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Abstract Background Mentoring’s success in nurturing professional identity formation (PIF) has been attributed to its ability to build personalised and enduring mentoring relationships. However, beyond functioning as communities of practice (CoPs) supporting socialisation processes, how mentoring integrates programme values and instils a shared identity amongst mentees remains unclear. The need for personalised guidance and timely attention to a mentee’s unique needs in evolving mentoring relationships point to the critical role of support mechanisms (‘mentoring support’). We conducted a systematic scoping review (SSR) studying “What is known about mentoring support’s role in nurturing PIF?”. Methods Adopting PRISMA-ScR guidelines, this SSR was guided by the Systematic Evidence-Based Approach (SEBA). Independent searches were carried out on publications featured between 1st January 2000 and 30th June 2023 in PubMed, Embase, ERIC and Scopus databases. The Split Approach saw concurrent, independent thematic and content analyses of the included articles. The Jigsaw Perspective combined complementary themes and categories, creating broader themes/categories. The subsequent Funnelling Process formed key domains that platformed the synthesis of the discussion. Results Two thousand three hundred forty-one abstracts were reviewed, 323 full-text articles were appraised and 151 articles were included and analysed. The key domains identified were (1) definitions and roles; (2) personalisation; (3) shepherding; and (4) PIF. Conclusion The success of mentoring in PIF lies in its ability to blend role modelling, supervision, mentoring, coaching and teaching, with self-care, guided reflection, apprenticeship and assessment to meet the individual needs of the mentee and their changing circumstances. Blending the contents of the mentoring umbrella emphasises the critical role of the mentor and host organisation in supporting mentor training, communications, support and assessment mechanisms. Mentee engagement and its active role in support measures complement the CoP-like mentoring programme’s use of blending mentoring support to advance the socialisation process. These insights reflect a complex interactive process scaffolding the development of mentoring relationships and PIF. The effect of the mentoring umbrella on clinical practice requires further study.

Purpose – This study employs advanced modelling to assess the effectiveness of Malaysia’s current energy policies in achieving a low-carbon future. By optimising a 100% renewable energy mix, including energy storage, the research identifies pathways to decarbonise the power sector while minimising costs. These findings will inform the development of future policies. Design/methodology/approach – This study employs the Stockholm Environment Institute-developed Low Emissions Analysis Platform (LEAP) and Next Energy Modeling system for Optimization (NEMO) to construct and optimise a comprehensive Malaysian power sector model. The model encompasses both electricity supply, including diverse electricity generation sources and demand across key sectors. Three scenarios – existing policy, optimised existing policy and more ambitious policy (near-zero emissions) – are analysed. Findings – Solar photovoltaic (PV) is the dominant technology, but realising its full potential requires significant grid upgrades. While natural gas expansion underpins Malaysia’s decarbonisation strategy, solar and storage offer a cleaner and potentially cost-effective alternative. Rapid technological advancements in clean energy increase stranded asset risk for new gas power plants. Malaysia’s abundant bioenergy resources need more tapping. This can contribute to decarbonisation and rural development. Transitioning to a fully renewable grid necessitates substantial investments in energy storage and grid infrastructure. While falling battery costs and regional interconnection can mitigate costs, careful consideration of potential disruptions and cost fluctuations is essential for resilience. Research limitations/implications – Energy sector modelling results are inherently dependent on input assumptions, such as future technology costs, resource availability and fossil fuel prices. These factors can be highly uncertain. While this study did not conduct sensitivity analyses to explore how variations in these assumptions might affect the results (e.g. cost variations across scenarios, technology mix fluctuations), the core findings provide valuable insights into potential decarbonisation pathways for Malaysia’s power sector. Future studies could build upon this work by incorporating sensitivity analyses to provide a more comprehensive understanding of how key results might change under a wider range of future possibilities. Originality/value – This study co-optimises a 100% renewable energy mix for Malaysia, incorporating a comprehensive range of renewable resources, battery and pumped hydro storage. The research also provides a unique perspective on the interplay of philosophical underpinnings, psychological maturity and energy policy.

Abstract Small interfering RNAs (siRNA) technology has emerged as a promising therapeutic tool for human health conditions like cancer due to its ability to regulate gene silencing. Despite FDA-approved, their delivery remains localized and limiting their systemic use. This study used single-walled carbon nanotubes (SWNTs) functionalized with polyethylene glycolated (PEGylated) phospholipids (PL-PEG) derivatives for systemic siRNA delivery. We developed an siRNA systemic delivery vehicle (SWNT-siRNA) by conjugating SWNT functionalized with PL-PEG containing either amine (PA) or maleimide (MA). The functionalized SWNT with a lower molecular weight of PA produced the SWNT-siRNA conjugate system with the highest stability and high siRNA loading quantity. The system delivered siRNA to a panel of tumour cell lines of different organs (i.e. HeLa, H1299 and MCF-7) and a non-cancerous human embryonic kidney 293 cells (HEK293T) with high biocompatibility and low toxicity. The cellular uptake of SWNT-siRNA conjugates by epithelial cells was found to be energy dependent. Importantly, the presence of P-glycoprotein, a marker for drug resistance, did not inhibit SWNT-mediated siRNA delivery. Mouse xenograft model further confirmed the potential of SWNT-siRNA conjugates with a significant gene knock-down without signs of acute toxicity. These findings pave the way for potential gene therapy applications using SWNTs as delivery vehicles.

Abstract The Yangtze River Delta (YRD) occupies 2.1% of China's territory but accounts for 1/4 of its GDP. Boosting efficiency of industrial water resources in YRD will drastically decrease water pollution and resource constraints. The current paper employed Network Super-SBM and the Global Malmquist-Luenberger index to evaluate industrial water use efficiency and wastewater treatment efficiency of YRD’ cities. Furthermore, digital inclusive finance and green innovation are introduced to investigate the mechanisms underlying their influence on the overall industrial water resources efficiency. The empirical findings posts that: (1) there is still room to improve the overall efficiency, especially the water treatment efficiency; (2) the MI value of each stages in most samples is greater than 1, indicating that the water treatment efficiency and water use efficiency are improving. It is mainly driven by the improvement of the efficiency of the management; (3) there are substantial differences in water resource efficiency among metropolitan areas, with Nanjing-metropolitan areas and Hefei-metropolitan areas having higher water use efficiency and water treatment efficiency for both stages, while Hangzhou-metropolitan areas and Shanghai-metropolitan areas have lower water treatment efficiency. As shown by the Kernel density Estimation, the degree of efficiency dispersion within same metropolitan area is reducing; and (4) digital inclusive finance will boost overall efficiency and water treatment efficiency, with green innovation as a mediating factor. The findings herein offer compelling evidence that financial development increases the effectiveness of water resources, introduce fresh perspectives for the government to put forward water-related policies, and provide ideas for high-quality economy.

Abstract This article presents two variants of memoryless quasi-Newton methods with backtracking line search for large-scale unconstrained minimization. These updating methods are derived by means of a least-change updating strategy subjected to some weaker form of secant relation obtained by projecting the secant equation onto the search direction. In such a setting, the search direction can be computed without the need of calculation and storage of matrices. We establish the convergence properties for these methods, and their performance is tested on a large set of test functions by comparing with standard methods of similar computational cost and storage requirement. Our numerical results indicate that significant improvement has been achieved with respect to iteration counts and number of function evaluations.

Keeping steps ahead of the bacteria in the race for more efficacious antibacterial strategies is increasingly difficult with the advent of bacterial resistance genes. Herein, we engineered copper sulfide nanoclusters (CuSx NCs) with variable sulfur defects for enhanced dual-treatment of bacterial infections by manipulating photothermal effects and Fenton-like activity. Next, by encasing CuSx NCs with a complex mixture of amino acids and short peptides derived from Luria-Bertani bacterial culture media as a protein corona, we managed to coax E. Coli to take up these CuSx NCs. As a whole, Amino-Pep-CuSx NCs was perceived as a food source and actively consumed by bacteria, enhancing their effective uptake by at least 1.5-fold greater than full length BSA protein BSA-corona CuSx NCs. Through strategically using defect-engineering, we successfully fine-tune photothermal effect and Fenton-like capacity of CuSx NCs. Increased sulfur defects lead to reduced but sufficient heat generation under solar-light irradiation and increased production of toxic hydroxyl radicals. By fine-tuning sulfur defects during synthesis, we achieve CuSx NCs with an optimal synergistic effect, significantly enhancing their bactericidal properties. These ultra-small and biodegradable CuSx NCs can rapidly break down after treatment for clearance. Thus, Amino-Pep-CuSx NCs demonstrate effective eradication of bacteria both in vitro and in vivo because of their relatively high uptake, optimal balanced photothermal and chemodynamic outcomes. Our study offers a straightforward and efficient method to enhance bacterial uptake of next generation of antibacterial agents.

Failure of valves in heavy-duty diesel engines is a significant challenge for engine reliability. This study aims to investigate the metallurgical factors that led to the failure of several exhaust valves made from a nitrogen-containing Fe–Mn–Cr–Mo–Nb–V alloy. The failures predominantly occurred in the hot section of the valve stem and were attributed to environmentally assisted fatigue. The primary cause of failure was identified as the low thermal stability of the valve microstructure, characterized by a high-volume fraction of discontinuous cellular precipitation of M23C6/austenite in the hot section of the valve stem. This microstructural instability played a crucial role in initiating and propagating corrosion/oxidation-assisted fatigue cracks due to the precipitation of low toughness Cr-rich carbides and formation of associated Cr-depleted zone the subsequent creation of Cr-depleted areas. To mitigate similar failures in heavy-duty diesel engines operating under increased peak cylinder pressures and temperatures, it is imperative to utilize materials with higher thermal stability and improved corrosion/oxidation resistance.

Introduction: Hospitalisations can pose hazards and may not be an appropriate care setting for frail nursing home (NH) residents. Few studies have quantified the extent of NH resident hospitalisations in Singapore, hence we aimed to address this knowledge gap by studying characteristics of unplanned hospitalisations over a 1-year period. Method: This was a retrospective cohort study of 9922 subsidised residents across 59 NHs in Singapore, with analysis using administrative healthcare data. Key measures included inpatient admission and emergency department visit rates, final discharge diagnoses and estimated costs. We examined correlates of inpatient admissions with a multivariable zero-inflated negative binomial regression model incorporating demographics, institutional characteristics and Charlson Comorbidity Index. Results: There were 6620 inpatient admissions in 2015, equivalent to 2.23 admissions per 1000 resident days, and the majority were repeat admissions (4504 admissions or 68.0%). Male sex (incidence rate ratio [IRR] 1.23), approaching end-of-life (IRR 2.14), hospitalisations in the past year (IRR 2.73) and recent NH admission within the last 6 months (IRR 1.31–1.99) were significantly associated with inpatient admission rate. Top 5 discharge diagnoses were lower respiratory tract infections (27.3%), urinary tract infection (9.3%), sepsis (3.1%), cellulitis (1.9%) and gastroenteritis (1.1%). We estimated the total system cost of admissions of subsidised residents to be SGD40.2 million (USD29.1 million) in 2015. Conclusion: We anticipate that unplanned hospitalisation rate will increase over time, especially with an increasing number of residents who will be cared for in NHs. Our findings provide a baseline to inform stakeholders and develop strategies to address this growing problem.

Abstract Altered mechanotransduction has been proposed as a putative mechanism for disease pathophysiology, yet evidence remains scarce. Here we introduce a concept we call single cell immuno-mechanical modulation, which links immunology, integrin biology, cellular mechanics, and disease pathophysiology and symptomology. Using a micropatterned hydrogel-laden coverslip compatible with standard fluorescence microscopy, we conduct a clinical mechanobiology study, specifically focusing on immune thrombocytopenia (ITP), an autoantibody-mediated platelet disorder that currently lacks a reliable biomarker for bleeding risk. We discover that in pediatric ITP patients (n = 53), low single platelet contraction force alone is a “physics-based” biomarker of bleeding (92.3% sensitivity, 90% specificity). Mechanistically, autoantibodies and monoclonal antibodies drive increases and decreases of cell force by stabilizing integrins in different conformations depending on the targeted epitope. Hence, immuno-mechanical modulation demonstrates how antibodies may pathologically alter mechanotransduction to cause clinical symptoms and this phenomenon can be leveraged to control cellular mechanics for research, diagnostic, and therapeutic purposes.

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) is common and associated with poor outcomes in critically ill patients. Acetaminophen is often used as an antipyretic and analgesic drug, but the association of acetaminophen use with mortality and recovery of renal function in SA-AKI patients remain unclear. We aimed to investigate the association between acetaminophen use and outcomes in SA-AKI patients. Methods This is a retrospective cohort study based on the MIMIC-IV database. Adult patients with SA-AKI were included in the analysis. The exposure was acetaminophen use within 7 days after the onset of SA-AKI. The primary outcome was 28-day mortality. Secondary outcomes included ICU mortality, in-hospital mortality, 90-day mortality, 1-year mortality, and renal recovery. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) with 95% confidence interval (CI) for mortality. Logistic regression models were used to estimate the odd ratio (OR) with 95% CI for renal recovery. Results 6752 patients with SA-AKI were included, and 3892 (57.6%) patients received acetaminophen. Acetaminophen use was associated with decreased 28-day mortality (HR 0.69, 95% CI 0.63–0.75), ICU mortality (HR 0.56, 95% CI 0.50–0.63), in-hospital mortality (HR 0.62, 95% CI 0.57–0.69), 90-day mortality (HR 0.73, 95% CI 0.68–0.79), and 1-year mortality (HR 0.62, 95% CI 0.57–0.69). Acetaminophen use also was associated with improved renal recovery (OR 1.15, 95% CI 1.04–1.28). Conclusions Acetaminophen use is associated with decreased mortality and improved renal recovery in SA-AKI patients.

Abstract Neck pain due to cervical facet joint pain has a prevalence of 36–60% in chronic neck pain. Pulsed radiofrequency for such pain has been verified. After proper patient selection, pulsed radiofrequency of the cervical facet joints provide long-term pain relief in a routine clinical setting. In the patient selection, clinical and sagittal alignment parameters are rarely discussed for the outcome. In the present study, we analyzed the factors from the clinical data and sagittal alignment parameters and investigated the associated predictors of pulsed radiofrequency for cervical facet joint pain. There were 204 patients with cervical facet joint pain who received a medial branch block and pulsed radiofrequency between 2015 and 2020 after excluding patients with neurological symptoms and other confounding factors. The patients were classified into good and poor outcome groups based on the improvement of the pain score(visual analog scale). Clinical and radiological data were analyzed. Multivariable logistic model showed that the predictors were cervical lordosis including two methods (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.89–0.96 for C2–C7 Cobb angle; OR 0.91, 95% CI: 0.88–0.95 for the angle measured by the Jackson method), ossification of the nuchal ligament, number of diseased facet joints, anterior cervical discectomy with fusion, and adjacent facet joint after anterior cervical discectomy with fusion. With the results, we demonstrated that the outcome were related to cervical lordosis including two methods, formation of ossification of nuchal ligament, the number of diseased facet joints, post anterior cervical discectomy with fusion, and adjacent facet joint post anterior cervical discectomy with fusion. The corresponding optimal cutoff for discriminating a poor outcome was 7° for the C2–C7 Cobb angle and − 2° for the angle measured using the Jackson method.

Abstract Advanced biofabrication techniques can create tissue-like constructs that can be applied for reconstructive surgery or as in vitro three-dimensional (3D) models for disease modeling and drug screening. While various biofabrication techniques have recently been widely reviewed in the literature, acoustics-based technologies still need to be explored. The rapidly increasing number of publications in the past two decades exploring the application of acoustic technologies highlights the tremendous potential of these technologies. In this review, we contend that acoustics-based methods can address many limitations inherent in other biofabrication techniques due to their unique advantages: noncontact manipulation, biocompatibility, deep tissue penetrability, versatility, precision in-scaffold control, high-throughput capabilities, and the ability to assemble multilayered structures. We discuss the mechanisms by which acoustics directly dictate cell assembly across various biostructures and examine how the advent of novel acoustic technologies, along with their integration with traditional methods, offers innovative solutions for enhancing the functionality of organoids. Acoustic technologies are poised to address fundamental challenges in biofabrication and tissue engineering and show promise for advancing the field in the coming years.

Solid waste recycling is an economically sound strategy for preserving the environment, safeguarding natural resources, and diminishing the reliance on raw material consumption. Geopolymer technology offers a significant advantage by enabling the reuse and recycling of diverse materials. This research assesses how including silica fume and glass powder enhances the impact resistance of ultra-high-performance geopolymer concrete (UHPGC). In total, 18 distinct mixtures were formulated by substituting ground granulated blast furnace slag with varying proportions of silica fume and glass powder, ranging from 10% to 40%. Similarly, for each of the mixtures above, steel fibre was added at a dosage of 1.5% to address the inherent brittleness of UHPGC. The mixtures were activated by combining sodium hydroxide and sodium silicate solution to generate geopolymer binders. The specimens were subjected to drop-weight impact testing, wherein an examination was carried out to evaluate various parameters, including flowability, density at fresh and hardened state, compressive strength, impact numbers indicative of cracking and failure occurrences, ductility index, and analysis of failure modes. Additionally, the variations in the impact test outcomes were analyzed using the Weibull distribution, and the findings corresponding to survival probability were offered. Furthermore, the microstructure of UHPGC was scrutinized through scanning electron microscopy. Findings reveal that the specimens incorporating glass powder exhibited lower cracking impact number values than those utilizing silica fume, with reductions ranging from 18.63% to 34.31%. Similarly, failure impact number values decreased from 8.26% to 28.46% across glass powder contents. The maximum compressive and impact strength was recorded in UHPGC, comprising 10% silica fume with fibres.

Abstract Background Karyomegalic interstitial nephritis (KIN) is a rare renal diagnosis associated with both genetic and medication etiologies. The primary gene associated with KIN is the FAN1 gene which encodes a protein responsible for DNA interstrand repair. Common medication triggers of KIN are chemotherapeutic agents, especially those which disrupt DNA structure such as carboplatin. Despite overlap between these mechanisms, it has not clearly been established if medication usage requires an underlying genetic predisposition for triggering KIN or if medications alone are sufficient. This ambiguous pathogenesis can make it difficult to appropriately assess risk of KIN development when starting patients on one of the known KIN-inducing therapies. Additionally, brentuximab vedotin, an antibody–drug conjugate directed against CD30, has not been previously implicated in KIN development. Case presentation. We present a 49-year-old woman previously diagnosed with metastatic Hodgkin’s lymphoma who was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine, then 3 cycles of ifosfamide, carboplatin, etoposide, all of which were discontinued due to side effects. Following an episode of acute kidney injury, the serum creatinine was 1.09 mg/dL. She then received 2 doses of brentuximab, the serum creatinine rose, and the drug was discontinued. Kidney biopsy done 2 months after brentuximab and 5 months following ifosfamide therapies showed karyomegalic interstitial nephritis. Genetic evaluation showed no FAN1 gene mutations. The patient was started on pembrolizumab; no steroids were given due to concerns about interference with lymphoma immunotherapy. She remains with stable disease and stable chronic kidney disease. Conclusions This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported.

Abstract Solution-processable 2D materials (2DMs) are gaining attention for applications in logic, memory, and sensing devices. This review surveys recent advancements in memristors, transistors, and sensors using 2DMs, focusing on their charge transport mechanisms and integration into silicon CMOS platforms. We highlight key challenges posed by the material’s nanosheet morphology and defect dynamics and discuss future potential for monolithic 3D integration with CMOS technology.

Abstract As a traditional Chinese medicine formula used in clinical practice for an extended period, Suxin-Hugan-Fang (SXHGF) exhibits excellent anti-inflammatory properties. However, the efficacy of SXHGF in treating ulcerative colitis (UC) and its mechanism of action are still unclear. In this study, the therapeutic effects of SXHGF on UC were evaluated using network pharmacology and experimental validation, while also investigating its mechanism of action. By administering DSS to C57BL/6 mice to construct a mouse model of ulcerative colitis, the therapeutic effect of SXHGF on ulcerative colitis was evaluated based on weight loss percentage, disease activity index, colon length changes, and pathological conditions as indicators. The main chemical components of SXHGF were determined by LC-MS-QTOF method. The potential targets and mechanisms of action of SXHGF in the treatment of UC were inferred using bioinformatics methods, and further validated through ELISA, IHC, and Western blotting assays. The experimental results demonstrate that SXHGF can suppress oxidative stress and oxidative damage in the colon tissue of UC mice, and alleviate DSS-induced ulcerative colitis by inhibiting the JAK2/STAT3 and NFκB pathways.

Abstract Structural variants (SVs) are significant contributors to inter-individual genetic variation associated with traits and diseases. Current SV studies using whole-genome sequencing (WGS) have a largely Eurocentric composition, with little known about SV diversity in other ancestries, particularly from Asia. Here, we present a WGS catalogue of 73,035 SVs from 8392 Singaporeans of East Asian, Southeast Asian and South Asian ancestries, of which ~65% (47,770 SVs) are novel. We show that Asian populations can be stratified by their global SV patterns and identified 42,239 novel SVs that are specific to Asian populations. 52% of these novel SVs are restricted to one of the three major ancestry groups studied (Indian, Chinese or Malay). We uncovered SVs affecting major clinically actionable loci. Lastly, by identifying SVs in linkage disequilibrium with single-nucleotide variants, we demonstrate the utility of our SV catalogue in the fine-mapping of Asian GWAS variants and identification of potential causative variants. These results augment our knowledge of structural variation across human populations, thereby reducing current ancestry biases in global references of genetic variation afflicting equity, diversity and inclusion in genetic research.

Abstract Eimeria tenella is among the protozoan parasites that cause the infectious disease coccidiosis in chickens, incurring huge economic losses to the global poultry industry. Surface antigens (EtSAGs) involved in host-parasite interaction are potential targets for control strategies. However, the occurrence of genetic diversity for EtSAGs in field populations is unknown, as is the risk of such diversity to the efficacy of EtSAG-based control approaches. Here, the extent of EtSAG genetic diversity and its implications on protein structure and function is assessed. Eighty-seven full-length EtSAG genomic sequences were identified from E. tenella genome assemblies of isolates sampled from continents including North America (United States), Europe (United Kingdom), Asia (Malaysia and Japan) and Africa (Nigeria). Limited diversity was observed in the EtSAG sequences. However, distinctive patterns of polymorphism were identified between EtSAG subfamilies, suggesting functional differences among these antigen families. Polymorphisms were sparsely distributed across isolates, with a small number of variants exclusive to specific geographical regions. These findings enhance our understanding of EtSAGs, particularly in elucidating functional differences among the antigens that could inform the development of more effective and long-lasting anticoccidial control strategies.

The bacterium Vibrio parahaemolyticus is ubiquitous in tropical and temperate waters throughout the world and causes infections in humans resulting from water exposure and from ingestion of contaminated raw or undercooked seafood, such as oysters. We describe a nationwide outbreak of enteric infections caused by Vibrio parahaemolyticus in Australia during September 2021–January 2022. A total of 268 persons were linked with the outbreak, 97% of whom reported consuming Australia-grown oysters. Cases were reported from all states and territories of Australia. The outbreak comprised 2 distinct strains of V. parahaemolyticus, sequence types 417 and 50. We traced oysters with V. parahaemolyticus proliferation back to a common growing region within the state of South Australia. The outbreak prompted a national recall of oysters and subsequent improvements in postharvest processing of the shellfish.

Abstract Nanobodies (Nbs) are antibody fragments derived from heavy-chain-only IgG antibodies found in the Camelidae family as well as cartilaginous fish. Their unique structural and functional properties, such as their small size, the ability to be engineered for high antigen-binding affinity, stability under extreme conditions, and ease of production, have made them promising tools for diagnostics and therapeutics. This potential was realized in 2018 with the approval of caplacizumab, the world’s first Nb-based drug. Currently, Nbs are being investigated in clinical trials for a broad range of treatments, including targeted therapies against PDL1 and Epidermal Growth Factor Receptor (EGFR), cardiovascular diseases, inflammatory conditions, and neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. They are also being studied for their potential for detecting and imaging autoimmune conditions and infectious diseases such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A variety of methods are now available to generate target-specific Nbs quickly and efficiently at low costs, increasing their accessibility. This article examines these diverse applications of Nbs and their promising roles. Only the most recent articles published in the last five years have been used to summarize the most advanced developments in the field. Graphical Abstract

Abstract Cancer cells are constantly evolving to adapt to environmental changes, particularly during exposure to drug treatment. In this work, we aimed to characterize genetic and epigenetic changes in mitochondrial DNA (mtDNA) that may increase the resistance of oral squamous cell carcinoma (OSCC) to cisplatin. We first derived drug-resistant cells from two human OSCC cell lines, namely SAS and H103, by continual cisplatin treatments for about 4 months. To determine mtDNA changes induced by cisplatin, we performed nanopore sequencing and quantitative polymerase chain reaction analysis of mtDNA extracted from the cells pre- and post-treatment. We also assessed the mitochondrial functions of the cells and their capacity to generate intracellular reactive oxygen species (ROS). We found that in the cisplatin-resistant cells derived from SAS, there was a reduction in mtDNA content and significant enrichment of a m.3910G > C mutation in the MT-ND1 gene. However, such changes were not detected in cisplatin-resistant H103 cells. The cisplatin treatment also altered methylation patterns in both SAS and H103 cells and decreased their sensitivity to ROS-induced cytotoxicity. We suggest that the sequence alterations and epigenetic changes in mtDNA and the reduction in mtDNA content could be key drivers of cisplatin resistance in OSCC. These mtDNA alterations may participate in cellular adaptation that serves as a response to adverse changes in the environment, particularly exposure to cytotoxic agents. Importantly, the observed mtDNA changes may be influenced by the distinct genetic landscapes of various cancer subtypes. Overall, this study reveals significant insights into cisplatin resistance driven by complex mtDNA dynamics, particularly in OSCC. This underscores the need for targeted therapies tailored to the genetic profiles of individual OSCC patients to improve disease prognosis.

Abstract Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution.

Abstract Introduction Several blood markers of inflammation are elevated in prostate cancer (PCa) and have prognostic value. Little is known about the relationship between these markers, PCa, and other factors associated with chronic inflammation, such as smoking and obesity. We analyzed the interaction between neutrophil and platelet counts indexed to lymphocyte count (NLR and PLR, resp.) and clinically significant PCa (csPCa), accounting for the potential confounding factors of systemic inflammation. Methods NLR and PLR were evaluated in a multicenter prospective study in 443 patients. CsPCa was defined as a Gleason ≥ 4 + 3. Differences between patients with csPCa and non-csPCA were evaluated using the chi-square test, analysis of variance or the Kruskal-Wallis test. Multivariable logistic regression analysis adjusted for smoking, hypertension, diabetes, and cardiovascular disease, and in separate models, either body mass index or waist-to-hip ratio was used to characterize the relationship between inflammation and csPCa. Results None of the factors such as plateletcrit, NLR, and PLR were significantly different between patients with csPCa or non-significant PCa. After adjustment, there was no association between PLR, NLR, plateletcrit or platelet count and csPCa. In an exploratory analysis, there was no association between markers of inflammation and PSA levels > 10 ng/mL. When testing different NLR cutoffs to predict csPCa in ROC analysis, none reached a clinically meaningful value. Conclusion In contrast to previous studies, we found no significant association between easily available blood markers of inflammation and indices of PCa aggressiveness. Further research is required to determine whether inflammation promotes PCa. (ClinicalTrials.gov: NCT03127631. Date of registration: April 25, 2017.

Abstract Background Common cold coronaviruses (ccCoVs) and influenza virus are common infectious agents causing upper respiratory tract infections (RTIs). However, clinical symptoms, comorbidities, and health effects of ccCoV infection remain understudied. Methods A retrospective study evaluated 3,935 outpatients with acute upper RTI at a tertiary teaching hospital. The presence of ccCoV and influenza virus was determined by multiplex molecular assay. The demographic, clinical symptoms, and health outcomes were compared between patients with ccCoV (n = 205) and influenza (n = 417) infections. Multivariable logistic regression was employed to evaluate predictors and health outcomes over a one-year follow-up. Results Sore throat, nasal discharge, headache, and myalgia were more predominant in ccCoV infection; fever was common in influenza. Most patients reported moderate symptoms severity (49.8% ccCoV, 56.1% influenza). Subsequent primary care visits with symptoms of RTI within a year were comparable for both infections (27.3% ccCoV vs. 27.6% influenza). However, patients with influenza reported increased primary care visits for non-RTI episodes and all-cause hospital admission. Baseline comorbidities were associated with increased primary care visits with symptoms of RTI in either ccCoV (adjusted odds ratio [aOR] 2.5; 95% confidence interval [CI] 1.1–5.9; P = 0.034) or influenza (OR 1.9; 95% CI 1.1–3.1; P = 0.017) infections, due probably to the dysregulation of the host immune response following acute infections. In patients infected with influenza infection, dyslipidemia was a predictor for subsequent primary care visits with symptoms of RTI (unadjusted OR 1.8; 95% CI 1.0–3.0; P = 0.040). Conclusions Both influenza and ccCoV infection pose significant disease burden, especially in patients with comorbidities. The management of comorbidities should be prioritized to mitigate poor health outcomes in infected individuals.

Abstract Background Stress-induced activation of ERK/Drp1 serves as a checkpoint in the segregation of damaged mitochondria for autophagic clearance (mitophagy). Elevated cytosolic calcium (Ca2+) activates ERK, which is pivotal to mitophagy initiation. This process is altered in Parkinson’s disease (PD) with mutations in leucine-rich repeat kinase 2 (LRRK2), potentially contributing to mitochondrial dysfunction. Pathogenic LRRK2 mutation is linked to dysregulated cellular Ca2+ signaling but the mechanism involved remains unclear. Methods Mitochondrial damages lead to membrane depolarization. To investigate how LRRK2 mutation impairs cellular response to mitochondrial damages, mitochondrial depolarization was induced by artificial uncoupler (FCCP) in wild-type (WT) and LRRK2R1441G mutant knockin (KI) mouse embryonic fibroblasts (MEFs). The resultant cytosolic Ca2+ flux was assessed using live-cell Ca2+ imaging. The role of mitochondria in FCCP-induced cytosolic Ca2+ surge was confirmed by co-treatment with the mitochondrial sodium-calcium exchanger (NCLX) inhibitor. Cellular mitochondrial quality and function were evaluated by Seahorse™ real-time cell metabolic analysis, flow cytometry, and confocal imaging. Mitochondrial morphology was visualized using transmission electron microscopy (TEM). Activation (phosphorylation) of stress response pathways were assessed by immunoblotting. Results Acute mitochondrial depolarization induced by FCCP resulted in an immediate cytosolic Ca2+ surge in WT MEFs, mediated predominantly via mitochondrial NCLX. However, such cytosolic Ca2+ response was abolished in LRRK2 KI MEFs. This loss of response in KI was associated with impaired activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and MEK, the two upstream kinases of ERK. Treatment of LRRK2 inhibitor did not rescue this phenotype indicating that it was not caused by mutant LRRK2 kinase hyperactivity. KI MEFs exhibited swollen mitochondria with distorted cristae, depolarized mitochondrial membrane potential, and reduced mitochondrial Ca2+ store and mitochondrial calcium uniporter (MCU) expression. These mutant cells also exhibited lower cellular ATP: ADP ratio albeit higher basal respiration than WT, indicating compensation for mitochondrial dysfunction. These defects may hinder cellular stress response and signals to Drp1-mediated mitophagy, as evident by impaired mitochondrial clearance in the mutant. Conclusions Pathogenic LRRK2R1441G mutation abolished mitochondrial depolarization-induced Ca2+ response and impaired the basal mitochondrial clearance. Inherent defects from LRRK2 mutation have weakened the cellular ability to scavenge damaged mitochondria, which may further aggravate mitochondrial dysfunction and neurodegeneration in PD.

Abstract Background Despite the ubiquity of adolescent screen use, there are limited longitudinal studies that examine the prospective relationships between screen time and child behavioral problems in a large, diverse nationwide sample of adolescents in the United States, which was the objective of the current study. Methods We analyzed cohort data of 9,538 adolescents (9–10 years at baseline in 2016–2018) with two years of follow-up from the Adolescent Brain Cognitive Development (ABCD) Study. We used mixed-effects models to analyze associations between baseline self-reported screen time and parent-reported mental health symptoms using the Child Behavior Checklist, with random effects adjusted for age, sex, race/ethnicity, household income, parent education, and study site. We tested for effect modification by sex and race/ethnicity. Results The sample was 48.8% female and racially/ethnically diverse (47.6% racial/ethnic minority). Higher total screen time was associated with all mental health symptoms in adjusted models, and the association was strongest for depressive (B = 0.10, 95% CI 0.06, 0.13, p

Studies on mathematics achievement status show that mathematical reasoning in Malaysian education is critical, especially among university students. Students' attitude toward mathematics is affected by affective, behavioural and cognitive factors. The present research investigated the connections between these variables and their impact on individuals' attitudes towards mathematics reasoning. A statistical analysis method, namely, AMOS-Structural Equation Modelling, was used in this approach. The survey method involving 378 university education students around the Klang Valley was selected using a proportional stratified random sampling technique. The respondents must complete the mathematics reasoning assessment and answer the questionnaire consisting of three components: affective, behavioural and cognitive towards mathematics reasoning. AMOS-Structural Equation Modelling (AMOS-SEM) was applied using data obtained from questionnaires. Results demonstrated that the measurement models showed acceptable validity and reliability by removing some indications from the scales. The findings illustrate the relationship between students' attitudes and mathematical reasoning. Moreover, attitude is significantly related to students' mathematical reasoning performance in university education. The next study's recommendation involves an interview session to explore more findings that might impact their learning in mathematical reasoning.

Abstract We report the development of a “Southeast Asian Specific (SEA-specific) Reference Panel” through a “Cross-panel Imputation” approach, consisting of 2550 samples derived from the GA100K, SG10K, and the Peninsular Malaysia Orang Asli (OA) datasets, covering 113,851,450 variants. The SEA-specific panel produced more high confidence variants than 1000 Genomes Project (1KGP) when imputing the OA (8.9 million SEA-specific vs 8.1 million 1KGP) and the Singapore Genome Variation Project (SGVP) (12.5 million SEA-specific vs 11.8 million 1KGP) genotyping datasets. Further, the SEA-specific panel imputed SNPs with better estimated quality scores (INFO, DR2 and R2) on the OA genotyping dataset when comparing with TOPMED and the Human Genome Diversity Project, but performed similarly on SGVP dataset. This panel also exhibited higher recall and non-reference disconcordance rates, indicating the influence of ancestry closeness of the reference panel. However, we note that the imputation accuracy may be compromised by the size of the reference panel.

Abstract Integrated photon-pair sources are crucial for scalable photonic quantum systems. Thin-film lithium niobate is a promising platform for on-chip photon-pair generation through spontaneous parametric down-conversion (SPDC). However, the device implementation faces practical challenges. Periodically poled lithium niobate (PPLN), despite enabling flexible quasi-phase matching, suffers from poor fabrication reliability and device repeatability, while conventional modal phase matching (MPM) methods yield limited efficiencies due to inadequate mode overlaps. Here, we introduce a layer-poled lithium niobate (LPLN) nanophotonic waveguide for efficient photon-pair generation. It leverages layer-wise polarity inversion through electrical poling to break spatial symmetry and significantly enhance nonlinear interactions for MPM, achieving a notable normalized second-harmonic generation (SHG) conversion efficiency of 4615% W−1cm−2. Through a cascaded SHG and SPDC process, we demonstrate photon-pair generation with a normalized brightness of 3.1 × 106 Hz nm−1 mW−2 in a 3.3 mm long LPLN waveguide, surpassing existing on-chip sources under similar operating configurations. Crucially, our LPLN waveguides offer enhanced fabrication reliability and reduced sensitivity to geometric variations and temperature fluctuations compared to PPLN devices. We expect LPLN to become a promising solution for on-chip nonlinear wavelength conversion and non-classical light generation, with immediate applications in quantum communication, networking, and on-chip photonic quantum information processing.

ABSTRACTHerpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi‑country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n = 78) and physicians (general practitioners and specialists; n = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.

Summary: Background: Detection and management of late-life depression largely relies on primary care. Yet in Singapore, older adults are unlikely to seek help for their mental health from their primary care providers. This qualitative descriptive study explores how late-life depression manifests to general practitioners (GPs) in the Singaporean primary care setting. Methods: Twenty-eight private GPs practicing in Singapore were asked about their clinical experience with late-life depression during semi-structured group and individual discussions conducted online. Participants were purposively sampled across age, gender, and ethnicity (Chinese, Malay, Indian). Transcripts were analysed with reflexive thematic analysis. Findings: To GPs, depression in older patients often manifests through somatic symptoms or subtle behavioural changes, only detectable through follow-ups or collateral history. GPs reported that older patients attribute depressive symptoms to normal ageing or do not mention them, particularly within an Asian culture encouraging stoic endurance. GPs perceived late-life depression as reactions to ageing-related stressors, with male, low-income, or institutionalised patients being at particular risk of insidious, severe depression. GPs noted ethnic differences regarding families’ involvement in care, which they described as helpful, but sometimes stress-provoking for patients. Fear of burdensomeness or loss of autonomy/social role could prompt rejection of diagnosis and treatment in patients. GPs considered good patient-doctor rapport as a facilitator at every step of the care process, noting more favourable prognosis in care-concordant patients. Interpretation: Depression in older adults in Singapore can be covert, with favourable outcomes relying on GPs’ ability to pick up on subtle changes, assess patients holistically, and build rapport with patients and families. Funding: This work was funded by the Division of Family Medicine Research Capabilities Building Budget under the project “Technology and Compassion: Improving Patient Outcomes Through Data Analytics and Patients’ Voice in Primary Care” [NUHSRO/2022/049/NUSMed/DFM].

Background: The impact of COVID-19 infection on physical and mental health of young adults remains unclear. This study aimed to investigate the changes in the physical fitness three months after recovering from acute COVID-19 infection, and examine if the infection could also influence the mental health of university students. Methods: A total of 460 university students (mean age 18.9 ± 1.3 years, with 30 males and 27 females uninfected with COVID-19) volunteered for the study. Participants underwent a fitness test initially, followed by another physical fitness test and a mental health assessment three months after the infection of COVID-19. Physical fitness tests included body composition, flexibility, cardiorespiratory fitness, muscle strength, and muscular endurance. Mental health was assessed using the Depression-Anxiety-Stress Self-Assessment Scale (DASS-21), the Pittsburgh Sleep Quality Inventory (PSQI), and the Post-Traumatic Stress Disorder Self-Assessment Scale (PTSD). Results: Three months after acute COVID-19 infection, the physical performance of university students had decreased compared to pre-infection levels by approximate 3–15 % (p

Biodegradable two-dimensional nanomaterials could be a significant breakthrough in the field of oncology nanotheranostic agents, which are rapidly emerging as promising candidates for tumor theranostic applications. Herein, a novel biodegradable ferrous sulfide nanosheet (FeS NS) is developed. Compared to the traditional photothermal material, black phosphorus nanosheet (BP NS), FeS demonstrates superior degradability and enhanced photothermal performance, and making it ideal for efficient photothermal therapy (PTT) of tumors. In the acidic tumor microenvironment, FeS degrades and releases H2S, which inhibits mitochondrial respiration and ATP production. This process leads to a reduction in heat shock protein expression, lowering the resistance of tumor cells to photothermal stimulation, and improving the efficacy of PTT. The released Fe2+ exhibits efficient peroxidase activity, triggering ferroptosis in tumor cells. Furthermore, due to its superparamagnetic nature, FeS NSs could accumulate at the tumor site and provide a strong magnetic resonance imaging (MRI) signal for imaging-guided tumor therapy. Overall, as a promising alternative to BP, the FeS NSs are a potentially innovative nanotheranostic agent of tumors, offering a synergistic approach to ferroptosis−PTT with MRI guidance.

Alopecia ranks among the most common clinical complaints encountered by dermatologists.1 In particular, affected women often experience great psycho-emotional stress leading to a reduction in quality of life.2 We conducted a prospective epidemiological study conducted over 77 weeks from 1 August 2022 to 23 January 2024 at an outpatient dermatology clinic at Singapore General Hospital. Our primary aim was to evaluate the aetiology of hair loss in adult women in Singapore. Patients above the age of 21 years consented to participation after a formal diagnosis of alopecia. Patient characteristics were analysed to reflect the various aetiologies causing hair loss in women.

Background and Purpose Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke. Methods Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR). Results From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P

Abstract Background Adolescent idiopathic scoliosis (AIS) corrective surgery may involve significant blood loss and blood transfusion requirements. Antifibrinolytic agents such as tranexamic acid (TXA) have been used to reduce blood loss, but its optimal dose is uncertain. The objective of this study is to determine the estimated blood loss and rate of blood transfusion between two groups of AIS patients receiving TXA as a single bolus versus bolus followed by infusion in scoliosis surgery. Methods This was a retrospective analysis of a single bolus versus bolus followed by infusion of TXA in AIS surgery. AIS patients undergoing posterior spinal fusion (PSF) from December 2018 to September 2019 at a tertiary university hospital were identified. Inclusion criteria were patients aged between 10 and 21 years who received either a single bolus of 30 mg/kg TXA (Group A) or a single bolus of 30 mg/kg followed by continuous infusion of 10 mg/kg/h of TXA (Group B). Patient demographics, operative data, estimated blood loss, blood transfusion rate, and complications were recorded. Results A total of 129 AIS patients were included. All operative surgeries were performed by two senior consultants. The mean age was 14.8 ± 3.4 years old, and 89.1% were female. The Cobb angle, number of fusion levels, number of screws, length of skin incision, and duration of surgery were comparable between the two groups. There was no difference in the total estimated blood loss between the two groups: 723.3 ± 279.4 mL (range: 175.0–1607.0 mL) in Group A and 819.4 ± 302.6 mL (range: 330.0–1556.0 mL) in Group B (p = 0.065). There were no complications, and none received blood transfusion. Conclusion TXA when administered as a single bolus or bolus followed by infusion in AIS patients undergoing PSF surgery was associated with similar estimated total surgical blood loss and blood transfusion requirement.

Abstract Background Comprehensive infection prevention and control (IPC) programmes are proven to reduce the spread of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR). However, published assessments of IPC programmes against the World Health Organization (WHO) IPC Core Components in Pacific Island Countries and Territories (PICTs) at the national and acute healthcare facility level are currently unavailable. Methods From January 2022 to April 2023, a multi-country, cross-sectional study was conducted in PICTs. The self reporting survey was based on the WHO Infection Prevention Assessment Framework (IPCAF) that supports implementing the minimum requirements of the WHO eight core components of IPC programmes at both the national and facility level. The results were presented as a ‘traffic light’ (present, in progress, not present) matrix. Each PICT’s overall status in achieving IPC core components was summarised using descriptive statistics. Results Fifteen PICTs participated in this study. Ten (67%) PICTs had national IPC programmes, supported mainly by IPC focal points (87%, n = 13), updated national IPC guidelines (80%, n = 12), IPC monitoring and feedback mechanisms (80%, n = 12), and waste management plans (87%, n = 13). Significant gaps were identified in education and training (20%, n = 3). Despite being a defined component in 67% (n = 10) of national IPC programmes, HAI surveillance and monitoring was the lowest scoring core component (13%, n = 2). National and facility level IPC guidelines had been adapted and implemented in 67% (n = 10) PICTs; however, only 40% (n = 6) of PICTs had a dedicated IPC budget, 40% (n = 6) had multimodal strategies for IPC, and 33% (n = 5) had daily environmental cleaning records. Conclusions Identifying IPC strengths, gaps, and challenges across PICTs will inform future IPC programme priorities and contribute to regional efforts in strengthening IPC capacity. This will promote global public health through the prevention of HAIs and AMR.

This study presents a novel approach to exploring the viewpoints of AI bots regarding the utilization of AI in business hotels using thematic analysis. Interviews were conducted with AI bots serving as the subjects. The rationale for this approach is that AI bots have undergone extensive training using a wide range of data from different internet sources. Therefore, having an interview with an AI bot can be viewed as an interaction with an entity that embodies collective viewpoints and information derived from the internet. The study has unearthed crucial themes that offer invaluable insights to industry participants and policymakers, contributing to the expansion of existing literature by generating novel knowledge and fostering a comprehensive understanding. The pioneering approach of incorporating AI bots as participants in interviews opens up fresh avenues for future research endeavours and engenders discussions and debates concerning the use of AI bots as participants.

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.

Abstract This study investigates how artificial intelligence (AI) perpetuates gender stereotypes in the accounting profession. Through experiments employing large language models (LLMs), we scrutinize how these models assign gender labels to accounting job titles. Our findings reveal differing tendencies among LLMs, with one favouring male labels, another female labels, and a third showing a balanced approach. Statistical analyses indicate significant disparities in labelling patterns, and job titles classified as male are associated with higher salary ranges, suggesting gender-related bias in economic outcomes. This study reaffirms existing literature on gender stereotypes in LLMs and uncovers specific biases in the accounting context. It underscores the transfer of biases from the physical to the digital realm through LLMs and highlights broader implications across various sectors. We propose raising public awareness as a means to mitigate these biases, advocating for proactive measures over relying solely on human intervention.

Abstract Background Cannabis sativa cultivars can be classified as marijuana or hemp, depending on its amount of the psychoactive cannabinoid Δ9‐tetrahydrocannabinolic acid (THCA). Hemp Cheungsam is a non-drug type Cannabis sativa that is characterized by low THCA content. However, the transcripts and expression profile of cannabinoid biosynthesis pathway genes of hemp Cheungsam have not been investigated. Methods RNA-sequencing (RNA-seq) was performed on three different tissue types (flower, leaf, and stem) of hemp Cheungsam to understand their transcriptomes. The expression of cannabinoid biosynthesis pathway genes was further analyzed in each tissue type. Multiple sequence alignment and conserved domain analyses were used to investigate the homologs of cannbinoid biosynthesis genes. Results We found that the cannabinoid biosynthesis pathway was mainly expressed in the flowers of hemp Cheungsam, similar to other Cannabis cultivars. However, expression of cannabidiolic acid (CBDA) synthase was much higher than THCA synthase and cannabichromenic acid (CBCA) synthase, suggesting that the transcription profile favors CBDA biosynthesis. Sequence analysis of cannabinoid biosynthesis pathway genes suggested the identity of orthologs in hemp Cheungsam. Conclusions Cannabinoid biosynthesis in hemp Cheungsam mostly occurs in the flowers, compared to other plant organs. While CBDA synthase expression is high, THCA and CBCA synthase expression is considerably low, indicating lesser THCA biosynthesis and thus low THCA content. Sequence analysis of key genes (CBDA, THCA, and CBCA synthases) of the cannabinoid biosynthetic pathway indicates that orthologs are present in hemp Cheungsam.

Seafood by-products from various organisms like fish, shellfish, squids, and bivalves are often thrown away as waste, even though they could be utilized in creating new types of valuable foods. Up to 75% of the entire organism consists of industrial processing wastes, which can lead to a loss of profit and ecological sustainability if natural resources are not recycled efficiently. Various types of fish parts and byproducts, such as heads, viscera, skin, bones, scales, exoskeletons, pens, ink, and clam shells, can be categorized as valuable waste based on their weight percentages, which vary depending on the species and taxonomy. This review paper delves into the extraction and valorization strategies of seafood by-products, with a focus on transforming waste into valuable resources. Marine by-products can provide bioactive substances such as collagen, peptides, polyunsaturated fatty acids, antioxidants, chitin, and catalysts for biodiesel production. This review highlights the utilization of innovative techniques like microwave- and ultrasound-assisted extraction as well as supercritical fluid extraction and subcritical water extraction to extract bioactive compounds from seafood waste efficiently. This section also discusses the optimization of extraction processes to enhance efficiency and yield. Furthermore, the paper explores the potential applications of seafood by-products across various industries, emphasizing sustainable resource utilization and the creation of high-value products to be applied in our current circular economy.

Arteriovenous hemodialysis fistulas play a critical role in maintaining life on hemodialysis. With the growing use of Doppler ultrasound in nephrology, its utility has expanded to improve the prognosis and quality of life of patients receiving hemodialysis. On a fistula care team, different health-care professionals, including nephrologists, dialysis technicians, and surgeons or vascular interventionalists, require different information. This review article comprehensively explains how Doppler ultrasound evaluation can be beneficial in the management of arteriovenous fistulas from different perspectives of health-care professionals. The article also introduces the pathophysiology of arteriovenous fistula disease and provides a thorough introduction to the use of Doppler ultrasound for the evaluation of arteriovenous fistulas and their associated diseases, addressing the need for a comprehensive understanding among ultrasound practitioners.

Introduction: Minimally invasive surgery (MIS) for limited resections for pancreatic uncinate lesions is not widely performed but can adequately treat benign or low-grade malignant lesions. The aim of this study was to evaluate the short-term outcomes of MIS-limited pancreatic resections for patients with suspected pancreatic neuroendocrine tumours (PNETs). Patients and Methods: This was a retrospective study of six consecutive patients who underwent MIS for PNET within a single institution between 2017 and 2022. Results: Six patients underwent limited pancreas-preserving MIS of the uncinate process (uncinectomy or enucleation), of which two were performed through the robotic approach and four through laparoscopic approach. The median operation time was 212.5 (175–338.75) min, and the median blood loss was 50 (50–112.5) ml. The median post-operative hospital length of stay was 5.5 (3.75-11.5) days. Two patients (33.3%) had major post-operative morbidities (Clavien–Dindo ≥Grade 3). There were no open conversions or post-operative mortalities. Five patients had histologically proven Grade 1 neuroendocrine tumours. One was T2 and four were T1. Conclusions: This study suggests that limited MIS resections of pancreatic uncinate PNETs are a feasible procedure with good patient outcomes. It offers a safe alternative to radical surgical resections like pancreatoduodenectomies in selected patients with low-grade malignant or benign tumours.

The emergence of gene therapy offers opportunities for treating a myriad of genetic disorders and complex diseases that previously had limited or no treatment options. The key basic strategies for gene therapy involve either the addition, inhibition, or introduction of a new gene, with a crucial component being the use of a delivery vector to effectively target cells. Particularly promising is the application of gene therapy for the treatment of inherited arrhythmia syndromes, conditions associated with significant mortality and morbidity that have limited treatment options, and a paucity of disease modifying therapy. This review aims to summarize the utility of gene therapy for the treatment of inherited arrhythmia syndromes by exploring the current state of knowledge, limitations, and future directions.

The introduction of endoscopic spine surgery has led to a paradigm shift in the treatment of spinal disorders. In particular, biportal endoscopic surgery has gained traction for its wider visual field and improved the maneuverability of instruments, familiar anatomy, and cost-effectiveness. In this study, we describe our en bloc removal of the ligamentum flavum using a “butterfly” technique. This approach had several advantages: (1) The flavum serves as a protective barrier for the dura during drilling. (2) There is less epidural bleeding, which provides (3) better visualization. (4) In an inadvertent durotomy, this usually occurs later in the procedure, which is more manageable than the early stages of decompression. Biportal decompression for spinal stenosis can be performed using an en bloc ligamentum flavum removal technique that is safe, reproducible, and efficient. A systematic approach will help early adopters overcome the steep learning curve.

Abstract Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors—such as pH, buffer types, ionic strength, protein concentrations, and temperatures—on its stability and the reversal of its self-associated aggregates. Mildly acidic, low-salt conditions were found optimal, ensuring bsAb stability for 30 days even at elevated temperature of 40 °C. Furthermore, these conditions facilitated the reversal of its self-associated aggregates to monomers during the initial 7-day incubation period. Our findings underscore the robustness and resilience of Fab-scFv format bsAb, further confirming its potential manufacturability despite its current absence as commercial products. Graphical Abstract