Search

I-Chun Tai,1–3 Yao-Hsien Wang,3 Chung-Hwan Chen,3,4 Shu-Chun Chuang,3 Je-Ken Chang,3–5 Mei-Ling Ho1–3,6 1Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Orthopaedic Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 5Department of Orthopedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 6Department of Marine Biotechnology and Resources, National Sun Yat-sen UniVersity, Kaohsiung, Taiwan Abstract: Recent studies have indicated that statins induce osteogenic differentiation both in vitro and in vivo. The molecular mechanism of statin-stimulated osteogenesis is unknown. Activation of RhoA signaling increases cytoskeletal tension, which plays a crucial role in the osteogenic differentiation of mesenchymal stem cells. We thus hypothesized that RhoA signaling is involved in simvastatin-induced osteogenesis in bone marrow mesenchymal stem cells. We found that although treatment with simvastatin shifts localization of RhoA protein from the membrane to the cytosol, the treatment still activates RhoA dose-dependently because it reduces the association with RhoGDIα. Simvastatin also increased the expression of osteogenic proteins, density of actin filament, the number of focal adhesions, and cellular tension. Furthermore, disrupting actin cytoskeleton or decreasing cell rigidity by using chemical agents reduced simvastatin-induced osteogenic differentiation. In vivo study also confirms that density of actin filament is increased in simvastatin-induced ectopic bone formation. Our study is the first to demonstrate that maintaining intact actin cytoskeletons and enhancing cell rigidity are crucial in simvastatin-induced osteogenesis. The results suggested that simvastatin, which is an osteoinductive factor and acts by increasing actin filament organization and cell rigidity combined with osteoconductive biomaterials, may benefit stem-cell-based bone regeneration. Keywords: statins, RhoA, cytoskeleton, osteogenic differentiation, BMSCs

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97). [ABSTRACT FROM AUTHOR]

Background: While single-incision laparoscopic cholecystectomy (SILC) has gained more popularity in recent years, its application to elderly patients needs further evaluation. Few SILC studies regarded this rapidly growing vulnerable population, and single-incision laparoscopic common bile duct exploration (SILCBDE) was never mentioned. We conducted an observational study of 146 routine SILCBDE to address this issue., Methods: One hundred forty-six consecutive patients underwent SILCBDE with concomitant cholecystectomies during a period of 6 years (July 2012-June 2016 and July 2018-July 2020). Forty patients with an age of 65 years or older were the study target. Characteristics and operative outcomes were compared with the remaining 106 younger patients by retrospective chart review. The primary outcomes include complications and mortality, while the secondary outcomes contain intraoperative blood loss, operative time, procedural conversions, postoperative length of hospital stay, and bile duct stone recurrence., Results: There was no mortality. The bile duct stone clearance rate was 98.6%. The elderly group had higher American Society of Anesthesiologists (ASA) scores, higher comorbidity rate, higher acute cholangitis rate, lower completion intraoperative cholangiography (IOC) rate, longer operative time, more blood loss, longer postoperative hospital stay (p < .001), longer total hospital stay (p < .001), higher procedural conversion rate (p < .05), higher complication rate (p < .001), and the exclusive open conversion (2.5%). The difference in complications derived from Clavien-Dindo grade I., Conclusion: Routine SILCBDE with concomitant cholecystectomy by experienced surgeons is safe and efficacious for elderly patients as for younger patients. Randomized controlled trials are anticipated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recently, species clustering within Dickeya zeae has been identified as complex, encompassing validly published names, including D. oryzae and D. parazeae , with some strains potentially delineating new species. In this study, genomes of strains isolated from a bacterial heart rot outbreak in pineapple ( Ananas comosus var. comosus ) on Oahu, Hawaii, along with two strains from pineapple in Malaysia, were sequenced. Orthologous average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values among the sequenced genomes ranged from 98.93-99.9% and 91.8-99.9%, respectively, supporting the classification of seven strains within the same species. Comparisons of ANI and dDDH values between these seven strains and type strains of D. zeae, D. parazeae, and D. oryzae ranged from 94.4-95.9% and 57.2-66.5%, respectively. These values fall below the proposed boundaries for new species designation, supporting the delineation of a novel species. Phylogenetic analyses, including 16S rRNA, gapA , multi-locus sequence analysis (MLSA) of 10 housekeeping genes, whole-genome, and pangenome analyses, were concordant and revealed a distinct monophyletic clade, separating these strains from other members of the D. zeae complex, with D. oryzae as the closest relative. Notably, a nitrogen fixation gene cluster comprising 28 genes, similar to the Klebsiella spp. nitrogenase gene cluster, was found in the genome of the seven pineapple strains. Based on polyphasic approaches, including ANI, dDDH, biochemical, physiological, and phylogenomic analyses, we propose the reclassification in a new species of the five pineapple strains from Hawaii A5391, A5410 T , A5611, A6136, and A6137, together with the two pineapple strains from Malaysia CFBP 1272 and CFBP 1278, previously classified as D. zeae . We propose the name Dickeya ananae sp. nov. for this taxon, represented by the type strain A5410 T (= ICMP 25020 T = LMG 33197 T ).

Background: Raynaud's phenomenon (RP) has recently been observed in recipients of the COVID-19 vaccine. It is unclear whether RP is directly caused by the COVID-19 vaccine. This study aims to investigate the potential causation between RP and COVID-19 vaccination., Methods: In this study, we searched PubMed, EMBASE, and Web of Science from January 1, 2020, to March 19, 2024. We included the articles with clinical related findings, specifically case reports and case series. Conference abstracts, editorial publications, preprint, and those not specifically related to COVID-19 vaccination are excluded. The refined selection process aimed to ensure a focused and clinically relevant analysis of the association between RP and COVID-19 vaccination., Results: A total of six articles were ultimately included in this study, comprising five case reports and one case series involving 24 patients with RP after vaccination. Baseline characteristics of the studies showed the RP post COVID-19 vaccination frequently occurred with females compared to males (70.83 vs. 29.17 %). Of the patients with RP post COVID-19 vaccination, 87.5 % (21/24) had either a history or possible predisposing factors of RP. Among the patients with detailed information of vaccination (n = 20), the number of vaccine doses was not related to RP development (45 % (1st) vs. 30 % (2nd) vs. 25 % 3rd dose). For types of vaccine, 75 % of RP were found to have received the administration of mRNA vaccine (15/20)., Conclusion: The risk of bias was increased due to the uncontrolled study designs and small sample size, making it impossible to attribute causation between RP and COVID-19 vaccination. These few cases may have occurred independently of vaccination. However, physicians should still remain vigilant for RP following COVID-19 vaccination, particularly as the number of vaccinated individuals continues to rise., 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. Published by Elsevier Ltd.)

Oxygen production within human cells plays a critical role in cellular metabolism and is implicated in various diseases, including cancer. Investigating cellular heterogeneity under oxygen stimulation is crucial for elucidating disease mechanisms and advancing early therapeutic design. In this study, the platinum-based wireless nanopore electrode (WNE) with a diameter of ≈200 nm is employed as a powerful tool to produce oxygen molecules near the cell nucleus. The oxygen production can be quantitatively controlled by adjusting the applied voltage. Through delivering oxygen near the cancer cell nucleus, this technique shows the capacity to alleviate the hypoxia microenvironment, a key factor in chemotherapy resistance. Furthermore, by modulating oxygen levels within individual living cells and delivering chemotherapeutic agents to the cancer cell nucleus, this approach offers significant potential for single-cell manipulation and the investigation of cellular heterogeneity under oxygen stimulation., (© 2024 Wiley‐VCH GmbH.)

Phosphine-promoted unprecedented [3 + 2] annulation reactions via ring expansion by using 2-benzylidene-indane-1,3-diones and diynoates for the synthesis of biologically interesting novel naphthoquinones fused with a five-membered ring bearing a phosphorus ylide up to 78% yield are described. Further ring contraction through [1,5] sigmatropic rearrangement to the spiro indan-1,3-diones by m CPBA oxidation was revealed and inferred through oxidation, followed by protonation. The relevant structures were confirmed by single-crystal X-ray diffraction. Electrochemical studies show that the naphthoquinones and lactones with phosphorus ylides could be applied to redox colorimetric materials.

In the Morita-Baylis-Hillman (MBH) reaction, a nucleophile undergoes β-addition to activated alkenes or alkynes, forming reactive intermediates for subsequent carbon-carbon or carbon-hetero bond formation. By using a π-conjugated acceptor, however, an unprecedented reactivity of 1,3-enynoates and indane-1,3-diones was uncovered in the presence of phosphines. When indan-1,3-diones were used, γ-addition of phosphines to 1,3-enynoates was observed for the first time; moderate to good yields were obtained for 14 substances containing the prominent spirocyclopropane scaffold with 100 % retention of (Z)-alkene. When 2-methyl-indan-1,3-diones were used, di(tri)-substituted furans were produced through the δ-addition pathway, with 20 substances and a yield of up to 88 % being achieved. Control experiments and density functional theory calculations were conducted to obtain insights into the unconventional γ-addition reaction pathway., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Abiotic stresses such as nitrogen deficiency, drought, and salinity significantly impact coconut production, yet the molecular mechanisms underlying coconut's response to these stresses are poorly understood. MYB proteins, a large and diverse family of transcription factors (TF), play crucial roles in plant responses to various abiotic stresses, but their genome-wide characterization and functional roles in coconut have not been comprehensively explored. This study identified 214 CnMYB genes (39 1R-MYB, 171 R2R3-MYB, 2 3R-MYB, and 2 4R-MYB) in the coconut genome. Phylogenetic analysis revealed that these genes are unevenly distributed across the 16 chromosomes, with conserved consensus sequences, motifs, and gene structures within the same subgroups. Synteny analysis indicated that segmental duplication primarily drove CnMYB evolution in coconut, with low nonsynonymous/synonymous ratios suggesting strong purifying selection. The gene ontology (GO) annotation of protein sequences provided insights into the biological functions of the CnMYB gene family. CnMYB47/70/83/119/186 and CnMYB2/45/85/158/195 were identified as homologous genes linked to nitrogen deficiency, drought, and salinity stress through BLAST, highlighting the key role of CnMYB genes in abiotic stress tolerance. Quantitative analysis of PCR showed 10 CnMYB genes in leaves and petioles and found that the expression of CnMYB45/47/70/83/85/119/186 was higher in 3-month-old than one-year-old coconut, whereas CnMYB2/158/195 was higher in one-year-old coconut. Moreover, the expression of CnMYB70 , CnMYB2 , and CnMYB2/158 was high under nitrogen deficiency, drought, and salinity stress, respectively. The predicted secondary and tertiary structures of three key CnMYB proteins involved in abiotic stress revealed distinct inter-proteomic features. The predicted interaction between CnMYB2/158 and Hsp70 supports its role in coconut's drought and salinity stress responses. These results expand our understanding of the relationships between the evolution and function of MYB genes, and provide valuable insights into the MYB gene family's role in abiotic stress in coconut.

In the post-pandemic era, medical education faces significant shifts in learning modes. This study, employing cross-sectional research from 2021 to 2022, surveyed 214 participants, including 104 medical interns and 110 Post-Graduate Year trainees in Taiwan. Findings revealed notable differences between the groups in age and current internship hospital. Medical interns spent significantly more time in daily self-directed learning, with a higher proportion exceeding 3 hours post-work. Although weekly self-directed learning hours did not show statistical significance, more medical students studied over 7 hours weekly. In terms of learning attitudes and motivations, medical interns outscored Post-Graduate Year trainees, indicating a substantial contrast. The study suggests strategic integration of online and traditional education, tailored to course characteristics. Future research should further explore the effectiveness of online learning, aiming to optimize digital learning while preserving traditional education values., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Previous cross-sectional studies have shown that higher magnesium intake is associated with better cognitive function, particularly in individuals with sufficient vitamin D status. The aim of this study was to evaluate the longitudinal associations between magnesium intake and cognitive impairment in a community-based cohort study in Taiwan., Methods: The study population included 5663 community-dwelling adults aged ≥ 55 years old recruited from 2009 to 2013 and followed up from 2013 to 2020. Magnesium intake was evaluated from a validated food frequency questionnaire at baseline. Cognitive performance was measured at baseline and follow-up for participants' Mini-Mental Status Examination (MMSE), Digit Symbol Substitution Test (DSST), and Clock-Drawing Test (CDT), and impairment was defined as MMSE < 24, DSST < 21, and CDT < 3, respectively. Multivariate logistic regression models were used to examine the associations and were stratified by sex and plasma vitamin D levels (≥ 50 or < 50 nmol/L)., Results: Higher baseline magnesium intake was associated with lower odds of a poor performance on the MMSE in both men and women (4th vs. 1st. quartile: OR = 0.43, 95% CI = 0.23-0.82, p trend  < 0.01 in men and OR = 0.53, 95% CI = 0.29-0.97, p trend  = 0.12 in women) and on the DSST in men (OR = 0.23, 95% CI = 0.09-0.61, p trend  < 0.01) at follow-up. Inverse associations between baseline magnesium intake and a poor performance on the MMSE or DSST were observed in men regardless of vitamin D status., Conclusion: Our study suggested that higher magnesium intake was associated with the development of cognitive impairment in men in a median follow-up period of 6 years., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Dietary patterns related to inflammation have garnered great interest in disease prevention. The aims of this study were to evaluate whether a proinflammatory diet affects the incidence of frailty and its reversal in a prospective follow-up study. Data were taken from 5663 community-dwelling individuals ≥ 55 years old in Taiwan. The energy-adjusted dietary inflammatory index (DII) and the Empirical Dietary Inflammatory Patterns-Healthy Aging Longitudinal Study in Taiwan (EDIP-HALT) at baseline were calculated using a food frequency questionnaire. Frailty was assessed with Fried's criteria in 2008-2013 and 2013-2020. Associations with changes in frailty status were assessed with multinominal logistic regressions and adjusted for major confounders. Higher EDIP-HALST scores (proinflammatory) were associated with higher odds of frailty among baseline robust participants in men (OR = 2.44, 95% CI = 1.42-4.21, p- trend < 0.01) and broadline associated in women (OR = 1.96, 95% CI = 0.96-3.98, p- trend = 0.05), but associated with lower odds of reversing back to robust among baseline prefrail participants. However, the later association was only observed in women, and the relationships were stronger in the middle tertile (second vs. first tertile, OR = 0.40, 95% CI = 0.25-0.65). A pro-inflammatory diet pattern was associated with higher odds of frailty onset in baseline robust participants and lower odds of reversal in baseline prefrail female participants.

The family Araceae, comprising ornamentals including Anthurium , Dieffenbachia , Philodendron , Colocasia , and Zantedeschia , is susceptible to Xanthomonas pathogens. Previous analyses have established heterogeneity in aroid strains, yet unresolved taxonomic positions and dynamics between Xanthomonas and frequently associated Stenotrophomonas in aroids necessitate in-depth genetic investigation to resolve these complex relationships. This study utilized multilocus sequence analysis of housekeeping genes atpD , dnaA , dnaK , gltA , and gyrB to investigate 59 aroid strains, selected based on hosts, time, and geographical origins. After adding sequences from additional strains from NCBI GenBank, analysis of 161 concatenated sequences indicated that all aroid strains fell within Xanthomonas and Stenotrophomonas . Thirty-six strains isolated from Anthurium grouped under X. phaseoli , with outliers including one strain each in X. arboricola and X. sacchari and two in Stenotrophomonas . Six strains from Caladium , Dieffenbachia , and Philodendron formed host-specific subgroups within X. euvesicatoria . One strain from Dieffenbachia aligned with X. campestris , whereas strains from Colocasia , Aglaonema , and Spathiphyllum clustered with X. sacchari. Apart from the zantedeschia strain described as X. arboricola pv. zantedeschiae , two colocasia, one epipremnum, and one anthurium strain joined the X. arboricola group. Overall, this study revealed significant heterogeneity among aroid strains, with anthurium strains clustering closely despite distant geographical origins. The analysis underscores the complexity of host-pathogen specificity within Xanthomonas and emphasizes the need for further taxonomic clarification through whole-genome analysis of representative strains. The findings of this research will facilitate strain selection for inclusivity and exclusivity panels in developing diagnostic assays for X. phaseoli and xanthomonads affecting aroids., Competing Interests: The author(s) declare no conflict of interest.

Objectives: This study examined the associations between pulse pressure, hypertension, and the decline in physical function in a prospective framework., Study Design: The Healthy Aging Longitudinal Study tracked a group of Taiwanese adults aged 55 or more over an average of 6.19 years to assess pulse pressure and decline in physical function, including in handgrip strength, gait speed, and 6-min walking distance, at baseline (2009-2013) and in the second phase of assessments (2013-2020)., Main Outcome Measures: Pulse pressure was calculated as the difference between systolic and diastolic blood pressure values. Weakness, slowness, and low endurance were defined as decreases of ≥0.23 m/s (one standard deviation) in gait speed, ≥5.08 kg in handgrip strength, and ≥ 57.73 m in a 6-min walk, as determined from baseline to the second phase of assessment. Linear and logistic regressions were employed to evaluate the associations between pulse pressure, hypertension, and decline in physical function., Results: Baseline pulse pressure was associated with future handgrip strength (beta = -0.017, p = 0.0362), gait speed (beta = -0.001, p < 0.0001), and 6-min walking distance (beta = -0.470, p < 0001). In multivariable models, only handgrip strength (beta = -0.016, p = 0.0135) and walking speed (beta = -0.001, p = 0.0042) remained significantly associated with future pulse pressure. Older adults with high systolic blood pressure (≥140 mmHg) and elevated pulse pressure (≥60 mmHg) exhibited a significantly increased risk of weakness (odds ratio: 1.30, 95 % confidence interval: 1.08-1.58), slowness (1.29, 1.04-1.59), and diminished endurance (1.25, 1.04-1.50) compared with the reference group, who exhibited systolic blood pressure of <140 mmHg and pulse pressure of <60 mmHg., Conclusions: Among older adults, pulse pressure is associated with a decline in physical function, especially in terms of strength and locomotion., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips., 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 B.V. All rights reserved.)

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: Common bile duct (CBD) stones commonly occur in cholecystectomy cases. The management options include laparoscopic CBD exploration (LCBDE) or endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Although ERCP is fully developed, it has complications, and LCBDE is a proven alternative. This study aimed to evaluate the safety and efficacy of these treatments in elderly individuals aged ≥70 years., Methods: A retrospective study between January 2015 and July 2022 included 160 elderly patients (aged ≥70 years) diagnosed with cholelithiasis and choledocholithiasis. The patients were divided into 1-stage (LCBDE [n = 80]) or 2-stage (ERCP followed by LC [n = 80]) treatment groups. Data collected encompassed comorbidities, symptoms, bile duct clearance, postoperative complications, and long-term outcomes for systematic analysis., Results: This study analyzed 160 patients treated for CBD stones, comparing 1-stage and 2-stage groups. The 1-stage group had more female patients than the 2-stage group (57.5% vs 37.5%, respectively). The 1-stage group had a mean age of 80.55 ± 7.00 years, which was higher than the mean age in the 2-stage group. American Society of Anesthesiologists classification, Charlson Comorbidity Index, and laboratory findings were similar. Pancreatitis and cholangitis occurred after ERCP in the 2-stage group. Stone clearance rates (92.35% [1-stage group] vs 95.00% [2-stage group]) and biliary leakage incidence (7.5% [1-stage group] vs 3.0% [2-stage group]) were similar, as were postoperative complications and long-term recurrence rates (13.0% [1-stage group] vs 12.5% [2-stage group])., Conclusion: Our research indicates that both the combination of LCBDE and LC and the sequence of ERCP followed by LC are equally efficient and secure when treating CBD stones in elderly patients. Consequently, the 1-stage procedure may be considered the preferred treatment approach for this demographic., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Prognostic indices can enhance personalized predictions of health burdens. However, a simple, practical, and reproducible tool is lacking for clinical use. This study aimed to develop a machine learning-based prognostic index for predicting all-cause mortality in community-dwelling older individuals., Methods: We utilized the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort, encompassing data from 5 663 participants. Over the 5-year follow-up, 447 deaths were confirmed. A machine learning-based routine blood examination prognostic index (MARBE-PI) was developed using common laboratory tests based on machine learning techniques. Participants were grouped into multiple risk categories by stratum-specific likelihood ratio analysis based on their MARBE-PI scores. The MARBE-PI was subsequently externally validated with an independent population-based cohort from Japan., Results: Beyond age, sex, education level, and BMI, 6 laboratory tests (low-density lipoprotein, albumin, aspartate aminotransferase, lymphocyte count, high-sensitivity C-reactive protein, and creatinine) emerged as pivotal predictors via stepwise logistic regression (LR) for 5-year mortality. The area under curves of MARBE-PI constructed by LR were 0.799 (95% confidence interval [95% CI]: 0.778-0.819) and 0.756 (95% CI: 0.694-0.814) for the internal and external validation data sets, and were 0.801 (95% CI: 0.790-0.811) and 0.809 (95% CI: 0.774-0.845) for the extended 10-year mortality in both data sets, respectively. Risk categories stratified by MARBE-PI showed a consistent dose-response association with mortality. The MARBE-PI also performed comparably with indices constructed with clinical health deficits and/or laboratory results., Conclusions: The MARBE-PI is considered the most applicable measure for risk stratification in busy clinical settings. It holds potential to pinpoint older individuals at elevated mortality risk, thereby aiding clinical decision-making., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Xanthomonas and Stenotrophomonas are closely related genera in the family Lysobacteraceae. In our previous study of aroid-associated bacterial strains, most strains isolated from anthurium and other aroids were reclassified as X. phaseoli and other Xanthomonas species. However, two strains isolated from Spathiphyllum and Colocasia were phylogenetically distant from other strains in the Xanthomonas clade and two strains isolated from Anthurium clustered within the Stenotrophomonas clade. Phylogenetic trees based on 16S rRNA and nine housekeeping genes placed the former strains with the type strain of X. sacchari from sugarcane and the latter strains with the type strain of S. bentonitica from bentonite. In pairwise comparisons with type strains, the overall genomic relatedness indices required delineation of new species; digital DNA-DNA hybridization and average nucleotide identity values were lower than 70 and 95%, respectively. Hence, three new species are proposed: S. aracearum sp. nov. and S. oahuensis sp. nov. for two strains from anthurium and X. hawaiiensis sp. nov. for the strains from spathiphyllum and colocasia, respectively. The genome size of X. hawaiiensis sp. nov. is ~4.88 Mbp and higher than S. aracearum sp. nov. (4.33 Mbp) and S. oahuensis sp. nov. (4.68 Mbp). Gene content analysis revealed 425 and 576 core genes present in 40 xanthomonads and 25 stenotrophomonads, respectively. The average number of unique genes in Stenotrophomonas spp. was higher than in Xanthomonas spp., implying higher genetic diversity in Stenotrophomonas ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chuang, Dobhal, Alvarez and Arif.)

Aim: Leisure-time physical activity (LTPA) promotes healthy aging; however, data on work-related physical activity (WPA) are inconsistent. This study was conducted to examine the disability-free life expectancy (DFLE) and disabled life expectancy (DLE) across physical activity levels, with a focus on WPA, in middle-aged and older adults., Methods: Data from 5663 community-dwelling participants aged ≥55 years and enrolled in the Healthy Aging Longitudinal Study in Taiwan were evaluated. Energy expenditures from LTPA and WPA were calculated from baseline questionnaires and categorized into sex-specific cutoffs. Disability was based on repeat measures of participants' activities of daily living and instrumental activities of daily living. Mortality was confirmed via data linkage with the Death Certificate database. DFLE and DLE were estimated from discrete-time multistate life-table models., Results: At age 65, women with low WPA had a DLE of 2.88 years (95% confidence interval [CI], 1.67-4.08), which was shorter than that of women without WPA (DLE, 5.24 years; 95% CI, 4.65-5.83) and with high WPA (DLE, 4.01 years; 95% CI, 2.69-5.34). DFLE and DLE were similar across WPA levels in men. DFLE tended to increase as the LTPA increased in men and women., Conclusion: Women with low WPA had shorter DLE than did those with no or high WPA. To reduce the risks of disability associated with physical activity, public policy should advocate for older people to watch the type, amount, and intensity of their activities as these may go ignored during WPA. Geriatr Gerontol Int 2024; 24: 229-239., (© 2024 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Synthesis of benzo[ c ]cinnolinium salts by copper(II)-promoted or electrochemical oxidation of 2-azobiaryls is described. A variety of diversely functionalized benzo[ c ]cinnolinium salts were easily constructed by this strategy with excellent functional group tolerance and high efficiency. An interesting fluorescence centered at 571 nm is revealed by a benzo[ c ]cinnolinium salt with electron push-pull substitutions. The mechanism is proposed to go through single-electron transfer driven by oxidant and intramolecular cyclization via nucleophilic addition, followed by an anion exchange.

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).)

Background and Objectives : Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods : Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results : The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op ( p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op ( p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions : An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.

A photocatalytic three-component reaction of a nitroarene, a thiophenol, and a ketone for the synthesis of multifunctional diaryl sulfides was reported using a nitro group as the nitrogen source and thiophenol as the sulfur source. Thiophenol also serves as a proton donor to reduce nitroarene to arylamine as a key intermediate for the formation of C-N and C-S bonds. Good functional group tolerance and mild reaction conditions make this method have practical synthetic value for diversified multifunctional diaryl sulfides.

Previously, the discrimination of collagen types I and II was successfully achieved using peptide pitch angle and anisotropic parameter methods. However, these methods require fitting polarization second harmonic generation (SHG) pixel-wise information into generic mathematical models, revealing inconsistencies in categorizing collagen type I and II blend hydrogels. In this study, a ResNet approach based on multipolarization SHG imaging is proposed for the categorization and regression of collagen type I and II blend hydrogels at 0%, 25%, 50%, 75%, and 100% type II, without the need for prior time-consuming model fitting. A ResNet model, pretrained on 18 progressive polarization SHG images at 10° intervals for each percentage, categorizes the five blended collagen hydrogels with a mean absolute error (MAE) of 0.021, while the model pretrained on nonpolarization images exhibited 0.083 MAE. Moreover, the pretrained models can also generally regress the blend hydrogels at 20%, 40%, 60%, and 80% type II. In conclusion, the multipolarization SHG image-based ResNet analysis demonstrates the potential for an automated approach using deep learning to extract valuable information from the collagen matrix., (© 2023. The Author(s).)

Background: Dietary patterns related to inflammation have become a focus of disease prevention but the patterns may vary among populations., Objectives: The study was conducted to determine Taiwanese dietary inflammatory patterns and evaluate their associations with biomarkers of lipid and glucose., Methods: Data were taken from 5664 community-dwelling individuals aged ≥55 y recruited in 2009-2013 in the Healthy Aging Longitudinal Study in Taiwan (HALST). Dietary data were obtained from an FFQ. An empirical dietary inflammatory pattern (EDIP) was derived from reduced rank regression models that explained the serum high-sensitivity CRP, plasma IL-6, and TNF receptor 1. Cross-sectional associations between dietary scores and biomarkers of total cholesterol (TC); HDL cholesterol; LDL cholesterol; TG; and ratios of TG/HDL cholesterol, TG/TC, fasting glucose, insulin, and HbA1c were analyzed via multiple linear regression and adjusted for major confounders. The false-discovery rate (FDR)-adjusted P < 0.05 was considered statistically significant. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥80 cm for women., Results: Higher EDIP-HALST scores were associated with higher TG (per score increment: 1.62%, 95% CI: 0.58%, 2.76%; P FDR = 0.01), TG/HDL cholesterol (2.01%, 95% CI: 0.67%, 3.37%; P FDR = 0.01), and TG/TC (1.42%, 95% CI: 0.41%, 2.43%; P FDR = 0.01) and nonlinearly associated with insulin, with those in the middle tertile had the highest serum insulin concentrations (means: 5.12 μIU/mL, 95% CI: 4.78, 5.78; P FDR = 0.04) in men, but not in women. No heterogeneity was detected between sexes. The associations with TG (1.23%, 95% CI: 0.19, 2.23%; P trend = 0.02), TG/HDL cholesterol (1.62%, 95% CI: 0.30%, 2.96%; P trend = 0.02), and TG/TC (1.11%, 95% CI: 0.11%, 2.13%; P trend = 0.03) were stronger in participants with abdominal obesity, but were borderline associated in participants with normal abdominal circumferences (all P trend = 0.05)., Conclusions: Inflammatory diets, as measured via EDIP-HALST, are associated with serum TG concentration, particularly in participants with abdominal obesity. These findings may suggest that developing disease prevention strategies using dietary inflammatory patterns may be different by populations. J Nutr 20xx;x:xx., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We developed a bipolar SiNx nanopore for the observation of single-molecule heterogeneous enzymatic dynamics. Single glucose oxidase was immobilized inside the nanopore and its electrocatalytic behaviour was real-time monitored via continuous recording of ionic flux amplification. The temporal heterogeneity in enzymatic properties and its spatial dynamic orientations were observed simultaneously, and these two properties were found to be closely correlated. We anticipate that this method offers new perspectives on the correlation of protein structure and function at the single-molecule level.

Objective: The purpose of the following study was to determine whether health insurance impacts the risk of suicidal ideation among patients with head and neck cancer (HNC)., Study Design: A retrospective cohort study was completed using the 2016 to 2018 National Inpatient Sample on adult patients (≥18 years) with HNC. The primary predictor was health insurance. The primary outcome was suicidal ideation. Multivariate logistic regression was employed to identify risk factors for the primary outcome variable., Results: The final study sample consisted of 29 231 patients with HNC. Not controlling for confounders, being a Medicaid patient was a risk factor for suicidal ideation (odds ratio [OR] 2.44; P < .01). However, after controlling for confounders, Medicaid was no longer a risk factor or suicidal ideation (OR 1.52; P = .190). Patients with alcohol dependence/abuse (OR 2.94; P < .01) and depression (OR 8.30; P < .01) were each more likely to experience suicidal ideation., Conclusions: Medicaid insurance was not a risk factor for suicidal ideation in our study. Depression and alcohol dependence/abuse were each risk factors for suicidal ideation. Oral cancer and oropharyngeal cancer each decreased the risk for suicidal ideations., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Situs inversus (SI) is a rare congenital condition characterized by a mirror-image transposition of the major visceral organs. Since the 1990s, more than one hundred SI patients have been reported to have successfully undergone laparoscopic cholecystectomy. In these cases, the major problem is to overcome is the left-right condition for right-handed surgeons. Laparoscopic common bile duct exploration (LCBDE), an alternative to treat patients with bile duct stones, has shown equivalent efficacy and is less likely to cause pancreatitis than endoscopic retrograde cholangiopancreatography. Recent updated meta-analyses revealed that a shorter postoperative hospital stay, fewer procedural interventions, cost-effectiveness, a higher stone clearance rate, and fewer perioperative complications are additional advantages of LCBDE. However, the technique is technically demanding, even for skilled laparoscopic surgeons. Conducting LCBDE in patients with difficult situations, such as SI, is more complex than usual. We herein review published SI patients with choledocholithiasis treated by LCBDE, including our own experience, and this paper focuses on the technical aspects., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Biomarkers for predicting the treatment efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with unresectable hepatocellular carcinoma (uHCC) are crucial. Previous studies demonstrated that C-reactive protein and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) score at baseline predicted treatment outcomes and that patients with uHCC with AFP response, defined as > 15% decline in AFP level within the initial 3 months of ICI-based therapy, had favorable outcomes when receiving ICI-based therapy. However, whether the combination of CRAFITY score and AFP response could be used to predict treatment efficacy of programmed death-1 (PD-1) blockade-based therapy in uHCC patients remains unclear. We retrospectively enrolled 110 consecutive uHCC patients from May 2017 to March 2022. The median ICI treatment duration was 2.85 (1.67-6.63) months, and 87 patients received combination therapies. The objective response and disease control rates were 21.8% and 46.4%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 2.87 (2.16-3.58) months and 8.20 (4.23-12.17) months, respectively. We categorized patients into three groups based on CRAFITY score (2 vs 0/1) and AFP response: patients with a CRAFITY score of 0/1 and AFP response (Group 1), those with a CRAFITY score of 2 and no AFP response (group 3), and those who did not belong to Group 1 and 3 (i.e., Group 2). The combination of CRAFITY score and AFP response could predict disease control and could predict PFS compared with CRAFITY score or AFP response alone. The combination of CRAFITY score and AFP response was an independent predictor of OS (Group 2 vs Group 1, HR: 4.513, 95% CI 1.990-10.234; Group 3 vs Group 1, HR: 3.551, 95% CI 1.544-8.168). Our findings indicated that the combination of CRAFITY score and AFP response could predict disease control, PFS, and OS in uHCC patients receiving PD-1 blockade-based immunotherapy., Competing Interests: Cheng-Yuan Peng has served as an advisory committee member for AbbVie, Bristol-Myers Squibb, Gilead, and Roche. All other coauthors have no conflicts of interest to declare., (AJCR Copyright © 2023.)