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Background & Aims: Liver cancer-related deaths are projected to exceed one million annually by 2030. Existing therapies have significant limitations, including severe side effects and inconsistent efficacy. Innovative therapeutic approaches to address primary liver cancer (PLC) have led to the ongoing development of tumor-derived organoids. These are sophisticated three-dimensional structures capable of mimicking native tissue architecture and function in vitro, improving our ability to model in vivo homeostasis and disease. Methods: This systematic review consolidates known literature on human and mouse liver organoids across all PLC subtypes, emphasizing diagnostic precision, disease modeling, and drug screening capabilities. Results: Across all 39 included studies, organoids were most frequently patient-derived, closely followed by cancer cell line-derived. The literature concentrated on hepatocellular carcinoma and intrahepatic cholangiocarcinoma, while exploration of other subtypes was limited. These studies demonstrate a valuable role for PLC organoid cultures in biomarker discovery, disease modeling, and therapeutic exploration. Conclusions: Encouraging advances such as organoid-on-a-chip and co-culturing systems hold promise for advancing treatment regimens for PLC. Standardizing in vitro protocols is crucial to integrate research breakthroughs into practical treatment strategies for PLC. Impact and implications:: This study provides an overview of the current understanding of tumor-derived organoids in primary liver cancers, emphasizing their potential in diagnostics, disease modeling, and drug screening. The scientific foundation rests on the organoids' ability to replicate the tumor microenvironment and genetic landscape, opening new avenues for personalized therapies. These insights are crucial for both researchers and clinicians, as patient-derived organoids can help identify biomarkers and therapeutic targets. Physicians and policymakers can harness these advances to drive progress in precision medicine, while recognizing the challenges involved in standardizing organoid models for clinical implementation.

Summary: Background: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. Methods: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). Primary endpoint: invasive loco-regional control (ILRC); secondary overall survival. Findings: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99–1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82–2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99–2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28–1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7–119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07–15.5, p = 0.978) radiotherapy. Interpretation: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial. Funding: Cancer Research UK, NIHR, MRC.

How the microstructure of steel affects a material’s response to microbially influenced corrosion (MIC) in marine applications remains largely unclear, partly because of the challenge in mapping local structure–property relationships. Focusing on sulphate-reducing bacteria, the onset and rate of MIC on low-carbon marine steel samples were analysed with a wide range of grain size and as a function of the local surface crystallography using a combination of optical and electron microscopy, mass loss measurements, and electrochemical testing. It is shown that the alloy’s resistance to MIC decreases with increasing in grain size. A significant effect of the local crystallographic orientation on the material’s dissolution rate is also recorded, which is lowest along the 〈100〉 crystallographic orientation in this steel when exposed to artificial seawater. These findings outline a clear relationship between the microstructure and the susceptibility to MIC in marine steel, which may be used to design alloys with enhanced resistance to MIC in marine applications.

This data article provides macroeconomic data that can be used to generate macroeconomic volatility. The data cover a sample of seven selected countries in the Asia Pacific region for the period 2004–2014, including both developing and developed countries. This dataset was generated to enhance our understanding of the sources of macroeconomic volatility affecting the countries in this region. Although the Asia Pacific region continues to remain as the most dynamic part of the world's economy, it is not spared from various sources of macroeconomic volatility through the decades. The reported data cover 15 types of macroeconomic data series, representing three broad categories of indicators that can be used to proxy macroeconomic volatility. They are indicators that account for macroeconomic volatility (i.e. volatility as a macroeconomic outcome), domestic sources of macroeconomic volatility and external sources of macroeconomic volatility. In particular, the selected countries are Malaysia, Thailand, Indonesia and Philippines, which are regarded as developing countries, while Singapore, Japan and Australia are developed countries. Despite the differences in level of economic development, these countries were affected by similar sources of macroeconomic volatility such as the Asian Financial Crisis and the Global Financial Crisis. These countries were also affected by other similar external turbulence arising from factors such as the global economic slowdown, geopolitical risks in the Middle East and volatile commodity prices. Nonetheless, there were also sources of macroeconomic volatility which were peculiar to certain countries only. These were generally domestic sources of volatility such as political instability (for Thailand, Indonesia and Philippines), natural disasters and anomalous weather conditions (for Thailand, Indonesia, Philippines, Japan and Australia) and over-dependence on the electronic sector (for Singapore). Keywords: Macroeconomic, Volatility, Asia Pacific

Notch signaling is an important regulator of stem cell differentiation. All canonical Notch signaling is transmitted through the DNA-binding protein CSL, and hyperactivated Notch signaling is associated with tumor development; thus it may be anticipated that CSL deficiency should reduce tumor growth. In contrast, we report that genetic removal of CSL in breast tumor cells caused accelerated growth of xenografted tumors. Loss of CSL unleashed a hypoxic response during normoxic conditions, manifested by stabilization of the HIF1α protein and acquisition of a polyploid giant-cell, cancer stem cell-like, phenotype. At the transcriptome level, loss of CSL upregulated more than 1,750 genes and less than 3% of those genes were part of the Notch transcriptional signature. Collectively, this suggests that CSL exerts functions beyond serving as the central node in the Notch signaling cascade and reveals a role for CSL in tumorigenesis and regulation of the cellular hypoxic response.

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disease characterized by painful, recurrent, inflamed lesions most commonly occurring in the axillary, inguinal, and anogenital regions. HS can inflict immense physical and psychological impact on patients who suffer from this distressing disease. Management of HS generally requires combining various medical and procedural treatment modalities; however, the disease is often recalcitrant to conventional treatments. In light of recent evidence supporting the effectiveness of biologic agents in the treatment of HS, the Taiwanese Dermatological Association established an expert panel of nine dermatologists to develop consensus statements aimed to provide up-to-date evidence-based guidance in optimizing HS patient management in Taiwan. The recommendations described in the statements were summarized in a management algorithm in terms of general care, topical treatment, systemic treatment, and procedural treatment.

Background: Meigs syndrome, pseudo-Meigs syndrome, and pseudo-pseudo-Meigs syndrome showcase a diagnostic challenge in the management of complex pediatric cases. Case report: We report a case of a 6-year-old girl who presented with progressive breathlessness, lethargy, and constipation for two weeks, associated with multiple episodes of joint pain and polymorphous rash. Imaging of the thorax, abdomen, and pelvis suggested bilateral pleural effusion, ascites, and an ovarian mass with abdominal involvement. The pleural and peritoneal fluids were exudative in nature. Unfortunately, she was not fit for a biopsy of the mass and was treated in the intensive care unit for one month. She was initiated on oral corticosteroids for suspicion of an underlying auto-inflammatory disease. However, subsequent investigations yielded inconclusive results. She gradually recovered and was well for a year. She presented again with constitutional symptoms and was diagnosed with diffuse large B-cell lymphoma (DLBCL). Thus, it was retrospectively apparent that this was a case of pseudo-Meigs syndrome. Conclusion: We describe an unusual presentation of DLBCL with a temporary resolution of symptoms.

X-linked myotubular myopathy (XLMTM) is a severe type of congenital skeletal muscle disorder usually presenting at birth requiring extensive resuscitation. While having phenotypic variability, its diagnosis carries a poor prognosis due to high rates of hospitalization and mortality by early infancy. Management of patients with XLMTM should therefore be guided by shared decision-making with parents, considering the severity and progression of the disease, quality of life, and demands on caregivers. We describe a family unit of two half-siblings presenting with the severe neonatal form of XLMTM, with varying prognosis and outcomes. Furthermore, a novel maternally-derived c.343-1G > A variant in intron-5 of the MTM1 gene was identified in this family. Hereby, we propose an algorithm for the management of XLMTM, outlining important considerations during the antenatal and postnatal follow-up period.

Pherosphaera fitzgeraldii, the Dwarf Mountain Pine, is a critically endangered conifer restricted to cliff ledges within waterfall spray zones in the Greater Blue Mountains Area of New South Wales, Australia. This species is under threat from pollution, invasive weeds, and limited recruitment, which are contributing to its declining population. Using a comprehensive conservation genomic approach, we assessed the population health of P. fitzgeraldii and developed strategic recommendations for its management.Genomic analysis of P. fitzgeraldii revealed the presence of two distinct genetic groups despite the limited distribution of the species. This genetic structure aligns with prevailing wind currents, indicating potential restrictions to pollen or seed exchange between subpopulations. Furthermore, limited gene flow was observed even among nearby subpopulations, emphasizing the risk of increased genetic differentiation due to ongoing isolation. Clonality is widespread in some subpopulations, and all subpopulations displayed signs of inbreeding and genetic depletion despite subdioecy, indicative of historical constraints on gene flow and small population sizes.We offer genomic-based recommendations for prioritizing conservation sites, enhancing genetic diversity in ex situ collections, and guiding future management. Further studies to uncover the sex determination mechanism of P. fitzgeraldii could help maintain balanced sex ratios in ex situ collections and support future genetic rescue efforts. This study underscores the value of genomics in informing protection and recovery of unique threatened species.

Background/purpose: Oral submucous fibrosis (OSF), characterized by excessive collagen deposition by myofibroblasts, is often linked to Areca nuts consumption. Probiotics consumption has shown protective effects against fibrotic diseases, and recently, their metabolic byproducts, known as postbiotics, have demonstrated superior advantages over probiotics. However, studies on the therapeutic impact of postbiotics on OSF have been scarce. Therefore, this study aims to examine the effect of PostBio GK4, a postbiotic derived from Lactobacillus pentosus GK4, on OSF and explore its underlying mechanisms. Materials and methods: The cytotoxicity of GK4 in normal buccal mucosal fibroblasts (BMFs) and fibrotic BMFs (fBMFs) were assessed. Following this, we evaluated the effects of GK4 on collagen contraction, migratory, and wound healing capacities in arecoline-induced fibrotic BMFs. Next, Western blotting and ELISA were employed to assess GK4's impact on fibrosis-related proteins such as COL1A1, and α-SMA, as well as on TGF-β and Smad2/3 signaling pathway. Results: Arecoline was shown to stimulate cell migratory, contractile and wound healing abilities as well as the expression of α-SMA and COL1A1 in BMFs. Treatment with GK4 reduced all arecoline-induced phenomena in BMFs. Moreover, GK4 diminished the increased expression of TGF-β and Smad2/3. Conclusion: Our findings proposed that GK4 may exert a suppressive effect on arecoline-induced myofibroblast activities via the inhibition of TGF-β and Smad2/3 signaling pathway. Therefore, GK4 holds promise as an adjunct therapeutic approach for intervening in OSF. Further in-vivo and clinical studies are warranted to validate these observations.

Objectives: This study aimed to assess the feasibility of an online compassion training program for nursing students and preliminarily investigate its effects on mindfulness, self-compassion, and stress reduction. Methods: This study employed a randomized controlled trial design. Second-year students from a nursing college in Guangzhou, China, were recruited as research participants in August 2023. The intervention group participated in an 8-week online compassion training program via the WeChat platform, comprising three stages: mindfulness (weeks 1–2), self-compassion (weeks 3–5), and compassion for others (weeks 6–8). Each stage included four activities: psychoeducation, mindfulness practice, weekly diary, and emotional support. Program feasibility was assessed through recruitment and retention rates, program engagement, and participant acceptability. Program effectiveness was measured with the Mindful Attention Awareness Scale, Self-Compassion Scale - Short Form, and Perceived Stress Scale. Results: A total of 28 students completed the study (13 in the intervention group, 15 in the control group). The recruitment rate was 36.46%, with a high retention rate of 93.3%. Participants demonstrated high engagement: 69.2% accessed learning materials every 1–2 days, 93.3% practiced mindfulness at least weekly, with an average of 4.69 diary entries submitted per person and 23.30 WeChat interactions with instructors. Regarding acceptability, all participants expressed satisfaction with the program, with 92.4% finding it “very helpful” or “extremely helpful.” In terms of intervention effects, the intervention group showed a significant increase in mindfulness levels from pre-intervention (51.54 ± 10.93) to post-intervention (62.46 ± 13.58) (P

Summary: MicroRNAs (miRNAs) are highly expressed in vertebrate neural tissues, but the contribution of specific miRNAs to the development and function of different neuronal populations is still largely unknown. We report that miRNAs are required for terminal differentiation of olfactory precursors in both mouse and zebrafish but are dispensable for proper function of mature olfactory neurons. The repertoire of miRNAs expressed in olfactory tissues contains over 100 distinct miRNAs. A subset, including the miR-200 family, shows high olfactory enrichment and expression patterns consistent with a role during olfactory neurogenesis. Loss of function of the miR-200 family phenocopies the terminal differentiation defect observed in absence of all miRNA activity in olfactory progenitors. Our data support the notion that vertebrate tissue differentiation is controlled by conserved subsets of organ-specific miRNAs in both mouse and zebrafish and provide insights into control mechanisms underlying olfactory differentiation in vertebrates., Molecular and Cellular Biology

Oral squamous cell carcinoma (OSCC) is known to be driven by multiple intricated receptor tyrosine kinases (RTKs) including EGFR, PI3K/AKT and MAPK signaling pathways. However, whilst targeting EGFR with cetuximab has been approved for the treatment of OSCC, other single-agent inhibitors of the RTKs have shown modest effects in improving survival. From the genome-wide CRISPR/Cas9 screen on 21 OSCC cell lines, we have identified PTPN11 among the top essential genes in OSCC. PTPN11 encodes for SHP2, a phosphatase that acts as a master signal transducer, downstream of various RTKs. Although PTPN11 overexpression has been reported in OSCC, little is known about its role as an essential gene for OSCC survival and its potential as a therapeutic target. Herein, we confirmed that PTPN11 is an essential gene in OSCC where its deletion significantly impacted cell survival. We evaluated three SHP2 inhibitors on 21 OSCC cell lines and found TNO155 to be significantly associated with CRISPR dependency score. We showed that TNO155 caused dose-dependent suppression on p-ERK and p-MEK, and suppresses the JAK/STAT pathway via downregulating p-JAK1, p-STAT1, p-STAT3. Furthermore, we confirmed that the combination of the mTOR inhibitor, everolimus with TNO155 is synergistic in OSCC. In summary, PTPN11 is a promising therapeutic target in OSCC that can be selectively targeted by SHP2 inhibitor such as TNO155. Our findings on the use of mTOR inhibitor, everolimus to overcome resistance to TNO155 are essential to inform on next phases of clinical trials which is warranted for the treatment of OSCC.

Background: Previous research has indicated a negative correlation between exclusive breastfeeding and the incidence of Kawasaki disease (KD). However, the validation of this discovery through meta-analytical studies has been lacking. Furthermore, uncertainties persist regarding whether breastfeeding reduces the risk of coronary artery lesions (CAL) or resistance to intravenous immunoglobulin (IVIG). Methods: A systematic exploration of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ClinicalTrials.gov databases was conducted to identify longitudinal or randomized controlled trials investigating the efficacy of breastfeeding in preventing KD. The primary focus was on the incidence of KD, with secondary emphasis placed on the incidence of CAL and IVIG resistance. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. Results: Of the 179 potentially eligible studies identified, five (n = 1,982,634) were included. The analysis revealed a significantly lower risk of KD (expressed as odds ratio, with 95% confidence intervals and p-values) in comparisons between exclusive breastfeeding and formula feeding (0.62, 0.43−0.91, p = 0.014), exclusive breastfeeding/partial breastfeeding and formula feeding (0.66, 0.46− 0.96, p = 0.03), and exclusive breastfeeding and partial breastfeeding/formula feeding (0.81, 0.74− 0.90, p

Objectives: The mechanisms underlying chromosomally encoded colistin resistance in Escherichia coli remain insufficiently investigated. In this study, we investigated the contribution of various pmrB mutations from E. coli clinical isolates to colistin resistance. Methods: The resistance mechanisms in eight mcr-negative colistin-resistant E. coli isolates obtained from a nationwide surveillance program in Taiwan using recombinant DNA techniques and complementary experiments were investigated. The minimal inhibitory concentrations (MICs) of colistin in the recombinant strains were compared with those in the parental strains. The expression levels of pmrA and pmrK (which are part of the pmrCAB and pmrHFIJKLM operons associated with colistin resistance) were measured using reverse transcription-quantitative real-time polymerase chain reaction. Results: In the complementation experiments, various mutated pmrB alleles from the eight mcr-negative colistin-resistant E. coli strains were introduced into an ATCC25922 mutant with a PmrB deletion, which resulted in colistin resistance. The MIC levels of colistin in the most complemented strains were comparable to those of the parental colistin-resistant strains. Increased expression levels of pmrA and pmrK were consistently detected in most complemented strains. The impact for colistin resistance was confirmed for various novel amino acid substitutions, P94L, G19E, L194P, L98R and R27L in PmrB from the parental clinical strains. The detected amino acid substitutions are distributed in the different functional domains of PmrB. Conclusions: Colistin resistance mediated by amino acid substitutions in PmrB is a major chromosomally encoded mechanism in E. coli of clinical origin.

Objectives: The World Health Organization named Stenotrophomonas maltophilia (SM) a critical multi-drug resistant threat, necessitating rapid diagnostic strategies. Traditional culturing methods require up to 96 h, including 72 h for bacterial growth, identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) through protein profile analysis, and 24 h for antibiotic susceptibility testing. In this study, we aimed at developing an artificial intelligence-clinical decision support system (AI-CDSS) by integrating MALDI-TOF MS and machine learning to quickly identify levofloxacin and trimethoprim/sulfamethoxazole resistance in SM, optimizing treatment decisions. Methods: We selected 8,662 SM from 165,299 MALDI-TOF MS-analysed bacterial specimens, collected from a major medical centre and four secondary hospitals. We exported mass-to-charge values and intensity spectral profiles from MALDI-TOF MS .mzML files to predict antibiotic susceptibility testing results, obtained with the VITEK-2 system using machine learning algorithms. We optimized the models with GridSearchCV and 5-fold cross-validation. Results: We identified distinct spectral differences between resistant and susceptible SM strains, demonstrating crucial resistance features. The machine learning models, including random forest, light-gradient boosting machine, and XGBoost, exhibited high accuracy. We established an AI-CDSS to offer healthcare professionals swift, data-driven advice on antibiotic use. Conclusions: MALDI-TOF MS and machine learning integration into an AI-CDSS significantly improved rapid SM resistance detection. This system reduced the identification time of resistant strains from 24 h to minutes after MALDI-TOF MS identification, providing timely and data-driven guidance. Combining MALDI-TOF MS with machine learning could enhance clinical decision-making and improve SM infection treatment outcomes.

Objective: To examine the association of left atrial (LA) function with incident chronic kidney disease (CKD) and assess the clinical utility of adding LA function to a CKD risk prediction equation. Patients and Methods: We included 4002 Atherosclerosis Risk in Communities study participants without prevalent CKD (mean ± SD age, 75±5 years; 58% female, 18% Black). Left atrial function (reservoir, conduit, and contractile strain) was evaluated by 2D-echocardiograms on 2011 to 2013. Chronic kidney disease was defined as greater than 25% decline in estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, end-stage kidney disease, or hospital records. Cox proportional hazards models were used. Risk prediction and decision curve analyses evaluated 5-year CKD risk by diabetes status. Results: Median follow-up was 7.2 years, and 598 participants developed incident CKD. Incidence rate for CKD was 2.29 per 100 person-years. After multivariable adjustments, the lowest quintile of LA reservoir, conduit, and contractile strain (vs highest quintile) had a higher risk of CKD (hazard ratios [95% CIs]: 1.94 [1.42-2.64], 1.62 [1.19-2.20], and 1.49 [1.12-1.99]). Adding LA reservoir strain to the CKD risk prediction equation variables increased the C-index by 0.026 (95% CI: 0.005-0.051) and 0.031 (95% CI: 0.006-0.058) in participants without and with diabetes, respectively. Decision curve analysis found the model with LA reservoir strain had a higher net benefit than the model with CKD risk prediction equation variables alone. Conclusion: Lower LA function is independently associated with incident CKD. Adding LA function to the CKD risk prediction enhances prediction and yields a higher clinical net benefit. These findings suggest that impaired LA function may be a novel risk factor for CKD.

Objectives: Excessive inflammation contributes to the pathogenesis of tendinopathy. Fatty acid binding protein 4 (FABP4) is a pro-inflammatory adipokine mediating various metabolic and inflammatory diseases. This study aimed to examine the expression of FABP4 and its association with the expressions of inflammatory cytokines in tendinopathy. The effects of a single injection of FABP4 on tendon pathology and inflammation were examined. The effect of FABP4 on the expressions of inflammatory cytokines and the effect of IL-1β on the expression of FABP4 in tendon-derived stem/progenitor cells (TDSCs) were also investigated. Methods: 1) Clinical patellar tendinopathy samples, healthy hamstring tendon samples, and healthy patellar tendon samples, 2) rotator cuff tendinopathy samples and healthy hamstring tendon samples; and 3) Achilles tendons of mice after saline or collagenase injection (CI) were stained for FABP4, IL-1β, IL-6, TNF-α and IL-10 by immunohistochemistry (IHC). For the rotator cuff tendinopathy samples, co-localization of FABP4 with IL-1β and TNF-α was done by immunofluorescent staining (IF). Mouse Achilles tendons injected with FABP4 or saline were collected for histology and IHC as well as microCT imaging post-injection. TDSCs were isolated from human and mouse tendons. The mRNA expressions of inflammatory cytokines in human and mouse TDSCs after the addition of FABP4 was quantified by qRT-PCR. The expression of FABP4 in TDSCs isolated from rotator cuff tendinopathy samples and healthy hamstring tendon samples was examined by IF. Mouse Achilles TDSCs were treated with IL-1β. The mRNA and protein expressions of FABP4 were examined by qRT-PCR and IF, respectively. Results: There was significant upregulation of FABP4 in the patellar tendinopathy samples and rotator cuff tendinopathy samples compared to their corresponding controls. FABP4 was mainly expressed in the pathological areas including blood vessels, hypercellular and calcified regions. The expressions of IL-1β and TNF-α increased in human rotator cuff tendinopathy samples and co-localized with the expression of FABP4. Collagenase induced tendinopathic-like histopathological changes and ectopic calcification in the mouse Achilles tendinopathy model. The expressions of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10) and FABP4 increased in hypercellular region, round cells chondrocyte-like cells and calcified regions in the mouse Achilles tendons post-collagenase injection. A single injection of FABP4 in mouse Achilles tendons induced histopathological changes resembling tendinopathy, with increased cell rounding, loss of collagen fiber alignment, and additionally presence of chondrocyte-like cells and calcification post-injection. The expressions of IL1-β, IL-6, TNF-α and IL-10 increased in mouse Achilles tendons post-FABP4 injection. FABP4 increased the expressions of IL10, IL6, and TNFa in human TDSCs as well as the expressions of Il1b, Il6, and Il10 in mouse TDSCs. Human tendinopathy TDSCs expressed higher level of FABP4 compared to healthy hamstring TDSCs. Besides, IL-1β increased the expression of FABP4 in mouse TDSCs. Conclusion: In conclusion, an upregulation of FABP4 is involved in excessive inflammation and pathogenesis of tendinopathy. TDSCs is a potential source of FABP4 during tendon inflammation. Translation potential of this article: FABP4 can be a potential treatment target of tendinopathy.

Background: Platelet–leukocyte aggregates (PLAs) play important roles in cardiovascular disease and sepsis. Red ginseng extract (RGE) has been well-studied for its antiplatelet and anti-inflammatory activities. However, the potential inhibitory effects of RGE on PLA have not been investigated. Methods: Six-week-old ICR mice were given oral gavage of RGE for 7 days, followed by an intraperitoneal injection of 15 mg/kg of lipopolysaccharide. Mice were euthanized 24 h later, and blood samples were collected for further analysis. Flow cytometry was utilized to sort populations of PLAs and platelet–neutrophil aggregates (PNAs). By using confocal microscopy, PNAs were validated. Morphological changes in platelets and leukocytes were visualized with scanning electron microscopy. Expressions of tissue factor (TF) and platelet factor 4 (PF4) were investigated using enzyme-linked immunosorbent assay. Results: Populations of activated platelets, PLAs and PNAs, were significantly increased with LPS-induction. Treatment with 200 and 400 mg/kg of RGE decreased platelet activation. Moreover, the populations of PLAs and PNAs were reduced. PNAs were visible in the blood of septic mice, and this was attenuated by treatment with 400 mg/kg of RGE. Morphologically, sepsisinduced platelet activation and fibrin formation in the blood. This was reduced with RGE treatment. Sepsis-induced increase in the plasma levels of TF and PF4 was also reduced with RGE treatment. Conclusion: This study shows that RGE is a potential therapeutic that reduces the activation of platelets and targets PLA and PNA formation. Detailed inhibitory mechanisms of RGE should be studied.

This case report details a rare presentation of unicentric Castleman disease (UCD), hyaline vascular type in a 22-year-old woman. The patient presented with a large, well-circumscribed mass in the paravertebral region causing back pain and shortness of breath. Diagnostic imaging and biopsy confirmed the diagnosis, and surgical excision led to a favorable outcome. This case underscores the critical need to include Castleman disease in the differential diagnosis for young adults presenting with mediastinal masses. Early recognition and surgical intervention are essential for a favorable prognosis in UCD cases.

With the digital affordances of augmented reality (AR) technologies, research has shown their value for contextualized, interactive and collaborative language learning through supporting real-world immersion. In recent years, CoSpaces has been a popular AR learning tool with an extensive library of 3D models and constructive gadgets, as well as a visual programming platform. With this tool, students can create projects of digital stories by building personalized AR artifacts, scenes, and storylines, and then share their projects in a dynamic and global community of children. This study examined the characteristics of 39 selected CoSpaces’ open projects via thematic analysis and categorization into five learning contexts: (1) art, history, culture and design, (2) STEM, (3) classroom English and everyday communication, (4) fairy tale/literature, and (5) campus tour. Furthermore, this study identified six language learning competencies derived from digital story creation: (1) discovering knowledge, (2) connecting to prior experience and knowledge, (3) conducting research, (4) problem-solving, (5) expressing and creating digitally, as well as (6) presenting, appreciating and evaluating. Digital literacy refers to the ability to use technology to find, evaluate, create, and communicate information. In addition, three major types of digital literacy skills necessary for AR digital storytelling processes have been identified, encompassing digital creativity, technoligcal proficiency, and research skills. Our results contribute to discovering educational values in developing digital language competency through AR digital story creation. Recommendations are offered for future research and for educators to design appropriate AR learning experiences.

Mental health is a state of mind influences one thinking, feeling and acting from inside and outside that are vital for children's normal growth and development. Psychological distress may results in serious mental health problem if left untreated. Hence, early diagnosis can largely improve the condition from being deteriorating. This study determined the prevalence of psychological distress and its associated risk factors among children in Penang, Malaysia. The study applied stratified multistage cluster sampling for the recruitment of children, and their socio-demographics background, health and lifestyle practices, and the prevalence and risk factors of psychological distress were succinctly studied. The study provides a fundamental platform for informing parents and policy makers about psychological distress, and the need to strategize potential health intervention for achieving optimum human well-being. • Stratified multistage cluster sampling was useful to study the prevalence and risk factors of psychological distress in a children population. • DASS-Y is robust for brief dimensional measure of depression, anxiety and stress among children.

Microplastic (MP) pollution is an emerging threat to the natural environment and has become a global problem. Plants have been used to remove heavy metals, toxic organic pollutants, and MPs from contaminated environments. However, current research on the interaction between MPs and plants has focused on the food safety evaluation of terrestrial plants, such as crops and vegetables. There are, consequently, limited studies on aquatic plants, particularly those at land–sea interfaces, and their remediation potential. To address this research gap, the present study employed a bibliometric analysis and statistics from Web of Science (WoS) data from 2017 to 2023 to detail the interactions between MPs and plants. Because the study of aquatic plants was far less extensive than that of terrestrial plants, there was a need to draw analogies regarding how different plant species interact with various microplastics. This primarily pertains to the following aspects: direct and indirect effects of MPs on plants (including combined pollution), which included growth and development; nutrient intake; and physiological, biochemical, and genetic functions. The growth environments and physiological structures of aquatic plants and terrestrial plants differed, resulted in a greater potential for the root systems of aquatic plants to capture MPs. The impacts of MPs on the microbial processes in rhizospheres and phyllospheres in aquatic plants were also assessed because these plants are often used to remediate contaminated environments and wastewater treatment in the form of natural and constructed wetlands. Therefore, we proposed the potential of phytoremediation, particularly by aquatic plants, and future research directions related to MPs in this study.

Food systems both influence and are influenced by environmental changes. Adopting a Planetary Health Diet (PHD) approach could alleviate the burden of food systems on the environment whilst increasing food security for the population. Here, we assess how the current Malaysian dietary guidelines and dietary intake compares to the PHD and investigate the relationship between the PHD, calorie intake, and food insecurity in Malaysia. We compared the percent of daily calorie intake by food group between the PHD, the Malaysian Dietary Guidelines 2020, and estimated dietary intake from publicly available data. Additionally, the Planetary Health Diet Index (PHDI) was used to compare alignment to the PHD across ethnicity, gender, and area of residence. Spearman's correlation tests assessed aggregated correlations between the PHD, daily calorie intake, and food insecurity. Compared to the PHD, the Malaysian diet lacked in legumes (3.6 % vs 23.0 % of daily calorie intake). There was an overconsumption of grains & tubers (53.1 % vs 34.0 %), added sugars (12.4 % vs 4.8 %), and meat (11.7 % vs 4.5 %). The ethnic Indian diet was most closely aligned to the PHD, with a PHDI score of 69.1 compared to the overall score of 46.2. The national dietary guidelines were well aligned to the PHD, however, a large proportion of recommended daily calorie intake was unaccounted for in the guidelines (43.4 %). Encouraging more whole grain and legumes and reducing meat and added sugar intake could help align Malaysian diets with the PHD, benefiting the health and wellbeing of people and their environment.

Illegal logging poses a significant threat to environmental conservation, contributing to deforestation, ecosystem disruption, and economic losses. Traditional detection methods, such as ground patrols and satellite imagery, are often ineffective, expensive, and time-consuming. This paper introduces a novel Unmanned Aerial Vehicles (UAV)-based IoT system for chainsaw noise detection and prevention. The system uses low-cost IoT nodes with microphones and microcontrollers to detect chainsaw sounds via a Convolutional Neural Network (CNN) model. These nodes reduce power consumption, allowing the battery to last at least 8 years. Detected chainsaw sounds are transmitted to a LoRaWAN gateway and forwarded to a cloud server. The cloud server processes the data and dispatches a drone equipped with a camera to the site. The drone streams live video to the cloud, where AI algorithms analyze the footage for human presence. If detected, the drone activates sound and light alarms to deter illegal logging. Experimental results show that IoT nodes can detect chainsaw sounds up to 100 m, with the CNN model achieving an accuracy of 99.37 % and a loss of 0.0185. Comparisons with Logistic Regression, Decision Tree, Random Forest, and SVM demonstrated the superior performance of CNN. This UAV-IoT system offers a fast, reliable, scalable, and real-time solution for detecting and preventing illegal logging. Leveraging advanced AI and IoT technologies, this system enhances environmental monitoring and conservation efforts. It represents a significant step forward in the fight against illegal logging, providing a practical, effective, and sustainable solution.

This study aims to pinpoint the key factors influencing customer loyalty and trust within the airline industry. The study investigates the impact of service quality (assessed through the SERVQUAL model), pricing fairness, and perceived value on passengers' loyalty and trust in airlines. Additionally, the research delves into the mediating influences of passenger satisfaction and airline image in this domain. The data has been collected from the passengers who have lately used air transport to travel. The respondents included 400 passengers and were targeted using a purposive sampling technique. The findings reveal a significant positive correlation between service quality, price fairness, and perceived value, as well as passengers' loyalty and trust in airlines. Furthermore, we discovered that customer satisfaction and the airline's image played crucial roles as mediators, enhancing our understanding of the core mechanisms driving loyalty and trust formation among passengers.

Mobile banking applications (apps) have become crucial in maintaining financial services accessibility during the COVID-19 pandemic. This study leverages the Unified Theory of Acceptance and Use of Technology (UTAUT) to examine Malaysian millennials' behavioral intentions toward mobile banking app adoption, aiming to aid banks in developing targeted strategies to expand their user base. Data collection was conducted from October 2020 to February 2021 during the peak of the COVID-19 pandemic. A survey was administered to 270 respondents using convenience and snowball sampling methods. The Sequential Least Square method was used for the analysis. Our findings reveal that performance expectancy, effort expectancy, trust, and personal innovativeness significantly influence mobile banking app adoption intentions, whereas social influence and facilitating conditions do not. Demographic factors also modulate these relationships to varying degrees. These insights contribute to theoretical discussions on technology adoption and offer practical guidance for banks looking to enhance their digital service offerings in a post-pandemic landscape. This study underscores the shifts in consumer behavior triggered by the pandemic and highlights the ongoing potential for digital banking growth in Malaysia.

This review analyzed the trends in conversational AI tools in ELT from January 2013 to November 2023. The study examined 32 papers, focusing on publication trends, tool types, research methods, learning outcomes, and factors influencing their use. Findings revealed a gradual increase in publications, with 4 (12%) from 2013 to 2021, 13 (41%) in 2022, and 15 (47%) in 2023. All studies (100%) were conducted in Asian EFL contexts. Among the AI chatbots, Google Assistant (25%) was the most widely used. Quasi-experimental (45%) and cross-section (41%) research designs were commonly employed. Mixed-method (50%) approaches were prevalent for data collection and analysis. Conversational AI yielded positive outcomes in affective (43%) and cognitive skills (41%). The main factors influencing user perceptions or behaviors were individual (47%) and microsystem layers (31%). Future studies should (a) include diverse contexts beyond Asia, (b) consider the use of up-to-date tools (e.g., ChatGPT), (c) employ rigorous experimental designs, (d) explore behavioral learning outcomes, and (e) investigate broader environmental factors. The systematic review enhances current knowledge of recent research trends, identifies environmental factors influencing conversational AI tools concentrating in ELT, and provides insights for future research and practice in this rapidly evolving field.

Algae are promising sources of nutritious and sustainable protein, but little is known about their metabolic health impact and acceptability as meal ingredients. This acute, randomized, controlled, five-way crossover trial compared whole algal biomasses and their corresponding protein concentrates to soy protein concentrate in terms of palatability, appetite, satiety, and metabolic response. Nineteen healthy Chinese males (21–50 years, 18.5–25.0 kg/m2) consumed noodle meals supplemented with 10 g of nori biomass/protein concentrate (NB/NC), Chlorella vulgaris biomass/protein concentrate (CB/CC) or soy protein concentrate control (CON) in randomized order. At regular intervals, blood samples were collected to measure biochemical markers, while gastrointestinal tolerance, palatability, and appetite were assessed using questionnaires and visual analog scales (VAS). Results indicated that algae-enriched meals were well-tolerated and comparable to soy in both visual appeal and smell, with NB and CC outperforming soy in aftertaste (p < 0.05). There were no significant differences between treatments in glucose, insulin, C-peptide, appetite/satiety, plasma ghrelin, and GLP-1. However, exploratory analysis of serum triglycerides revealed significant time × treatment effects (p < 0.004) and differences in incremental area under the curve (iAUC0–120, p = 0.0249). Our findings reveal that algal biomasses and protein concentrates are as comparable to soy protein concentrate in palatability, satiety, and metabolic outcomes, highlighting their potential as practical, sustainable, and nutritious ingredients.

Acute kidney injury (AKI) is primarily caused by renal ischemia-reperfusion injury (IRI), which is one of the most prevalent triggers. Currently, preventive and therapeutic measures remain limited. Ferroptosis plays a significant role in the pathophysiological process of IRI-induced AKI and is considered a key target for improving its outcomes. Silibinin, a polyphenolic flavonoid, possesses diverse pharmacological properties and is widely used as an effective therapeutic agent for liver diseases. Recent studies have reported that silibinin may improves kidney diseases, though the underlying mechanism remain unclear. In this study, we investigated whether silibinin protects against IRI-induced AKI and explored its mechanism of action. Our findings indicated that pretreatment with silibinin alleviated renal dysfunction, pathological damage, and inflammation in IRI-AKI mice. Furthermore, the results demonstrated that silibinin inhibited ferroptosis both in vivo and in vitro. Proteome microarrays were used to identify silibinin's target, and our results revealed that silibinin binds to FTH1. This binding affinity was confirmed through molecular docking, SPRi, CETSA, and DARTS. Additionally, co-IP assays demonstrated that silibinin disrupted the NCOA4-FTH1 interaction, inhibiting ferritinophagy. Finally, the inhibitory effects of silibinin on ferroptosis were reversed by knocking down FTH1 in vitro. In conclusion, our study shows that silibinin effectively alleviates AKI by targeting FTH1 to reduce ferroptosis, suggesting that silibinin could be developed as a potential therapeutic agent for managing and treating AKI.

Histopathology image segmentation and classification are essential for diagnosing and treating breast cancer. This study introduced a highly accurate segmentation and classification for histopathology images using a single architecture. We utilized the famous segmentation architectures, SegNet and U-Net, and modified the decoder to attach ResNet, VGG and DenseNet to perform classification tasks. These hybrid models are integrated with Stardist as the backbone, and implemented in a real-time pathologist workflow with a graphical user interface. These models were trained and tested offline using the ER-IHC-stained private and H&E-stained public datasets (MoNuSeg). For real-time evaluation, the proposed model was evaluated using PR-IHC-stained glass slides. It achieved the highest segmentation pixel-based F1-score of 0.902 and 0.903 for private and public datasets respectively, and a classification-based F1-score of 0.833 for private dataset. The experiment shows the robustness of our method where a model trained on ER-IHC dataset able to perform well on real-time microscopy of PR-IHC slides on both 20x and 40x magnification. This will help the pathologists with a quick decision-making process.

Complementing discourse following a February 2023 event on dietary protein needs in Southeast Asia (SEA), this symposium report summarizes the region’s protein intake, while simultaneously examining the impact of dietary shift toward complementary and alternative proteins and their health implications. It highlights the importance of protein quality in dietary evaluations, optimal intake, and sustainability, advocating for environmentally conscious protein production and innovation in future foods. Discussion points, expert opinions, national nutrition data, and relevant literature, addressing protein intake and quality, their impact on human health, and various technologies for future foods production, have been included. Despite increased protein supply in SEA, protein requirements, particularly during crucial life stages, are often unmet owing to insufficient focus on protein quality. Factoring in amino acids content and bioaccessibility are crucial for assessing nutritional requirement and sustainability evaluations, rather than solely relying on protein quantity alone. Different food sources of protein also have different key conutrients for health relevance such as vitamin B-12 and ω-3 fatty acids. Innovations in food structure, processing, and technology are key to developing nutritious, sustainable, and appealing future foods, including from complementary and alternative protein sources, while considering safety aspects, especially allergenicity. Addressing protein needs in SEA requires a dual focus on protein quantity and quality, underlining the role of public health policies and guidelines that consider key nutritional differences of animal-source and plant-based proteins. To address regional demands, future food innovations should aim at creating unique yet needful food categories or supplementing current existing sources, rather than mimicking current products.

Background/objectives: Dry eye disease (DED) and myopia are common ocular disorders. This systematic review and meta-analysis investigated the association between DED and myopia. Methods: PubMed and EMBASE were searched for articles published between 1984 and 2022. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist, and analysis was conducted using the DerSimonian–Laird random-effects model. Results: Of the 1,313 studies identified, 15 studies on DED and myopia were included. The meta-analysis revealed that the overall prevalence of subjective DED symptoms in the myopia population was 45.1 % (95 % confidence interval: 0.287–0.616). There was a significant association between DED and myopia. The myopia population had higher Ocular Surface Disease Index scores and shorter tear film breakup times than the non-myopia population. Additionally, the meta-regression analysis showed that spherical equivalent was significantly associated with the prevalence of DED symptoms in adults with myopia. Conclusion: Interventions to prevent DED are required in the myopia population. Enhancing patient awareness and self-management for DED, in addition to early screening and detection, is especially critical for younger populations who are at a higher risk of developing myopia.

Input of pollutants to estuaries is one of the major threats to marine biodiversity and fishery resources, and pharmaceuticals are one of the most important contaminants of emerging concern in aquatic ecosystems. To synthesize pharmaceutical pollution levels in estuaries over the past 20 years from a global perspective, this review identified 3229 individual environmental occurrence data for 239 pharmaceuticals across 91 global estuaries distributed in 26 countries. The highest cumulative weighted average concentration level (WACL) of all detected pharmaceuticals in estuarine water was observed in Africa (145,461.86 ng/L), with 30 pharmaceuticals reported. North America (24,316.39 ng/L) was ranked second in terms of WACL, followed by South America (20,784.13 ng/L), Asia (5958.38 ng/L), Europe (4691.23 ng/L), and Oceania (2916.32 ng/L). Carbamazepine, diclofenac, and paracetamol were detected in all continents. A total of 41 functional categories of pharmaceuticals were identified, and analgesics, antibiotics, and stimulants were amongst the most ubiquitous groups in estuaries worldwide. Although many pharmaceuticals were observed to present lower than or equal to moderate ecological risk, 34 pharmaceuticals were identified with high or very high ecological risks in at least one continent. Pharmaceutical pollution in estuaries was positively correlated with regional unemployment and poverty ratios, but negatively correlated with life expectancy and GDP per capita. There are some limitations that may affect this synthesis, such as comparability of the sampling and pretreatment methodology, differences in the target pharmaceuticals for monitoring, and potentially limited number and diversity of estuaries covered, which prompt us to standardize methods for monitoring these pharmaceutical contaminants in future global studies.

Diastolic dysfunction is increasingly common in preterm infants exposed to supplemental oxygen (hyperoxia). Previous studies in neonatal mice showed hyperoxia suppresses fatty acid synthesis genes required for proliferation and survival of atrial cardiomyocytes. The loss of atrial cardiomyocytes creates a hypoplastic left atrium that inappropriately fills the left ventricle during diastole. Here, we show that hyperoxia stimulates adenosine monophosphate-activated kinase (AMPK) and peroxisome proliferator activated receptor-gamma (PPARγ) signaling in atrial cardiomyocytes. While both pathways can regulate lipid homeostasis, PPARγ was the primary pathway by which hyperoxia inhibits fatty acid gene expression and inhibits proliferation of mouse atrial HL-1 cells. It also enhanced the toxicity of hyperoxia by increasing expression of activating transcription factor (ATF) 5 and other mitochondrial stress response genes. Silencing PPARγ signaling restored proliferation and survival of HL-1 cells as well as atrial cardiomyocytes in neonatal mice exposed to hyperoxia. Our findings reveal PPARγ enhances the toxicity of hyperoxia on atrial cardiomyocytes, thus suggesting inhibitors of PPARγ signaling may prevent diastolic dysfunction in preterm infants.

Background: Effective and rapid diagnostic strategies are required to manage antibiotic resistance in Klebsiella pneumonia (KP). This study aimed to design an artificial intelligence-clinical decision support system (AI-CDSS) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and machine learning for the rapid detection of ceftazidime-avibactam (CZA) resistance in KP to improve clinical decision-making processes. Methods: Out of 107,721 bacterial samples, 675 specimens of KP with suspected multi-drug resistance were selected. These specimens were collected from a tertiary hospital and four secondary hospitals between 2022 and 2023 to evaluate CZA resistance. We used MALDI-TOF MS and machine learning to develop an AI-CDSS with enhanced speed of resistance detection. Results: Machine learning models, especially light gradient boosting machines (LGBM), exhibited an area under the curve (AUC) of 0.95, indicating high accuracy. The predictive models formed the core of our newly developed AI-CDSS, enabling clinical decisions quicker than traditional methods using culture and antibiotic susceptibility testing by a day. Conclusions: The study confirms that MALDI-TOF MS, integrated with machine learning, can swiftly detect CZA resistance. Incorporating this insight into an AI-CDSS could transform clinical workflows, giving healthcare professionals immediate, crucial insights for shaping treatment plans. This approach promises to be a template for future anti-resistance strategies, emphasizing the vital importance of advanced diagnostics in enhancing public health outcomes.

Objectives: We studied the immunogenicity after primary and booster vaccinations of the Abdala COVID-19 vaccine, a receptor-binding domain protein subunit vaccine, in Vietnamese people by determining the level of neutralization and cross-neutralization activities against the ancestral SARS-CoV-2 and its variants and SARS-CoV-1. Methods: We performed a prospective observational study, enrolling adults aged 19-59 years in Dong Thap province, southern Vietnam, and collected blood samples from baseline until 4 weeks after the booster dose. We measured anti-nucleocapsid, anti-spike, and neutralizing antibodies against SARS-CoV-2 and assessed the cross-neutralization against 14 SARS-CoV-2 variants and SARS-CoV-1. Complementary antibody data came from Vietnamese health care workers fully vaccinated with ChAdOx1-S. Results: After primary vaccination, anti-spike antibody and neutralizing antibodies were detectable in 98.4% and 87% of 251 study participants, respectively, with neutralizing antibody titers similar to that induced by ChAdOx1-S vaccine. Antibody responses after a homologous (Abdala COVID-19) or heterologous (messenger RNA BNT162b2) booster could neutralize 14 SARS-CoV-2 variants (including Omicron) and SARS-CoV-1. Conclusions: Abdala COVID-19 vaccine is immunogenic in Vietnamese people. Enhanced antibody response after a booster dose could cross-neutralize 14 SARS-CoV-2 variants and SARS-CoV-1. Our results have added to the growing body of knowledge about the contribution of protein subunit vaccine platforms to pandemic control.

Colorectal cancer (CRC) remains a significant global health challenge, with an alarming upward trend in Asia. Early detection is crucial for improving outcomes, but there is no consensus on the optimal screening approach. Despite advances in diagnosis and therapy, CRC mortality rates remain substantial. Apoptosis and autophagy, key processes in cancer cell death, exhibit complex molecular crosstalk, particularly involving BH-3-only proteins, which present potential therapeutic targets. Recent studies suggest that manipulating these pathways could enhance cancer treatment by exploiting their regulatory networks. The B-cell lymphoma 2 (BCL-2) family proteins, central to apoptosis regulation, are implicated in CRC initiation, progression, and therapy resistance. BH3-only proteins like BIM and PUMA are linked to caspase-independent cell death, suggesting alternative pathways for CRC treatment and highlighting the potential for targeted therapies. This review provides an overview of CRC management, including the current landscape and challenges of screening programs and delves into the interplay between apoptosis and autophagy in CRC cell death. It emphasizes the critical role of BCL-2 family proteins in CRC pathogenesis and calls for future research to focus on developing non-invasive, cost-effective diagnostic biomarkers, establishing prognostic biomarker panels, and defining predictive biomarkers for existing treatments. These advancements are essential for improving screening strategies, therapeutic interventions, and ultimately, patient outcomes and quality of life.

Antibiotic resistant bacteria (ARB) with antibiotic resistance genes (ARGs) can reduce or eliminate the effectiveness of antibiotics and thus threaten human health. The United Nations Environment Programme considers antibiotic resistance the first of six emerging issues of concern. Advanced oxidation processes (AOPs) that combine ultraviolet (UV) irradiation and chemical oxidation (primarily chlorine, hydrogen peroxide, and persulfate) have attracted increasing interest as advanced water and wastewater treatment technologies. These integrated technologies have been reported to significantly elevate the efficiencies of ARB inactivation and ARG degradation compared with direct UV irradiation or chemical oxidation alone due to the generation of multiple reactive species. In this study, the performance and underlying mechanisms of UV/chlorine, UV/hydrogen peroxide, and UV/persulfate processes for controlling ARB and ARGs were reviewed based on recent studies. Factors affecting the process-specific efficiency in controlling ARB and ARGs were discussed, including biotic factors, oxidant dose, UV fluence, pH, and water matrix properties. In addition, the cost-effectiveness of the UV-based AOPs was evaluated using the concept of electrical energy per order. The UV/chlorine process exhibited a higher efficiency with lower energy consumption than other UV-based AOPs in the wastewater matrix, indicating its potential for ARB inactivation and ARG degradation in wastewater treatment. Further studies are required to address the trade-off between toxic byproduct formation and the energy efficiency of the UV/chlorine process in real wastewater to facilitate its optimization and application in the control of ARB and ARGs.

Objectives: Type 2 diabetes mellitus (T2DM) shares a complex relationship with bone metabolism and few studies investigated the effect of impaired bone health on the risk of T2DM. This study was conducted to investigate the association between hip fractures and the risk of incident T2DM. Methods: This is a retrospective cohort study using data from the real-world hip fracture cohort. Hong Kong Chinese patients aged ≥ 65 years without T2DM who were admitted to public hospitals due to a fall between 2008 and 2015 were included in the study. Patients who sustained falls with and without hip fractures were matched by propensity score (PS) at a 1:1 ratio. Competing risk regression was used to evaluate the association between hip fracture and incident T2DM, with death being the competing event. Results: A total of 23,314 hip fracture cases were matched to 23,314 controls. The median follow-up time was 5.09 years. The incidence rate of T2DM was 11.947 and 14.505 per 1000 person-years for the hip fracture and control group respectively. After accounting for the competing risk of death, the hip fracture group had a significantly lower risk of developing T2DM (HR: 0.771, 95% CI: 0.719–0.827). Similar results were observed in all subgroups after stratification by age and sex. Conclusions: Hip fracture was found to be associated with a reduced risk of T2DM. These findings provide insight into the topic of bone and glucose metabolism and prompt further research in evaluating the role of bone health in the management of T2DM.

Background: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. Methods: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians’ decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. Results: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97–1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94–1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12–1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02–1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01–1.98). Conclusion: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.

Background: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. Methods: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. Results: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64–15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04–5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45–19.15), and receiving

Objective: To evaluate the performance of maternal factors, biophysical and biochemical markers at 11–13 + 6 weeks’ gestation in the prediction of gestational diabetes mellitus with or without large for gestational age (GDM ± LGA) fetus and great obstetrical syndromes (GOS) among singleton pregnancy following in-vitro fertilisation (IVF)/embryo transfer (ET). Materials and methods: A prospective cohort study was conducted between December 2017 and January 2020 including patients who underwent IVF/ET. Maternal mean arterial pressure (MAP), ultrasound markers including placental volume, vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI), mean uterine artery pulsatility index (mUtPI) and biochemical markers including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 11–13 + 6 weeks’ gestation. Logistic regression analysis was performed to determine the significant predictors of complications. Results: Among 123 included pregnancies, 38 (30.9%) had GDM ± LGA fetus and 28 (22.8%) had GOS. The median maternal height and body mass index were significantly higher in women with GDM ± LGA fetus. Multivariate logistic regression analysis demonstrated that in the prediction of GDM ± LGA fetus and GOS, there were significant independent contributions from FI MoM (area under curve (AUROC) of 0.610, 95% CI 0.492–0.727; p = 0.062) and MAP MoM (AUROC of 0.645, 95% CI 0.510–0.779; p = 0.026), respectively. Conclusion: FI and MAP are independent predictors for GDM ± LGA fetus and GOS, respectively. However, they have low predictive value. There is a need to identify more specific novel biomarkers in differentiating IVF/ET pregnancies that are at a higher risk of developing complications.

The deep cement mixing (DCM) is used to improve the capacity and reduce the settlement of the soft ground by forming cemented clay columns. The investigation on the mechanical behaviour of the DCM samples is limited to either laboratory-prepared samples or in-situ samples under unconfined compression. In this study, a series of drained and undrained triaxial shearing tests was performed on the in-situ cored DCM samples with high cement content to assess their mechanical behaviours. It is found that the drainage condition affects significantly the stiffness, peak and residual strengths of the DCM samples, which is mainly due to the state of excess pore water pressure at different strain levels, i.e. being positive before the peak deviatoric stress and negative after the peak deviatoric stress, in the undrained tests. The slope of the failure envelope changes obviously with the confining pressures, being steeper at lower stress levels and flatter at higher stress levels. The strength parameters, effective cohesion and friction angle obtained from lower stress levels (c′0 and φ′0) are 400 kPa and 58°, respectively, which are deemed to be true for design in most DCM applications where the in-situ stress levels are normally at lower values of 50–200 kPa. Additionally, the computed tomography (CT) scanning system was adopted to visualize the internal structures of DCM samples. It is found that the clay pockets existing inside the DCM samples due to uneven mixing affect markedly their stress-strain behaviour, which is one of the main reasons for the high variability of the DCM samples.

In current dual porosity/permeability models, there exists a fundamental assumption that the adsorption-induced swelling is distributed uniformly within the representative elementary volume (REV), irrespective of its internal structures and transient processes. However, both internal structures and transient processes can lead to the non-uniform swelling. In this study, we hypothesize that the non-uniform swelling is responsible for why coal permeability in experimental measurements is not only controlled by the effective stress but also is affected by the adsorption-induced swelling. We propose a concept of the swelling triangle composed of swelling paths to characterize the evolution of the non-uniform swelling and serve as a core link in coupled multiphysics. A swelling path is determined by a dimensionless volumetric ratio and a dimensionless swelling ratio. Different swelling paths have the same start and end point, and each swelling path represents a unique swelling case. The swelling path as the diagonal of the triangle represents the case of the uniform swelling while that as the two perpendicular boundaries represents the case of the localized swelling. The paths of all intermediate cases populate inside the triangle. The corresponding relations between the swelling path and the response of coal multiphysics are established by a non-uniform swelling coefficient. We define this method as the triangle approach and corresponding models as swelling path-based ones. The proposed concept and models are verified against a long-term experimental measurement of permeability and strains under constant effective stress. Our results demonstrate that during gas injection, coal multiphysics responses have a close dependence on the swelling path, and that in both future experiments and field predictions, this dependence must be considered.

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous lesion in the oral cavity, commonly results from the Areca nut chewing habit. Arecoline, the main component of Areca nut, is known to stimulate the activation of myofibroblasts, which can lead to abnormal collagen I deposition. Meanwhile, Resveratrol is a non-flavonoid phenolic substance that can be naturally obtained from various berries and foods. Given that resveratrol has significant anti-fibrosis traits in other organs, but little is known about its effect on OSF, this study aimed to investigate the therapeutic impact of resveratrol on OSF and its underlying mechanism. Materials and methods: The cytotoxicity of resveratrol was tested using normal buccal mucosal fibroblasts (BMFs). Myofibroblast phenotypes such as collagen contractile, enhanced migration, and wound healing capacities in dose-dependently resveratrol-treated fBMFs were examined. Results: Current results showed that arecoline induced cell migration and contractile activity in BMFs as well as upregulated the expressions of α-SMA, type I collagen, and ZEB1 markers. Resveratrol intervention, on the other hand, was shown to inhibit arecoline-induced myofibroblast activation and reduce myofibroblast hallmarks and EMT markers. Additionally, resveratrol was also demonstrated to restore the downregulated miR-200a in the arecoline-stimulated cells. Conclusion: In a nutshell, these findings implicate that resveratrol may have an inhibitory influence on arecoline-induced fibrosis via the regulation of miR-200a. Hence, resveratrol may be used as a therapeutic strategy for OSF intervention.

Background/purpose: Periodontitis is an inflammatory condition of the tooth-supporting structures triggered by the host's immune response towards the bacterial deposits around the teeth. It is well acknowledged that pro-inflammatory interleukin (IL)-6, IL-8, MCP-1 as well as the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, are the key modulators in the activation of this response. Erbium-doped yttrium-aluminium-garnet (Er:YAG) laser, a solid-state crystal laser have been commonly used in the treatment of periodontal diseases. However, little is understood about the molecular mechanism of the Er:YAG laser, especially in targeting the host immune response brought on by periodontal pathogens. Hence, the current study focused on the protective effects of Er:YAG laser on periodontitis in-vitro in terms of pro-inflammatory cytokines, chemokines and NLRP3 inflammasome expressions. Materials and methods: Human periodontal ligament fibroblast (PDLFs) were first stimulated with lipopolysaccharides (LPS) from P. gingivalis (Pg-LPS) to simulate periodontitis. Cells were then irradiated with Er:YAG laser of ascending energy densities (3.6–6.3 J/cm2), followed by cell proliferation and wound healing assay. Next, the effects of Er:YAG laser on the expressions of IL-6, IL-8, MCP-1, NLRP3, and cleaved GSDMD were examined. Results: Pg-LPS was found to reduce cell's proliferation rate and wound healing ability in PDLFs and these were rescued by Er:YAG laser irradiation. In addition, LPS stimuli resulted in a marked upregulation in the secretion of IL-6, IL-8 and MCP-1 as well as the mRNA and protein expression of NLRP3 and cleaved-GSDMD protein whereas Er:YAG laser suppressed the elicited phenomena. Conclusion: To our knowledge, this is the first study to look into the laser's implication on the NLRP3 inflammasome in periodontitis models. Our study reveals a crucial role of Er:YAG laser in ameliorating periodontitis in-vitro through the modulation of IL-6, IL-8, MCP-1 and the NLRP3 inflammasome and highlights that the control of the NLRP3 inflammasome may become a potential approach for periodontitis.

Treatment of dye polluted water using sustainable and efficient approaches is essential to mitigate the detrimental effects of dyes. The present work reports on the adsorption effectiveness of a graphene-based adsorbent configured into a practical engineering structure, namely three-dimensional graphene oxide integrated with chitosan biopolymer (3D-GCB). This unique graphene configuration enabled its application in continuous fixed-bed adsorption of Metanil Yellow (MY) and Remazol Black B (RBB) dyes from polluted water for the first time. The breakthrough attributes of the fixed-bed of 3D-GCB were established in terms of bed depth (3 – 5 cm), influent concentration (100 – 200 mg/L for MY and 100 – 300 mg/L for RBB) and feed flowrate (2 – 4 mL/min). The greatest bed adsorption capacities attained were 157.06 and 247.96 mg/g for MY and RBB, respectively. The column parameters for obtaining these results were 5 cm bed depth, 2 mL/min feed flowrate, and 150 and 200 mg/L influent concentrations respectively for MY and RBB. The fixed-bed performance of the 3D-GCB was well correlated to the Thomas and Yoon-Nelson models, and the corresponding kinetic properties were determined. Furthermore, the higher affinity of the 3D-GCB for RBB as compared to MY was elucidated based on the ionic strengths of the dye molecule. The utilisation of sustainable and renewable raw materials, such as graphite and chitosan, have resulted in a 3D-GCB production cost of approximately RM 10.72 per gram. This work revealed the suitability of 3D-GCB as the state-of-the-art graphene composite for continuous adsorption of anionic dyes, specifically MY and RBB.