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Background: Neoadjuvant use of immune checkpoint inhibitors (ICIs) before liver resection results in pathological tumour regression in patients with hepatocellular carcinoma. We aimed to describe the characteristics of pathological responses after preoperative ICI therapy for hepatocellular carcinoma and to evaluate the association between the depth of tumour regression and relapse-free survival., Methods: In this cross-trial, patient-level analysis, we performed a pooled analysis of data from patients with hepatocellular carcinoma receiving ICI therapy before liver resection as part of a global collaborative consortium (NeoHCC) of five phase 1 and 2 clinical trials and standardised observational protocols conducted in 12 tertiary referral centres across the USA, UK, and Taiwan. Eligible patients were adults (aged ≥18 years) diagnosed with hepatocellular carcinoma by tissue core biopsy before treatment initiation, a Liver Imaging Reporting and Data System score of 5 on imaging, or both, with an Eastern Cooperative Oncology Group performance status score of 0-1, and no extrahepatic spread or previous ICI treatment. Pathological response was measured as the percentage of non-viable tumour in the resected surgical specimen, with major pathological response corresponding to at least 70% tumour regression and pathological complete response corresponding to 100% tumour regression. We correlated pathological response with radiological overall response using RECIST criteria (version 1.1) and relapse-free survival, and evaluated the threshold of tumour regression that could be optimally associated with relapse-free survival., Findings: At data cutoff on Jan 31, 2024, 111 patients were included in the study, of whom data on pathological response were available for 104 (94%) patients. Patients received treatment from Oct 5, 2017, to Nov 15, 2023, mostly ICI combinations (76 [69%]), for a median of 1·4 months (IQR 0·7-2·9). 87 (78%) patients were men and 24 (22%) were women. Most patients had underlying viral chronic liver disease (73 [66%]) and Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (61 [55%]), without portal vein thrombosis (87 [78%]). We observed major pathological response in 33 (32%) patients and pathological complete response in 19 (18%) patients. Radiological overall response was associated with major pathological response, with 23 (74%) of 31 patients with radiological response showing major pathological response compared with ten (14%) of 73 patients without radiological response (p<0·0001). However, ten (30%) of 33 major pathological responses were not predicted by radiological response. After a median follow-up of 27·2 months (95% CI 22·3-32·1), median relapse-free survival for the whole cohort was 43·6 months (95% CI 28·3-not evaluable). Relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable-not evaluable] vs 28·3 months [12·8-43·8]; hazard ratio 0·26 [0·10-0·66]; p=0·0024) and in patients with pathological complete response than in those who did not have a pathological complete response (NR [95% CI not evaluable-not evaluable] vs 32·8 months [15·0-50·5]; 0·19 [0·05-0·78]; p=0·010). Unbiased recursive partitioning of the cohort for the risk of relapse, death, or both identified a threshold of 90% as the optimal cutoff of pathological tumour regression to predict improved relapse-free survival., Interpretation: The extent of tumour regression following neoadjuvant ICI therapy could identify patients with improved relapse-free survival following liver resection. The threshold of at least 90% tumour regression should be validated for its surrogate role for relapse-free survival in phase 3 randomised controlled trials., Funding: None., Competing Interests: Declaration of interests AD received educational support for congress attendance and consultancy fees from Roche; and speaker fees from Roche, AstraZeneca, Eisai, and Chugai. SS reports consultancy fees from Eisai and Pfizer. CAMF reports speaker fees from EISAI. CC received consulting fees from Eisai and MSD; speaker fees from Eisai, MSD, AstraZeneca, and Ipsen; and travel expenses from Roche. SCW received speaker fees from AstraZeneca and Intercept; and research funding (to their institution) from Boehringer Ingelheim. AC received consulting fees from Regeneron, MSD, Bristol Myers Squibb, AstraZeneca, and Roche; speaker fees from Sanofi–Regeneron, MSD, Roche, and AstraZeneca; and travel expenses from MSD, Roche, and Sanofi–Regeneron. CH received speaker fees from AstraZeneca, Bristol Myers Squibb–ONO, and Roche; and research funding (to their institution) from National Science and Technology Council (Taiwan) and Bristol Myers Squibb–ONO. MB received consulting fees from AstraZeneca and Eisai. MY received speaker fees from Genentech, Exelixis, AstraZeneca, Replimune, Hepion, and Lantheus; grant or research support (to their institution) from the National Cancer Institute–National Institutes of Health, Fibrolamellar Cancer Foundation, Cancer Research Institute, Bristol Myers Squibb, Exelixis, Incyte, and Genentech; and is cofounder with equity of Adventris Pharmaceuticals. TUM received consulting fees from Avammune Therapeutics and ONO; participated on boards for Rockefeller, AbbVie, Celldex, Regeneron, AbbVie, Merck, Bristol-Meyers Squibb, Boehringer Ingelheim, Atara, AstraZeneca, Genentech, Chimeric, Glenmark, Simcere, Surface, G1 Therapeutics, NGM Bio, DBV Technologies, Arcus, Fate, EMD Serono, and Astellas; and received research funding (to their institution) from Regeneron, Genentech, Bristol Myers Squibb, Merck, and Boehringer Ingelheim. DJP received lecture fees from Roche, Bristol Myers Squibb, Eisai, and Boston Scientific; travel expenses from Roche, Bristol Myers Squibb, and MSD; consulting fees for Mina Therapeutics, Eisai, Roche, Avamune, Da Volterra, Mursla, H3B, Ipsen, Boston Scientific, Starpharma, Exact Sciences, and AstraZeneca; participated on advisory boards for Mina Therapeutics, Eisai, Roche, Avamune, Da Volterra, Mursla, H3B, Ipsen, LIfT Biosciences, Exact Sciences, and AstraZeneca; and received research funding (to their institution) from MSD, GSK, and Bristol Myers Squibb. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis ( P =0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P =0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis ( P =0.007, log-rank test) and higher IPI score (63% vs. 30%, P =0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD ( MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH , SLC1A1 , CD96 , INPP4B , and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN . Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Suicide and suicidal behaviour strongly contribute to overall male youth mortality. An understanding of worldwide data contextualises suicide and suicidal behaviour in young men within any given country., Method: Members and colleagues of the World Federation of Societies of Biological Psychiatry's Task Force on Men's Mental Health review the relevant data from several regions of the world. The review identifies notable findings across regions of relevance to researchers, policymakers, and clinicians., Results: Male suicide and suicidal behaviour in adolescence and emerging adulthood within North America, Latin America and the Caribbean, Europe, the Mediterranean and the Middle East, Continental Africa, South Asia, East Asia, China, and Oceania share similarities as well as significant points of divergence., Conclusions: International data provide an opportunity to obtain a superior understanding of suicide and suicidal behaviour amongst young men.

Background: Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers., Methods: A 3 + 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety., Results: Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively., Conclusion: The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation., Clinicaltrials.gov Identifier: NCT03162510., (© The Author(s) 2024. Published by Oxford University Press.)

Target and distractor templates play a pivotal role in guiding attentional control during visual search, with the former template facilitating target search and the latter template leading distractor suppression. We first investigated whether task-irrelevant colors could earn their value through color-target contingency in the training phase and bias attention when they became a distractor in search for a singleton shape during the test phase. Colors provided useful information for target selection, with high- and low-informational values, respectively, in Experiments 1 and 2. Experience-based attentional biases were observed in the first half of the former experiment, and null results were observed in the latter. Experiment 3 verified whether the null results were elicited because the response-relevant feature inside of the singleton shape was also a singleton. Colors were task defined in the training phase, and the test display was the same as that used in Experiment 2. Experience-based attentional biases were observed in the first half of the test phase. In Experiment 4, we tested whether decreasing the consistency of distractor processing can lengthen the duration of experience-based attentional biases by increasing the number of possible response-relevant features inside of the colored distractor. The results showed experience-based attentional biases throughout the test phase. The results highlight the ideas that the informational value provided by a feature dimension for facilitating target selection can modify a target template and that the consistency of rejecting a distractor feature can play a role in the formation of a distractor template., (© 2024. The Psychonomic Society, Inc.)

Objective: Many people at risk of suicide do not actively seek help. Suicide prevention efforts need to involve the general public to provide appropriate support to those in need. It is important to investigate the intention to help those at risk of suicide and the factors associated with helping intentions in the general population. We aimed to assess the intention to help people at risk and associated factors using a national representative sample., Method: We conducted a national telephone survey of 1,087 Taiwanese adults and collected data regarding participants' socio-demographic characteristics, mental health status, helping intentions, misconceptions about suicide, and attitudes toward suicide and suicide prevention., Results: The prevalence of high intentions to help people at risk of suicide was 56.5%. Helping intentions did not differ by sex, educational level, employment status, marital status, or mental health status. Those with high helping intentions were younger, less likely to have misconceptions about suicide or agree that suicide is a personal choice, and more likely to believe that suicide is preventable and support suicide prevention measures., Conclusions: Suicide prevention education programs aimed to enhance helping intentions may usefully target debunking misconceptions about suicide and cultivating positive attitudes toward suicide prevention.

Introduction: Proton pump inhibitor (PPI) has revolutionized the treatment of erosive esophagitis (EE) in the past few decades. However, roughly 30-40% of the patients, especially those with severe EE (Los Angeles Grade C/D), remain poorly responsive to this medication. Novel drugs have been formulated and/or repurposed to address this problem., Areas Covered: This review highlights novel drugs that have been investigated for use in EE, such as mucosal protectants, prokinetics, transient lower esophageal sphincter relaxation (TLESR) reducers, novel PPIs, and the new potassium-competitive acid blocker (PCAB). Studies have demonstrated that PCAB has promising results (efficacy and safety) compared to PPI for the healing of EE, especially in severe diseases., Expert Opinion: PCAB has gained interest in recent years, with pharmacokinetics and pharmacodynamics properties surpassing PPI. Although recent data on PCABs, which comprised mainly of Vonoprazan, have shown promising results, more randomized controlled trials for other PCAB drugs are needed to elucidate and confirm the superiority of this drug class to PPI, the current first-line treatment of EE.

Background: This SRMA reviewed and assessed the changes in the severity of disorders of gut-brain interaction (DGBI) symptoms during the COVID-19 pandemic, and evaluated factors associated with symptom severity changes., Methods: Electronic databases were searched until February 2024, for articles reporting on changes in symptom severity in DGBI patients during the COVID-19 pandemic. The proportion of DGBI patients who reported a change in their symptom severity were pooled using a random-effects model, and subgroup analyses were conducted to assess the effect of socio-cultural modifiers on symptom severity in DGBI., Key Results: Twelve studies including 3610 DGBI patients found that 31.4% (95% CI, 15.9-52.5) of DGBI patients experienced symptom deterioration, while 24.3% (95% CI, 10.2-47.5) experienced improvement. Countries with high gross domestic product (GDP) had a 43.5% (95% CI, 16.3-75.2) likelihood of symptom deterioration, compared to 9.2% (95% CI, 1.4-42.2) in lower GDP countries. Similarly, countries with low COVID fatality rates had a 60.1% (95% CI, 19.7-90.3) likelihood of symptom deterioration, compared to 18.3% (95% CI, 7.8-36.9) in higher fatality rate countries. Countries with lenient COVID policies had a 58.4% (95% CI, 14.1-92.3) likelihood of symptom deterioration, compared to 19% (95% CI, 8.2-38.1) in countries with stricter policies. Patients in high vaccine hesitancy countries had a 51.4% (95% CI, 19.5-82.2) likelihood of symptom deterioration, compared to 10.6% (95% CI, 2.7-33.4) in low vaccine hesitancy countries., Conclusions & Inferences: This meta-analysis reveals that a significantly higher proportion of DGBI patients experienced deterioration of symptoms during the COVID-19 pandemic. Various sociocultural, economic and environmental factors potentially modify the effects of the COVID-19 pandemic on DGBI., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Purpose: The Palliative Care Outcomes Collaboration (PCOC) aims to enhance patient outcomes systematically. However, identifying crucial items and accurately determining PCOC phases remain challenging. This study aims to identify essential PCOC data items and construct a prediction model to accurately classify PCOC phases in terminal patients., Methods: A retrospective cohort study assessed PCOC data items across four PCOC phases: stable, unstable, deteriorating, and terminal. From July 2020 to March 2023, terminal patients were enrolled. A multinomial mixed-effect regression model was used for the analysis of multivariate PCOC repeated measurement data., Results: The dataset comprised 1933 terminally ill patients from 4 different hospice service settings. A total of 13,219 phases of care were analyzed. There were significant differences in the symptom assessment scale, palliative care problem severity score, Australia-modified Karnofsky performance status, and resource utilization groups-activities of daily living among the four PCOC phases of care. Clinical needs, including pain and other symptoms, declined from unstable to terminal phases, while psychological/spiritual and functional status for bed mobility, eating, and transfers increased. A robust prediction model achieved areas under the curves (AUCs) of 0.94, 0.94, 0.920, and 0.96 for stable, unstable, deteriorating, and terminal phases, respectively., Conclusions: Critical PCOC items distinguishing between PCOC phases were identified, enabling the development of an accurate prediction model. This model enhances hospice care quality by facilitating timely interventions and adjustments based on patients' PCOC phases., (© 2024. The Author(s).)

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Disorders of gut-brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world., Methods: We performed an ecological study utilizing peer-reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized β coefficients with 95% confidence intervals (CI)., Key Results: The regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (β = -0.57, 95% CI: -0.92, -0.22, p = 0.002) and happiness scores (β = -0.433 95% CI: 0.821, -0.065, p = 0.023), while being positively associated with H. pylori prevalence (β = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (β = -0.50, 95% CI: -0.86, -0.13, p = 0.01) and happiness scores (β = -0.497, 95% CI: -0.863, -0.132, p = 0.01), while being positively associated with H. pylori prevalence (β = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (β = -0.43, 95% CI: -0.82, 0.038, p = 0.033) and suicide rates (β = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (β = -0.40, 95% CI: -0.79, -0.014, p = 0.043) and happiness scores (β = -0.390, 95% CI: -0.778, -0.003, p = 0.049)., Conclusions & Inferences: Utilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio-cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Purpose: Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (atezo-bev). This study investigates the outcome of these patients and the histopathology of the residual tumors., Patients and Methods: The IMbrave150 study's atezo-bev group was analyzed. PR or SD per RECIST v1.1 lasting more than 6 months was defined as durable. For histologic analysis, a comparable real-world group of patients from Japan and Taiwan who had undergone resection of residual tumors after atezo-bev was investigated., Results: In the IMbrave150 study, 56 (77.8%) of the 72 PRs and 41 (28.5%) of the 144 SDs were considered durable. The median overall survival was not estimable for patients with durable PR and 23.7 months for those with durable SD. The median progression-free survival was 23.2 months for patients with durable PR and 13.2 months for those with durable SD. In the real-world setting, a total of 38 tumors were resected from 32 patients (23 PRs and nine SDs) receiving atezo-bev. Pathologic complete responses (PCRs) were more frequent in PR tumors than SD tumors (57.7% v 16.7%, P = .034). PCR rate correlated with time from atezo-bev initiation to resection and was 55.6% (5 of 9) for PR tumors resected beyond 8 months after starting atezo-bev, a time practically corresponding to the durable PR definition used for IMbrave150. We found no reliable radiologic features to predict PCR of the residual tumors., Conclusion: Durable PR patients from the atezo-bev group showed a favorable outcome, which may be partly explained by the high rate of PCR lesions. Early recognition of PCR lesions may help subsequent treatment decision.

Introduction: The beneficial effects of using antidepressants in improving functional dyspepsia (FD) symptoms have been reported in previous meta-analyses; however, the results have not been conclusive. The aim was to perform an updated meta-analysis coupled with trial sequential analysis (TSA) to assess the efficacy of the use of any antidepressants in the treatment of FD in adults., Methods: Electronic databases were searched up to March 2024 for randomized controlled trials (RCTs) recruiting adults with FD. Data of overall symptoms improved between the antidepressants and placebo groups was pooled to obtain risk ratio (RR) employing the random-effects model. The effect of random errors was evaluated with TSA. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence. Analyses were performed using STATA version 16.0., Results: Nine RCTs with 924 patients met the eligible criteria. The RRs of FD symptoms improving with any antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors were (n = 9, RR = 1.30 [95% CI, 1.02-1.67]), (n = 5, RR = 1.41 [95% CI, 1.07-1.85]) and (n = 2, RR = 0.97 [95% CI, 0.72-1.29]), respectively. TSA demonstrated conclusive evidence for the beneficial effect of TCAs. The number needed to treat (NNT) with any depressants and TCAs were 11 (95% CI, 7-36) and 6 (95% CI, 4-15), respectively. The certainty of the evidence for an effect of TCAs was that of moderate GRADE quality. The benefit, however, was limited to the western population (n = 3, RR = 1.43 [95% CI, 1.04-1.96]) and did not extend to the Asian population (n = 2, RR = 1.32 [95% CI, 0.75-2.32]). Conversely, antidepressant-using patients experienced adverse events more frequently. However, no statistically significant association was found between TCAs and any adverse events (n = 3; RR = 1.36 [95% CI, 0.91-2.04])., Conclusion: Evidence was obtained suggesting TCAs can be an effective alternative in the treatment of FD, but more evidence from high-quality large trials is required to support their use, especially in the Asian population., (© 2024. Indian Society of Gastroenterology.)

Background: Research on microplastics has largely focused on the environment and marine organisms until recently. A growing body of evidence has detected microplastics in human organs and tissues, with their exact entry routes being unclear and their potential health effects remain unknown. This scoping review aimed to characterise microplastics in human tissues and organs, examine their entry routes and addressing gaps in research analytical techniques., Methods: Eligibility criteria included English language full text articles, in-vivo human studies only, and searching the databases using pre-defined terms. We based our analysis and reporting on the PRISMA guideline and examined the quality of evidence using the risk of bias assessment tool., Results: Of 3616 articles screened, 223 evaluated and 26 were eventually included in this review. Nine were high risk for bias, three were unclear risk and the rest low risk for bias. Microplastics were detected in 8/12 human organ systems including cardiovascular, digestive, endocrine, integumentary, lymphatic, respiratory, reproductive and urinary. Microplastics were also observed in other human biological samples such as breastmilk, meconium, semen, stool, sputum and urine. Microplastics can be characterised based on shape, colours, and polymer type. Potential entry routes into human included atmospheric inhalation and ingestion through food and water. The extraction techniques for analysis of microplastics in human tissues vary significantly, each offering distinct advantages and limitations., Conclusions: Microplastics are commonly detected in human tissues and organs, with distinct characteristics and entry routes, and variable analytical techniques exist., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: Abdominal bloating (AB) is a common, bothersome symptom that negatively affects most adults. Although social support may help people suffering from AB, limited validated questionnaire is available. This study aimed to validate the newly developed Abdominal Bloating Social Support (SS-Bloat) scale for the Malaysian context., Method: We conducted a cross-sectional study in which we used purposive sampling and a self-administered questionnaire. Based on the literature review, experts' input and in-depth interviews, new items were generated for SS-Bloat scale. Content validity was assessed by experts and pre-tested with 30 individuals with AB. Construct validity was determined based on exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Reliability was determined based on Cronbach's alpha and composite reliability (CR)., Results: During the development stage, eight items were generated for SS-Bloat scale and remained the same after content validity and pre-testing. A total of 152 participants with a mean age of 31.27 years old (68.3% female, 32.7% male) completed the questionnaire. Based on the EFA, three problematic items were removed. The total variance explained was 35.6% with acceptable reliability (α = 0.66). The model was then tested using CFA. The initial model did not fit the data well. After several model re-specifications, the final measurement model of SS-Bloat scale fit the data well with acceptable fit indices (comparative fit index [CFI] = 0.994 and Tucker-Lewis index [TLI] = 0.984). The CR was satisfactory with value of 0.84., Conclusion: SS-Bloat scale was deemed valid and reliable for assessing the level of social support among AB patients. The questionnaire can be useful for both research studies and clinical purposes, as it is easy to use., Competing Interests: Conflict of Interest: None., (© Penerbit Universiti Sains Malaysia, 2024.)

Background and Aim: Measurements of gastric emptying and accommodation for alternative test-meal protocol during gastric emptying scintigraphy (GES), such as high-calorie nutrient drinks, are not fully established. We aimed to compare the effects of standardized egg-white meal (EWM) versus high-calorie nutrient drink (Vital ® ; Abbott Laboratories) on global GES parameters and intragastric meal distribution at immediate scan (IMD 0h )., Methods: Of 84 screened participants, 60 asymptomatic healthy Asian population (38 females; 24.0 ± 1.5 years; 23.8 ± 2.6 kg/m 2 ) were recruited in this 2 × 2 (AB/BA) crossover trial. Participants were randomized to a 4-h GES with 99m Tc-radiolabeled EWM (~255.8 kcal), followed by a 200 mL Vital ® (300 kcal), or vice versa, separated by a 2-week washout period. Global meal retention (GMR), power-exponential model emptying parameters (half-emptying [T 1/2 ], lag phases [T lag2% , T lag5% , T lag10% ]), and IMD 0h were determined and compared., Results: GMRs for both test meals were within the international standard references for solid GES. Compared to EWM, Vital ® exhibited significantly lower GMRs (faster emptying) from 0.5 to 3 h (all P < 0.001) but comparable at 4 h (P = 0.153). Similar observations were found for the model-based T 1/2 and the different T lag thresholds (all P < 0.001). Furthermore, IMD 0h was found to be lower with Vital ® , indicating lower gastric accommodation (faster antral filling) immediately post-ingestion (P < 0.001). Both test meals showed significant moderate-to-strong positive associations at the late-phase GE (GMR 2-4 h, T 1/2 ) (all P < 0.05)., Conclusions: Overall, Vital ® is an acceptable alternative test meal to the EWM for GES; however, exercise caution when interpreting early-phase GE. The normative values for global GES parameters and IMD 0h are also established., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: IDH2 mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear., Methods: In this study, we aimed to elucidate the roles of IDH2 mutation in the development and progression of MF by transcriptomic and molecular techniques using the Idh2 R172K transgenic mice., Results: We found that thrombopoietin (TPO)-overexpressed Idh2 R172K ( Idh2 R172K + TPO) mice had accelerated progression to MF, compared with TPO-overexpressed Idh2- wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced. Single-cell transcriptomes of the marrow cells in early MF showed that S100a8/a9 expression was mainly confined to neutrophil progenitors in the WT + TPO mice, but highly expressed in several types of myeloid precursor cells, including the megakaryocyte progenitors in the Idh2 R172K + TPO group. Furthermore, Idh2 R172K mice at age of 18 months had larger spleens, increased S100a8/a9-Tlr4 expression, and elevated serum S100a8/a9 levels compared with WT mice. PMF patients with IDH2 mutations had higher bone marrow plasma S100A8/A9 levels than those without IDH2 mutations., Conclusion: Overall, our findings showed that IDH2 mutation induced proinflammatory effects, which further exacerbated MF, as evidenced by the increase in S100a8/a9 levels and NFκB hyperactivation in Idh2 R172K + TPO mice., Competing Interests: The authors declare they have no conflicts of interest., (© 2024 The Author(s). eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Competing Interests: Y-TC and S-SC are supported by grants from Taiwan National Science and Technology Council (NSTC 112-2314-B-002-213-MY3). S-SC is supported by Ministry of Health and Welfare (M1202303) and Ministry of Education (113M316, 112M311), Taiwan. S-SC is affiliated with the Population Health and Welfare Research Center from the Featured Areas Research Center Program within the framework of the Higher Education SPROUT Project by the Ministry of Education (MOE), Taiwan (grant number NTU-113L900401). PSFY is supported by the Strategic Topic Grants Scheme (STG4/M-701/23-N) and a grant from the Hong Kong Research Grants Council General Research Fund (17606521).

Egalitarian gender attitudes are linked to increased support for same-sex marriage, with previous studies mainly focusing on Western countries. Limited existing research from Asian countries often relied on non-representative, convenient samples. Taiwan, the first Asian country to legalize same-sex marriage in 2019, offers a valuable context. Since surveys before 2020 lacked questions on attitudes toward same-sex marriage, we utilized the 2020 PSFD data for a cross-sectional analysis. Logistic regression analyses were conducted to explore the relationship between gender attitudes (assessed through six questions) and attitudes toward same-sex marriage, along with examining the moderation effects of socio-demographic variables. The results revealed significant associations between embracing egalitarian gender attitudes and increased support for same-sex marriage (adjusted odds ratio [aOR] ranged from 1.34 to 2.08, 95% CI = [1.15, 2.45]). Moderation analysis indicated that this connection appeared to be more pronounced among younger individuals, those who were not currently married, and those with higher educational attainment. Individuals who are older, less educated, or married and hold negative views on gender equality should be targeted for efforts to enhance their support for same-sex marriage. Advocating for gender equality aligns with principles of equality, nondiscrimination, and recognizing fundamental rights for all, irrespective of sexual orientation.

East Asian countries are known to take a more permissive attitude towards suicide. However, the nuanced beliefs fostering these attitudes remain unexplored. This study aimed to examine socio-demographic and clinical factors associated with the three normative beliefs on suicide in Taiwan - suicide as human rights, suicide as an individual choice, and that suicide is irrational - and the association of these beliefs with supportive attitudes towards governmental suicide prevention measures. A nationally representative survey, based on calls to landlines and mobile phones, was conducted in 2020 with a sample size of 1,087. Logistic regression analyses were employed to examine the associations between socio-demographic variables, mental health status, normative suicide beliefs, and attitudes towards suicide prevention. We found that the prevalence rates for the three normative beliefs were 55.3% for human rights, 26.7% for individual choice, and 73.7% for irrationality, respectively. Human rights belief was more prevalent among younger, unmarried, and highly educated individuals. Individual choice belief was more common among the younger, those in the 'other' marital group, less educated individuals, and those without mental conditions. The irrationality belief was more likely to be endorsed by the unemployed group. Regardless of participants' normative suicide beliefs, a significant majority (89.0%) supported governmental investment in suicide prevention. However, human rights and individual choice beliefs were associated with diminished support for governmental suicide prevention measures (aOR = 0.6, p  = 0.003, and aOR = 0.6, p  = 0.005, respectively). Taiwanese society overwhelmingly supports governmental suicide prevention measures, suggesting a leaning towards hard paternalism. However, those who believed that suicide is a human right and individual choice were less likely to support governmental suicide prevention efforts. Our findings suggest that health education addressing these two normative beliefs, particularly among the youth and unmarried individuals, could be potential strategies in future suicide prevention measures.

Objective: A definitive diagnosis of gastroesophageal reflux disease (GERD) depends on endoscopic and/or pH-study criteria. However, high resolution manometry (HRM) can identify factors predicting GERD, such as ineffective esophageal motility (IEM), esophago-gastric junction contractile integral (EGJ-CI), evaluating esophagogastric junction (EGJ) type and straight leg raise (SLR) maneuver response. We aimed to build and externally validate a manometric score (Milan Score) to stratify the risk and severity of the disease in patients undergoing HRM for suspected GERD., Methods: A population of 295 consecutive patients undergoing HRM and pH-study for persistent typical or atypical GERD symptoms was prospectively enrolled to build a model and a nomogram that provides a risk score for AET > 6%. Collected HRM data included IEM, EGJ-CI, EGJ type and SLR. A supplemental cohort of patients undergoing HRM and pH-study was also prospectively enrolled in 13 high-volume esophageal function laboratories across the world in order to validate the model. Discrimination and calibration were used to assess model's accuracy. Gastroesophageal reflux disease was defined as acid exposure time >6%., Results: Out of the analyzed variables, SLR response and EGJ subtype 3 had the highest impact on the score (odd ratio 18.20 and 3.87, respectively). The external validation cohort consisted of 233 patients. In the validation model, the corrected Harrel c-index was 0.90. The model-fitting optimism adjusted calibration slope was 0.93 and the integrated calibration index was 0.07, indicating good calibration., Conclusions: A novel HRM score for GERD diagnosis has been created and validated. The MS might be a useful screening tool to stratify the risk and the severity of GERD, allowing a more comprehensive pathophysiologic assessment of the anti-reflux barrier., Trial Registration: ClinicalTrials.gov (Identifier: NCT05851482)., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis. Over the past decade, significant therapeutic advancements have improved the survival rates of patients with pancreatic cancer. One of the primary factors contributing to these positive outcomes is the evolution of chemotherapy, from monotherapy to doublet or triplet regimens, and the integration of multimodal approaches. Additionally, targeted agents tailored to patients with specific genetic alterations and the development of cell therapies show promise in benefiting certain subpopulations. This article focuses on examining pivotal studies that explore the role of chemotherapy in neoadjuvant, adjuvant, maintenance, and salvage settings; highlights interesting findings related to cell therapy; and provides an overview of ongoing trials concerning metastatic settings. This review primarily aimed to offer recommendations based on therapeutic evidence, recent advancements in new treatment combinations, and the most innovative approaches. A unique aspect of this review is the inclusion of published papers on clinical trials and real-world data in Taiwan, thus adding a valuable perspective to the overall analysis., Competing Interests: Declaration of competing interest None, (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background/objectives: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study., Methods: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups., Results: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02)., Conclusions: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC., Competing Interests: Declaration of competing interest Sz-Chi Chiu was employed by the company PharmaEngine, Inc. The remaining authors declare that there is no conflict of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Charcoal-burning has become a predominant method of suicide in many East-Asian countries since the 1990s. Aims: To explore charcoal-burning suicide trends from 1996 to 2020 in Taiwan. Methods: Joinpoint regression models were applied to identify suicide trends over the study period. Decompositional analyses quantified the contributions of age, sex, suicide method, and area of residence to suicide rate trends, accounting for age and geographical distribution of the general population, with a focus on charcoal-burning suicide. Results: There were three stages of suicide rate trends: increasing (1996-2006), descending (2006-2011), and levelling-off (2011-2020). Suicide by charcoal-burning accounted for 70% of the increasing suicide rates between 1996 and 2006 and 50% of the decreasing rates in the descending stage (2011-2020). During the levelling-off stage, suicide by charcoal-burning continued to decrease, albeit slowly. During the descending stage, there was a partial "substitution" of jumping for charcoal-burning. During the levelling-off stage, suicide by hanging partially "substituted" for suicide by charcoal-burning. Limitations: The variables included were limited by data availability. Conclusions: Charcoal-burning remains the second most common method of suicide in Taiwan today. Charcoal-burning has been partially replaced in the last 10 years by jumping and hanging. Monitoring suicide methods and trends is essential for suicide prevention interventions.

Background: The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats., Methods: Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[ 18 F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT., Results: MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction., Conclusion: Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[ 18 F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article, (Copyright © 2024, the Chinese Medical Association.)

Background: The objective of this study was to investigate the inter-relationship between psychosocial variables and their impact on symptom severity and quality of life (QoL) concerning abdominal bloating., Methods: The study adopted a cross-sectional design with purposive sampling. Participants who consented and met the criteria for bloating based on the Rome IV classification completed designated questionnaires. Independent variables comprised health beliefs, intentions, health-promoting behaviors, social support, depression, and anxiety, while dependent variables included bloating severity (general and within 24 h) and QoL. Structural Equation Modeling (SEM) was conducted utilizing Mplus 8.0 to analyze the relationships between these factors., Results: A total of 323 participants, with a mean age of 27.69 years (SD = 11.50), predominantly females (64.7%), volunteered to participate in the study. The final SEM model exhibited good fit based on various indices (CFI = 0.922, SRMR = 0.064, RMSEA (95% CI) = 0.048 (0.041-0.054), p -value = 0.714), with 15 significant path relationships identified. The model explained 12.0% of the variance in severity within 24 h, 6% in general severity, and 53.8% in QoL., Conclusion: The findings underscore the significant influence of health beliefs, intentions, behaviors, social support, depression, and anxiety on symptom severity and QoL in individuals experiencing abdominal bloating., Competing Interests: Yeong Yeh Lee is an Academic Editor for PeerJ., (© 2024 Abdullah et al.)

Objective: Female labor-force participation (FLFP) has been theorized as contributing to higher suicide rates, including among women. Evidence on this relationship, however, has been mixed. This study explored the association between FLFP and suicide in an understudied context, Taiwan, and across 40-years., Methods: Annual national labor-participation rates for women ages 25-64, and female and male suicide-rates, for 1980-2020, were obtained from Taiwan's Department of Statistics. The associations between FLFP rates and sex/age-stratified suicide-rates, and between FLFP rates and male-to-female suicide-rates ratios were assessed via time-series regression-analyses, accounting for autoregressive effects., Results: Higher FLFP rates were associated with lower female suicide-rates ( ß  = -0.06, 95% CI (Credibility Interval) = [-0.19, -0.01]) in the adjusted model. This association held in the age-stratified analyses. Associations for FLFP and lower male suicide-rates were observed in the ≥45 age-groups. FLFP rates were significantly and positively associated with widening male-to-female suicide-rates ratios in the adjusted model ( ß  = 0.24, 95% CI = [0.03, 0.59])., Conclusion: This study's findings suggest that FLFP protects women from suicide, and point to the potential value of FLFP as a way of preventing suicide. In Taiwan, employed women carry a double-load of paid and family unpaid care-work. Child care-work is still done by mothers, often with grandmothers' support. Therefore, this study's findings contribute to evidence that doing both paid work and unpaid family care-work has more benefits than costs, including in terms of suicide-protection. Men's disengagement from family care-work may contribute to their high suicide rates, despite their substantial labor-force participation.

In 2022, two novel classification systems for myelodysplastic syndromes/neoplasms (MDS) have been proposed: the International Consensus Classification (ICC) and the 2022 World Health Organization (WHO-2022) classification. These two contemporary systems exhibit numerous shared features but also diverge significantly in terminology and the definition of new entities. Thus, we retrospectively validated the ICC and WHO-2022 classification and found that both systems promoted efficient segregation of this heterogeneous disease. After examining the distinction between the two systems, we showed that a peripheral blood blast percentage ≥ 5% indicates adverse survival. Identifying MDS/acute myeloid leukemia with MDS-related gene mutations or cytogenetic abnormalities helps differentiate survival outcomes. In MDS, not otherwise specified patients, those diagnosed with hypoplastic MDS and single lineage dysplasia displayed a trend of superior survival compared to other low-risk MDS patients. Furthermore, the impact of bone marrow fibrosis on survival was less pronounced within the ICC framework. Allogeneic transplantation appears to improve outcomes for patients diagnosed with MDS with excess blasts in the ICC. Therefore, we proposed an integrated system that may lead to the accurate diagnosis and advancement of future research for MDS. Prospective studies are warranted to validate this refined classification., (© 2024. The Author(s).)

Background: Catharanthus roseus, a Madagascar native flowering plant, is known for its glossy leaves and vibrant flowers, and its medicinal significance due to its alkaloid compounds. As a source of vinblastine and vincristine used in chemotherapy, Catharanthus roseus is also employed in traditional medicine with its flower and stalks in dried form. Its toxicity can lead to various adverse effects. We report a case of Catharanthus roseus juice toxicity presenting as acute cholangitis, emphasizing the importance of healthcare providers obtaining detailed herbal supplement histories., Case Presentation: A 65-year-old woman presented with abdominal pain, fever, anorexia, and lower limb numbness. Initial diagnosis of acute cholangitis was considered, but imaging excluded common bile duct stones. Further investigation revealed a history of ingesting Catharanthus roseus juice for neck pain. Laboratory findings showed leukocytosis, elevated liver enzymes, and hyperbilirubinemia. The patient developed gastric ulcers, possibly due to alkaloids in Catharanthus roseus. No bacterial growth was noted in blood cultures. The patient recovered after discontinuing the herbal extract., Conclusions: Catharanthus roseus toxicity can manifest as fever, hepatotoxicity with cholestatic jaundice, and gastric ulcers, mimicking acute cholangitis. Awareness of herbal supplement use and potential toxicities is crucial for healthcare providers to ensure prompt diagnosis and appropriate management. This case emphasizes the need for public awareness regarding the possible toxicity of therapeutic herbs and the importance of comprehensive patient histories in healthcare settings., (© 2024. The Author(s).)

Disorders of esophagogastric junction (EGJ) outflow, including achalasia and EGJ outflow obstruction, are motility disorders characterized by inadequate relaxation of lower esophageal sphincter with or without impaired esophageal peristalsis. Current guidelines are technical and less practical in the Asia-Pacific region, and there are still massive challenges in timely diagnosis and managing these disorders effectively. Therefore, a Malaysian joint societies' task force has developed a consensus on disorders of EGJ outflow based on the latest evidence, while taking into consideration the practical relevance of local and regional context and resources. Twenty-one statements were established after a series of meetings and extensive review of literatures. The Delphi method was used in the consensus voting process. This consensus focuses on the definition, diagnostic investigations, the aims of treatment outcome, non-surgical or surgical treatment options, management of treatment failure or relapse, and the management of complications. This consensus advocates the use of high-resolution esophageal manometry for diagnosis of disorders of EGJ outflow. Myotomy, via either endoscopy or laparoscopy, is the preferred treatment option, while pneumatic dilatation can serve as a secondary option. Evaluation and management of complications including post-procedural reflux and cancer surveillance are recommended., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non-alcoholic fatty liver disease (NAFLD/MASLD)., Aims: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients., Methods: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria)., Results: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p < 0.001, each). ML models showed 7%-12% better discrimination than FIB-4 to detect SF. Optimised random forest (RF) yielded best NPV/F1 in overall set (0.947/0.754), test set (0.798/0.588) and validation set (0.852/0.559), as compared to FIB4 in overall set (0.744/0.499), test set (0.722/0.456), and validation set (0.806/0.507). Compared to FIB-4, RF could pick 10 times more patients with SF, reduce unnecessary referrals by 28%, and prevent missed referrals by 78%. Age, AST, ALT fasting plasma glucose, and platelet count were top features determining the SF. Sequential use of SAFE < 140 and FIB4 < 1.2 (when SAFE > 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set)., Conclusions: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients., (© 2024 John Wiley & Sons Ltd.)

Perineural invasion and neurogenesis are frequently observed in pancreatic ductal adenocarcinoma (PDAC) and link to poor outcome. However, how neural factors affect PDAC prognosis and the underlying mechanism as well as counteracting therapeutic are still unclear. In silico systematic analysis was performed with PROGgene to identify potential neural factor and its receptor in pancreatic cancer. In vitro assays including migration, invasion, 3D recruitment, and gemcitabine resistance were performed to study the effect of neuron-derived neurotensin (NTS) on pancreatic cancer behavior. Orthotopic animal study was used to validate the in vitro findings. Gene set enrichment analysis (GSEA) was performed to confirm the results from in silico to in vivo . Expression of NTS and its receptor 1 (NTSR1) predicted poor prognosis in PDAC. NTS synthetic peptide or neuron-derived condition medium promoted pancreatic cancer invasiveness and recruitment in 2D and 3D assays. NTS-induced effects depended on NTSR1 and PI3K activation. GDC-0941, a clinically approved PI3K inhibitor, counteracted NTS-induced effects in vitro . Inhibition of NTSR1 in pancreatic cancer cells resulted in decreased tumor dissemination and diminished PI3K activation in vivo . NTS boosted gemcitabine resistance via NTSR1 in pancreatic cancer. Our results suggest that neural cell-secreted NTS plays an important role in promoting PDAC., Competing Interests: None., (AJCR Copyright © 2024.)

Background: Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population., Methods: Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHR mut , including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy., Results: Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0-43.7), the median overall survival (OS) was not significantly different among patients with gHR mut , non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHR mut . Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7-33.7) versus 9.6 months (95% CI 5.9-17.6), P = 0.001. However, the median OS of patients without gHR mut was 14.5 months (95% CI 13.2-16.9) and 12.6 months (95% CI 10.8-14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis., Conclusions: Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHR mut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis., (© 2024. The Author(s).)

Introduction: The progression patterns, dispositions, and outcomes of patients with advanced hepatocellular carcinoma (HCC) who achieved durable responses with immunotherapy remain poorly characterized., Methods: Patients with advanced HCC who received immune checkpoint inhibitor (ICI)-based immunotherapy and achieved durable responses were retrospectively included. A durable response was defined as partial response (PR) or stable disease (SD) per RECIST 1.1 for more than 8 months after initiation of immunotherapy. Oligoprogression and polyprogression were defined as progression at ≤3 and >3 lesions, respectively., Results: A total of 91 durable responders (63 PR and 28 SD) were identified. The majority had chronic viral hepatitis ( n = 69, 75.8%). Forty-seven (51.6%) and 44 (48.4%) patients received the index immunotherapy as first-line and second- or beyond-line therapy, respectively. Fifty-four (59.3%) patients subsequently developed progression, with a predominant pattern of oligoprogression (66.7%). The median overall survival (OS) was 46.2 months (95% CI: 34.1-58.3). For patients with subsequent progression, employment of locoregional therapy (LRT) for progression was associated with prolonged OS (univariate analysis: hazard ratio [HR] 0.397, p = 0.009; multivariate analysis: HR 0.363, p = 0.050). Patients with oligoprogression who received LRT showed longer median OS than those who did not (48.4 vs. 20.5 months, p < 0.001). In contrast, the median OS of patients with polyprogression who received LRT was not different from those without LRT (27.7 vs. 25.5 months, p = 0.794)., Conclusion: Approximately 60% of the post-immunotherapy durable responders of HCC subsequently develop progression. Proactive LRT may further rescue patients who develop subsequent oligoprogression. Prospective studies are mandatory to clarify the proper management of durable responders with subsequent progression., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: From 2010 to 2021, suicide rates in 15-24 age group in Taiwan increased by 70%, with jumping being the most common method in 2021. We examined the link between the rise in youth suicides and the increase in high-rise buildings during this period., Methods: Spearman's correlation coefficients and negative binomial mixed-effects models were employed to assess the association between the increase in high-rise buildings and jumping suicides over time., Results: Spearman's correlation coefficients of high-rise buildings and jumping suicide rates in youth decreased from 0.692 (p < 0.001) in 2010 to 0.354 (p = 0.11) in 2021. Negative binomial mixed-effects models showed that although jumping suicide rates in youths increased over time, the increase in numbers of high-rise buildings was not related to rates of youth suicide by jumping. Conversely, in older age groups, the correlations were still prominent., Conclusion: Despite the rising trend in youth suicides by jumping over the past 11 years, our study refutes the intuitive notion that the increase in high-rise buildings contributes to this trend. It is imperative to identify and address other potential factors, such as academic stress and/or family disruptions, for effective prevention of youth suicide., (© 2024 The Authors. Suicide and Life-Threatening Behavior published by Wiley Periodicals LLC on behalf of American Association of Suicidology.)

Background: While certain socioeconomic factors have been studied in relation to suicide, housing-price-related indexes have rarely been investigated., Aims: This article aims to examine the impact of housing-price-related indexes on suicide rates in the general population of Taiwan, a country with high housing costs and suicide rates., Methods: The study utilized three national housing-price-related indexes from 2012 to 2019: (1) housing price index, (2) housing price to income ratio, and (3) housing rental index. Cause of Death Data was employed to calculate suicide rate. A linear regression model with autoregressive errors was used to analyze the association between housing-price-related indexes and suicide rates among different sex and age groups., Results: The findings revealed that higher housing rental index values were associated with increased suicide rates in young and middle-aged adults compared to the elderly population, regardless of sex. However, this association was not observed with the other two housing-price-related indexes (i.e. housing price index and housing price to income ratio)., Conclusion: These results offer valuable insights for policymakers, mental health professionals, and housing advocates to improve housing affordability and reduce the burden of suicide in the general population, particularly among younger generations.

Acute myeloid leukemia (AML) with CEBPA bZIP in-frame mutations (CEBPA bZIP-inf ) is classified within the favorable-risk group by the 2022 European LeukemiaNet (ELN-2022). However, heterogeneous clinical outcomes are still observed in these patients. In this study, we aimed to investigate the mutation profiles and transcriptomic patterns associated with poor outcomes in patients with CEBPA bZIP-inf . One hundred and thirteen CEBPA bZIP-inf patients were identified in a cohort of 887 AML patients homogeneously treated with intensive chemotherapy. Concurrent WT1 or DNMT3A mutations significantly predicted worse survival in AML patients with CEBPA bZIP-inf . RNA-sequencing analysis revealed an enrichment of interferon (IFN) signaling and metabolic pathways in those with a shorter event-free survival (EFS). CEBPA bZIP-inf patients with a shorter EFS had higher expression of IFN-stimulated genes (IRF2, IRF5, OAS2, and IFI35). Genes in mitochondrial complexes I (NDUFA12 and NDUFB6) and V (ATP5PB and ATP5IF1) were overexpressed and were associated with poorer survival, and the results were independently validated in the TARGET AML cohort. In conclusion, concurrent WT1 or DNMT3A mutations and a dysregulated immune and metabolic state were correlated with poor survival in patients with CEBPA bZIP-inf , and upfront allogeneic transplantation may be indicated for better long-term disease control., (© 2024. The Author(s).)

The International Rome Committee defines Disorders of Gut-Brain Interactions (DGBI) based upon distinct combinations of chronic and/or recurrent unexplained gastrointestinal symptoms. Yet patients often experience overlapping DGBI. Patients with DGBI frequently also suffer from extraintestinal symptoms, including fatigue, sleep disturbances, anxiety, and depression. Patients with overlapping DGBI typically experience more severe GI symptoms and increased psychosocial burden. Concerning the pathophysiology, DGBI are associated with disruptions in gut motility, function of the brain and enteric neurons, immune function, and genetic markers, with recent findings revealing gut microbiome alterations linked to these mechanisms of DGBI. Emerging evidence summarized in this review suggests that the microbiome influences various established disease mechanisms of different DGBI groups. Overall, changes in the gastrointestinal microbiome do not seem to be linked to a specific DGBI subgroup but may play a key role in the manifestation of different DGBI and, subsequently, overlap of DGBI. Understanding these shared mechanisms and the role of the gastrointestinal microbiome, particularly for overlapping DGBI, might aid in developing more precise diagnostic criteria and treatment strategies while developing personalized interventions that target specific mechanisms to improve patient outcomes.

Background: Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management., Materials and Methods: Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide., Results: There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p < 0.001)., Conclusions: Choosing inappropriate regimens containing antibiotics with high resistance rates is not uncommon in Southeast Asia, especially among non-GI physicians. In countries with high clarithromycin resistance, the PBMT regimen is underutilized., (© 2023 John Wiley & Sons Ltd.)

Purpose of Review: Esophageal disorders, including gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), and esophageal cancer, may be affected by climate change. Our review describes the impact of climate change on risk factors associated with esophageal diseases and speculates how these climate-related factors impacted esophageal disorders and their management., Recent Findings: Climate change is responsible for extreme weather conditions (shifts in rainfall, floods, droughts, and forest fires) and global warming. These consequences affect basic human needs of water and food, causing changes in population dynamics and pose significant threats to digestive health, including common esophageal disorders like GERD, EoE, and esophageal cancers. The changing patterns of esophageal diseases with climate change are likely mediated through risk factors, including nutrition, pollutants, microplastics, and the microbiota-gut-brain axis. The healthcare process itself, including GI endoscopy practices commonly employed in diagnosing and therapeutics of esophageal diseases, may, in turn, contribute to climate change through plastic wastage and greenhouse gas emissions, thus creating the climate change lifecycle. Breaking the cycle would involve changes at the individual level, community level, and national policy level. Prevention is key, with individuals identifying and remediating risk factors and reducing carbon footprints. The ABC (Advocacy, Broadcast, and Collaborate) activities would help enhance awareness at the community level. Higher-level programs such as the Bracing Resilience Against Climate Effects (BRACE) would lead to broader and larger-scale adoption of public health adaptation strategies at the national level. The impact of climate change on esophageal disorders is likely real, mediated by several risk factors, and creates a climate change lifecycle that may only break if changes are made at individual, community, and national levels., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Older people have the highest suicide rate across age groups in most countries. The prevalence of cardiometabolic risk factors also increases with age. We investigated the association between body mass index (BMI), cardiometabolic risk factors, and suicide in a large cohort of older people in Taiwan., Methods: We conducted a cohort study using data from an elderly health examination program in Taipei City, Taiwan (2005-2010), linked to the national cause-of-death data files. We used competing risk Cox regression models to investigate the associations of BMI (kg/m 2 ) and cardiometabolic factors with suicide after adjusting for sex, age, socioeconomic variables, chronic diseases, psychological distress, and cognitive function., Results: Among 101,518 individuals aged ≥ 65 years, 92 died by suicide during an average follow-up of 3.9 years. Underweight (BMI<18.5) was associated with increased suicide risk (adjusted hazard ratio [aHR]=2.33, 95% confidence interval [CI] 1.20-4.52) (reference: normal weight). Low diastolic blood pressure was associated with increased suicide risk - aHR was 0.51 (95% CI 0.29-0.91) and 0.55 (95% CI 0.31-0.99) for the third and fourth quartiles of diastolic blood pressure (reference: the lowest quartile), respectively. Older people with a higher waist circumference (aHR per 1-standard-deviation increase=0.60 [95% CI 0.37-0.98]) and a higher number of metabolic syndrome criteria (aHR per 1-criterion increase=0.65 [95% 0.46-0.92]) had lower suicide risk. Systolic blood pressure, pulse rate, fasting blood glucose, and lipid profiles were not associated with suicide risk., Conclusions: Underweight, low diastolic blood pressure, and low waist circumference may be markers of increased suicide risk in older people., Competing Interests: DISCLOSURES All authors declare no conflict of interest in the publication of this manuscript., (Copyright © 2023 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Debunking suicide misconceptions is an important suicide prevention measure. Few studies on suicide misconceptions and their correlates have been conducted in East Asia, where suicide is known to be more permissible. Aims: We investigated the prevalence and associated characteristics of suicide misconceptions in Taiwan. Whether holding suicide misconceptions was associated with reduced support for governmental suicide prevention measures was also assessed. Method: A dual-frame nationally representative telephone survey combining landlines and mobiles was conducted with 1,087 respondents. Logistic regression analyses were used to examine factors associated with suicide misconceptions. Results: Nearly 82% of the respondents held at least one type of suicide misconceptions. The most commonly held misconception was "Talking about suicide would encourage suicide" (49.5%), followed by "People who talk about suicide do not mean to do it" (47.3%) and "Most suicides happen suddenly without any warning" (46.5%). Suicide misconceptions were more common in younger people, divorced/widowed individuals, and those with lower educational attainment. Individuals with suicide misconceptions were less likely to support governmental investments in suicide prevention. Limitations: Causality could not be inferred from the cross-sectional study. Conclusions: Suicide misconceptions are prevalent in Taiwan. Debunking suicide misconceptions should be an integral part of national suicide prevention strategies.

Rising social media use over the past decade has been linked with increasing suicide rates among young people. Previous studies that assessed the impact of social media on suicide have typically focused on single social media platforms, such as Twitter, and assumed unidirectional associations, where social media posts leads to suicide. Our study focused on the past decade (2012-2021) which has witnessed a rapid increase of social media platforms and use. Poisson and negative binominal auto-regression models were employed to examine the dynamic reciprocity between social media, traditional media and youth suicides in Taiwan. Increased volume in suicide-related social media posts positively correlated with increased youth suicide rates (β = 2.53 × 10 -5 , 95% CI= (0.83 × 10 -5 , 4.24 × 10 -5 ), P < 0.01), but increased rates of youth suicide was not related to an increase in suicide-related social media posts. Suicide-related posts on social media triggered reporting of suicide-related news on traditional media platforms (β = 3.35 × 10 -2 , 95% CI= (2.51 × 10 -2 , 4.19 × 10 -2 ), P < 0.001), whilst traditional media reports of suicide led to increased suicide-related social media posts (β = 6.13 × 10 -1 , 95% CI = (4.58 × 10 -1 , 7.68 × 10 -1 ); P < 0.001). However, suicide-related reports on traditional media platforms did not directly lead to an increase in youth suicide rates. Our findings highlight challenges for suicide prevention strategies in the 21st Century, in dealing with the increasing prominence of social media over traditional media. As social media is more difficult to regulate than traditional media, suicide prevention efforts must adapt to this new landscape by developing innovative strategies that address the unique risks and opportunities presented by social media., Competing Interests: None declared., (© 2023 The Authors. Published by Elsevier Ltd.)

Poly(polyol sebacate) (PPS) polymer family has been recognized as promising biomaterials for biomedical applications with their characteristics of easy production, elasticity, biodegradation, and cytocompatibility. Poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-PEG) has been developed to fabricate PPS-based hydrogels; however, current PXS-co-PEG hydrogels presented limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. Here, we fabricate a new type of PXS-co-PEG hydrogels through the use of multifunctional crosslinkers as well as dynamic bonds. In our design, polyethyleneimine-polydopamine (PEI-PDA) macromers are utilized to crosslink aldehyde-functionalized PXS-co-PEG (APP) through imine bonds and hydrogen bonds. PEI-PDA/APP hydrogels present multiple functional properties (e.g., fluorescent, elastomeric, biodegradable, self-healing, bioadhesive, antioxidant, and antibacterial behaviors). These properties of PEI-PDA/APP hydrogels can be fine-tuned by changing the PDA grafting degrees in the PEI-PDA crosslinkers. Most importantly, PEI-PDA/APP hydrogels are considered promising wound dressings to promote tissue remodeling and prevent bacterial infection in vivo. Taken together, PEI-PDA/APP hydrogels have been demonstrated as versatile biomaterials to provide multiple tailorable properties and desirable functions to expand the utility of PPS-based hydrogels for advanced biomedical applications. STATEMENT OF SIGNIFICANCE: Various strategies have been developed to fabricate poly(polyol sebacate) (PPS)-based hydrogels. However, current PPS-based hydrogels present limited properties and functions due to the limitations of the crosslinkers and crosslinking chemistry used in the hydrogel formation. This work describes that co-engineering crosslinkers and interfacial crosslinking is a promising approach to synthesizing a new type of poly(xylitol sebacate)-co-poly(ethylene glycol) (PXS-co-PEG) hydrogels as multifunctional hydrogels to expand the utility of PPS-based hydrogels for advanced biomedical applications. The fabricated hydrogels present multiple functional properties (e.g., fluorescent, biodegradable, elastomeric, self-healing, bioadhesive, antioxidative, and antibacterial), and these properties can be fine-tuned by the defined crosslinkers. The fabricated hydrogels are also used as promising wound dressing biomaterials to exhibit promoted tissue remodeling and prevent bacterial infection in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)