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Abstract Background As hypothermic circulatory arrest (HCA) is being more frequently induced in patients undergoing aortic arch surgery, its safety at different degrees has become a crucial area of study. The aim of this study was to assess the surgical outcomes of mild hypothermic circulatory arrest (MI-HCA) during aortic arch surgery. Methods Acute type A aortic dissection (ATAAD) patients who underwent total arch replacement (TAR) and frozen elephant trunk (FET) surgery between January 2014 and December 2023 were enrolled in this study. The patients were divided into two groups according to the minimum nasopharyngeal temperature: the moderate hypothermic circulatory arrest (MHCA) group (20–28 °C) and the MI-HCA group (> 28 °C). The inverse probability of treatment weighting (IPTW) was used to balance differences in the baseline characteristics. Perioperative variables were analysed via pairwise comparisons, multivariable logistic regression, and subgroup forest plots to assess the impact of MI-HCA on surgical outcomes. Results A total of 447 patients were included in this study, and the mean minimum nasopharyngeal temperature was 24.80 (23.98, 27.30) °C in the MHCA group and 30.10 (29.80, 30.70) °C in the MI-HCA group. The incidence of acute kidney injury (AKI) in the MI-HCA group was lower than that in the MHCA group (52% vs. 78%, p

Abstract Aortic dissection (AD) poses a significant threat to cardiovascular health globally, yet its underlying mechanisms remain elusive. Smooth muscle cells death and phenotypic switching are critically important pathological processes in AD. Currently, no pharmacological therapies have proven effective in managing AD. This study aims to elucidate the involvement of ferroptosis in AD progression and explore ferroptosis inhibition as a potential therapeutic approach for AD management. Elevated expression of ferroptosis markers (HMOX1, ACSL4, and 4-HNE) was observed in AD patients and β-Aminopropionitrile (BAPN)-induced mice. In vivo administration of silibinin (SIL) attenuated aortic dilation, inflammation, mitochondrial injury, and ferroptosis. SIL treatment enhanced cell viability and mitochondrial function while reducing reactive oxygen species (ROS) generation and mitigating ferroptosis in primary human aortic smooth muscle cells (HASMCs) induced by RSL3 or IKE. Mechanistically, RNA-sequencing analysis identified dysregulation of iron homeostasis and endoplasmic reticulum stress, which were modulated by SIL. Molecular docking, cellular thermal shift assay, drug affinity responsive target stability, and surface plasmon resonance analysis confirmed HMOX1 as a direct target of SIL, highlighting its role in modulating iron homeostasis. Moreover, NCT-502, a PHGDH inhibitor, reversed the protective effect of SIL in RSL3-induced HASMCs. Conversely, 4-PBA and ZnPP demonstrate a facilitative role. This suggests that SIL plays a crucial role in ferroptosis development by modulating iron homeostasis and endoplasmic reticulum stress-mediated serine biosynthesis, both in vitro and in vivo. Iron homeostasis and endoplasmic reticulum stress of HASMCs drive the development of aortic dissection. These findings unveil a novel role of SIL in mitigating ferroptosis in HASMCs, offering a promising therapeutic avenue for treating AD.

Abstract Background Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging. Methods PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age. Phenotypic age acceleration (PhenoAgeAccel), an aging biomarker, represents PhenoAge after adjusting for CA. This study conducts an in-depth association analysis of PhenoAgeAccel with clinical, nutritional, lipidomic, gut microbiome, and genetic factors. Results Higher adiposity, glycaemia, plasma saturated fatty acids, kynurenine pathway metabolites, GlycA, riboflavin, nicotinamide, and insulin-like growth factor binding proteins were positively associated with PhenoAgeAccel. Conversely, a healthier diet and higher levels of pyridoxal phosphate, all-trans retinol, betaine, tryptophan, glutamine, histidine, apolipoprotein B, and insulin-like growth factors were inversely associated with PhenoAgeAccel. Lipidomic analysis found 132 lipid species linked to PhenoAgeAccel, with PC(O-36:0) showing the strongest positive association and CE(24:5) demonstrating the strongest inverse association. A genome-wide association study identified rs9864994 as the top genetic variant (P = 5.69E-07) from the ZDHHC19 gene. Gut microbiome analysis revealed that Erysipelotrichaceae UCG-003 and Bacteroides vulgatus were inversely associated with PhenoAgeAccel. Integrative network analysis of aging-related factors underscored the intricate links among clinical, nutritional and lipidomic variables, such as positive associations between kynurenine pathway metabolites, amino acids, adiposity, and insulin resistance. Furthermore, potential mediation effects of blood biomarkers related to inflammation, immune response, and nutritional and energy metabolism were observed in the associations of diet, adiposity, genetic variants, and gut microbial species with PhenoAgeAccel. Conclusions Our findings provide a comprehensive analysis of aging-related factors across multiple platforms, delineating their complex interconnections. This study is the first to report novel signatures in lipidomics, gut microbiome and blood biomarkers specifically associated with PhenoAgeAccel. These insights are invaluable in understanding the molecular and metabolic mechanisms underlying biological aging and shed light on potential interventions to mitigate accelerated biological aging by targeting modifiable factors.

Abstract Natural products encompass a diverse range of compounds with high impact applications in consumer care, agriculture and most notably, therapeutics. However, despite the expansive chemical repertoire indicated in genomic information of microbes, only a small subset can be obtained under laboratory conditions. To increase accessible chemical space and realize Nature’s full chemical potential, a multi-pronged genetic- and cultivation-based strategy has been employed to activate and upregulate natural product biosyntheses in native and heterologous strains. This data descriptor documents a characterized collection of 2,138 liquid chromatography-tandem mass spectrometry (LC/MS-MS) spectra of fermentation extracts from 54 native actinobacterial strains collected from soil and marine environments in Singapore, and their 459 activated mutants in 3 to 5 media. A total of 743 unique metabolites have been identified, with the activated mutants demonstrating an approximately 2-fold expansion in accessible chemical space over wild type strains. Interrogating this expanded chemical diversity with cheminformatic tools can provide direction for the discovery of novel natural products with desirable functional activity.

Summary: Background: Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with maternal metabolic health and offspring birth outcomes. Methods: Quantification of apolipoproteins was performed on maternal plasma samples (N = 243 trios) collected at preconception, 26–28 weeks’ pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Linear regression models and network analysis were implemented to investigate the association of apolipoproteins with maternal genetic variants, biochemical measures, metabolic risk factors, and offspring birth outcomes. Findings: The concentrations of ApoC-III, ApoB and ApoL1 substantially increased in pregnancy compared to preconception and postpartum. Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) associated with plasma apolipoproteins (P

Abstract Solar hydrogen peroxide (H2O2) production has garnered increased research interest owing to its safety, cost‐effectiveness, environmental friendliness, and sustainability. The synthesis of H2O2 relies mainly on renewable resources such as water, oxygen, and solar energy, resulting in minimal waste. Bismuth vanadate (BiVO4) stands out among various oxide semiconductors for selective H2O2 production under visible light via direct two‐electron oxygen reduction reaction (ORR) and two‐electron water oxidation reaction (WOR) pathways. Significant advancements have been achieved using BiVO4‐based materials in solar H2O2 production over the last decade. This review explores advancements in BiVO4‐based photocatalysts for H2O2 production, focusing on photocatalytic powder suspension (PS) and photoelectrochemical (PEC) systems, representing the main approaches for heterogenous artificial photosynthesis. An overview of fundamental principles, performance assessment methodologies, photocatalyst and photoelectrode development, and optimization of reaction conditions is provided. While diverse strategies, such as heterojunction, doping, crystal facet engineering, cocatalyst loading, and surface passivation, have proven effective in enhancing H2O2 generation, this review offers insights into their similar and distinct implementations within the PS and PEC systems. The challenges and future prospects in this field are also discussed to facilitate the rational design of high‐performing BiVO4‐based photocatalysts and photoelectrodes for H2O2 generation under visible light.

Interdisciplinary learning is essential for equipping future health professionals to tackle the complexities of contemporary public health. This mixed-methods study investigates the experiences and perspectives of undergraduate public health students in Singapore on interdisciplinary learning in higher education and employed a convergent parallel design by combining a cross-sectional survey with in-depth interviews. Quantitative data were used to assess the relationship between students’ exposure to interdisciplinary learning and its perceived value, while qualitative analysis explored key themes related to facilitators and barriers. Among 52 survey respondents and 11 interview participants, nearly half regularly engaged in interdisciplinary learning. Students with greater exposure to interdisciplinary experiences demonstrated more positive perceptions. Facilitators identified included career development opportunities, faculty engagement, and diverse learning experiences. Barriers such as disciplinary disconnects and the challenge of managing varied skill sets were also highlighted. This study provides valuable insights into interdisciplinary learning in higher education pertaining to public health, particularly within the context of health professions training. The findings suggest that enhancing curricular design, integrating interdisciplinary approaches more effectively, and increasing faculty support can address identified barriers and better prepare students for the demands of their future public health careers.

Abstract Molybdenum sulfide (MoS2) and modified MoS2 with different percentages of CdS (10%, 30%, and 50% CdS@MoS2) were successfully synthesized and characterized. The photocatalytic performance of the MoS2 and CdS@MoS2 was evaluated by degrading brilliant green (BG), methylene blue (MB), and rhodamine B (RhB) dyes under visible light irradiation. Amongst the synthesized photocatalysts, 50% CdS@MoS2 exhibited the highest photocatalytic activity, degrading 97.6%, 90.3%, and 75.5% of BG, MB, and RhB dyes, respectively within 5 h. The active species involved in the degradation processes were investigated. All trapping agents inhibited BG and MB degradation to a similar extent, indicating that all of the probed active species play an important role in the degradation of BG and MB. In contrast, h+ and O2 •− were found to be the main reactive species in the photocatalytic RhB degradation. A potential mechanism for the photocatalytic degradation of dyes using CdS@MoS2 has been proposed. This work highlights the potential of CdS@MoS2 as a photocatalyst for more efficient water remediation applications.

Abstract The environmental contamination by extremophile Aspergillus species, i.e., Aflatoxin B1, is hardly controllable in Southeast Asia and Sub-Saharan Africa, which lack handling resources and controlled storage facilities. Acute aflatoxicosis poisoning from aflatoxin-prone dietary staples could cause acute hepatic necrosis, acute liver failure, and death. Here, as the cheaper, more straightforward, and facile on-site diagnostic kit is needed, we report an ultraviolet-excitable optical aptasensor based on a fluorinated ethylene propylene film strip. Molecular dynamics on the aptamer.AFB1 complex revealed that the AFB1 to the aptamer increases the overall structural stability, suggesting that the aptamer design is suitable for the intended application. Under various influencing factors, the proposed label-free strategy offers a fast 20-min on-site fabrication simplicity and 19-day shelf-life. The one-pot incubation provides an alternative to catalytic detection and exhibited 4 times reusability. The recovery of crude brown sugar, processed peanuts, and long-grain rice were 102.74 ± 0.41 (n = 3), 86.90 ± 3.38 (n = 3), and 98.50 ± 0.42 (n = 3), comparable to High-Performance Liquid Chromatography-Photodiode Array Detector results. This study is novel owing to the peculiar UV-active spectrum fingerprint and the convenient use of hydrophobic film strips that could promote breakthrough innovations and new frontiers for on-site/forensic detection of environmental pollutants.

Abstract Introduction Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. Methods A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. Results Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. Conclusions TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. Trial Registration ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

This study investigates the mediating role of Green Intellectual Capital (GIC) in the relationship between Corporate Social Responsibility (CSR) and Sustainable Social Performance within the context of Islamic banks in Pakistan. The population of interest comprises bank employees, including managers, operation managers, operations officers, and cash officers, from 15 Islamic banks operating 150 branches in the southern region of Khyber Pakhtunkhwa, Pakistan. The total population in these banks is 1600 employees. Using Yamani’s (1967) formula, a sample of 320 employees was selected. Non-probability sampling, involving non-random selection based on convenience, was employed to facilitate data collection. The methodology involves employing mediation analysis to explore the complex relationships among CSR, GIC, and Sustainable Social Performance. The analysis reveals a robust correlation between CSR and GIC (R = 0.866), with GIC significantly predicting CSR (Beta = 0.772, p

This study investigates the impact of rookie independent directors (RIDs) on agency costs. Utilizing a sample of Chinese listed firms, we employ panel ordinary least square estimations. Our findings reveal that increased RIDs is positively associated with agency costs, suggesting that rookie independent directors may exacerbate agency conflicts within Chinese firms. Also, qualified financial institutional investors and gender diversity within the board composition mitigate the positive effect of RIDs on agency costs. Overall, our study contributes to understanding corporate governance dynamics in Chinese listed firms by shedding light on the nuanced relationship between rookie independent directors and agency costs.

Background Simulation training, an important component of the Emergency Medicine (EM) training curriculum, was affected by the COVID-19 pandemic due to social distancing policies. As a result, there was a need to find alternative approaches to medical simulation that could facilitate effective teaching and practising of team resuscitation. Objectives This paper describes an alternative approach to face-to-face simulation teaching due to pandemic-related limitations. Methods We conducted a virtual simulation session for nine junior doctors (medical officers, emergency medicine residents, and internal medicine residents). The sessions were carried out through video conferencing and medical simulation software. The session included pre-class readings, prior briefing on what to expect during the simulation case scenario, running of three case scenarios, team debriefing, and post-class feedback of the session conducted via Google Forms. Results Student feedback was obtained via a post-class survey. Feedback was largely positive as most participants found the session interactive and the pre-specified outcomes during the pre-simulation brief were achieved. Most participants also felt that fully online simulation training was an effective alternative to face-to-face simulation training. Conclusions A virtual simulation method is a feasible alternative to face-to-face simulation amidst the COVID-19 pandemic. We hope to increase awareness of this mode of teaching in the broader medical education community to benefit more learners.

Abstract Background Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. Methods A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. Discussion Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.

Abstract Background Microbial cell surface display technology allows immobilizing proteins on the cell surface by fusing them to anchoring motifs, thereby endowing the cells with diverse functionalities. However, the assessment of successful protein display and the quantification of displayed proteins remain challenging. The green fluorescent protein (GFP) can be split into two non-fluorescent fragments, while they spontaneously assemble and emit fluorescence when brought together through complementation. Based on split-GFP assembly, we aim to: (1) confirm the success display of passenger proteins, (2) quantify the number of passenger proteins displayed on individual cells. Results In this study, we propose two innovative methods based on split-green fluorescent protein (split-GFP), named GFP1-10/GFP11 and GFP1-9/GFP10-11 assembly, for the purpose of confirming successful display and quantifying the number of proteins displayed on individual cells. We evaluated the display efficiency of SUMO and ubiquitin using different anchor proteins to demonstrate the feasibility of the two split-GFP assembly systems. To measure the display efficiency of functional proteins, laccase expression was measured using the split-GFP assembly system by co-displaying GFP11 or GFP10-11 tags, respectively. Conclusions Our study provides two split-GFP based methods that enable qualitative and quantitative analyses of individual cell display efficiency with a simple workflow, thus facilitating further comprehensive investigations into microbial cell surface display technology. Both split-GFP assembly systems offer a one-step procedure with minimal cost, simplifying the fluorescence analysis of surface-displaying cells.

Abstract Aim The purpose of this study was to compare the long-term outcomes of laparoscopic hepatectomy (LH) and percutaneous radiofrequency ablation (PRFA) for the treatment of small hepatocellular carcinoma. Methods We systematically searched PubMed, Embase, Web of Science, and Medline from January 2000 to May 2022 for literature comparing the efficacy of LH and PRFA in the treatment of small hepatocellular carcinoma (largest tumour diameter ≤ 3 cm, number of intrahepatic tumours ≤3, or diameter of a single intrahepatic lesion ≤5 cm. ). We assessed overall survival (OS), recurrence-free survival (RFS), local recurrence and complication rates. Results A total of 1886 patients with small HCC were included in the 8 studies included in this study, of which 839 underwent LH and 1047 underwent PRAF. The results of the meta-analysis showed that the two groups had the same 3-year (HR: 0.99, 95% CI: 0.67 to 1.47) and 5-year (HR: 1.30, 95% CI: 0.90 to 1.87) OS rates, and the LH group had better 3-year (HR: 0.58, 95% CI: 0.49 to 0.68) and 5-year (HR: 0.56, 95% CI: 0.37 to 0.85) RFS rates. The LH group had a lower local recurrence rate (OR: 0.19, 95% CI: 0.12 to 0.32), but the PRFA group had a lower complication rate (OR: 2.49, 95% CI: 1.76 to 3.54). Conclusion There was no difference in OS between LH and PRFA in the treatment of small HCC. LH had a higher RFS rate and a lower local recurrence rate, but PRFA had a lower complication rate. In general, the long-term efficacy of LH in the treatment of small HCC is better than that of PRFA. Considering the advantages of less trauma and a low complication rate of PRFA, a large number of RCT studies are needed for further verification in the future.

Abstract Background Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. Methods This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. Results There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p

Fetal bovine serum (FBS) has long been the standard supplement in cell culture media, providing essential growth factors and proteins that support cell growth and differentiation. However, ethical concerns and rising costs associated with FBS have driven researchers to explore alternatives, particularly human platelet lysate (HPL). Among these alternatives, fibrinogen-depleted HPL (FD-HPL) has gained attention due to its reduced thrombogenicity, which minimizes the risk of clot formation in cell cultures and enhances the safety of therapeutic applications. This study investigates two preparation methods for FD-HPL from human platelet concentrates: the calcium chloride method and a mechanical approach. The concentrations of critical growth factors, including vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF), and keratinocyte growth factor (KGF), were evaluated for both methods. Additionally, the impact of FD-HPL on the proliferation and morphology of umbilical cord-derived mesenchymal stem cells (UC-MSCs) was assessed. The findings revealed that the calcium chloride method produced significantly higher concentrations of all measured growth factors compared to the mechanical method. Moreover, UC-MSCs cultured in calcium chloride-prepared FD-HPL exhibited enhanced cellular characteristics, including increased cell size, elongation, and improved overall morphology compared to those cultured in mechanically processed FD-HPL. These results indicate that the preparation method significantly influences the biological properties of HPL and the effectiveness of UC-MSC culture. The calcium chloride method emerges as a superior technique for producing FD-HPL, offering a promising alternative to FBS in regenerative medicine applications. This study underscores the importance of preparation methods in optimizing HPL for cell culture and therapeutic uses.

The Jinshajiang fault zone is the western boundary fault of the Sichuan–Yunnan block, located east of the Qinghai–Tibetan Plateau. It is a complex tectonic suture belt with multi-phase activity and is characterized by multiple sets of parallel or intersecting faults. Using high-resolution image interpretation, seismic geological surveys, and trench studies, we examined the Holocene activity and obtained the paleoseismic sequences on the middle segment of the fault zone. Thus, we could analyze the kinematic characteristics of the fault and its potential risk of strong earthquakes. Our results indicated that the predominant movement of the fault zone was strike-slip motion. In the Jinshajiang fault zone, the Late Quaternary horizontal slip rates of the north-northeast-trending Yarigong fault and the northeast-trending Ciwu fault were 3.6 ± 0.6 mm/a and 2.5 ± 0.5 mm/a, respectively. Three paleoseismic events were identified on the Yarigong fault, dated 6745–3848, 3742–1899, and 1494–1112 cal BP, and on the Ciwu fault, constrained to 32,566–29,430, 24,056–22,990, and 2875–2723 cal BP. The last major earthquake on the Ciwu fault occurred approximately 2800 years ago; therefore, its future seismic hazard deserves attention.

Abstract Background Pneumothorax can cause distressing breathlessness, however the effect of the accumulated air in the pleural space and its association with diaphragmatic function and symptoms of breathlessness is not well understood. Bendopnoea is an evolving clinical symptom that has been demonstrated as clinically useful in some heart and lung conditions. Whether bendopnoea is present in patients with pneumothorax, and its potential clinical usefulness has not yet been investigated. The PASE study is a pilot study to explore the incidence and clinical relevance of bendopnoea in patients with pneumothorax and may provide better understanding of pneumothorax related dyspnoea. Methods PASE is a prospective study. Eligible patients are assessed at baseline (pre air drainage/lung reinflation) and in patients whose pneumothorax resolves once the lung has re‐expanded (post conservative management or air drainage procedure). Outcome measures include the incidence of bendopnoea, correlation of the associated symptoms (pain and breathlessness) to the severity of bendopnoea and the size of pneumothorax; and correlation with clinical outcome (i.e., response to air drainage/lung reinflation). The study will recruit 50 participants. Discussion This is the first study to explore bendopnoea in patients with pneumothorax. The presence and significance of bendopnoea in relation to clinical and physiological parameters in patients with pneumothorax requires investigation. The findings of this study may further current understanding of dyspnoea related pneumothorax. Trial Registration Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12623001109695p. URL of the trial registry record for this trial: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386631&isReview=true Date of registration: Registered on 24 October 2023. Funding of the trial: This study has not received grant support. The study is sponsored by the Institute for Respiratory Health, a not‐for‐profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands, WA 6009. Role of sponsor: The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript. Protocol version: 1.

Air embolism is a rare cause of ischaemic stroke. It is known that air can enter the cerebral arterial circulation from pulmonary venous circulation through a bronchovenous fistula, or in cases of pulmonary barotrauma in deep-sea diving. We describe a case of spontaneous cerebral air embolism against a background of advanced interstitial lung disease (ILD). To our knowledge, this case demonstrates a mechanism of stroke in ILD patients that has not been previously described.

Abstract Background Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a ‘trial and error’ basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE‐3 study will evaluate bendopnoea as a screening test for effusion‐related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism. Methods PLEASE‐3 is a multi‐centre prospective study. Eligible patients are assessed at baseline (pre‐drainage) and for patients undergoing drainage, up to 72 h post‐procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants. Discussion This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes. Trial Registration Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12622000465752. URL of the trial registry record for this trial: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true Date of registration: Registered on 24 March 2022. Funding of the trial: This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not‐for‐profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ bi.lam@resphealth.uwa.edu.au Role of sponsor: The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.

Low-value investigations provide marginal benefit and may result in harm to the patient or disproportionate healthcare costs. The introduction of Singapore’s Choosing Wisely (CW) campaign in 2012 aims to reduce such investigations. CW was designed to encourage conversations between physicians and patients to weigh the risk-benefit ratio behind each clinical decision. A CW campaign was launched in July 2023 at Singapore General Hospital to reduce unnecessary tests and treatments.

Superficial acral fibromyxoma, also known as digital fibromyxoma, is a slow-growing, benign, solitary soft tissue tumor. First described in 2001 by Fetsch et al., it is a condition that often occurs in middle-aged individuals. However, it has also been reported across a wide range of ages, ranging from 4 to 86 years, with males more commonly reported. The condition often presents as solitary soft tissue swelling over the periungual or subungual. We present the management experience of the rare presentation of this rare tumor and a detailed review of the past literature on this condition. Detailed management of the condition has been described, along with the outcome after 2 years of follow-up and treatment experience. Our detailed analysis shows that 2 years is the shortest duration of follow-up to rule out recurrence. Hence, most of the cases reported earlier had given the false sense of the recurrence rate of the tumor, which could lead to undertreatment of the condition. The purpose of this article is to allow the readers to understand better the tumor’s characteristics with bone involvement and the tumor's diagnostic strategies and treatment options.

Abstract Introduction High incidences of burnout has been reported amongst emergency department (ED) personnel during the COVID‐19 pandemic. Emerging from the pandemic, organisational support for psychological health may dwindle and become secondary to economic priorities. We aimed to ascertain the level of burnout within ED staff at our hospital, identify professional groups, which were more vulnerable and domains, which contributed most towards burnout. Methods We conducted a cross‐sectional study approximately 8 months after major moves to remove COVID‐19 restrictions in Singapore. Data was collected via a self‐administered survey employing the Copenhagen Burnout Inventory (CBI). Demographics, occupational details, work satisfaction and motivation to stay in the job were also collected and analysed. Results A total of 115 ED staff participated. Overall CBI score was 62.3 ± 22.0. Scores for personal, work‐related and client burnout were 64.9 ± 23.2, 61.6 ± 23.1 and 60.4 ± 26.1, respectively. A total of 44.5% had to take medical leave because of burnout. Nurses had higher overall CBI scores than doctors (67.5 ± 20.5 vs. 54.6 ± 23.0, p = 0.01). Those who were satisfied with their present job had lower overall CBI scores compared to those not satisfied (42.7 ± 17.9 vs. 84.0 ± 14.4, p

Abstract The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses. The mRNA-LNP vaccines have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (90%). We employ in vivo bioluminescence imaging to illustrate the capacity of our LNPs to induce robust mRNA expression in secondary lymphoid organs. In a BALB/c mouse model, a three-dose subcutaneous immunization of mRNA-LNPs vaccines achieved remarkably high levels of cross-neutralization against the Omicron B1.1.529 and BA.2 variants for extended periods of time (28 weeks) with good safety profiles for all constructs when used in a booster regime, including the YN2016C bat virus sequences. These findings have important implications for the design of mRNA-LNP vaccines that aim to trigger durable cross-protective immunity against the current and newly emerging variants.

Background As aging process continues to accelerate in China, multimorbidity have become a major public problem that threatens the health of the entire population. In the current context of "Healthy China 2030", the health management of patients with multimorbidity needs to be urgently addressed. Objective To understand the preferences influencing the choice of community health services for patients with multimorbidity, explore the willingness to pay (WTP) of patients, so as to provide recommendations for improvements to the existing community health service system for chronic diseases. Methods Patients with multimorbidity were randomly selected from eight community health service centers in Chengdu during the period from May to August 2022 as survey subjects. General patient data and preferences related to discrete choice experiments were collected through on-site questionnaire surveys. Based on different types of comorbidities, patients with type 2 diabetes combined with hypertension, hypertension combined with coronary heart disease, type 2 diabetes combined with hypertension and coronary heart disease were categorized into ClassⅠ, ClassⅡ, and ClassⅢ. Regression analysis was conducted using mixed Logit model to analyze the preferences of multimorbidity patients for community health services, and to quantitatively analyze their WTP for community health services. Result A total of 360 questionnaires were distributed and 296 valid questionnaires were recovered, with a valid recovery rate of 82.7%. ClassⅠpatients (β=3.260, 95%CI=2.610 to 3.910), ClassⅡpatients (β=3.697, 95%CI=2.612 to 4.781), and ClassⅢpatients (β=3.220, 95%CI=2.271 to 4.169) expressed the strongest preference for services with high accessibility to drugs, followed by appointment referral services and traditional Chinese medicine (TCM) services. Regarding physician types and prescription service duration, both ClassⅠpatients (β=0.971, 95%CI=0.585 to 1.357) and ClassⅡpatients (β=0.686, 95%CI=0.176 to 1.197) preferred services with extended prescription services, while ClassⅢpatients (β=0.804, 95%CI=0.196 to 1.413) preferred services provided by general practitioners (β=0.804, 95%CI=0.196 to 1.413). ClassⅠpatients (β=-0.049, 95%CI=-0.057 to -0.041), ClassⅡpatients (β=-0.040, 95%CI=-0.051 to -0.029), and ClassⅢpatients (β=-0.037, 95%CI=-0.048 to -0.027) preferred services with lower out-of-pocket expenses. The results of the regression analysis of WTP for patients with different chronic comorbidity types showed that the WTP of all 3 types of patients was related to their level of preference for each attribute, with ClassⅠ, ClassⅡ, and ClassⅢpatients all had the highest WTP for a high level of drug accessibility, which were RMB 66.77/month, RMB 91.97/month, and RMB 85.95/month, respectively. Conclusion Patients with multimorbidity exhibit significant preferences for six attributes considered in this study (physician type, TCM service, prescription service duration, drug accessibility, appointment referral, and monthly out-of-pocket costs). Drug accessibility is the most important attribute influencing multimorbidity patients' health service preferences. It is recommended to target patients' specific needs accurately, improve appointment referral services, establish standards for the management of chronic diseases in the community, and accelerate the integration of TCM into the prevention and treatment of chronic diseases in the community.

Introduction: We presented the key findings from Singapore’s Changi General Hospital Breast Centre’s lymphedema surveillance strategy that used patients’ reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research. Method: We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors. We defined BCRL prevalence rates based on patients’ self-reporting, objective arm circumference measure-ments and clinical diagnosis based on International Society of Lymphology (ISL) staging. Results: The median follow-up of patients was 88.8 months. The cumulative prevalence rate in the cohort was 30.9%. The cohort of BCRL patients were older (58.4 versus [vs] 54.9 years), had higher mean Body Mass Index (27.7 vs 25.2), higher proportion of mastectomy (77% vs 64.3%), axillary clearance, less likely breast reconstruction, higher-grade tumour, more lymph nodes excised, more advanced nodal disease, and had undergone adjuvant chemotherapy. However, clinically apparent BCRL was only 6.5% (33 out of 511 patients). The proportion of clinically significant BCRL in patients undergoing sentinel lymph node biopsy (SLNB) or axillary sampling was 1.7% compared to 9.9% in patients who had undergone axillary clearance. Majority of the BCRL were subclinical or mild in severity. Conclusion: Our study showed that our rates of BCRL were comparable to international rates and highlighted similar patient profiles who were at risk of developing the disease. Having a comprehensive lymphedema surveillance strategy is paramount in paving the way for future studies.

Abstract Halogenation of pyrrole requires strong electrophilic reagents and often leads to undesired polyhalogenated products. Biocatalytic halogenation is a highly attractive approach given its chemoselectivity and benign reaction conditions. While there are several reports of enzymatic phenol and indole halogenation in organic synthesis, corresponding reports on enzymatic pyrrole halogenation have been lacking. Here we describe the in vitro functional and structural characterization of PrnC, a flavin-dependent halogenase that can act on free-standing pyrroles. Computational modeling and site mutagenesis studies identified three key residues in the catalytic pocket. A moderate resolution map using single-particle cryogenic electron microscopy reveals PrnC to be a dimer. This native PrnC can halogenate a library of structurally diverse pyrrolic heterocycles in a site-selective manner and be applied in the chemoenzymatic synthesis of a chlorinated analog of the agrochemical fungicide Fludioxonil.

Abstract Objective To investigate the effectiveness of focused extracorporeal shock wave therapy (FESWT) in treating postpartum sacroiliac joint (SIJ) dysfunction. Methods A total of 90 patients with SIJ dysfunction were included and randomly assigned to FESWT, manual therapy (MT), or combination therapy (CT) groups. Pain intensity and Oswestry Disability Index (ODI) score were measured upon admission, after 1 and 2 weeks of treatments. The treatment efficacy and adverse events of each group were also assessed. Results There were no significant differences among three groups regarding clinical data, pain intensity, and ODI score on admission (all P > 0.05). After 1 week of treatment, FESWT exhibited similar pain intensity and lower ODI score (P

Abstract Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature’s chemical repertoire.

Abstract This article investigates a mobile edge computing (MEC) network assisted by multiple unmanned aerial vehicles (UAVs) to address the computational and offloading requirements for mobile intelligent terminals (MITs) within crowded venues. The objective is to tackle intricate task processing and diminish MITs' waiting times. Considering the randomness of task arrival at the MITs and the imbalance between the amount of data and computation for complex tasks, a dual‐queue model with data cache queue and computation queue is proposed, with minimizing the weighted system total energy consumption and average delay as the optimization objectives. Lyapunov optimization theory is employed to convert the stochastic optimization problem into a deterministic one, and the initial deployment quantity and hovering position of the UAVs are determined by the density‐based spatial clustering of applications with noise (DBSCAN) method with noise. Then PPO algorithm for MIT task, resource allocation, and UAV trajectory optimization. Numerical results display the proposed scheme can efficaciously diminish energy consumption and delay by 10% and 33% respectively, compared with the baseline scheme. This paper proposes a practical and feasible solution for stochastic computing offloading in UAV‐assisted MEC, which fills the gap in existing research on regarding the consideration of complex task imbalances.

Narratives about STEM (science, technology, engineering, and mathematics) education are strongly connected with conversations about developing learners' humanistic knowledge and their ability to listen with understanding and empathy. This is challenging because learners need to find resonance through first-hand contextual experiences with the issues at hand. In this paper, we describe and discuss an activity that was enacted to actively engage 74 teachers from Thailand in constructing a prototype cutting device for the blind to prepare food themselves. This activity underscores important considerations for inclusive design and offers affordances for teachers to develop their learners' inclusive mindsets. Findings were generated from voice recordings of reflections and written reflections collected after the activity. We highlight the importance of creating opportunities for learning to listen and resonate with others' experiences and argue that such STEM activities can offer a platform for learners to develop humanistic qualities such as social empathy.

Abstract Background Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism’s survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance. Methods MicroRNA profiling was performed on circulating tumor cells collected from the blood of treated breast cancer patients. Cancer cell lines ectopically expressing candidate miRNA were used in co-culture experiments and treated with docetaxel. Ecological parameters like relative survival and relative fitness were assessed using flow cytometry. Functional studies and characterization performed in vitro and in vivo include proliferation, iTRAQ-mass spectrometry, RNA sequencing, inhibition by small molecules and antibodies, siRNA knockdown, CRISPR/dCas9 inhibition and fluorescence imaging of promoter reporter-expressing cells. Mathematical modeling based on evolutionary game theory was performed to simulate spatial organization of cancer cells. Results Opposing cancer processes underlie altruism: an oncogenic process involving secretion of IGFBP2 and CCL28 by the altruists to induce survival benefits in neighboring cells under taxane exposure, and a self-sacrificial tumor suppressive process impeding proliferation of altruists via cell cycle arrest. Both processes are regulated concurrently in the altruists by miR-125b, via differential NF-κB signaling specifically through IKKβ. Altruistic cells persist in the tumor despite their self-sacrifice, as they can regenerate epigenetically from non-altruists via a KLF2/PCAF-mediated mechanism. The altruists maintain a sparse spatial organization by inhibiting surrounding cells from adopting the altruistic fate via a lateral inhibition mechanism involving a GAB1-PI3K-AKT-miR-125b signaling circuit. Conclusions Our data reveal molecular mechanisms underlying manifestation, persistence and spatial spread of cancer cell altruism. A minor population behave altruistically at a cost to itself producing a collective benefit for the tumor, suggesting tumors to be dynamic social systems governed by the same rules of cooperation in social organisms. Understanding cancer cell altruism may lead to more holistic models of tumor evolution and drug response, as well as therapeutic paradigms that account for social interactions. Cancer cells constitute tractable experimental models for fields beyond oncology, like evolutionary ecology and game theory.

Anion–π catalysis, introduced in 2013, stands for the stabilization of anionic transition states on π-acidic aromatic surfaces. Anion–π catalysis on carbon allotropes is particularly attractive because high polarizability promises access to really strong anion–π interactions. With these expectations, anion–π catalysis on fullerenes has been introduced in 2017, followed by carbon nanotubes in 2019. Consistent with expectations from theory, anion–π catalysis on carbon allotropes generally increases with polarizability. Realized examples reach from enolate addition chemistry to asymmetric Diels–Alder reactions and autocatalytic ether cyclizations. Currently, anion–π catalysis on carbon allotropes gains momentum because the combination with electric-field-assisted catalysis promises transformative impact on organic synthesis.

Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington’s disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting.

Abstract Background Sarcopenia is a chronic disease marked by gradual muscle system and functional decline. Prior research indicates its prevalence in those under 60 varies from 8 to 36%. There is limited evidence on the effectiveness of non-pharmacological interventions for sarcopenia prevention in menopausal women aged 40–60. This study examines the influence of such interventions for sarcopenia prevention on these women. Methods PubMed, EMBASE, Medline, Cochrane Library, CINAHL, PEDro, and Airiti Library were searched from inception until May 5, 2023. Randomized controlled trials that examined exercise, vitamin D and protein supplementation effects on muscle mass, strength, and physical function. Quality assessment used the Cochrane risk of bias tool, and analysis employed Comprehensive Meta-Analysis version 2.0. Results A total of 27 randomized controlled trials, involving 1,989 participants were identified. Meta-analysis results showed exercise improved lean body mass (SMD = 0.232, 95% CI: 0.097, 0.366), handgrip strength (SMD = 0.901, 95% CI: 0.362, 1.441), knee extension strength (SMD = 0.698, 95% CI: 0.384, 1.013). Resistance training had a small effect on lean body mass, longer exercise duration (> 12 weeks) and higher frequency (60–90 min, 3 sessions/week) showed small to moderate effects on lean body mass. Vitamin D supplementation improved handgrip strength (SMD = 0.303, 95% CI: 0.130, 0.476), but not knee extension strength. There was insufficient data to assess the impact of protein supplementation on muscle strength. Conclusions Exercise effectively improves muscle mass, and strength in menopausal women. Resistance training with 3 sessions per week, lasting 20–90 min for at least 6 weeks, is most effective. Vitamin D supplementation enhances small muscle group strength. Further trials are needed to assess the effects of vitamin D and protein supplementation on sarcopenia prevention. Registration number This review was registered on PROSPERO CRD42022329273.

Abstract Background Females are underrepresented in Science, Technology, Engineering, and Mathematics (STEM) fields all over the world. To encourage more girls to choose STEM majors and careers, it is critical to increase their interest in STEM careers. Many studies have investigated the factors that influence females' entry into STEM fields, but few studies have explored the gender differences in the relationships between these factors. Therefore, based on the Social Cognitive Career Theory, this study explored the gender differences in the effects of environmental factors (school education, informal education, social support, and media) on high school students' interest in STEM careers through the mediating roles of STEM self-efficacy and STEM careers perceptions. Results A questionnaire survey was conducted among 1240 high school students in Hunan Province, China, and the results of t-test, regression analysis, and structural equation model multi-group comparison showed that: Firstly, the scores of male students in all the dimensions except for STEM career perception were significantly higher than those of female students. Secondly, the environmental factor that had the greatest effect on male and female students' interest in STEM careers was different. Finally, there were gender differences in the mediating roles of STEM self-efficacy and STEM careers perceptions between environmental factors and interest in STEM careers. Conclusions This study revealed the influence mechanisms and gender differences in male and female students' interest in STEM careers in the context of Chinese Confucian culture, and the conclusions are as follows: (1) Male students' interest in STEM careers was significantly higher than that of female students; (2) The environmental factors that had the greatest effect on male and female students' interest in STEM careers were social support and media, respectively; and (3) Environmental factors could affect male students' interest in STEM careers through the mediating roles of STEM self-efficacy and STEM career perception, while environmental factors could affect female students' interest in STEM careers through the mediating role of STEM self-efficacy. Finally, the mediating mechanisms of STEM self-efficacy and STEM career perception between environmental factors and interest in STEM careers, and the importance of STEM self-efficacy for female students were discussed.

Methylobacterium species, the representative bacteria distributed in phyllosphere region of plants, often synthesize carotenoids to resist harmful UV radiations. Methylobacterium extorquens is known to produce a carotenoid pigment and recent research revealed that this carotenoid has a C30 backbone. However, its exact structure remains unknown. In the present study, the carotenoid produced by M. extorquens AM1 was isolated and its structure was determined as 4-[2-O-11Z-octadecenoyl-β-glucopyranosyl]-4,4′-diapolycopenedioc acid (1), a glycosylated C30 carotenoid. Furthermore, the genes related to the C30 carotenoid synthesis were investigated. Squalene, the precursor of the C30 carotenoid, is synthesized by the co-occurrence of META1p1815, META1p1816 and META1p1817. Further overexpression of the genes related to squalene synthesis improved the titer of carotenoid 1. By using gene deletion and gene complementation experiments, the glycosyltransferase META1p3663 and acyltransferase META1p3664 were firstly confirmed to catalyze the tailoring steps from 4,4′-diapolycopene-4,4′-dioic acid to carotenoid 1. In conclusion, the structure and biosynthetic genes of carotenoid 1 produced by M. extorquens AM1 were firstly characterized in this work, which shed lights on engineering M. extorquens AM1 for producing carotenoid 1 in high yield.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients’ poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

Background: Aortic dissection refers to the true and false two-lumen separation of the aortic wall, in which the blood in the aortic lumen enters the aortic mesomembrane from the tear of the aortic intima to separate the mesomembrane and expand along the long axis of the aorta. Purpose: In view of the problems of individual differences, complex complications and many small targets in clinical aortic dissection detection, this paper proposes a convolution neural network MFF-FPN (Multi-scale Feature Fusion based Feature Pyramid Network) for the detection of aortic dissection complications. Methods: The proposed model uses Resnet50 as the backbone for feature extraction and builds a pyramid structure to fuse low-level and high-level feature information. We add an attention mechanism to the backbone network, which can establish inter-dependencies between feature graph channels and enhance the representation quality of CNN. Results: The proposed method has a mean average precision (MAP) of 99.40% in the task of multi object detection for aortic dissection and complications, which is higher than the accuracy of 96.3% on SSD model and 99.05% on YoloV7 model. It greatly improves the accuracy of small target detection such as cysts, making it more suitable for clinical focus detection. Conclusions: The proposed deep learning model achieves feature reuse and focuses on local important information. By adding only a small number of model parameters, we are able to greatly improve the detection accuracy, which is effective in detecting small target lesions commonly found in clinical settings, and also performs well on other medical and natural datasets.

Abstract The ear canal is usually described as an S-shaped funnel. In attempting to classify ear-canal shapes obtained from point clouds digitized from molds of 300 ears, the problem of designing criteria for distinguishing and organizing the canal shapes arose. In this work, we extracted features inspired by the S-shape characteristic (critical point, maximum, minimum, twist, writhe, translation, rotation) and, through them, introduced 14 types of ear-canal shapes. This classification allowed comparison of ears within a type and of ears between different types. It expanded our range of descriptors of canal shapes and unlocked perspectives for applications.

In recent years, with the support of national policies, Cross Border E-Commerce (CBEC) has developed rapidly. This business model not only brings significant benefits to the national economy, but also has many unique challenges, especially at the level of supply chain management. Therefore, to enable CBEC enterprises to develop sustainable supply chain, this study discusses the performance evaluation model of supply chain and proposes a CBEC Supply Chain Performance Evaluation Model (CBECSC-EM) based on the Levenberg–Marquardt Backpropagation (LMBP) algorithm. This experiment constructs performance evaluation indicators for the supply chain of CBEC enterprises. On this basis, the LMBP algorithm is introduced, and improved in the experiment to make the overall performance of the evaluation model more scientific and reasonable. In the verification set, the maximum F1 values of LMBP, DEA, SBM, and BP are 98.46%, 93.78%, 87.29%, and 78.95%, respectively. The MAPE value of LMBP model is 0.102%, which is lower than the other three methods (0.282%, 0.343%, and 0.385%) selected in the experiment. The maximum standard deviation rates of importance and operability of the evaluation indexes are 0.1346 and 0.1405, respectively, and there is a significant consistency between the expert scores. Therefore, the LMBP algorithm has broad application prospects in supply chain performance evaluation of CBEC enterprises.

With the advent of rapid automated in silico identification of biosynthetic gene clusters (BGCs), genomics presents vast opportunities to accelerate natural product (NP) discovery. However, prolific NP producers, Streptomyces, are exceptionally GC-rich (>80%) and highly repetitive within BGCs. These pose challenges in sequencing and high-quality genome assembly which are currently circumvented via intensive sequencing. Here, we outline a more cost-effective workflow using multiplex Illumina and Oxford Nanopore sequencing with hybrid long-short read assembly algorithms to generate high quality genomes. Our protocol involves subjecting long read-derived assemblies to up to 4 rounds of polishing with short reads to yield accurate BGC predictions. We successfully sequenced and assembled 8 GC-rich Streptomyces genomes whose lengths range from 7.1 to 12.1 Mb with a median N50 of 8.2 Mb. Taxonomic analysis revealed previous misrepresentation among these strains and allowed us to propose a potentially new species, Streptomyces sydneybrenneri. Further comprehensive characterization of their biosynthetic, pan-genomic and antibiotic resistance features especially for molecules derived from type I polyketide synthase (PKS) BGCs reflected their potential as alternative NP hosts. Thus, the genome assemblies and insights presented here are envisioned to serve as gateway for the scientific community to expand their avenues in NP discovery.

The distinct clinical and radiological characteristics of right temporal variant FTD have only been recently recognized. Methods: Eight patients with right temporal variant FTD were prospectively recruited and underwent a standardised neuropsychological assessment, clinical MRI, and quantitative neuroimaging. Results: Our voxelwise grey analyses captured bilateral anterior and mesial temporal grey matter atrophy with a clear right-sided predominance. Bilateral hippocampal involvement was also observed, as well as disease burden in the right insular and opercula regions. White matter integrity alterations were also bilateral in anterior temporal and sub-insular regions with a clear right-hemispheric predominance. Extra-temporal white matter alterations have also been observed in orbitofrontal and parietal regions. Significant bilateral but right-predominant thalamus, putamen, hippocampus, and amygdala atrophy was identified based on subcortical segmentation. The clinical profile of our patients was dominated by progressive indifference, decline in motivation, loss of interest in previously cherished activities, incremental social withdrawal, difficulty recognising people, progressive language deficits, increasingly rigid routines, and repetitive behaviours. Conclusions: Right temporal variant FTD has an insidious onset and may be mistaken for depression at symptom onset. It manifests in a combination of apathy, language, and behavioural features. Quantitative MR imaging captures a characteristic bilateral but right-predominant temporal imaging signature with extra-temporal frontal and parietal involvement.

Background: While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods: A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72. A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results: Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72-positive ALS patients. Conclusions: Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype.

Multipotent mesenchymal stromal cells (MSCs) hold promises for cell therapy and tissue engineering due to their self-renewal and differentiation abilities, along with immunomodulatory properties and trophic factor secretion. Extracellular vesicles (EVs) from MSCs offer similar therapeutic effects. However, MSCs are heterogeneous and lead to variable outcomes. In vitro priming enhances MSC performance, improving immunomodulation, angiogenesis, proliferation, and tissue regeneration. Various stimuli, such as cytokines, growth factors, and oxygen tension, can prime MSCs. Two classical priming methods, interferon-gamma (IFN-γ) and hypoxia, enhance MSC immunomodulation, although standardized protocols are lacking. This review discusses priming protocols, highlighting the most commonly used concentrations and durations, along with mechanisms and in vivo therapeutics effects of primed MSCs and their EVs. The feasibility of up-scaling their production was also discussed. The review concluded that priming with IFN-γ or hypoxia (alone or in combination with other factors) boosted the immunomodulation capability of MSCs and their EVs, primarily via the JAK/STAT and PI3K/AKT and Leptin/JAK/STAT and TGF-β/Smad signalling pathways, respectively. Incorporating priming in MSC and EV production enables translation into cell-based or cell-free therapies for various disorders.