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Yi-Hung Lai,1,2 Ming-Ju Wu,3 Hsin-Hua Chen,4,5 Shih-Ping Lin,4,6 Chun-Yi Wu,3,4 Chun-Shih Chin,4,7 Cheng-Hsien Lin,4,8 Sz-Iuan Shiu,4,9 Ying-Cheng Lin,4,9 Hui-Chi Chen,1 Shu-Chin Hou,1 Ching-Wein Chang1 1Department of Nursing, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 3Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 5Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 6Division of Infection, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 7Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 8Division of Hematology and Oncology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 9Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, TaiwanCorrespondence: Ching-Wein Chang, Department of Nursing, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, Email wen6081@gmail.comObjective: A huddle is a short, regular meetings to discuss existing or emerging patient safety issues. Hospital administrators can encourage healthcare staff to voluntarily examine the potential occurrence and severity of risks, thereby enhancing awareness of patient safety. The purpose of this study is to explore the effects of huddle intervention on patient safety culture among medical team members and related factors.Methods: We used a one-group pretest-posttest research design and convenience sampled 109 members of the general internal medicine ward team members from a medical center in central Taiwan. They participated 2 times per week in 15-min huddles from 08:15 to 08:30 in the morning, which lasted for a total of 4 weeks. The process was based on submitted ideas, approved ideas, research ideas and standardization, and data on the safety attitudes questionnaire (SAQ) were collected during the huddles’ intervention pretest and posttest.Results: After the huddle intervention, we found significantly improved scores for safety attitude, teamwork climate (76.49± 16.13 vs 83.26± 13.39, p < 0.001), safety climate (75.07± 16.07 vs 82.63± 13.72, p < 0.001), job satisfaction (73.67± 19.84 vs 83.39± 17.21, p < 0.001), perceptions of management (77.87± 19.99 vs 84.86± 16.03, p < 0.001) and working conditions (78.96± 18.16 vs 86.18± 14.90, p < 0.001). Correlation analyses on the differences between pretest and posttest showed that age had a significant correlation with safety climate (r = 0.22, p = 0.022) and working conditions (r = 0.20, p = 0.035). The number of times to participate in a huddle had a significant correlation with teamwork climate (r = 0.33, p =< .001), safety climate (r = 0.30, p = 0.002), job satisfaction (r = 0.19, p = 0.043), and work conditions (r = 0.28, p = 0.003).Conclusion: Huddles improve clinical team members’ understanding of different dimensions and relate factors of safety attitudes. Implementation of the huddles involved standardized process will help hospital administrators understand the steps to parallel expansion to other wards.Keywords: huddle, patient safety, patient care team

Shih Ping Lin,1– 3 Ching-Wein Chang,4 Chun-Yi Wu,1,5 Chun-Shih Chin,1,6 Cheng-Hsien Lin,1,7 Sz-Iuan Shiu,1,8 Yun-Wen Chen,1,9 Tsai-Hung Yen,1,9 Hui-Chi Chen,4 Yi-Hung Lai,4 Shu-Chin Hou,4 Ming-Ju Wu,3,5 Hsin-Hua Chen1,3,9– 11 1Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Division of Infection, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 4Department of Nursing, Taichung Veterans General Hospital, Taichung, Taiwan; 5Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 6Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 7Division of Hematology and Oncology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 8Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 9Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 10Institute of Biomedical Science and Rong Hsing Research Centre for Translational Medicine, Big Data Center, Chung Hsing University, Taichung, Taiwan; 11School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Hsin-Hua Chen, Division of General Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, Email shc5555@hotmail.comObjective: Huddles are short, regular debriefings that are designed to provide frontline staff and bedside caregivers environments to share problems and identify solutions. Daily huddle implementation could improve medical safety work, problem identification and improvement, situation awareness and teamwork enhancement, the collaboration and communication between professionals and departments, and patient safety. This study aimed evaluated the effectiveness of a hospital-based huddle at a general medical ward in Taiwan.Methods: A Continuous Integration team was conducted by combining multidisciplinary frontline staff to huddle at a 74-bed general medical ward. Team Huddles started twice a week. A physical huddle run board was created, which contained four parts, including idea submitted, idea approved, working on an idea and standardizing. Problems were submitted to the board to be identified, and the solutions were evaluated through huddle discussion. We divided the problems into two groups: quick hits (resolved within 24– 48hrs) and complex issues (resolved > 48hrs). An anonymous questionnaire was designed to evaluate the huddle response.Results: A total of 44 huddles occurred from September 9th, 2020, to September 30th, 2021, and 81 issues were identified and resolved. The majority issues were policy documentation (n=23; 28.4%). Sixty-seven (82.7%) issues were defined as quick hits, and the other fourteen (17.3%) issues were complex. The mean hours to the resolution of quick hits was 5.17 hours, median 3.5 hours, and range from 0.01– 15.4 hours. The mean days to resolve completion issues were 19.73 days, median 7.5 days, and range 3.57– 26.14 days. An overwhelming 92.9% of staff responded that huddles help to expedite the process to reach treatment goals, reduce clinical mistakes, near misses, reduce patient incidences, and help teamwork enhancement, with rating of 4.52 (on a 5-point Likert scale).Conclusion: Implementing of multidisciplinary team huddle improved the accountability of issue identification, problem-solving and teamwork enhancement.Keywords: huddle run, safety culture, teamwork, patient safety

Chung-Lin Lee,1– 5 Chih-Kuang Chuang,6,7 Huei-Ching Chiu,1 Ru-Yi Tu,6 Yun-Ting Lo,5 Ya-Hui Chang,1,5 Shuan-Pei Lin,1,3,5,6,8 Hsiang-Yu Lin1,3– 6,9 1Department of Pediatrics, MacKay Memorial Hospital, Taipei, Taiwan; 2Institute of Clinical Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan; 3Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; 4MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; 5Department of Rare Disease Center, MacKay Memorial Hospital, Taipei, Taiwan; 6Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan; 7College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; 8Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 9Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, TaiwanCorrespondence: Shuan-Pei Lin; Hsiang-Yu LinDepartment of Pediatrics, MacKay Memorial Hospital, No. 92, Sec. 2, Chung-Shan North Road, Taipei, 10449, TaiwanTel +886-2-2543-3535 ext. 3090; +886-2-2543-3535 ext. 3089Fax +886-2-2543-3642Email 4535lin@gmail.com; lxc46199@ms37.hinet.netAbstract: Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive disorder and is one of the lysosomal storage diseases. Patients with MPS IVA have a striking skeletal phenotype but normal intellect. The phenotypic continuum of MPS IVA ranges from severe and rapid progress to mild and slow progress. The diagnosis of MPS IVA is usually suspected based on abnormal bone findings and dysplasia on physical examination and radiographic investigation in the preschool years. In the past, only supportive care was available. Due to the early and severe skeletal abnormalities, the orthopedic specialist was usually the main care provider. However, patients need aggressive monitoring and management of their systemic disease. Therefore, they need an interdisciplinary team for their care, comprising medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. After the US Food and Drug Administration approved elosulfase alfa in 2014, patients older than 5 years could benefit from this treatment. Clinical trials showed clinically meaningful improvements with once-a-week intravenous dosing (2.0 mg/kg per week), significantly improving the 6min walk test, the 3min stair climb test, and respiratory function when compared with placebo. Elosulfase alfa is well-tolerated, and there is a good response indicated by decreasing urine glycosaminoglycans.Keywords: elosulfasealfa, enzyme replacement therapy, GALNS, lysosomal storage disorder, Morquio A, MPS IVA, mucopolysaccharidosis

Pin-Kuei Fu,1–4 Yu-Chi Tung,1 Chen-Yu Wang,2 Sheau-Feng Hwang,5,6 Shin-Pin Lin,7 Chiann-Yi Hsu,8 Duan-Rung Chen9 1Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 2Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Biotechnology, Hungkuang University, Taichung, Taiwan; 4School of Chinese Medicine, China Medical University, Taichung, Taiwan; 5Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan; 6Palliative Care Unit, Taichung Veterans General Hospital, Taichung, Taiwan; 7Computer and Communications Center, Taichung Veterans General Hospital, Taichung, Taiwan; 8Biostatistics Task Force, Taichung Veterans General Hospital, Taichung, Taiwan; 9Institute of Health Behaviors and Community Sciences, National Taiwan University, Taipei, Taiwan Purpose: The unpredictable trajectory of COPD can present challenges for patients when faced with a decision regarding a do-not-resuscitate (DNR) directive. The current retrospective analysis was conducted to investigate factors associated with an early DNR decision (prior to last hospital admission) and differences in care patterns between patients who made DNR directives early vs late. Patients and methods: Electronic health records (EHR) were reviewed from 271 patients with terminal COPD who died in a teaching hospital in Taiwan. Clinical parameters, patterns of DNR decisions, and medical utilization were obtained. Those patients who had a DNR directive earlier than their last (terminal) admission were defined as “Early DNR” (EDNR). Results: A total of 234 (86.3%) patients died with a DNR directive, however only 30% were EDNR. EDNR was associated with increased age (OR=1.07; 95% CI: 1.02–1.12), increased ER visits (OR=1.22; 95% CI: 1.10–1.37), rapid decline in lung function (OR=3.42; 95% CI: 1.12–10.48), resting heart rate ≥100 (OR=3.02; 95% CI: 1.07–8.51), and right-sided heart failure (OR=2.38; 95% CI: 1.10–5.19). The median time period from a DNR directive to death was 68.5 days in EDNR patients and 5 days in “Late DNR” (LDNR) patients, respectively (P

Developing effective methods for helping athletes recover from muscle fatigue is deemed essential, particularly on the eves' important competitions. This study aimed to investigate the effects of acupuncture stimulation on athletes' recovery abilities. Subjects were selected from 30 male elite university basketball players who were randomly assigned to 3 groups: acupuncture group, sham group, and normal (control) group, each containing 10 subjects. Acupuncture was carried out on each athlete in acupuncture group at the Neiguan (PC6) and Zusanli (ST36) acupoints, beginning at 15 min prior to exercise and continuing until exhaustion of the subject. Similar acupuncture was also carried out on each athlete in the sham group but the positions were 1 cm away from the PC6 and ST36 acupoints. No acupuncture was conducted on the athletes in the normal group. During the experiments, each subject performed separate runs on the treadmill. The data of heart rate (HR(max)), oxygen consumption (VO(2max)), and blood lactic acid were measured during the rest period and at 3 recovery points of time (5th, 30th and 60th min) post-exercise. The results showed that the acupuncture group (PC6 and ST36) has significantly lower HR(max), VO(2max) and blood lactic acid than both the sham and normal groups at the 30th min post-exercise. Blood lactic acid of the acupuncture group was also significantly lower than that of the other two groups in the 60th min post-exercise. Our findings have shed some light on the development of effective acupuncture schemes to enhance the recovery ability for elite basketball athletes. [ABSTRACT FROM AUTHOR]

Recently, in-vitro maturation (IVM) of immature human oocytes recovered from non-stimulated follicles has been applied in the treatment of infertility. However, in previous reports, very few embryos cultured in conventional medium have reached the expanded blastocyst stage following in-vitro maturation and fertilization (IVM/IVF). The objective of this study was to investigate whether the developmental competence of human embryos following IVM/IVF could be enhanced by the use of a human ampullary cell co-culture system. Immature human oocytes were aspirated from small follicles at Caesarean section and then cultured in medium containing human menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes were randomly cultured either in conventional culture medium alone or in the co-culture system. Of 48 embryos cultured in conventional medium alone, all arrested at the 2-16-cell stage on day 3 after insemination. Of 46 embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at the 2-16-cell stage. Six embryos (13%) developed to the morula stage. Fourteen embryos (30.4%) developed to expanded blastocysts and two blastocysts were hatching on day 7 after insemination. We conclude that co-culture significantly enhances the development of blastocysts in embryos resulting from IVM/IVF. [ABSTRACT FROM PUBLISHER]

As global warming and the energy crisis receive increasing attention, the development of ecofriendly functional food packaging materials has also garnered significant interest. In this study, curdlan was combined with foaming agents (Cremodan and xanthan) and a crosslinking agent (sodium trimetaphosphate) to form a porous curdlan hydrogel. The material properties of the curdlan hydrogels were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and a thermogravimetric analysis (TGA). Results showed that the 2 % curdlan hydrogel exhibited a high water content (96.2 %), and swelling (89.2 %) and reswelling abilities (89.5 %), with a distinctly porous structure and excellent thermostability. These properties make it suitable for loading carvacrol, resulting in the formation of a carvacrol/curdlan hydrogel. In the results of antimicrobial testing, the carvacrol/curdlan hydrogel showed greater antimicrobial properties against Shewanella putrefaciens (32.3 mm) and Vibrio harveyi (33.1 mm) compared to V. parahaemolyticus (24.5 mm) in inhibition zone test. Noteworthy was the certain degree of antimicrobial ability of the carvacrol/curdlan hydrogel, which continuously exhibited microbial inhibition of the total viable count (TVC) of the no-inoculated and V. parahaemolyticus-inoculated group on sea bass fillets during 6 days of storage. In addition, the carvacrol/curdlan hydrogel inhibited the S. putrefaciens-caused microbial spoilage of fish. However, the continuous antibacterial ability of carvacrol/curdlan hydrogel needs to be improved. In future work, changing the porous size of curdlan hydrogel to control the carvacrol release for elongating the durability and long-term usage will be accomplished to fit the need in functional packaging 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 B.V. All rights reserved.)

Owing to a lack of specific biological functions, bacterial cellulose (BC) has been restricted in its application to the field of active packaging. In this study, we developed antimicrobial packaging materials using foaming BC (FBC) with chitosan (CS) and applied it to the preservation of chilled sea bass. The material property analysis demonstrated that 1.5 % CS/FBC maintained a high water content of 91 %, a swelling ratio of 75.6 %, great stress of 1.61 MPa, and great strain of 1.87 %. CS incorporation into FBC also decreased its crystallinity from 73.39 % to 69.3 %. Meanwhile, 1.5 % CS/FBC also provided great antimicrobial ability against Escherichia coli and Staphylococcus aureus by approximately 2 log colony-forming units/mL inhibition utilizing contact-killing. Results of the preservation assessment indicated that 1.5 % CS/FBC efficiently inhibited Shewanella putrefaciens growth, reduced total volatile basic nitrogen release, and slightly inhibited lipid oxidation. Based on the above results, CS/FBC is an ecofriendly biomaterial produced from a microorganism that possesses high absorbency and strong antibacterial properties, making it suitable for development as antibacterial active packaging., 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.)

Purpose: Mucopolysaccharidosis IVA (MPS IVA) is a rare lysosomal storage disorder arising from a deficiency in N-acetylgalactosamine-6-sulfatase., Methods: From September 2019 to October 2023, a total of 264,843 Taiwanese newborns underwent screening for MPS IVA using dried blood spots and tandem mass spectrometry., Results: Among the 95 referred infants, 9 (9%) were confirmed to have MPS IVA (group 1), 18 (19%) were highly suspected to have MPS IVA (group 2), 61 (64%) were identified as heterozygotes of MPS IVA (group 3), and 7 (7%) were determined not to have MPS IVA (group 4). A total of 34 different GALNS (HGNC:4122) gene variants were identified through our MPS IVA newborn screening program. The most prevalent variant was c.857C>T p.(Thr286Met), found in 33 cases (29%), followed by c.953T>G p.(Met318Arg) in 22 cases (19%). Intravenous enzyme replacement therapy was initiated in 5 patients at ages ranging from 0.3 to 1.7 years. The estimated incidence of MPS IVA in this screening program was 3.4 per 100,000 live births., Conclusion: Because of the progressive nature of MPS IVA, an early diagnosis facilitated by newborn screening and prompt initiation of enzyme replacement therapy before irreversible organ damage occurs may result in improved clinical outcomes., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: The perioperative administration of low-dose ketamine has shown potential in postoperative pain management, opioid sparing, and enhancing pain control. This study aimed to investigate the impact of low-dose ketamine on processed electroencephalography (EEG) signals during anesthesia., Methods: Forty patients with American Society of Anesthesiologists physical status I-II undergoing elective gynecological surgery were enrolled. EEG monitoring was initiated upon induction of anesthesia. Anesthesia was maintained with desflurane and alfentanil immediately after induction. Fifteen minutes after induction, the ketamine group received a 0.3 mg/kg bolus followed by 0.05 mg/kg/h infusion until completion of surgery. The control group received equivalent saline. Postoperative assessments included pain score (visual analog scale), morphine usage, and quality of recovery., Results: The ketamine group had significantly higher Patient State Index (PSi) values at 10, 20, and 30 minutes after ketamine administration compared to the controls. Ketamine administration led to significant alterations in EEG patterns, including reduced relative power in delta and theta frequency bands, and increased relative power in beta and gamma frequency bands at 10 minutes post-administration. Relative power in the alpha frequency band significantly decreased at 10, 20, and 30 minutes post-administration. However, there were no differences in intraoperative alfentanil consumption, postoperative morphine usage, and pain scores between the two groups., Conclusion: Low-dose ketamine administration during desflurane anesthesia led to notable changes in EEG patterns and PSi values. These findings provide valuable insights into the impact of ketamine on brain activity, and offer essential information for clinical anesthesiologists., 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.)

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset., Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset., Design, Setting, and Participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023., Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone., Main Outcomes and Measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage., Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages., Conclusions and Relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study., Trial Registration: ClinicalTrials.gov Identifier: NCT03805308.

Kabuki syndrome (KS) is a rare genetic disorder characterized by distinct facial features, intellectual disability, and multiple congenital anomalies. We conducted a comprehensive analysis of the genetic and phenotypic spectrum of KS in a Taiwanese patient group of 23 patients. KMT2D variants were found in 22 individuals, with missense (26.1%), nonsense (21.7%), and frameshift (17.4%) variants being the most prevalent. One patient had a KMT2D variant of uncertain significance. The most common clinical characteristics included distinct facial features (100%), intellectual disability (100%), developmental delay (95.7%), speech delay (78.3%), hypotonia (69.6%), congenital heart abnormalities (69.6%), and recurrent infections (65.2%). Other abnormalities included hearing loss (39.1%), seizures (26.1%), cleft palate (26.1%), and renal anomalies (21.7%). This study broadens the mutational and phenotypic spectrum of KS in the Taiwanese population, highlighting the importance of comprehensive genetic testing and multidisciplinary clinical evaluations for diagnosis and treatment.

Background: We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole-exome sequencing revealed a de novo gain-of-function variant, p.Tyr715Cys, in the C-terminal domain of ClC-7 encoded by CLCN7., Methods: Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents., Results: The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC-7 antiporter activity in maintaining appropriate lysosomal pH., Conclusion: Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype-phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC-7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Ethnopharmacological Relevance: The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties., Aim of the Study: The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy., Methods and Materials: G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-β1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations., Results: The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-β1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-β receptor 1., Conclusion: Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts., 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/purpose: Congenital nephrotic syndrome (CNS) is one of the important causes of end-stage kidney disease in children. Studies on the genotype, phenotype, and clinical outcome in infants with CNS caused by genetic mutations are scarce., Methods: We analyzed the genetic background, clinical manifestations, treatment response, and prognosis of pediatric patients with CNS in Taiwan., Results: Fifteen infants with CNS were enrolled, and 11 patients of median age 21 (interquartile range 3∼44) days caused by genetic mutations from 10 unrelated families were included in the study. Of the eleven patients, 9 had extra-renal manifestations including microcephaly, facial dysmorphism, and skeletal anomalies. More than two-thirds of the patients had disease onset before 1 month of age. Diffuse meningeal sclerosis was the most common histological characteristic. Whole exome sequencing followed by direct Sanger sequence revealed mutations in OSGEP (R247Q), WT1 (R366H and R467Q), LAMB2 (Q1209∗ and c. 5432-5451 19 bp deletion), NUP93 (D302V), and LAGE3 (c.188+1G > A). Three of the variants were novel. Corticosteroids and/or immunosuppressants were administered in 2 patients, but both were refractory to treatment. During the mean 3.5 years of follow-up, all but two died of uremia and sepsis. The two survivors reached end-stage kidney disease and required peritoneal dialysis, and one of them underwent uneventful renal transplantation., Conclusion: The majority of patients with CNS in Taiwan were caused by OSGEP followed by WT1 mutation. R247Q is the hotspot mutation of OSGEP in Taiwan. CNS patients in Taiwan suffer from significant morbidity and mortality., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Muscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity., Methods: This study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification-negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%)., Results: WES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes., Conclusion: WES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling., 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., (Copyright © 2024 Lee, Chuang, Chiu, Chang, Tu, Lo, Lin and Lin.)

Background: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments., Materials and Methods: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included., Results: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001)., Conclusions: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT., Methods: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia., Results: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia., Conclusions: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Mucopolysaccharidosis (MPS) type II is caused by a deficiency of iduronate-2-sulfatase and is characterized by the accumulation of glycosaminoglycans (GAGs). Without effective therapy, the severe form of MPS II causes progressive neurodegeneration and death. This study generated multiple clones of induced pluripotent stem cells (iPSCs) and their isogenic controls (ISO) from four patients with MPS II neurodegeneration. MPS II-iPSCs were successfully differentiated into cortical neurons with characteristic biochemical and cellular phenotypes, including axonal beadings positive for phosphorylated tau, and unique electrophysiological abnormalities, which were mostly rescued in ISO-iPSC-derived neurons. RNA sequencing analysis uncovered dysregulation in three major signaling pathways, including Wnt/β-catenin, p38 MAP kinase, and calcium pathways, in mature MPS II neurons. Further mechanistic characterization indicated that the dysregulation in calcium signaling led to an elevated intracellular calcium level, which might be linked to compromised survival of neurons. Based on these dysregulated pathways, several related chemicals and drugs were tested using this mature MPS II neuron-based platform and a small-molecule glycogen synthase kinase-3β inhibitor was found to significantly rescue neuronal survival, neurite morphology, and electrophysiological abnormalities in MPS II neurons. Our results underscore that the MPS II-iPSC-based platform significantly contributes to unraveling the mechanisms underlying the degeneration and death of MPS II neurons and assessing potential drug candidates. Furthermore, the study revealed that targeting the specific dysregulation of signaling pathways downstream of GAG accumulation in MPS II neurons with a well-characterized drug could potentially ameliorate neuronal degeneration., (© 2024. The Author(s).)

Congenital heart defects (CHDs) affect a substantial proportion of patients with Kabuki syndrome. However, the prevalence and type of CHD and the genotype-phenotype correlations in Asian populations are not fully elucidated. This study performed a retrospective analysis of 23 Taiwanese patients with molecularly confirmed Kabuki syndrome. Twenty-two patients presented with pathogenic variants in the KMT2D gene. Comprehensive clinical assessments were performed. A literature review was conducted to summarize the spectrum of CHDs in patients with Kabuki syndrome. In total, 16 (73.9%) of 22 patients with pathogenic KMT2D variants had CHDs. The most common types of CHD were atrial septal defects (37.5%), ventricular septal defects (18.8%), coarctation of the aorta (18.8%), bicuspid aortic valve (12.5%), persistent left superior vena cava (12.5%), mitral valve prolapse (12.5%), mitral regurgitation (12.5%), and patent ductus arteriosus (12.5%). Other cardiac abnormalities were less common. Further, there were no clear genotype-phenotype correlations found. A literature review revealed similar patterns of CHDs, with a predominance of left-sided obstructive lesions and septal defects. In conclusion, the most common types of CHDs in Taiwanese patients with Kabuki syndrome who presented with KMT2D mutations are left-sided obstructive lesions and septal defects.

Background: The aim of this study was to examine the risk factors associated with the use of vasopressors to prevent hypotension that occurs after spinal anesthesia during cesarean section. Although the prophylactic use of vasopressors is already suggested as routine care in many parts of the world, the occurrence of spinal anesthesia-induced hypotension (SAIH) is still common in parturients., Methods: This retrospective study included parturients receiving elective cesarean deliveries under spinal anesthesia from April 2016 to March 2020. Risk factors related to ephedrine dosage were analyzed using a hurdle model, and risk factors related to SAIH were further analyzed with logistic regression., Results: Five risk factors, namely maternal body mass index (BMI, p < 0.001), baseline systolic blood pressure (SBP, p < 0.001), baseline heart rate (HR, p = 0.047), multiparity ( p = 0.003), and large fetal weight ( p = 0.005) were significantly associated with the requirement for ephedrine. Furthermore, a higher ephedrine dosage was significantly associated with maternal BMI ( p < 0.001), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p = 0.027), large fetal weight ( p = 0.030), maternal age ( p = 0.009), and twin pregnancies ( p < 0.001). Logistic regression analysis also showed that the same five risk factors-maternal BMI ( p = 0.030), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p < 0.001), and large fetal weight ( p < 0.001)-were significantly associated with SAIH, even in cases where vasopressors were administered., Conclusion: These findings can be useful for clinicians when deciding the dose of prophylactic ephedrine or phenylephrine to prevent SAIH., 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.)

Purpose: Weight cycling is a phenomenon characterized by fluctuating body weight that is commonly observed in individuals employing intentional weight loss methods. Despite its prevalence, the impact of weight cycling on health remains equivocal. The current investigation aimed to examine the effects of weight cycling on liver health., Methods: The weight cycling model was established by switching the feeding method of mice between ad libitum (AL) and restricted intake (DR or 60% of AL) of the breeding diet to cause weight gain and weight loss, respectively. The weight cycling model comprised two and a half cycles, with one group terminating the experience during the weight-gain period (S-AL) and the other during the weight-loss period (S-DR). Liver tissue was collected to investigate morphology alterations, apoptosis, lipid metabolism, and mitochondrial homeostasis., Results: The results demonstrated that the termination point of weight cycling affected body weight and hepatic steatosis. All parameters examined in the S-DR mice exhibited a comparable trend to those observed in the DR mice. Notably, S-AL mice showed a significant increase in lipid metabolism-related proteins in the liver compared to AL-fed mice, along with reduced lipid droplets. Moreover, hepatic apoptosis and fibrosis were exacerbated in the S-AL mice compared to AL mice, whereas mitochondrial fusion, biogenesis, and mitophagy were decreased in the S-AL mice., Conclusion: Weight cycling ending in weight gain exacerbated hepatic fibrosis, potentially by inducing apoptosis or disrupting mitochondrial homeostasis. Conversely, weight cycling ending in weight loss demonstrated beneficial effects on hepatic health., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Objectives: Huddles among members of interdisciplinary medical teams involve short stand-up sessions and allow team members to focus on existing or emerging patient safety issues, thereby facilitating team communication. Hospital managers are able to recognize the current situation of the organization through patient safety attitudes, strengthen team members' awareness of patient safety, and improve the quality of health care. The purpose of this study was to determine the effects of huddles on improving team members' attitudes toward patient safety., Methods: We used a quasi-experimental design and selected 2 adult wards with similar properties as the experimental and comparison groups by convenience sampling. Data collection was from December 1, 2021, to June 30, 2022, at a teaching hospital in central Taiwan. Team members of the ward performing huddles formed the experimental group, and they participated 2 times per week in 15-minute huddles from 8:15 to 8:30 am for a total of 4 weeks. The comparison group adopted the routine team care process. Both groups completed the Safety Attitudes Questionnaire during the pre- and post-tests of the study., Results: The experimental group scored significantly higher in the post-test than in the pre-test in all aspects of safety attitudes, with the exception of stress recognition. These improved aspects were teamwork climate (76.47 ± 15.90 vs 83.29 ± 13.52, P < .001), safety climate (75.94 ± 16.14 vs 82.81 ± 13.74, P < .001), job satisfaction (74.34 ± 20.22 vs 84.40 ± 17.22, P <.001), perceptions of management (78.02 ± 19.99 vs 85.51 ± 15.97, P < .001), and working conditions (78.85 ± 17.87 vs 86.81 ± 14.74, P < .001)., Conclusion: Through the huddles, clinical team members improved their understanding of different aspects of safety attitudes. Such a study provided ward units with real-time improvement and adjustment in terms of patient safety during their medical work processes with better patient safety., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The early detection of cognitive decline in Parkinson's disease is important for providing drug therapy and non-pharmacological management. The circulating microRNAs present in plasma are promising biomarkers of PD with dementia (PDD) due to their critical roles in synaptic plasticity and the regulation of neurodegeneration-associated proteins. In this study, we aimed to identify plasma microRNAs that may differentiate PD with or without cognitive impairment. Global microRNA expression was obtained from a discovery set of 123 participants who were divided into four groups, namely normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI), and PDD, using next-generation sequencing. The BOLD selector was used for microRNA candidate selection. Six miRNAs, namely miR-203a-3p, miR-626, miR-662, miR-3182, miR-4274, and miR-4295, were clustered as potential candidates for use in identifying PDND from PD-MCI. Another independent cohort of 120 participants was further recruited in a validation step in order to detect candidate microRNAs via droplet digital PCR (ddPCR), which was used for its high sensitivity in detecting low miRNA concentrations. Our results show that the ratio of miR-203a-3p/miR-16-5p, in which miR-16-5p was used as a reference control miRNA, was significantly increased in PDD compared to that seen in PD-MCI and PDND individually, and was negatively correlated with the MoCA scores (r = -0.237, p = 0.024) in patients with PD. However, there was no significant difference in the ratio of miR-203a-3p/miR-16-5p between HC and PDND, PD-MCI, or PDD individually. The ROC curve of the logistic regression model, factoring in the variables of age, the ratio of miR-203a-3p/miR-16-5p, and the UPDRS III score, demonstrated an AUC of 0.883. Our findings suggest that the ratio of miR-203a-3p/miR-16-5p, used with age and motor score, could be a predictor of dementia among PD patients.

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC 0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC 0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC 0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Human adipose-derived stem cells (ASCs) have shown immense potential for regenerative medicine. Our previous work demonstrated that chitosan nano-deposited surfaces induce spheroid formation and differentiation of ASCs for treating sciatic nerve injuries. However, the underlying cell fate and differentiation mechanisms of ASC-derived spheroids remain unknown. Here, we investigate the epigenetic regulation and signaling coordination of these therapeutic spheroids. During spheroid formation, we observed significant increases in histone 3 trimethylation at lysine 4 (H3K4me3), lysine 9 (H3K9me3), and lysine 27 (H3K27me3), accompanied by increased histone deacetylase (HDAC) activities and decreased histone acetyltransferase activities. Additionally, HDAC5 translocated from the cytoplasm to the nucleus, along with increased nuclear HDAC5 activities. Utilizing single-cell RNA sequencing (scRNA-seq), we analyzed the chitosan-induced ASC spheroids and discovered distinct cluster subpopulations, cell fate trajectories, differentiation traits, and signaling networks using the 10x Genomics platform, R studio/language, and the Ingenuity Pathway Analysis (IPA) tool. Specific subpopulations were identified within the spheroids that corresponded to a transient reprogramming state (Cluster 6) and the endpoint cell state (Cluster 3). H3K4me3 and H3K9me3 were discovered as key epigenetic regulators by IPA to initiate stem cell differentiation in Cluster 6 cells, and confirmed by qPCR and their respective histone methyltransferase inhibitors: SNDX-5613 (a KMT2A inhibitor for H3K4me3) and SUVi (an SUV39H1 inhibitor for H3K9me3). Moreover, H3K9me3 and HDAC5 were involved in regulating downstream signaling and neuronal markers during differentiation in Cluster 3 cells. These findings emphasize the critical role of epigenetic regulation, particularly H3K4me3, H3K9me3, and HDAC5, in shaping stem cell fate and directing lineage-specific differentiation., (© The Author(s) 2023. Published by Oxford University Press.)

In this paper, we explore the challenges associated with biomarker identification for diagnosis purpose in biomedical experiments, and propose a novel approach to handle the above challenging scenario via the generalization of the Dantzig selector. To improve the efficiency of the regularization method, we introduce a transformation from an inherent nonlinear programming due to its nonlinear link function into a linear programming framework under a reasonable assumption on the logistic probability range. We illustrate the use of our method on an experiment with binary response, showing superior performance on biomarker identification studies when compared to their conventional analysis. Our proposed method does not merely serve as a variable/biomarker selection tool, its ranking of variable importance provides valuable reference information for practitioners to reach informed decisions regarding the prioritization of factors for further investigations., Competing Interests: Declaration of competing interest We declare that this paper has not been previously published in any form, and it is not under consideration nor in press elsewhere. We know of no conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024. Published by Elsevier B.V.)

Surface modification of durian rind cellulose (DCell) was done by utilizing the strong coordination effect of polyphenol-based metal phenolic networks (MPNs). MPNs from Fe(III)-tannic acid (FTN) and Fe(III)-gallic acid (FGN) were coated on DCell via a self-assembly reaction at pH 8, resulting in adsorbent composites of FTN@DCell and FGN@DCell for removal of Cr(VI). Batch adsorption experiments revealed that FTN coating resulted in an adsorbent composite with higher adsorption capacity than FGN coating, owing to the greater number of additional adsorption sites from phenolic hydroxyl groups of tannic acid. FTN@DCell exhibits an equilibrium adsorption capacity at 30°C of 110.9 mg/g for Cr(VI), significantly higher than FGN@DCell (73.63 mg/g); the adsorption capacity was increased at higher temperature (i.e., 155.8 and 116.8 mg/g at 50°C for FTN@DCell and FGN@DCell, respectively). Effects of pH, adsorbent dose, initial concentration, and coexisting ions on Cr(VI) removal were investigated. The kinetics fractal-based model Brouers-Sotolongo indicates the 1st and 2nd order reaction for Cr(VI) adsorption on FTN@DCell and FGN@DCell, respectively. The isotherm data can be described with a fractal-based model, which implies the heterogeneous nature of the adsorbent surface sites. The Cr(VI) adsorption via surface complexation with phenolic hydroxyl groups was confirmed by evaluating the functional groups shifting. FGN@DCell and FTN@DCell were found to have good reusability, maintaining over 50 % of their adsorption efficiency after four adsorption-desorption cycles. Environmental assessment with Arabidopsis thaliana demonstrated their potential in eliminating the Cr(VI) phytotoxic effect. Thus, this study has shown the efficient and economical conversion of durian waste into environmentally benign adsorbent for heavy metal treatment., 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 Elsevier B.V. All rights reserved.)

By employing co-cultivation technique on Komagataeibacter xylinum and Lactococcus lactis subsp. lactis, bacterial cellulose (BC)/nisin films with improved antibacterial activity and mechanical properties were successfully produced. The findings demonstrated that increased nisin production is associated with an upregulation of gene expression. Furthermore, results from Scanning electronic microscopy (SEM), Fourier transform infrared (FTIR), X-ray diffraction (XRD), and Thermogravimetric analysis (TG) confirmed the integration of nisin within BC. While being biocompatible with human cells, the BC/nisin composites exhibited antimicrobial activity. Moreover, mechanical property analyses showed a noticeable improvement in Young's modulus, tensile strength, and elongation at break by 161, 271, and 195 %, respectively. Additionally, the nisin content in fermentation broth was improved by 170 % after co-culture, accompanied by an 8 % increase in pH as well as 10 % decrease in lactate concentration. Real-time reverse transcription PCR analysis revealed an upregulation of 11 nisin-related genes after co-cultivation, with the highest increase in nisA (5.76-fold). To our knowledge, this is the first study which demonstrates that an increase in secondary metabolites after co-culturing is modulated by gene expression. This research offers a cost-effective approach for BC composite production and presents a technique to enhance metabolite concentration through the regulation of relevant genes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The Swarm Intelligence Based (SIB) method has widely been applied to efficient optimization in many fields with discrete solution domains. E-commerce raises the importance of designing suitable selling strategies, including channel- and direct sales, and the mix of them, but researchers in this field seldom employ advanced metaheuristic techniques in their optimization problem due to the complexities caused by the high-dimensional problems and cross-dimensional constraints., Method: In this work, we introduce an extension of the SIB method that can simultaneously tackle these two challenges. To pursue faster computing, CPU parallelization techniques are employed for algorithm acceleration., Results: The performance of the SIB method is examined on the problems of designing selling schemes in different scales. It outperforms the Genetic Algorithm (GA) in terms of both the speed of convergence and the optimized capacity as measured using improvement multipliers., 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., (Copyright © 2024 Liu, Phoa, Chen-Burger and Lin.)

Background: Transthyretin cardiomyopathy (ATTR-CM) is a debilitating disease that has received much attention since the emergence of novel treatments. The Transthyretin Cardiomyopathy Clinical Trial showed that tafamidis, a transthyretin tetramer stabilizer, effectively reduced the declines in functional capacity and quality of life. However, Ala97Ser (A97S) hereditary ATTR-CM is underrepresented in major ATTR-CM tafamidis trials., Objectives: We aim to investigate the change in global longitudinal strain (GLS) of A97S ATTR-CM patients after 12 months of tafamidis treatment., Methods: We retrospectively analysed a prospective cohort of patients with A97S ATTR-CM who received tafamidis meglumine (61 mg/day) at the National Taiwan University Hospital. Echocardiography with speckle tracking strain analysis was performed at baseline and 12 months after treatment., Results: In all, 20 patients were included in the cohort. The baseline left ventricular ejection fraction (LVEF) and interventricular septum (IVS) thickness were 59.20 ± 13.23% and 15.10 ± 3.43 mm, respectively. After 12 months of tafamidis treatment, the LVEF and IVS were 61.83 ± 15.60% ( p  = 0.244) and 14.59 ± 3.03 mm ( p  = 0.623), respectively. GLS significantly improved from -12.70 ± 3.31% to -13.72 ± 3.17% ( p  = 0.048), and longitudinal strain (LS) in apical and middle segments significantly improved from -16.05 ± 4.82% to -17.95 ± 3.48% ( p  = 0.039) and -11.89 ± 4.38% to -13.58 ± 3.12% ( p  = 0.039), respectively. Subgroup analysis showed that patients with LVEF < 50% had a better treatment response and improvement in GLS. The patients with an IVS ⩾ 13 mm had an improvement in two-chamber LS from -10.92 ± 4.25% to -13.15 ± 3.87% ( p  = 0.042) and an improvement in apical left ventricular LS from -15.30 ± 5.35% to -17.82 ± 3.99% ( p  = 0.031)., Conclusion: Tafamidis significantly improved GLS, and particularly apical and middle LS in A97S ATTR-CM patients., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Ethnopharmacological Relevance: Particulate matter 2.5 (PM2.5) is a dangerous airborne pollutant that has become a global issue due to its detrimental effect on macrophages. Chenopodium formosanum Koidz (Djulis), a native plant from Taiwan well known for its high antioxidant content and is frequently used in ethnomedicine, shows promise as a novel phytomedicine to combat against oxidative stress caused by PM2.5. However, the protective mechanism of Djulis against PM2.5 still remains unclear., Aim of the Study: This study aimed to characterize the deleterious effect of emerging PM2.5 contaminants on the alveolar macrophage cell of the respiratory system and explore the underlying mechanisms in the suppression of PM2.5-induced inflammation using the extract of fermented Djulis., Methods and Materials: RNA sequencing, immunoblot, and ChIP assay approaches were used to gain insight into the deleterious effect of PM2.5 on the macrophage cell at the transcriptional and translational level; and to elucidate the contribution of fermented Djulis extract (FCS) as the remedy of PM-induced MH-S cell inflammation. UHPLC-ESI-MS/MS and LC-QQQ/MS were used to identify the bioactive compounds potentially contributing to phytomedicinal properties in the water fraction of FCS. Multiple ligands docking analysis was conducted to predict the in-silico interaction of Djulis metabolites and NF-κB., Results: Here, we showed that PM2.5 exposure at 200 ppm accelerated the production of intracellular ROS and phosphorylated NF-κB (p-NFκB), and negatively affecting the alveolar macrophage cell viability. Treating the cells with water-extracted FCS can restore their viability to 76% while simultaneously suppressing the generation of ROS and p-NFκB up to 38%. These ameliorative effects can be attributed to the occurrence of bioactive compounds such as gluconic acid, uridine, pantothenic acid, L-pyroglutamic acid, L-(-)-malic acid, and acetyl-L-carnitine in the water-extracted FCS which potentially dock to the RELA subunit site and consequently inhibit NF-κB activity along with its downstream inflammation signaling cascade., Conclusion: This work demonstrated the hazardous effect of PM2.5 on alveolar macrophage and unveiled the potential of FCS as a therapeutic phytomedicine to alleviate PM-induced inflammation., 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 Elsevier B.V. All rights reserved.)

Response surface models (RSMs) are a new trend in modern anesthesia. RSMs have demonstrated significant applicability in the field of anesthesia. However, the comparative analysis between RSMs and logistic regression (LR) in different surgeries remains relatively limited in the current literature. We hypothesized that using a total intravenous anesthesia (TIVA) technique with the response surface model (RSM) and logistic regression (LR) would predict the emergence from anesthesia in patients undergoing video-assisted thoracotomy surgery (VATS). This study aimed to prove that LR, like the RSM, can be used to improve patient safety and achieve enhanced recovery after surgery (ERAS). This was a prospective, observational study with data reanalysis. Twenty-nine patients (American Society of Anesthesiologists (ASA) class II and III) who underwent VATS for elective pulmonary or mediastinal surgery under TIVA were enrolled. We monitored the emergence from anesthesia, and the precise time point of regained response (RR) was noted. The influence of varying concentrations was examined and incorporated into both the RSM and LR. The receiver operating characteristic (ROC) curve area for Greco and LR models was 0.979 (confidence interval: 0.987 to 0.990) and 0.989 (confidence interval: 0.989 to 0.990), respectively. The two models had no significant differences in predicting the probability of regaining response. In conclusion, the LR model was effective and can be applied to patients undergoing VATS or other procedures of similar modalities. Furthermore, the RSM is significantly more sophisticated and has an accuracy similar to that of the LR model; however, the LR model is more accessible. Therefore, the LR model is a simpler tool for predicting arousal in patients undergoing VATS under TIVA with Remifentanil and Propofol.

Background/aim: X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH., Patients and Methods: We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing., Results: The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis., Conclusion: Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.