMD are limited to specific subpopulations of patients, highlighting the need for therapies with wider applications. Pharmacologic inhibition of myostatin, an endogenous inhibitor of muscle growth produced almost exclusively in skeletal muscle, has been shown to increase muscle mass in several species, including humans. Taldefgrobep alfa is an anti-myostatin recombinant protein engineered to bind to and block myostatin signaling. Preclinical studies of taldefgrobep alfa demonstrated significant decreases in myostatin and increased lower limb volume in three animal species, including dystrophic mice. Methods This manuscript reports the cumulative data from three separate clinical trials of taldefgrobep alfa in DMD: a phase 1 study in healthy adult volunteers (NCT02145234), and two randomized, double-blind, placebo-controlled studies in ambulatory boys with DMD–a phase 1b/2 trial assessing safety (NCT02515669) and a phase 2/3 trial including the North Star Ambulatory Assessment (NSAA) as the primary endpoint (NCT03039686). Results In healthy adult volunteers, taldefgrobep alfa was generally well tolerated and resulted in a significant increase in thigh muscle volume. Treatment with taldefgrobep alfa was associated with robust dose-dependent suppression of free myostatin. In the phase 1b/2 trial, myostatin suppression was associated with a positive effect on lean body mass, though effects on muscle mass were modest. The phase 2/3 trial found that the effects of treatment did not meet the primary endpoint pre-specified futility analysis threshold (change from baseline of ≥ 1.5 points on the NSAA total score). Conclusions The futility analysis demonstrated that taldefgrobep alfa did not result in functional change for boys with DMD. The program was subsequently terminated in 2019. Overall, there were no safety concerns, and no patients were withdrawn from treatment as a result of treatment-related adverse events or serious adverse events. Trial Registration NCT02145234, NCT02515669, NCT03039686.

Abstract In early sensory systems, cell-type diversity generally increases from the periphery into the brain, resulting in a greater heterogeneity of responses to the same stimuli. Surround suppression is a canonical visual computation that begins within the retina and is found at varying levels across retinal ganglion cell types. Our results show that heterogeneity in the level of surround suppression occurs subcellularly at bipolar cell synapses. Using single-cell electrophysiology and serial block-face scanning electron microscopy, we show that two retinal ganglion cell types exhibit very different levels of surround suppression even though they receive input from the same bipolar cell types. This divergence of the bipolar cell signal occurs through synapse-specific regulation by amacrine cells at the scale of tens of microns. These findings indicate that each synapse of a single bipolar cell can carry a unique visual signal, expanding the number of possible functional channels at the earliest stages of visual processing.

Abstract Proteins in the plasma/serum mirror an individual’s physiology. Circulating extracellular vesicles (EVs) proteins constitute a large portion of the plasma/serum proteome. Thus, deep and unbiased proteomic analysis of circulating plasma/serum extracellular vesicles holds promise for discovering disease biomarkers as well as revealing disease mechanisms. We established a workflow for simple, deep, and reproducible proteome analysis of both serum large and small EVs enriched fractions by ultracentrifugation plus 4D-data-independent acquisition mass spectrometry (4D-DIA-MS). In our cohort study of obstetric antiphospholipid syndrome (OAPS), 4270 and 3328 proteins were identified from large and small EVs enriched fractions respectively. Both of them revealed known or new pathways related to OAPS. Increased levels of von Willebrand factor (VWF) and insulin receptor (INSR) were identified as candidate biomarkers, which shed light on hypercoagulability and abnormal insulin signaling in disease progression. Our workflow will significantly promote our understanding of plasma/serum-based disease mechanisms and generate new biomarkers.

Abstract Pure cellulose nanofibers (CNFs) rapidly degrade in soil, limiting their prospective applications in agriculture. We incorporated lignin into CNFs as an antimicrobial and crosslinking agent to control the biodegradation rate. CNFs with different lignin concentrations were prepared by mechanochemical treatment in the presence of choline chloride-urea deep eutectic solvent. These were characterized using conductometric titration, scanning electron microscopy, and FT-IR. The fibers were applied to soil to determine the effect of lignin on soil respiration and nanocellulose degradation, and were used as a substrate for radish and cress seed germination. Modifying the lignin content of the fibers successfully modulated the biodegradation rate in soil. Fibers containing 35% lignin degraded 5.7% in 14 days, while fibers with 20% lignin degraded 20.8% in 14 days. Nanofiber suspensions showed low chemical inhibition for the germination of radish and cress seeds but higher lignin contents reduced the imbibition rate as a seed coating. This study presents the first use of lignin to control the biodegradation rate of cellulose nanofibers in a one-pot, scalable and sustainable system, allowing the advancement of lignocellulose nanofibers for applications such as seed coatings, mulches, and controlled release fertilizers. Graphical Abstract

Abstract Introduction Mutations in the 79 exons of the dystrophin gene result in muscle wasting and weakness of varying clinical severity, ranging from severe/typical Duchenne muscular dystrophy (DMD) to intermediate DMD and mild Becker muscular dystrophy (BMD), depending on the frameshift of the mutation. We previously reported that males with DMD have progressively declining appendicular lean mass (ALM) and ALM index (ALMI) with age and worsening functional motor ability compared with healthy controls. These indices have not been studied in patients with intermediate DMD and BMD phenotypes and across DMD genotypes. In this study, we compared age‐related trajectories of ALM and ALMI of patients who had (1) BMD without functional mobility deficits with patients who had DMD at different stages of disease and healthy controls; (2) a DMD intermediate phenotype with patients who had a typical DMD phenotype; and (3) DMD categorized by genotype. Methods We conducted a retrospective review of ALM and ALMI data from 499 patients (ages 5–23 years) with DMD (466 typical and 33 intermediate) and 46 patients (ages 5–21 years) with BMD (without functional mobility deficits and functional mobility score of 1). Patients were grouped according to age reflecting disease stage (ages 5 to

Lifts, or elevators, are transportation facilities that are indispensable for countless end users in high-rise buildings. They require proper maintenance to ensure safe operation. In addition to technological applications, effective management and legislative controls play a crucial role in ensuring lift safety. Given the limited understanding of an optimal regulatory model for governing lift maintenance, a cross-discipline comparative study was conducted to examine lift maintenance regulations in regions with different legal systems. Following a systematic and comparative review approach, this study focused on regulatory controls across civil and common law jurisdictions, specifically Beijing, Hong Kong, and London. Relevant statutes and publications were searched from engineering, law and management databases, which included Scopus, JSTOR, Lexis+, Lexis China, Lexis Advance Hong Kong, and Westlaw Asia. Through scrutinizing the retrieved documents, key features of the regulations were identified and compared in terms of lift classifications, types and frequencies of mandatory maintenance works, qualifications for authorized parties, and legal liabilities for non-compliance. Validated by industry experts, the results reveal both similarities and differences in the regulations among the three jurisdictions. While these findings serve as valuable references for policymakers in formulating optimal legislative controls to enhance lift safety in the future, further research could expand the scope of this study to examine the regulations in other regions and investigate the effectiveness of existing statutory controls on lift maintenance.

Abstract MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.

Abstract Soft materials in nature are formed through reversible supramolecular assembly of biological polymers into dynamic hierarchical networks. Rational design has led to self-assembling peptides with structural similarities to natural materials. However, recreating the dynamic functional properties inherent to natural systems remains challenging. Here we report the discovery of a short peptide based on the tryptophan zipper (trpzip) motif, that shows multiscale hierarchical ordering that leads to emergent dynamic properties. Trpzip hydrogels are antimicrobial and self-healing, with tunable viscoelasticity and unique yield-stress properties that allow immediate harvest of embedded cells through a flick of the wrist. This characteristic makes Trpzip hydrogels amenable to syringe extrusion, which we demonstrate with examples of cell delivery and bioprinting. Trpzip hydrogels display innate bioactivity, allowing propagation of human intestinal organoids with apical-basal polarization. Considering these extensive attributes, we anticipate the Trpzip motif will prove a versatile building block for supramolecular assembly of soft materials for biotechnology and medicine.

Abstract Newborns can acquire immunological protection to SARS-CoV-2 through vaccine-conferred antibodies in human breast milk. However, there are some concerns around lactating mothers with regards to potential short- and long-term adverse events and vaccine-induced changes to their breast milk microbiome composition, which helps shape the early-life microbiome. Thus, we sought to explore if SARS-CoV-2 mRNA vaccine could change breast milk microbiota and how the changes impact the levels of antibodies in breast milk. We recruited 49 lactating mothers from Hong Kong who received two doses of BNT162b2 vaccine between June 2021 and August 2021. Breast milk samples were self-collected by participants pre-vaccination, one week post-first dose, one week post-second dose, and one month post-second dose. The levels of SARS-CoV-2 spike-specific IgA and IgG in breast milk peaked at one week post-second dose. Subsequently, the levels of both antibodies rapidly waned in breast milk, with IgA levels returning to baseline levels one month post-second dose. The richness and composition of human breast milk microbiota changed dynamically throughout the vaccination regimen, but the abundances of beneficial microbes such as Bifidobacterium species did not significantly change after vaccination. Additionally, we found that baseline breast milk bacterial composition can predict spike-specific IgA levels at one week post-second dose (Area Under Curve: 0.72, 95% confidence interval: 0.58–0.85). Taken together, our results identified specific breast milk microbiota markers associated with high levels of IgA in the breast milk following BNT162b2 vaccine. Furthermore, in lactating mothers, BNT162b2 vaccines did not significantly reduce probiotic species in breast milk.

Abstract Altered reactivity and responses to auditory input are core to the diagnosis of autism spectrum disorder (ASD). Preclinical models implicate ϒ-aminobutyric acid (GABA) in this process. However, the link between GABA and auditory processing in humans (with or without ASD) is largely correlational. As part of a study of potential biosignatures of GABA function in ASD to inform future clinical trials, we evaluated the role of GABA in auditory repetition suppression in 66 adults (n = 28 with ASD). Neurophysiological responses (temporal and frequency domains) to repetitive standard tones and novel deviants presented in an oddball paradigm were compared after double-blind, randomized administration of placebo, 15 or 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. We first established that temporal mismatch negativity was comparable between participants with ASD and those with typical development (TD). Next, we showed that temporal and spectral responses to repetitive standards were suppressed relative to responses to deviants in the two groups, but suppression was significantly weaker in individuals with ASD at baseline. Arbaclofen reversed weaker suppression of spectral responses in ASD but disrupted suppression in TD. A post hoc analysis showed that arbaclofen-elicited shift in suppression was correlated with autistic symptomatology measured using the Autism Quotient across the entire group, though not in the smaller sample of the ASD and TD group when examined separately. Thus, our results confirm: GABAergic dysfunction contributes to the neurophysiology of auditory sensory processing alterations in ASD, and can be modulated by targeting GABAB activity. These GABA-dependent sensory differences may be upstream of more complex autistic phenotypes.

Abstract Vagus nerve stimulation (VNS) is used to deliver electric current to stimulate the vagus nerve. The aim of this study is to carry out a systematic review and meta-analysis to determine its effects on motor function in patients with stroke. PubMED, Embase, Web of Science (WoS), and Scopus were searched. Data on time since stroke, and mean scores and standard deviation on outcomes such as level of impairment and motor function were extracted. The results showed that invasive (MD 2.66, 95% CI 1.19–4.13, P = 0.0004) and non-invasive (MD 24.16, 95% CI 23.56–24.75, P = 0.00001) VNS are superior at improving level of motor impairment than the control post intervention and at follow-up respectively. Similarly, VNS improved motor function post intervention (MD 0.28, 95% CI 0.15–0.41, P

Abstract Background Subthreshold depression is a highly prevalent mood disorder in young adults. Mind–body exercises, such as Tai Chi, have been adopted as interventions for clinical depressive symptoms. However, the possible effect and underlying mechanism of Tai Chi on subthreshold depression of young individuals remain unclear. This randomized controlled study aimed to evaluate the effects of Tai Chi training and tested the combined stress and reward circuitry model for subthreshold depression. Results A total of 103 participants completed this trial, with 49 in the 12-week 24-style Tai Chi group and 54 participants in control group. Our results showed significantly lower scores on depressive symptoms (P = 0.002) and anxiety symptoms (P = 0.009) and higher scores on quality of life (P = 0.002) after Tai Chi training. There were significant reductions in salivary cortisol levels (P = 0.007) and putamen gray matter volume (P

Abstract Background Heart diseases are among the leading causes of death worldwide, many of which lead to pathological cardiomyocyte hypertrophy and capillary rarefaction in both patients and animal models, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology, termed HeartJ, by generating macros in ImageJ, a broadly used, open-source, Java-based software. Methods We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining. The latter can be easily combined with other stainings, allowing additional quantitative analysis on the same section, e.g., the size of cardiomyocyte nuclei, capillary density, or single-cardiomyocyte protein expression. We validated the pipeline in a mouse model of cardiac hypertrophy induced by transverse aortic constriction, and in autopsy samples of patients with and without aortic stenosis. Results In both animals and humans, HeartJ-based histology quantification revealed significant hypertrophy of cardiomyocytes reflecting other parameters of hypertrophy and rarefaction of microvasculature and enabling the analysis of protein expression in individual cardiomyocytes. The analysis also revealed that murine and human cardiomyocytes had similar diameters in health and extent of hypertrophy in disease confirming the translatability of our murine cardiac hypertrophy model. HeartJ enables a rapid analysis that would not be feasible by manual methods. The pipeline has little hardware requirements and is freely available. Conclusions In summary, our analysis pipeline can facilitate effective and objective quantitative histological analyses in preclinical and clinical heart samples.

Abstract The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P

Abstract Cancer is globally a disease of significant public health concern owing to its prevalence, and association with morbidity and mortality. Thus, cost‐effective treatments for cancer are important to help reduce its significant morbidity and mortality. However, the current therapeutic options for cancer such as chemotherapy, radiotherapy, and surgery may produce serious adverse events such as nausea, vomiting, fatigue, and peripheral neuropathy, especially in the long term. In addition, these therapeutic options may not be well tolerated by the elderly especially those who are frail. The current article is aimed at discussing an alternative therapeutic option, non‐invasive vagus nerve stimulation (VNS), and the roles it plays in cancer pathology and immunotherapy. The VNS does this by reducing oxidative stress via silent information regulator 1 (SIRT1); inhibiting inflammation via both hypothalamic–pituitary–axis (HPA) and the release of corticosteroid from the adrenal gland, and cholinergic anti‐inflammatory pathway (CAP), and increasing vagal activity which helps in the regulation of cell proliferation, differentiation, apoptosis, and metabolism, and increase chance of survival. Furthermore, it helps with reducing complications due to cancer or its treatments such as postoperative ileus and severity of peripheral neuropathy induced by chemotherapy, and improves cancer‐related fatigue, lymphopenia, and quality of life. These suggest that the importance of non‐invasive VNS in cancer pathology and immunotherapy cannot be overemphasized. Therefore, considering the safety of non‐invasive VNS and its cost‐effectiveness, it is a therapeutic option worth trying for these patients, especially in combination with other therapies.