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Abstract Background and purpose This study aimed to summarize the clinical outcomes of patients with metastatic melanoma who received high‐dose radiation prior to or during systemic therapy at a single academic institution. Methods We identified patients with metastatic melanoma who underwent high‐dose radiation therapy (HDRT) for extracranial metastases prior to or during systemic therapy from 2010 to 2018. Treatment indications included oligometastases, oligoprogression, and local control. Using the Kaplan‐Meier method, we plotted overall survival (OS), progression‐free survival‐1 (PFS1), and PFS2. Competing risk analysis determined the cumulative incidence of local failure (LF) and the time to start or change systemic therapy (SCST). Univariate and multivariable analyses were used to identify predictive factors. Results We analyzed 34 patients with 79 lesions, with a median follow‐up of 17.4 months. Sixty‐eight percent of patients received systemic therapy after the first HDRT. The median OS was 22 months, with brain metastases before HDRT being a significant predictor in multivariable analysis. The median PFS1 for first‐line HDRT was 4.1 months, and the median PFS2 was 3.9 months. Rates of LF were 10.3% at 12 months and 11.7% at 24 months. The incidence of SCST following HDRT was 59.8% at 12 months and 76.1% at 24 months, with radiation targeted at the lung associated with a lower incidence of SCST. Conclusion HDRT for treating metastatic lesions in melanoma demonstrated excellent local control and may play a role in delaying SCST. Additional courses of HDRT may provide cumulative benefits.

Abstract Optimal treatment of infants with many renally cleared drugs must account for maturational differences in renal transporter (RT) activity. Pediatric physiologically‐based pharmacokinetic (PBPK) models may incorporate RT activity, but this requires ontogeny profiles for RT activity in children, especially neonates, to predict drug disposition. Therefore, RT expression measurements from human kidney postmortem cortical tissue samples were normalized to represent a fraction of mature RT activity. Using these data, maximum likelihood estimated the distributions of RT activity across the pediatric age spectrum, including preterm and term neonates. PBPK models of four RT substrates (acyclovir, ciprofloxacin, furosemide, and meropenem) were evaluated with and without ontogeny profiles using average fold error (AFE), absolute average fold error (AAFE), and proportion of observations within the 5–95% prediction interval. Novel maximum likelihood profiles estimated ontogeny distributions for the following RT: OAT1, OAT3, OCT2, P‐gp, URAT1, BCRP, MATE1, MRP2, MRP4, and MATE‐2 K. Profiles for OAT3, P‐gp, and MATE1 improved infant furosemide and neonate meropenem PBPK model AFE from 0.08 to 0.70 and 0.53 to 1.34 and model AAFE from 12.08 to 1.44 and 2.09 to 1.36, respectively, and improved the percent of data within the 5–95% prediction interval from 48% to 98% for neonatal ciprofloxacin simulations, respectively. Even after accounting for other critical population‐specific maturational differences, novel RT ontogeny profiles substantially improved neonatal PBPK model performance, providing validated estimates of maturational differences in RT activity for optimal dosing in children.

Abstract It remains a challenge to produce soft robots that can mimic the responsive adaptability of living organisms. Rather than fabricating soft robots from bulk hydrogels,hydrogels are integrated into the interfacial assembly of aqueous two‐phase systems to generate ultra‐soft and elastic all‐aqueous aquabots that exhibit responsive adaptability, that can shrink on demand and have electrically conductive functions. The adaptive functions of the aquabots provide a new platform to develop minimally invasive surgical devices, targeted drug delivery systems, and flexible electronic sensors and actuators.

ABSTRACT Background To investigate the feasibility of conducting COVID‐19 testing in kindergarten‐grade 12 schools, saliva‐based testing was implemented in five schools. The purpose of this study was to understand staff's perspectives of the barriers and facilitators to conducting saliva‐based testing in their settings. Methods Thirty‐three school staff who worked in five target schools were interviewed in the summer of 2021. Participants were recruited from June–August 2021 via a flyer that was distributed through email and school‐affiliated social media and websites, and word‐of‐mouth. Semi‐structured interviews were conducted over Zoom by a trained interviewer; interviews were audio recorded and auto transcribed using this Zoom feature. Constant comparative analysis and emergent coding were used to analyze the data. Results The majority of participants had positive experiences with conducting saliva‐based testing during school hours. Participants reported that saliva‐based testing did not interrupt their school routine because (1) the testing was simple and quick, (2) the testing schedule was consistent and organized, and (3) school staff maintained open lines of communication. Barriers to implementing the testing were as follows: (1) obtaining parental consent, (2) not being allowed to drink or eat an hour before testing, and (3) struggling to provide enough saliva for testing. Participants suggested the following strategies to facilitate testing in schools: being more proactive, giving families fewer things to sign (i.e., consent forms), improving communication, adding needed consents to the school registration process, using social media, and increasing community outreach. Conclusion As schools weigh the benefits and the risks of closing for extended periods of time versus remaining open for in‐person learning, saliva‐based testing is a feasible and efficient way to support programs in this decision‐making process. This approach can be used in future pandemics and in areas with outbreaks or poor vaccine coverage.

Background In adults with large‐vessel occlusion stroke, the extent of the baseline infarct measured using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) predicts outcome and is used during patient selection for mechanical thrombectomy. The relationship between ASPECTS and clinical outcome is unknown in pediatric large‐vessel occlusion stroke. Methods Secondary analysis of a retrospective multicenter case–control study assessing mechanical thrombectomy versus medical management alone for pediatric large‐vessel occlusion stroke across 5 centers in Australia and Canada from 2011 to 2022. ASPECTS was measured on baseline computed tomography or magnetic resonance imaging–diffusion‐weighted imaging while blinded to clinical outcome and treatment status. The relationship between ASPECTS and pediatric modified Rankin scale scores at 3 months following stroke was assessed using ordinal logistic regression. Results In total, n = 24 thrombectomy patients (F = 10, mean age, 11.3 years [SD, 4.36]) and n = 24 control patients (F = 10, mean age, 10.2 years [SD, 4.32) were included. Mean ASPECTS was 6.3 (SD, 2.37) in the thrombectomy group and 6.1 (SD, 2.64) in the control group. In patients undergoing thrombectomy, baseline ASPECTS significantly correlated with pediatric modified Rankin scale scores at 3 months (odds ratio, 1.58 [95% CI, 1.10–2.27]; P = 0.013). In control patients, there was no significant correlation (odds ratio, 1.17 [95% CI, 0.87–1.55]; P = 0.298). Six of 7 thrombectomy patients with a large baseline infarct (ASPECTS

Background Shock‐reduction implantable cardioverter‐defibrillator programming (SRP) was associated with fewer therapies and improved survival in randomized controlled trials, but real‐world studies investigating SRP and associated outcomes are limited. Methods and Results The BIOTRONIK CERTITUDE registry was linked with the Medicare database. We included all patients with an implantable cardioverter‐defibrillator implanted between August 22, 2012 and September 30, 2021 in the United States. SRP was defined as programming to either a therapy rate cutoff ≥188 beats per minute or number of intervals to detection ≥30/40 for treatment. Among 6781 patients (mean 74±9 years; 27% women), 3393 (50%) had SRP. Older age, secondary prevention indication, and device implantation in the southern or western United States were associated with lower use of SRP. The cumulative incidence rate of implantable cardioverter‐defibrillator shocks was lower in the SRP group (5.1% shocks/patient year) compared with the non‐SRP group (7.2% shocks/patient year) (adjusted hazard ratio [HR], 0.83 [95% CI, 0.73–0.96]; P=0.005). Over a median follow‐up of 2.9 years, 739 deaths occurred in the SRP group and 822 deaths occurred in the non‐SRP group (adjusted HR, 0.97 [95% CI, 0.88–1.07]; P=0.569). SRP was associated with a lower all‐cause mortality among patients without ischemic heart disease compared with patients with ischemic heart disease (adjusted HR, 0.64 [95% CI, 0.48–0.87] versus adjusted HR, 1.02 [95% CI, 0.92–1.14]; Pinteraction=0.004). Conclusions Adoption of SRP is low in real‐world clinical practice. Age, clinical variables, and geographic factors are associated with use of SRP. In this study, SRP‐associated decrease in mortality was limited to patients without ischemic heart disease.

Abstract Coordinated policies and effective global environmental governance are needed to address the global biodiversity crisis. Human dimensions like geopolitics influence conservation decision‐making and outcomes. The importance of considering these complex social factors is heightened in an era of renewed great‐power politics, as the intensifying US–China rivalry has direct implications for environmental governance and biodiversity outcomes. Can the US–China rivalry and its confrontational dynamics be channeled into conservation policymaking to improve biodiversity outcomes? Drawing from international relations and policy studies, policy diffusion theory can provide conservationists with useful insights into the interdependency of policy decisions. Here, we examine the four mechanisms—competition, coercion, learning, and emulation—of the classic model of policy diffusion theory in the context of environmental policymaking. We explore a case study for each mechanism to illustrate how it can benefit biodiversity conservation, and point to examples of relevant policies and actions that could improve outcomes. To operationalize this concept for conservation, we present a decision tree that conservationists can use to determine the most relevant policy diffusion mechanism in different policy contexts. Upon determining the appropriate mechanism, conservationists can take further steps to intentionally trigger the mechanism and catalyze conservation policy diffusion across jurisdictions.

Abstract Background and Aim Obesity has been a global public health issue due to the increasing mortality rate and prevalence among children. However, there are scarce studies on obesity prevalence in Hong Kong children. The study aims to identify the risk factors of obesity among primary and secondary school students by assessing the relationship between sociodemographic factors, health‐related behaviors, and social relationships. Methods Self‐administrated surveys were collected from 30 primary schools and 25 secondary schools participating in the “Quality Education Fund Thematic Network on Health Schools” project. Descriptive analysis was conducted to examine the proportions of different characteristics and to compare the disparity between primary and secondary school students with obesity. Results A total of 4884 responses were collected. A larger proportion of primary school students with obesity were male (adjusted odds ratio [aOR]: 2.55, 95% confidence interval [CI]: 1.77–3.67, p

Abstract Pediatric obstructive sleep apnea poses a significant health risk, with potential long‐term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex‐specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole‐body plethysmography, treadmill stress‐tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age‐matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex‐based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH‐related arrhythmia. These findings emphasize the importance of considering sex‐specific responses in understanding the cardiovascular implications of pediatric sleep apnea.

Abstract Background Lenvatinib (LEN) and atezolizumab + bevacizumab (A + B) have drastically changed the treatment paradigm for advanced hepatocellular carcinoma (HCC). Before these landmark trials, sorafenib (SOR) served as the standard first‐line treatment for a decade. Our study aimed to assess the outcomes of HCC patients treated during the SOR era (2008–2018) in contrast to those in the post‐SOR era (2018–2021), of which the predominant first‐line treatments were LEN or A + B. Methods Inclusion criteria of the study were all HCC patients in the Canadian province of Alberta who started first‐line systemic therapy at cancer centers between 1 January 2008 and 31 December 2021. Survival outcomes, including overall survival (OS) and progression‐free survival (PFS), along with clinician‐assessed response rate (RR), were subject to retrospective analysis. Results Of 372 total patients, 230 received treatment in the SOR era and 142 in the post‐SOR era. The demographic and clinical characteristics for the SOR era and post‐SOR era groups are as follows, respectively: the median age was 63 and 64 years, 80% and 81% were male, and 24% and 11% were of East Asian ethnicity. Before receiving systemic treatment, 40% and 33% received TACE, 7% and 9% received TARE, and 3% and 14% received SBRT in the two eras, respectively. In the post‐SOR era, patients received A + B (23%), LEN (51%), and SOR (23%) as first‐line treatment. There was a statistically significant improvement in RR (15% vs. 26%; p = 0.02), median PFS (3.8 months vs. 7.9 months; p

Abstract Objectives Randomized controlled trials (RCTs) are the gold standard for evaluating the comparative efficacy and safety of new cancer therapies. However, enrolling patients in control arms of clinical trials can be challenging for rare cancers, particularly in the context of precision oncology and targeted therapies. External Control Arms (ECAs) are a potential solution to address these challenges in clinical research design. We conducted a scoping review to explore the use of ECAs in oncology. Methods We systematically searched four databases, namely MEDLINE, EMBASE, Web of Science, and Scopus. We screened titles, abstracts, and full texts for eligible articles focusing on patients undergoing therapy for cancer, employing ECAs, and reporting clinical outcomes. Results Of the 629 articles screened, 23 were included in this review. The earliest included studies were published in 1996, while most studies were published in the past 5 years. 44% (10/23) of ECAs were employed in blood‐related cancer studies. Geographically, 30% (7/23) of studies were conducted in the United States, 22% (5/23) in Japan, and 9% (2/23) in South Korea. The primary data sources used to construct the ECAs involved pooled data from previous trials (35%, 8/23), administrative health databases (17%, 4/23) and electronic medical records (17%, 4/23). While 52% (12/23) of the studies employed methods to align treatment and ECAs characteristics, 48% (11/23) lacked explicit strategies. Conclusion ECAs offer a valuable approach in oncology research, particularly when alternative designs are not feasible. However, careful methodological planning and detailed reporting are essential for meaningful and reliable results.

Abstract Predictive high‐fidelity modeling of wind turbines with computational fluid dynamics, wherein turbine geometry is resolved in an atmospheric boundary layer, is important to understanding complex flow accounting for design strategies and operational phenomena such as blade erosion, pitch‐control, stall/vortex‐induced vibrations, and aftermarket add‐ons. The biggest challenge with high‐fidelity modeling is the realization of numerical algorithms that can capture the relevant physics in detail through effective use of high‐performance computing. For modern supercomputers, that means relying on GPUs for acceleration. In this paper, we present ExaWind, a GPU‐enabled open‐source incompressible‐flow hybrid‐computational fluid dynamics framework, comprising the near‐body unstructured grid solver Nalu‐Wind, and the off‐body block‐structured‐grid solver AMR‐Wind, which are coupled using the Topology Independent Overset Grid Assembler. Turbine simulations employ either a pure Reynolds‐averaged Navier–Stokes turbulence model or hybrid turbulence modeling wherein Reynolds‐averaged Navier–Stokes is used for near‐body flow and large eddy simulation is used for off‐body flow. Being two‐way coupled through overset grids, the two solvers enable simulation of flows across a huge range of length scales, for example, 10 orders of magnitude going from O(μm) boundary layers along the blades to O(10 km) across a wind farm. In this paper, we describe the numerical algorithms for geometry‐resolved turbine simulations in atmospheric boundary layers using ExaWind. We present verification studies using canonical flow problems. Validation studies are presented using megawatt‐scale turbines established in literature. Additionally presented are demonstration simulations of a small wind farm under atmospheric inflow with different stability states.

Abstract Objective To determine how caregivers describe dystonia in people with cerebral palsy (CP). Methods In this prospective cohort study, paper surveys were administered to caregivers between September 7, 2021 and October 28, 2021 during CP Center visits at a large tertiary care center. Caregivers were asked to describe involuntary movements triggered by voluntary movement or triggered by tactile stimulation in the people with CP they cared for. Their CP Center medical provider separately assessed people with CP for dystonia. Movement features described exclusively by caregivers of people with CP and dystonia were determined using conventional content analysis. Results 113 caregivers responded on behalf of 56 people with and 57 people without dystonia. If caregivers noted that both voluntary movement and tactile stimulation triggered involuntary movements, that had a 92% positive predictive value for a dystonia diagnosis. Movement features exclusively described in people with CP and dystonia included: (1) stiffening, tensing, or tightening (15% of respondents); (2) involvement of the head (10%), torso (5%), or feet (5%); and (3) triggers of stretching (12.5%), excitement (5%), or transfers (5%). Interpretation In addition to a thorough exam, asking caregivers of people with CP to describe involuntary movements triggered by voluntary movement or tactile stimulation may inform clinical dystonia diagnosis.

Abstract Elevated serum gamma‐glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)‐related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month‐6) after initiating NAs were measured to explore their association with all‐cause, liver‐related, and non‐liver‐related mortality. The annual incidence of all‐cause mortality was 0.9/100 person‐years over a follow‐up period of 17,436.3 person‐years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month‐6‐GGT levels (62.1 vs. 38.4 U/L, p 75 percentile of pretreatment GGT levels was observed with respect to the all‐cause mortality (trend p

Abstract Kikuchi‐Fujimoto Disease (KFD), also known as Kikuchi disease or Kikuchi histiocytic necrotizing lymphadenitis, is a rare and self‐limiting condition characterized by cervical lymphadenopathy and fever, primarily affecting young Asian adults. The aetiology of KFD remains unknown, although various infectious agents have been suggested as potential triggers. With the emergence of the COVID‐19 pandemic, cases of post‐COVID‐19 KFD and post‐COVID‐19 vaccine KFD have been reported. In this article, we present the first case of post‐COVID‐19 KFD in Hong Kong. A 24‐year‐old man developed fever and painful neck swelling 1 month after recovering from COVID‐19. Diagnostic evaluation, including ultrasound‐guided fine needle aspiration cytology (FNAC), confirmed the diagnosis of KFD. The patient's symptoms resolved spontaneously with supportive care. This case underscores the importance of considering KFD as a potential differential diagnosis in patients presenting with cervical lymphadenopathy and fever following COVID‐19 recovery or vaccination.

Abstract Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis‐Specific Protein, Y‐Encoded‐Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFβ causing proliferation arrest. TSPYL1, another TSPYL family member, has been poorly characterized and is the only TSPYL family member known to be causal of a lethal recessive disease in humans. This study shows that TSPYL1 and TSPYL2 play an opposite role in TGFβ signaling. TSPYL1 partners with the transcription factor FOXA1 and histone methyltransferase EZH2, and at the same time represses TGFBR1 and epithelial‐mesenchymal transition (EMT). Depletion of TSPYL1 increases TGFBR1 expression, upregulates TGFβ signaling, and elevates the protein stability of TSPYL2. Intriguingly, TSPYL2 forms part of the SMAD2/3/4 signal transduction complex upon stimulation by TGFβ to execute the transcriptional responses. Depletion of TSPYL2 rescues the EMT phenotype of TSPYL1 knockdown in A549 lung carcinoma cells. The data demonstrates the prime role of TSPYL2 in causing the dramatic defects in TSPYL1 deficiency. An intricate counter‐balancing role of TSPYL1 and TSPYL2 in regulating TGFβ signaling is also unraveled.

Abstract The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo‐responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B‐type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank‐sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo‐responsiveness to NPs.

Abstract A cavity‐magnonic system composed of a superconducting microwave resonator coupled to a magnon mode hosted by the organic‐based ferrimagnet vanadium tetracyanoethylene (V[TCNE]x) is demonstrated. This work is motivated by the challenge of scalably integrating a low‐damping magnetic system with planar superconducting circuits. V[TCNE]x has ultra‐low intrinsic damping, can be grown at low processing temperatures on arbitrary substrates, and can be patterned via electron beam lithography. The devices operate in the strong coupling regime, with a cooperativity exceeding 1000 for coupling between the Kittel mode and the resonator mode at T≈0.4 K, suitable for scalable quantum circuit integration. Higher‐order magnon modes are also observed with much narrower linewidths than the Kittel mode. This work paves the way for high‐cooperativity hybrid quantum devices in which magnonic circuits can be designed and fabricated as easily as electrical wires.

Abstract Aim To evaluate the acceptability, feasibility and potential effectiveness of a group‐based instrumental musical training programme in improving resilience, depressive symptoms, self‐esteem and quality of life among school‐aged children from low‐income families. Design Assessor‐blinded pilot randomised waitlist controlled trial with process evaluation. Methods This study was conducted in the community from January 2022 to July 2023. Sixty‐four children from low‐income families (aged 8–12 years) were randomised (1:1) to intervention and waitlist control groups. The intervention group (n = 32) received weekly 1‐hour instrumental musical training for 6 months in groups of four to five from professionally qualified musicians at a music centre. The participants in the waitlist control group (n = 32) received the same intervention as the participants in the intervention group after the completion of all outcome assessments. The primary outcome was the children's levels of resilience, measured using the Resilience Scale for Children – 10. The secondary outcomes were depressive symptoms, self‐esteem and quality of life. Assessments were conducted at baseline (T0) and immediately post‐intervention (T1). An intention‐to‐treat analysis was performed. Results The 64 participants had a mean (SD) age of 9.5 (1.44) years, and 37 (57.8%) were boys. Compared with the waitlist control group, participants in the intervention group showed significantly greater improvements in resilience levels from baseline to T0 (group‐by‐time interaction coefficient β = 4.41; 95% CI, 1.82–6.99; p = 0.001), depressive symptoms (β = −6.42; 95% CI, −11.12 to −1.71; p = 0.008), self‐esteem (β = −2.60; 95% CI, 0.28–4.92; p = 0.028) and quality of life (β = 6.69; 95% CI, 0.18–13.2; p = 0.044). Conclusion The group‐based instrumental musical training programme was feasible and acceptable for school‐aged underprivileged children and showed the potential to improve the resilience and quality of life of this vulnerable population.

Abstract Aims Blood glucose control is central to the management of diabetes, and continuous glucose monitoring (CGM) improves glycemic control. We aimed to describe the perspectives of people with diabetes using CGM. Materials and methods We performed a systematic review of qualitative studies. Results Fifty‐four studies involving 1845 participants were included. Six themes were identified: gaining control and convenience (reducing pain and time, safeguarding against complications, achieving stricter glucose levels, and sharing responsibility with family); motivating self‐management (fostering ownership, and increasing awareness of glycemic control); providing reassurance and freedom (attaining peace of mind, and restoring social participation); developing confidence (encouraged by the endorsement of others, gaining operational skills, customizing settings for ease of use, and trust in the device); burdened with device complexities (bewildered by unfamiliar technology, reluctant to rely on algorithms, overwhelmed by data, frustrated with malfunctioning and inaccuracy, distressed by alerts, and bulkiness of machines interfering with lifestyle); and excluded by barriers to access (constrained by cost, lack of suppliers). Conclusions CGM can improve self‐management and confidence in patients managing diabetes. However, the technical issues, uncertainty in readings, and cost may limit the uptake. Education and training from the health professionals may help to reduce the practical and psychological burden for better patient outcomes.

Abstract Background Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy. Objective To explore the relationships between self‐reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy. Methods Cross‐sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks’ gestation to evaluate sleep. BMI 5 days/month was higher in class II and class III obesity (1.38 (1.03–1.85) and 1.34 (1.01–1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25–2.02), 2.68 (2.07–3.48), 4.35 (3.21–5.88) to 4.96 (3.65–6.74), respectively)). Conclusions Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI.

Abstract Objective There are limited effectiveness and potential side effects of existing pharmacological approach in treating mild neurocognitive disorder (NCD). Transcranial pulse stimulation (TPS) applies repetitive single high‐pressure ultrashort shockwave pulses to stimulate the brain, which has been shown to effectively improve cognition in major NCD. However, the effectiveness of TPS in mild NCD patients remained unknown. This study aims to assess the effectiveness and tolerability of TPS with neuro‐navigation in old‐age adults with mild NCD by both clinical and biochemical assessments. Methods An open‐label study recruited older adults with mild NCD to receive neuro‐navigated TPS intervention for two weeks with three sessions per week. Assessments included detailed cognitive assessments, APOE genotype, and brain‐derived neurotrophic factor (BDNF). Results Nineteen participants (12 females and 7 males) completed the whole TPS interventions with no serious adverse effects reported. Repeated measures ANOVA showed statistically significant effects of time on HK‐MoCA (F (3, 54) = 4.99, P = 0.004), 30‐sec interval of Verbal Fluency Test (F (3, 54) = 2.94, P = 0.041), Stroop interference (F (3, 54) = 3.46, P = 0.023), and Chinese IADL (F (3, 54) = 2.78, P = 0.050) after receiving the intervention. Bonferroni post hoc comparisons on HK‐MoCA showed a significant improvement after intervention. There was no significant change in serum BDNF level. Interpretation TPS has brought significant improvement in cognition of elderly with mild NCD. It has a great potential to delay the deterioration of cognition in older adults. The long‐term effect of TPS in cognition would benefit from further large‐scale, randomized, sham‐controlled trials.

Background and objective Adjacent segment disease (ASD) is a well‐known complication after interbody fusion. Revision surgery is necessary for symptomatic ASD to further decompress and fix the affected segment. However, no optimal construct is accepted as a standard in treating ASD. The purpose of this study was to compare the biomechanical effects of different surgical approaches for the treatment of ASD after primary transforaminal lumbar interbody fusion (TLIF). Methods A finite element model of the L1‐S1 was conducted based on computed tomography scan images. The primary surgery model was developed with a single‐level TLIF at L4‐L5 segment. The revision surgical models were developed with anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), or TLIF at L3‐L4 segment. The range of motion (ROM), intradiscal pressure (IDP), and the stress in cages were compared to investigate the biomechanical influences of different surgical approaches. Results The results indicated that all the three surgical approaches can stabilize the spinal segment by reducing the ROM at revision level. The ROM and IDP at adjacent segments of revision model of TLIF was greater than those of other revision models. While revision surgery with ALIF and LLIF had similar effects on the ROM and IDP of adjacent segments. Compared among all the surgical models, cage stress in revision model of TLIF was the maximum in extension and axial rotation. Conclusion The IDP at adjacent segments and stress in cages of revision model of TLIF was greater than those of ALIF and LLIF. This may be that direct extension of the surgical segment in the same direction results in stress concentration.

Abstract Background and Aims Unhealthy diets were found to be the main contributor to the overweight problem among adolescents. In this study, we aim to identify the factors causing unhealthy eating habits in adolescents. Methods School‐aged children and adolescents participated in this cross‐sectional observational study with additional school and parental consent. A self‐administered survey was conducted by 30 primary schools and 25 secondary schools. Participants were asked about the frequency of consuming unhealthy food and the types of unhealthy food consumed. A descriptive analysis was performed to demonstrate the proportions of characteristics. The prevalence of the outcome among participants of various factors was also analyzed using separate binary regression models. Results A total of 4884 responses were collected. Among primary school students (grade 4, mean age: 10.06), people who (1) were actively gaining weight (aOR: 1.651, 95% CI 1.006–2.708, p = 0.047), (2) went to bed after 11 p.m. (aOR: 1.652, 95% CI 1.065–2.563, p = 0.025), (3) had more than 2 h of gaming (aOR: 2.833, 95% CI 1.913–4.195, p

Abstract Invasive species offer insights into rapid adaptation to novel environments. The iconic cane toad (Rhinella marina) is an excellent model for studying rapid adaptation during invasion. Previous research using the mitochondrial NADH dehydrogenase 3 (ND3) gene in Hawai'ian and Australian invasive populations found a single haplotype, indicating an extreme genetic bottleneck following introduction. Nuclear genetic diversity also exhibited reductions across the genome in these two populations. Here, we investigated the mitochondrial genomics of cane toads across this invasion trajectory. We created the first reference mitochondrial genome for this species using long‐read sequence data. We combined whole‐genome resequencing data of 15 toads with published transcriptomic data of 125 individuals to construct nearly complete mitochondrial genomes from the native (French Guiana) and introduced (Hawai'i and Australia) ranges for population genomic analyses. In agreement with previous investigations of these populations, we identified genetic bottlenecks in both Hawai'ian and Australian introduced populations, alongside evidence of population expansion in the invasive ranges. Although mitochondrial genetic diversity in introduced populations was reduced, our results revealed that it had been underestimated: we identified 45 mitochondrial haplotypes in Hawai'ian and Australian samples, none of which were found in the native range. Additionally, we identified two distinct groups of haplotypes from the native range, separated by a minimum of 110 base pairs (0.6%). These findings enhance our understanding of how invasion has shaped the genetic landscape of this species.

Abstract Background Health literacy is essential in the promotion of healthy lifestyle habits and chronic disease prevention. Objective To assess the health literacy level among Hong Kong adolescents; to evaluate the association between access of an online health information platform (GoSmart Channel) and health literacy level; and to examine the association between health literacy level and various unhealthy behaviours. Design This study recruited students from 10 local secondary schools in Hong Kong to assess the health literacy level among adolescents. Settings and Participants Participants were required to complete a self‐administered questionnaire on health behaviours and health literacy using the Health Literacy Measure for Adolescents (HELMA). Main Outcome Measure Data were analysed using descriptive statistics and multivariate regression modelling. Results A total of 777 responses were collected. Overall, most (74.4%) of the adolescents in Hong Kong have limited health literacy (HELMA score

Compact, low‐inertia, and soft compliant robotic joint mechanisms are in great demand for ensuring safe interactions in human–robot collaborative tasks. Tensegrity, of which the structural integrity is constrained by tension, does not involve static/sliding friction among the rigid components. However, this mechanical stability is very susceptible to actuation errors. It requires complex kinematics modeling and sophisticated control model with sensing feedback. Herein, a low‐inertia tensegrity joint that is covered/protected by a fiber Bragg grating (FBG)‐embedded silicone sheath is proposed, with the aim to reinforce the joint motion stability and enable self‐contained sensing feedback. A learning‐based closed‐loop controller is also designed and trained with the proper joint configurations selected by a two‐step sampling method. Both the kinematics and static equilibriums of such configurations can be well satisfied. The experiments demonstrate that the joint can follow paths accurately in 2D by compensating manipulation error shortly under the closed‐loop control. The joint stiffness can also be varied against the external/impulsive disturbances. It can be foreseen that this primitive robot joint component with 2 degrees of freedom (DoFs) can provide safe, compliant interaction with human, for which a simple test of maneuvering a portable ultrasound probe (≈210 g) for abdominal imaging is demonstrated.

Abstract Magnetic resonance imaging (MRI) demonstrates clear advantages over other imaging modalities in neurosurgery with its ability to delineate critical neurovascular structures and cancerous tissue in high‐resolution 3D anatomical roadmaps. However, its application has been limited to interventions performed based on static pre/post‐operative imaging, where errors accrue from stereotactic frame setup, image registration, and brain shift. To leverage the powerful intra‐operative functions of MRI, e.g., instrument tracking, monitoring of physiological changes and tissue temperature in MRI‐guided bilateral stereotactic neurosurgery, a multi‐stage robotic positioner is proposed. The system positions cannula/needle instruments using a lightweight (203 g) and compact (Ø97 × 81 mm) skull‐mounted structure that fits within most standard imaging head coils. With optimized design in soft robotics, the system operates in two stages: i) manual coarse adjustment performed interactively by the surgeon (workspace of ±30°), ii) automatic fine adjustment with precise (

Background Venoarterial extracorporeal membrane oxygenation (VA‐ECMO) is increasingly used for patients with cardiogenic shock. Although Impella or intra‐aortic balloon pump (IABP) is frequently used for left ventricular unloading (LVU) during VA‐ECMO treatment, there are limited data on comparative outcomes. We compared outcomes of Impella and IABP for LVU during VA‐ECMO. Methods and Results Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes in 3 groups of patients with cardiogenic shock requiring VA‐ECMO based on LVU strategies: extracorporeal membrane oxygenation (ECMO) only, ECMO with IABP, and ECMO with Impella. Of 15 980 patients on VA‐ECMO, IABP and Impella were used in 19.4% and 16.4%, respectively. The proportion of patients receiving Impella significantly increased from 2016 to 2020 (6.5% versus 25.8%; P‐trend

Abstract Dry pea (Pisum sativum) seeds are valuable sources of plant protein, dietary fiber, and starch, but their uses in food products are restricted to some extent due to several off‐flavor compounds. Saponins are glycosylated triterpenoids and are a major source of bitter, astringent, and metallic off‐flavors in pea products. β‐amyrin synthase (BAS) is the entry point enzyme for saponin biosynthesis in pea and therefore is an ideal target for knock‐out using CRISPR/Cas9 genome editing to produce saponin deficient pea varieties. Here, in an elite yellow pea cultivar (CDC Inca), LC/MS analysis identified embryo tissue, not seed coat, as the main location of saponin storage in pea seeds. Differential expression analysis determined that PsBAS1 was preferentially expressed in embryo tissue relative to seed coat and was selected for CRISPR/Cas9 genome editing. The efficiency of CRISPR/Cas9 genome editing of PsBAS1 was systematically optimized in pea hairy roots. From these optimization procedures, the AtU6‐26 promoter was found to be superior to the CaMV35S promoter for gRNA expression, and the use of 37°C was determined to increase the efficiency of CRISPR/Cas9 genome editing. These promoter and culture conditions were then applied to stable transformations. As a result, a bi‐allelic mutation (deletion and inversion mutations) was generated in the PsBAS1 coding sequence in a T1 plant, and the segregated psbas1 plants from the T2 population showed a 99.8% reduction of saponins in their seeds. Interestingly, a small but statistically significant increase (~12%) in protein content with a slight decrease (~5%) in starch content was observed in the psbas1 mutants under phytotron growth conditions. This work demonstrated that flavor‐improved traits can be readily introduced in any pea cultivar of interest using CRISPR/Cas9. Further field trials and sensory tests for improved flavor are necessary to assess the practical implications of the saponin‐free pea seeds in food applications.

Abstract Introduction Endometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in‐situ‐carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions. Methods Pathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed. Results Totally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma‐in‐situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia–8.5%; without atypia–2.3%) (p

Abstract Objective This methodological research aimed to investigate and compare the sensitivity and specificity of conventional and new face validation in identifying incomprehensible items empirically. Methods A purposive sample of 15 older people living in three residential care homes (RCHs) in Hong Kong was used to evaluate a newly developed 106 items covering seven quality‐of‐life dimensions. The abbreviated Mental Test (Hong Kong version; AMT) was used as a screening tool for excluding those with impaired cognition. The interview was audiotaped, and incomprehensible items were identified by the research panel accordingly (served as the gold standard). The socio‐demographics of the respondents were described. Understandability (yes/no, conventional face validation method) and interpretability (4‐point Likert scale, new method) were compared and used to compute the Kappa value (representing chance agreement), sensitivity, and specificity analysis. Results Fifteen older people were interviewed and responded to the structured interview of 106 items regarding understandability and interpretability. 61 items (57%) obtained 100% positive understandability while only 35 items (33%) obtained 100% correct interpretability. The Kappa coefficient was 0.388 (P

Abstract Aim This study developed, implemented and tested the effectiveness of a music‐with‐movement exercise programme in improving the pain situations of older adults with chronic pain. Design A pilot randomized controlled trial. Methods This was a pilot randomized controlled trial. The intervention was an 8‐week music‐with‐movement exercise (MMEP) programme for older adults with chronic pain recruited in elders’ community centres. The control group received the usual care and a pain management pamphlet. Outcome variables were pain intensity, pain self‐efficacy and pain interference, depression and loneliness. Results Seventy‐one participants joined this study. Pain intensity was significantly reduced between the experimental group compared to the control group. The experimental group participants reported significant improvements in pain self‐efficiency, pain interference and reduced loneliness and depressive symptoms. However, no significant difference was observed between groups.

Abstract Background Adolescent and young adult cancer patients (AYAs) who are sexual and gender minorities (SGM) are a rapidly increasing population that experiences unmet cancer‐related needs. Despite emerging awareness, little is known about cancer care and outcomes for this vulnerable population. The purpose of this scoping review was to explore current knowledge and gaps in the literature on cancer care and outcomes for AYAs who identify as SGM. Methods We reviewed empirical knowledge on SGM AYAs by identifying, describing, and critically appraising the literature to date. We conducted a comprehensive search on OVID MEDLINE, PsycINFO, and CINAHL in February 2022. Additionally, we developed and piloted a conceptual framework for appraising SGM AYA research. Results A total of 37 articles were included in the final review. Most studies focused exclusively on SGM‐related outcomes as the primary aim of the study (81.1%, n = 30), whereas others included some focus on SGM‐related outcomes (18.9%, n = 7). The majority of studies included AYAs as part of a broader age range (86.0%, n = 32), and only a few studies examined exclusively AYA samples (14.0%, n = 5). Gaps in scientific evidence on SGM AYAs were seen across the cancer care continuum. Conclusion Numerous gaps in knowledge of cancer care and outcomes exist for SGM AYAs diagnosed with cancer. Future efforts should fill this void with high‐quality empirical studies that reveal unknown disparities in care and outcomes and are inclusive of the intersectionality of SGM AYAs with other minoritized experiences, thereby advancing health equity in meaningful ways.

Abstract RO7062931 is an N‐acetylgalactosamine (GalNAc)‐conjugated single‐stranded oligodeoxyribonucleotide complementary to hepatitis B virus RNA. GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR). This phase I single ascending dose (SAD) study evaluated the safety, tolerability, and pharmacokinetics of RO7062931 in Chinese healthy volunteers. There were four SAD cohorts (0.3, 1.0, 2.0, and 4.0 mg/kg), in each of which healthy volunteers were randomized to a single subcutaneous (s.c.) injection of RO7062931 or matching placebo in a 4:1 ratio. Placebo recipients were pooled as one treatment group for safety assessments. A total of 41 healthy Chinese men received one dose of RO7062931 (n = 33) or placebo (n = 8) and completed the study (85‐day follow‐up). Adverse events (AEs) were reported in 22 of 33 (66.6%) RO7062931 recipients (n = 80 treatment‐related) and seven of eight (87.5%) placebo recipients (n = 1 treatment‐related). Apart from two moderate‐intensity AEs, all AEs were mild. The most frequently reported AEs were influenza, injection‐related reactions, and headache. Dose‐proportional increases in plasma RO7062931 exposure were observed between the 0.3 and 1.0 mg/kg doses, whereas a supra‐dose‐proportional increase occurred at doses greater than or equal to 2.0 mg/kg, along with a marked increase in urinary excretion. Single s.c. dose of RO7062931 up to 4.0 mg/kg were safe and well‐tolerated in healthy Chinese volunteers. Pharmacokinetic data suggested that ASGPR saturation had commenced between doses of 2.0 and 4.0 mg/kg. Results were broadly consistent with observations in primarily White subjects in the global first‐in‐human study of RO7062931.

Abstract Background Cancer is currently the second leading cause of death globally. There is much uncertainty regarding the comparative risks of new‐onset overall cancer and pre‐specified cancer for Type 2 diabetes mellitus (T2DM) patients on sodium‐glucose cotransporter 2 inhibitors (SGLT2I) versus DPP4I. Methods This population‐based cohort study patients included patients who were diagnosed with T2DM and administered either SGLT2 or DPP4 inhibitors between 1 January 2015 and 31 December 2020 in public hospitals of Hong Kong. Results This study included 60,112 T2DM patients (mean baseline age: 62.1 ± 12.4 years, male: 56.36%), of which 18,167 patients were SGLT2I users and 41,945 patients were dipeptidyl peptidase 4 inhibitor (DPP4I) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of all‐cause mortality (HR: 0.92; 95% CI: 0.84–0.99; p= 0.04), cancer‐related mortality (HR: 0.58; 95% CI: 0.42–0.80; p ≤ 0.001) and new diagnoses of any cancer (HR: 0.70; 95% CI: 0.59–0.84; p ≤ 0.001). SGLT2I use was associated with a lower risk of new‐onset breast cancer (HR: 0.51; 95% CI: 0.32–0.80; p ≤ 0.001), but not of other malignancies. Subgroup analysis on the type of SGLT2I, dapagliflozin (HR: 0.78; 95% CI: 0.64–0.95; p = 0.01) and ertugliflozin (HR: 0.65; 95% CI: 0.43–0.98; p = 0.04) use was associated with lower risks of new cancer diagnosis. Dapagliflozin use was also linked to lower risks of breast cancer (HR: 0.48; 95% CI: 0.27–0.83; p = 0.001). Conclusion Sodium‐glucose cotransporter 2 inhibitor use was associated with lower risks of all‐cause mortality, cancer‐related mortality and new‐onset overall cancer compared to DPP4I use after propensity score matching and multivariable adjustment.

Abstract Background Avascular necrosis (AVN) of bone is a debilitating complication of pediatric patients with acute lymphoblastic leukemia (ALL). While it is extensively studied and reported in Western population, studies focused on Orientals are limited. This study aims to evaluate the incidence, risk factors, and clinical outcomes of AVN among Chinese children with ALL. Methods This study is a retrospective, territory‐wide population‐based cohort study of pediatric patients with ALL enrolled on one of the three consecutive ALL study protocols (ALL‐IC‐BFM 2002, CCLG‐ALL 2008, and CCCG‐ALL 2015). Results A total of 24 out of 533 pediatric subjects with ALL (4.5%) had symptomatic AVN. Age was the single most important risk factor associated with the development of AVN. Only three patients were below age of 10 at the time of diagnosis of ALL. The incidences of AVN in patients aged above and below 10 years were 18.2% ± 3.6% and 0.8% ± 0.5%, respectively, and were significantly different (p

Abstract Background Cancer‐associated fibroblasts (CAFs), integral to the tumour microenvironment, are pivotal in cancer progression, exhibiting either pro‐tumourigenic or anti‐tumourigenic functions. Their inherent phenotypic and functional diversity allows for the subdivision of CAFs into various subpopulations. While several classification systems have been suggested for different cancer types, a unified molecular classification of CAFs on a single‐cell pan‐cancer scale has yet to be established. Methods We employed a comprehensive single‐cell transcriptomic atlas encompassing 12 solid tumour types. Our objective was to establish a novel molecular classification and to elucidate the evolutionary trajectories of CAFs. We investigated the functional profiles of each CAF subtype using Single‐Cell Regulatory Network Inference and Clustering and single‐cell gene set enrichment analysis. The clinical relevance of these subtypes was assessed through survival curve analysis. Concurrently, we employed multiplex immunofluorescence staining on tumour tissues to determine the dynamic changes of CAF subtypes across different tumour stages. Additionally, we identified the small molecule procyanidin C1 (PCC1) as a target for matrix‐producing CAF (matCAF) using molecular docking techniques and further validated these findings through in vitro and in vivo experiments. Results In our investigation of solid tumours, we identified four molecular clusters of CAFs: progenitor CAF (proCAF), inflammatory CAF (iCAF), myofibroblastic CAF (myCAF) and matCAF, each characterised by distinct molecular traits. This classification was consistently applicable across all nine studied solid tumour types. These CAF subtypes displayed unique evolutionary pathways, functional roles and clinical relevance in various solid tumours. Notably, the matCAF subtype was associated with poorer prognoses in several cancer types. The targeting of matCAF using the identified small molecule, PCC1, demonstrated promising antitumour activity. Conclusions Collectively, the various subtypes of CAFs, particularly matCAF, are crucial in the initiation and progression of cancer. Focusing therapeutic strategies on targeting matCAF in solid tumours holds significant potential for cancer treatment.

Abstract This study tested the effects of skin and core cooling on cognitive function in 0°C cold air. Ten males completed a randomized, repeated measures study consisting of four environmental conditions: (i) 30 min of exposure to 22°C thermoneutral air (TN), (ii) 15 min to 0°C cold air which cooled skin temperature to ~27°C (CS), (iii) 0°C cold air exposure causing mild core cooling of ∆‐0.3°C from baseline (C‐0.3°C) and (iv) 0°C cold air exposure causing mild core cooling of ∆‐0.8°C from baseline (C‐0.8°C). Cognitive function (reaction time [ms] and errors made [#]) were tested using a simple reaction test, a two–six item working memory capacity task, and vertical flanker task to assess executive function. There were no condition effects (all p > 0.05) for number of errors made on any task. There were no significant differences in reaction time relative to TN for the vertical flanker and item working memory capacity task. However, simple reaction time was slower in C‐0.3°C (297 ± 33 ms) and C‐0.8°C (296 ± 41 ms) compared to CS (267 ± 26 ms) but not TN (274 ± 38). Despite small changes in simple reaction time (~30 ms), executive function and working memory was maintained in 0°C cold air with up to ∆‐0.8°C reduction in core temperature.

Abstract The growth and development of plants are the result of the interplay between the internal developmental programming and plant–environment interactions. Gene expression regulations in plants are made up of multi‐level networks. In the past few years, many studies were carried out on co‐ and post‐transcriptional RNA modifications, which, together with the RNA community, are collectively known as the “epitranscriptome.” The epitranscriptomic machineries were identified and their functional impacts characterized in a broad range of physiological processes in diverse plant species. There is mounting evidence to suggest that the epitranscriptome provides an additional layer in the gene regulatory network for plant development and stress responses. In the present review, we summarized the epitranscriptomic modifications found so far in plants, including chemical modifications, RNA editing, and transcript isoforms. The various approaches to RNA modification detection were described, with special emphasis on the recent development and application potential of third‐generation sequencing. The roles of epitranscriptomic changes in gene regulation during plant–environment interactions were discussed in case studies. This review aims to highlight the importance of epitranscriptomics in the study of gene regulatory networks in plants and to encourage multi‐omics investigations using the recent technical advancements.

Abstract Background Gastric cancer (GC) is one of the most common tumours in East Asia countries and is associated with Helicobacter pylori infection. H. pylori utilizes virulence factors, CagA and VacA, to up‐regulate pro‐inflammatory cytokines and activate NF‐κB signaling. Meanwhile, the PIEZO1 upregulation and cancer‐associated fibroblast (CAF) enrichment were found in GC progression. However, the mechanisms of PIEZO1 upregulation and its involvement in GC progression have not been fully elucidated. Methods The CAF enrichment and clinical significance were investigated in animal models and primary samples. The expression of NF‐κB and PIEZO1 in GC was confirmed by immunohistochemistry staining, and expression correlation was analysed in multiple GC datasets. GSEA and Western blot analysis revealed the YAP1‐CTGF axis regulation by PIEZO1. The stimulatory effects of CTGF on CAFs were validated by the co‐culture system and animal studies. Patient‐derived organoid and peritoneal dissemination models were employed to confirm the role of the PIEZO1‐YAP1‐CTGF cascade in GC. Results Both CAF signature and PIEZO1 were positively correlated with H. pylori infection. PIEZO1, a mechanosensor, was confirmed as a direct downstream of NF‐κB to promote the transformation from intestinal metaplasia to GC. Mechanistic studies revealed that PIEZO1 transduced the oncogenic signal from NF‐κB into YAP1 signaling, a well‐documented oncogenic pathway in GC progression. PIEZO1 expression was positively correlated with the YAP1 signature (CTGF, CYR61, and c‐Myc, etc.) in primary samples. The secreted CTGF by cancer cells stimulated the CAF infiltration to form a stiffened collagen‐enrichment microenvironment, thus activating PIEZO1 to form a positive feedback loop. Both PIEZO1 depletion by shRNA and CTGF inhibition by Procyanidin C1 enhanced the efficacy of 5‐FU in suppressing the GC cell peritoneal metastasis. Conclusion This study elucidates a novel driving PIEZO1‐YAP1‐CTGF force, which opens a novel therapeutic avenue to block the transformation from precancerous lesions to GC. H. pylori‐NF‐κB activates the PIEZO1‐YAP1‐CTGF axis to remodel the GC microenvironment by promoting CAF infiltration. Targeting PIEZO1‐YAP1‐CTGF plus chemotherapy might serve as a potential therapeutic option to block GC progression and peritoneal metastasis.

Abstract Clostridioides difficile spores are considered as the major source responsible for the development of C. difficile infection (CDI), which is associated with an increased risk of death in patients and has become an important issue in infection control of nosocomial infections. Current treatment against CDI still relies on antibiotics, which also damage normal flora and increase the risk of CDI recurrence. Therefore, alternative therapies that are more effective against C. difficile bacteria and spores are urgently needed. Here, we designed an oxidation process using H2O2 containing PBS solution to generate Cl− and peroxide molecules that further process Ag and Au ions to form nanoboxes with Ag–Au peroxide coat covering Au shell and AgCl core (AgAu‐based nanoboxes). The AgAu‐based nanoboxes efficiently disrupted the membrane structure of bacteria/spores of C. difficile after 30–45 min exposure to the highly reactive Ag/Au peroxide surface of the nano structures. The Au‐enclosed AgCl provided sustained suppression of the growth of 2 × 107 pathogenic Escherichia coli for up to 19 days. In a fecal bench ex vivo test and in vivo CDI murine model, biocompatibility and therapeutic efficacy of the AuAg nanoboxes to attenuate CDI was demonstrated by restoring the gut microbiota and colon mucosal structure. The treatment successfully rescued the CDI mice from death and prevented their recurrence mediated by vancomycin treatment. The significant outcomes indicated that the new peroxide‐derived AgAu‐based nanoboxes possess great potential for future translation into clinical application as a new alternative therapeutic strategy against CDI.

Abstract Introduction We explored the longitudinal relationship between retinal vascular features and dementia incidence over 10 years. Methods Among 584 participants from the Three‐City‐Alienor (3C‐Alienor) population‐based cohort, quantitative retinal vascular features (caliber, tortuosity, fractal dimension) were measured using semi‐automated software. Dementia was actively diagnosed over the follow‐up period. Results One hundred twenty‐eight participants (21.9%) developed dementia over a median of 7.1 years. In Cox proportional hazards models adjusted for sociodemographic characteristics, apolipoprotein E (APOE) ε4, and vascular factors, increased retinal arteriolar tortuosity was associated with all‐cause dementia (hazard ratio per standard deviation increase, 1.21; 95% confidence interval: 1.02–1.44). Wider retinal calibers and a higher venular tortuosity were associated with mixed/vascular dementia, but not Alzheimer's disease. Fractal dimensions were not associated with dementia. Discussion Changes in the retinal microvasculature were associated with dementia risk. More studies are needed to replicate these findings and determine which features might help identify persons at risk at an early stage. HIGHLIGHTS The retinal microvasculature might reflect the brain microvasculature We explored the association between retinal vascular features and incident dementia 584 participants from the Three‐City‐Alienor cohort were followed‐up over 10 years Increased arteriolar tortuosity and venular calibers were associated with dementia risk Retinal imaging might help identify persons at risk of future dementia

Abstract Objective Tracheostomy tube change is a multistep skill that must be performed rapidly and precisely. Despite the critical importance of this skill, there is wide variation in teaching protocols. Methods An innovative operant conditioning teaching methodology was employed and compared to traditional educational techniques. Medical student volunteers at a tertiary care academic institution (Albert Einstein College of Medicine) were recruited and randomly distributed into 2 groups: operant vs traditional (control). Following the educational session, each group was provided with practice time and then asked to perform 10 tracheostomy tube changes. Performance was recorded and scored by blinded raters using deidentified video recordings. Results The operant learning group (OLG) demonstrated greater accuracy in performing a tracheostomy tube change than the traditional demonstration group. Twelve of 13 operant learners performed the skill accurately each time compared to 3 of 13 in the traditional group (P = 0.002). The median lesson time was longer for the OLG (535 seconds) than for the traditional group, (200 seconds P

Abstract Organizing pneumonia, a form of interstitial lung disease, may occur in patients who have recovered from COVID‐19. In this article, we report three cases of post COVID‐19 organizing pneumonia, proven histologically with transbronchial biopsies showing fibroblastic plugs in the alveolar spaces. Our patients received a range of 86–166 days of continuous corticosteroid therapy and all of them made excellent recovery.

Abstract To date, allogenic stem cell transplant (ASCT) remains the only potential curative option for patients with primary myelofibrosis (PMF). However, relapse rates and associated mortality remain a concern. A second ASCT may not be feasible due to advancing age, declined functional status, donor unavailability, toxicities associated with a second ASCT. Herein, we report the first case of utilizing initially azacitidine and subsequently oral decitabine + cedazuridine (decitabine), in the context of relapsed PMF post‐ASCT. Utilizing both hypomethylating agents provided disease control and improved donor/myeloid lineage chimerism levels, and the patient also remained transfusion independent, with preserved functional status and quality of life.