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Under Taiwan's National Health Insurance (NHI) system, it's crucial for all healthcare providers to accurately submit medical expense claims to the National Health Insurance Administration (NHIA) to avoid incorrect deductions. With changes in healthcare policies and adjustments in hospital management strategies, the complexity of claiming rules has resulted in hospitals expending significant manpower and time on the medical expense claims process. Therefore, this study utilizes the Lean Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) management approach to identify wasteful and non-value-added steps in the process. Simultaneously, it introduces Robotic Process Automation (RPA) tools to replace manual operations. After implementation, the study effectively reduces the process time by 380 min and enhances Process Cycle Efficiency (PCE) from 69.07 to 95.54%. This research validates a real-world case of Lean digital transformation in healthcare institutions. It enables human resources to be allocated to more valuable and creative tasks while assisting hospitals in providing more comprehensive and patient-centric services., (© 2024. The Author(s).)

Introduction: Impaired lung function has been observed in patients following COVID-19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID-19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID-19 infection, focusing on the relationship between time and symptoms., Material and Method: The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date., Result: The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways., Conclusion: The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post-COVID-19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post-COVID-19 patients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren's syndrome dry eye disease) from non-Sjögren's dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren's and Sjögren's syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren's dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren's syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p < 0.0001). Further, lactoferrin levels were lower in patients with Sjögren's syndrome dry eye disease than in those with non-Sjögren's dry eye disease (p < 0.001). Our cost-effective, antibody-free, highly sensitive photo-detection device for evaluating tear lactoferrin levels can assist ophthalmologists in differentiating different types of dry eye diseases., (© 2024. The Author(s).)

Introduction: Information about causes of injury is key for injury prevention efforts. Historically, cause-of-injury coding in clinical practice has been incomplete due to the need for extra diagnosis codes in the International Classification of Diseases-Ninth Revision-Clinical Modification (ICD-9-CM) coding. The transition to ICD-10-CM and increased use of clinical support software for diagnosis coding is expected to improve completeness of cause-of-injury coding. This paper assesses the recording of external cause-of-injury codes specifically for those diagnoses where an additional code is still required., Methods: We used electronic health record and claims data from 10 health systems from October 2015 to December 2021 to identify all inpatient and emergency encounters with a primary diagnosis of injury. The proportion of encounters that also included a valid external cause-of-injury code is presented., Results: Most health systems had high rates of cause-of-injury coding: over 85% in emergency departments and over 75% in inpatient encounters with primary injury diagnoses. However, several sites had lower rates in both settings. State mandates were associated with consistently high external cause recording., Conclusions: Completeness of cause-of-injury coding improved since the adoption of ICD-10-CM coding and increased slightly over the study period at most sites. However, significant variation remained, and completeness of cause-of-injury coding in any diagnosis data used for injury prevention planning should be empirically determined., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This study explores the synthesis and characterization of aggregation-induced emission enhancement (AIEE)-active gold nanoclusters (AuNCs), focusing on their near-infrared luminescence properties and potential applications in biological imaging. These AIEE-active AuNCs were synthesized via the NaBH 4 -mediated reduction of HAuCl 4 in the presence of peptides. We systematically investigated the influence of the peptide sequence on the optical features of the AuNCs, highlighting the role of glutamic acid in enhancing their quantum yield (QY). Among the synthesized peptide-stabilized AuNCs, EECEE-stabilized AuNCs exhibited the maximum QY and a pronounced AIEE effect at pH 5.0, making them suitable for the luminescence imaging of intracellular lysosomes. The AIEE characteristic of the EECEE-stabilized AuNCs was demonstrated through examinations using transmission electron microscopy, dynamic light scattering, zeta potential analysis, and single-particle imaging. The formation of the EECEE-stabilized AuNCs was confirmed by size-exclusion chromatography and mass spectrometry. Spectroscopic and electrochemical examinations uncover the formation process of EECEE-stabilized AuNCs, comprising EECEE-mediated reduction, NaBH 4 -induced nucleation, complex aggregation, and subsequent cluster growth. Furthermore, we demonstrated the utility of these AuNCs as luminescent probes for intracellular lysosomal imaging, leveraging their pH-responsive AIEE behavior. Additionally, cyclic arginylglycylaspartic acid (RGD)-modified AIEE dots, derived from cyclic RGD-linked peptide-induced aggregation of EECEE-stabilized AuNCs, were developed for single- and two-photon luminescence imaging of α v β 3 integrin receptor-positive cancer cells.

Background: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis and pneumonia in infants and young children. Starting in December 2010, RSV monoclonal antibody (RSV mAb) was endorsed by Taiwan National Health Insurance and given to children with prematurity and/or congenital heart diseases, which are considered high-risk factors for severe RSV diseases. Investigating other important contributing risk factors is warranted., Methods: We conducted a cohort study at National Taiwan University Hospital to determine the rate of severe outcomes among children hospitalized due to RSV infection from 2008 to 2018. Adjusted for age, sex and birth cohorts born before and after RSV mAb endorsement, we identified risk factors for severe RSV infection, defined as the requirement of invasive ventilator support., Results: There were 1985 admissions due to RSV infections. Among them, 66 patients (3.3%) had severe RSV infection. The proportion of severe RSV infections decreased significantly after RSV mAb endorsement. Multivariable analysis revealed that age <1.5 months and cardiovascular and congenital/genetic diseases were high-risk underlying conditions. In addition, bacterial coinfections, elevated creatinine levels and initial abnormal chest radiograph findings posed warning signs for severe RSV infection., Conclusions: Children younger than 1.5 months of age with cardiovascular or congenital/genetic diseases were predisposed to severe RSV infection and might benefit from RSV mAb prophylaxis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Two Gram-stain-positive, aerobic, oxidase- and catalase-negative, non-motile, and short rod-shaped actinomycetes, named SYSU T00b441 T and SYSU T00b490, were isolated from tidal flat sediment located in Guangdong province, PR China. The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU T00b441 T and SYSU T00b490 were 99.3, 99.5 and 97.1 %, respectively. Strains SYSU T00b441 T and SYSU T00b490 exhibited the highest 16S rRNA gene sequence similarities to Actinotalea ferrariae CF 5-4 T (97.1 %/98.2 %), with ANI values of 74.01/73.88 % and dDDH values of 20.5/20.4 %. In the phylogenomic tree, the two isolates were affiliated with the genus Actinotalea . The genomes of strains SYSU T00b441 T and SYSU T00b490 were 3.31 and 3.34 Mb, and both had DNA G+C contents of 72.8 mol%, coding 3077 and 3085 CDSs, three and three rRNA genes, and 53 and 51 tRNAs, respectively. Growth occurred at 15-40 °C (optimum, 28-30 °C), pH 4.0-10.0 (optimum, 7.0) and in the presence of 0-7 % (w/v) NaCl (optimum, 3 %). The major fatty acids (>10  %) of strains SYSU T00b441 T and SYSU T00b490 were anteiso-C 15 : 0 and C 16 : 0 . The major respiratory quinone was identified as MK-10(H 4 ). The polar lipids of strains SYSU T00b441 T and SYSU T00b490 were diphosphatidyl glycerol, phosphatidylglycerol, phosphoglycolipid, phosphatidyl ethanolamine, two phosphatidylinositol mannosides, two glycolipids and two phospholipids. Based on these data, the two strains (SYSU T00b441 T and SYSU T00b490) represent a novel species of the genus Actinotalea , for which the name Actinotalea lenta sp. nov is proposed. The type strain is SYSU T00b441 T (=GDMCC 1.3827 T =KCTC 49943 T ).

High-entropy alloys (HEAs) provide new research avenues for alloy combinations in the periodic table, opening numerous possibilities in novel-alloy applications. However, their electrical characteristics have been relatively underexplored. The challenge in establishing an HEA electrical conductivity model lies in the changes in electronic characteristics caused by lattice distortion and complexity of nanostructures. Here we show a low-frequency electrical conductivity model for the Nb-Mo-Ta-W HEA system. The cocktail effect is found to explain trends in electrical-conductivity changes in HEAs, while the magnitude of the reduction is understood by the calculated plasma frequency, free electron density, and measured relaxation time by terahertz spectroscopy. As a result, the refractory HEA Nb 15 Mo 35 Ta 15 W 35 thin film exhibits both high hardness and excellent conductivity. This combination of Nb 15 Mo 35 Ta 15 W 35 makes it suitable for applications in atomic force microscopy probe coating, significantly improving their wear resistance and atomic-scale image resolution., (© 2024. The Author(s).)

Angiostrongylus cantonensis , a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigated pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis . The study evaluates the critical role of Cav-1 regulation through the TLR4/MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis -induced meningoencephalitis.

Purpose: Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota's contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods., Methods: Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis., Results: A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. "Probiotics" and "inflammation" are the keywords in the research., Conclusion: This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed., 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 Luo, Huang, Chen, Lu, Zhou, Gong, Shen and Wang.)

Due to variability in pharmacokinetics and pharmacodynamics, clinical outcomes of antimicrobial drug therapy vary between patients. As such, personalised medication management, considering both pharmacokinetics and pharmacodynamics, is a growing concept of interest in the field of infectious diseases. Therapeutic drug monitoring is used to adjust and individualise drug regimens until predefined pharmacokinetic exposure targets are achieved. Minimum inhibitory concentration (drug susceptibility) is the best available pharmacodynamic parameter but is associated with many limitations. Identification of other pharmacodynamic parameters is necessary. Repurposing diagnostic biomarkers as pharmacodynamic parameters to evaluate treatment response is attractive. When combined with therapeutic drug monitoring, it could facilitate making more informed dosing decisions. We believe the approach has potential and justifies further research.

Objectives: The aim of this meta-analysis is to evaluate the potential benefits of postoperative radiotherapy (PORT) in patients with pN1 oral cavity squamous cell carcinoma., Methods: A literature search through major databases was conducted until January 2023. The adjusted hazard ratio (aHR) or risk ratio (RR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled., Results: Ten studies published between 2005 and 2022, with a pooled patient population of 2888, were included in this meta-analysis. Due to differences in study design and reported outcomes, the studies were categorized into distinct groups. In pN1 patients without extranodal extension (ENE), PORT was associated with a significant improvement in overall survival (OS) (aHR 0.76, 95% CI: 0.61-0.94). In pN1 patients without ENE and positive margins, PORT improved OS (aHR 0.71, 95% CI: 0.56-0.89) and was associated with a lower regional recurrence rate (RR 0.35, 95% CI: 0.15-0.83). However, in pN1 patients without ENE, positive margins, perineural invasion, and lymphovascular invasion, there were no significant differences observed between the PORT and observation groups in either 5-year OS (RR 0.48, 95% CI: 0.07-3.41) or 5-year disease-free survival (RR 0.37, 95% CI: 0.07-2.06)., Conclusions: The current study demonstrated that PORT has the potential to improve OS in pN1 disease. However, the decision of whether to administer PORT still hinges on diverse clinical scenarios, and additional research is necessary to furnish a more conclusive resolution., Level of Evidence: 2., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The objective of this paper is to provide a comprehensive overview of the development and features of the Taipei Medical University Clinical Research Database (TMUCRD), a repository of real-world data (RWD) derived from electronic health records (EHRs) and other sources., Methods: TMUCRD was developed by integrating EHRs from three affiliated hospitals, including Taipei Medical University Hospital, Wan-Fang Hospital and Shuang-Ho Hospital. The data cover over 15 years and include diverse patient care information. The database was converted to the Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) for standardisation., Results: TMUCRD comprises 89 tables (eg, 29 tables for each hospital and 2 linked tables), including demographics, diagnoses, medications, procedures and measurements, among others. It encompasses data from more than 4.15 million patients with various medical records, spanning from the year 2004 to 2021. The dataset offers insights into disease prevalence, medication usage, laboratory tests and patient characteristics., Discussion: TMUCRD stands out due to its unique advantages, including diverse data types, comprehensive patient information, linked mortality and cancer registry data, regular updates and a swift application process. Its compatibility with the OMOP CDM enhances its usability and interoperability., Conclusion: TMUCRD serves as a valuable resource for researchers and scholars interested in leveraging RWD for clinical research. Its availability and integration of diverse healthcare data contribute to a collaborative and data-driven approach to advancing medical knowledge and practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Fractional quantum Hall (FQH) states are known for their robust topological order and possess properties that are appealing for applications in fault-tolerant quantum computing. An engineered quantum platform would provide opportunities to operate FQH states without an external magnetic field and enhance local and coherent manipulation of these exotic states. We demonstrate a lattice version of photon FQH states using a programmable on-chip platform based on photon blockade and engineering gauge fields on a two-dimensional circuit quantum electrodynamics system. We observe the effective photon Lorentz force and butterfly spectrum in the artificial gauge field, a prerequisite for FQH states. After adiabatic assembly of Laughlin FQH wave function of 1/2 filling factor from localized photons, we observe strong density correlation and chiral topological flow among the FQH photons. We then verify the unique features of FQH states in response to external fields, including the incompressibility of generating quasiparticles and the smoking-gun signature of fractional quantum Hall conductivity. Our work illustrates a route to the creation and manipulation of novel strongly correlated topological quantum matter composed of photons and opens up possibilities for fault-tolerant quantum information devices.

Objectives: This study investigated the outcomes of underweight patients with COVID-19 and the effectiveness of antiviral agents in this population., Methods: A retrospective cohort study using theTriNetX research network was conducted. Propensity score matching (PSM) was employed to balance the first cohort involving COVID-19 patients with underweight and normal-weight. In the second cohort, underweight patients receiving antiviral agents and untreated individuals were matched using PSM. The primary outcome was a composite of all-cause hospitalization and death during the 7-30-day follow-up period., Results: After PSM, the first cohort including each group of 13,502 patients with balanced baseline characteristics were identified for comparing the outcome of patients with underweight and normal weight. The underweight group had a higher risk of the composite primary outcome than those with normal weight (hazard ratio [HR], 1.251; 95% confidence interval [CI], 1.132-1.382). The second cohort included each 884 underweight patients with and without receiving antivirals.Compared with untreated patients, those receiving antiviral treatment had a lower risk of composite primary outcomes (HR, 0.426; 95% CI, 0.278-0.653)., Conclusion: Underweight status may be associated with a higher risk of all-cause hospitalization and death in patients with COVID-19.Among underweight patients, antiviral agents demonstrated clinically beneficial effects.

Lay Abstract: Currently, the prevalence of autism spectrum disorder (henceforth "autism") is 1 in 36, an increasing trend from previous estimates. In 2015, the United States adopted a new version (International Classification of Diseases, 10th Revision) of the World Health Organization coding system, a standard for classifying medical conditions. Our goal was to examine how the transition to this new coding system impacted autism diagnoses in 10 healthcare systems. We obtained information from electronic medical records and insurance claims data from July 2014 through December 2016 for each healthcare system. We used member enrollment data for 30 consecutive months to observe changes 15 months before and after adoption of the new coding system. Overall, the rates of autism per 1000 enrolled members was increasing for 0- to 5-year-olds before transition to International Classification of Diseases, 10th Revision and did not substantively change after the new coding was in place. There was variation observed in autism diagnoses before and after transition to International Classification of Diseases, 10th Revision for other age groups. The change to the new coding system did not meaningfully affect autism rates at the participating healthcare systems. The increase observed among 0- to 5-year-olds is likely indicative of an ongoing trend related to increases in screening for autism rather than a shift associated with the new coding.

Mental health remains an urgent global priority, alongside efforts to address underlying social determinants of health (SDoH) that contribute to the onset or exacerbate mental illness. SDoH factors can be captured in the form of International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM), SDoH Z codes. In this scoping review, we describe current SDoH Z-code documentation practices, with a focus on mental health care contexts. Among 2 743 061 374 health care encounters noted across 12 studies in the United States, SDoH Z-code documentation rates ranged from 0.5% to 2.4%. Documentation often involved patients under 64 years of age who are publicly insured and experience comorbidities, including depression, bipolar disorder and schizophrenia, chronic pulmonary disease, and substance abuse disorders. Documentation varied across hospital types, number of beds per facility, patient race/ethnicity, and geographic region. Variation was observed regarding patient sex/gender, although SDoH Z codes were more frequently documented for males. Documentation was most observed in government, nonfederal, and private not-for-profit hospitals. From these insights, we offer policy and practice recommendations, as well as considerations for patient data privacy, security, and confidentiality, to incentivize more routine documentation of Z codes to better assist patients with complex mental health care needs., Competing Interests: Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2024. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a novel disease associated with COVID-19. The COVID-19 epidemic peaked in May 2022 in Taiwan, and we encountered our first case of MIS-C in late May 2022. We aimed to present patients' clinical manifestations and identify risk factors for shock., Methods: We included patients diagnosed with MIS-C at two medical centers from May 2022 to August 2022. We separated those patients into two groups according to whether they experienced shock. We collected demographic, clinical manifestation, and laboratory data of the patients and performed statistical analysis between the two groups., Results: We enrolled 28 patients, including 13 (46 %) with shock and 15 (54 %) without shock. The median age was 6.4 years (IQR: 1.9-7.5). In single variable analysis, patients with shock tended to be older, had more neurological symptoms, more conjunctivitis and strawberry tongue, lower lymphocyte count, lower platelet counts, and higher C-reactive protein, higher procalcitonin, higher ferritin, and higher D-dimer levels than those without shock. The area under the ROC curve that used procalcitonin to be the risk factor of shock with MIS-C was 0.815 (95 % CI 0.644 to 0.987). The cutoff value obtained by ROC analysis of procalcitonin was 1.68 ng/mL. With this cutoff, the test characteristics of procalcitonin were as follows: sensitivity 77 %, specificity 93 %, positive predictive value 91 %, negative predictive value 82 %. Multivariable analysis revealed that procalcitonin was the only independent risk factor of shock with MIS-C on admission (OR, 26.00, 95 % CI, 1.01-668.89)., Conclusions: MIS-C patients with high initial procalcitonin levels have higher risks of experiencing shock and may need ICU admission., 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 Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.

Addressing the limitations observed in previous studies, where the quantitative range of nanoprobes for detecting K + and adenosine triphosphate (ATP) did not cover concentrations found within living cells, the present study aimed to develop ratiometric nanoprobes that can accurately sense changes in K + and ATP levels in living cells and quantify them in human fluids. The proposed nanoprobes consisted of recognition flares modified with 6-carboxyfluorescein (FAM) and 5-carboxytetramethylrhodamine (TAMRA), along with thiolate single-stranded DNA (ssDNA) and molybdenum disulfide nanosheets (MoS 2 NSs). The thiolate ssDNA acts as a linker between the flares and the MoS 2 NSs, directly forming a functional nanostructure at room temperature. The direct conjugation of labeled flares to the MoS 2 NSs simplifies the fabrication process. In the absence of K + and ATP, the hybridization of flares and thiolate ssDNA caused FAM to move away from TAMRA, suppressing the fluorescence resonance energy transfer (FRET) process. However, upon the introduction of K + and ATP, the flares undergo a structural transformation via the formation of G-quadruplex formation and the generation of hairpin-shaped structures, respectively. This structural change leads to the release of the flares from the ssDNA-conjugated nanosheet surface. The release of the flares brings FAM and TAMRA into close proximity, allowing FRET to occur, leading to FRET and static quenching. By monitoring the ratio between the fluorescence intensities of FAM and TAMRA, the concentration of K + (5-100 mM) and ATP (0.3-5 mM) can be accurately determined by the proposed nanoprobes. The advantages of these nanoprobes lie in their ability to provide ratiometric measurements, which enhance the accuracy and reliability of the quantification process. The proposed nanoprobes offer potential applications as ratiometric imaging probes for monitoring K + and ATP-related reactions in living cells, providing valuable insights into cellular processes. Additionally, they can be employed for determining the levels of K + and ATP in human fluids, offering potential diagnostic applications in various clinical settings., 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.)

Electroporation, or the use of electric pulses to facilitate the intracellular delivery of DNA, RNA, and other molecules, is a well-established technique, that has been demonstrated to significantly augment the immunogenicity of DNA/mRNA vaccines and therapeutics. However, the clinical translation of traditional electroporators has been limited due to high costs, large size, complex user operation, and poor tolerability in humans due to nerve stimulation. In prior work, we introduced ePatch: an ultra-low-cost, handheld, battery-free electroporator employing a piezoelectric pulser coupled with a microneedle electrode array that showed enhanced immunogenic responses to an intradermal SARS-CoV-2 DNA vaccine in mice. The current study shifts focus from efficacy to tolerability, hypothesizing that ePatch's microneedle array, which localizes the electric field to the superficial skin strata, will minimize nerve stimulation and improve patient comfort. We tested this hypothesis in 14 healthy adults, monitoring pain and other potential adverse effects associated with electroporation. Compared to the insertion of a traditional hypodermic needle, the ePatch was less painful. Adverse effects such as pain, tenderness, erythema and swelling at the application sites were minimal, transient, and statistically indistinguishable between the experimental and placebo ePatch application, suggesting excellent tolerability towards electroporation. In summary, ePatch has a favorable tolerability profile in humans and offers the potential for the safe use of electroporation in a variety of clinical settings, including DNA and mRNA vaccination., Competing Interests: MSB, GB and MRP are inventors of patents and co‐founders of Piezo Therapeutics, which is commercializing ePatch technology. Georgia Institute of Technology manages the associated conflicts of interest through its established procedures. The remaining authors declare no conflicts of interest., (© 2024 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Neutron irradiation (E ≥ 1 MeV) and 400 keV Kr+ ion irradiation tests were carried out and compared to study the formation and growth mechanism of dislocation loops in zirconium alloys. The results show that, as the irradiation reached 1.9 × 1025 n/m2 and 1.0 × 1020 Kr+/m2, a large number of -type dislocation loops and a small amount of large-sized -type dislocations hundreds of nanometers or even micrometers in size are observed in both samples. EDS results confirmed that the concentrations of Nb and Fe in the -type dislocation loops are higher than that in the matrix. With the increases of the dislocation loop size, part of the loop structure will decompose into the twisted, small-sized dislocation lines. Between two of the small-sized dislocation lines, a cubic structure was observed., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The incidence of pediatric hospitalizations has significantly increased since the spread of the omicron variant of COVID-19. Changes of characteristics in respiratory and neurological symptoms have been reported. We performed a retrospective, cross-sectional study to characterize the MRI change in children with an emphasis on the change of cerebral vasculatures., Methods: We retrospectively collected clinical and MRI data of 31 pediatric patients with neurological symptoms during the acute infection and abnormalities on MRI during the outbreak of omicron variant from April 2022 to June 2022 in Taiwan. The clinical manifestations and MRI abnormalities were collected and proportion of patients with vascular abnormalities was calculated., Results: Among 31 pediatric patients with post-COVID-19 neurological symptoms, MRI abnormalities were observed in 15 (48.4%), predominantly encephalitis/encephalopathy (73.3%). Notable MRI findings included focal diffusion-weighted imaging (DWI) hyperintensity in cerebral cortex and thalamus, diffuse cortical T2/DWI hyperintensity, and lesions in the medulla, pons, cerebellum, and splenium of corpus callosum. Vascular abnormalities were seen in 12 (80%) patients with MRI abnormalities, mainly affecting the middle cerebral arteries. The spectrum of neurological manifestations ranged from seizures to Alice in Wonderland syndrome, underscoring the diverse impact of COVID-19 on pediatric patients., Conclusion: A high proportion of vascular abnormalities was observed in pediatric patients with neurological involvements, suggesting that vascular involvement is an important mechanism of neurological manifestations in omicron variant infection., Competing Interests: Declaration of competing interest None of the authors has any potential conflict exists., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Lack of exercise is a leading risk factor for stroke, and it has been demonstrated that increasing physical activity (PA) can prevent ischemic stroke. However, there has been limited research on the relationship between ischemic stroke and PA, especially among Asian populations. This study therefore investigates whether the level of PA in the Taiwanese population affects its risk of first-ever ischemic stroke, utilizing screening data on 58,857 individuals collected by the Keelung Health Bureau between 2005 and 2012. These subjects were divided into three groups based on their weekly exercise frequency and duration, i.e., 1) a no PA (NPA) group, 2) a low PA (LPA) group (less than 90 min of exercise per week), and 3) a high PA (HPA) group (90 min or more of exercise per week). The results showed that, as compared to the NPA group, the adjusted hazard ratio for ischemic stroke in the LPA group was 0.86 (95 % CI, 0.78-0.95, p < 0.0001); and that in the HPA group, it was also 0.86 (95 % CI, 0.79-0.94, p < 0.0001). In other words, even engaging in PA for less than 90 min per week may lower the risk of first-ever ischemic stroke. Importantly, LPA is more accessible, more sustainable, and easier to promote for the general population than the 150 min per week recommended by the World Health Organization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The relationship between different puncture points and perioperative complications and length of stay in hospital (LOS) in SCCAG patients has rarely been reported., Aim: To compare the curative effect and safety of the transradial artery approach and the transfemoral artery approach in combined heart-brain angiography., Material and Methods: 120 patients who received combined cardio-cerebral angiography in our hospital were selected and divided into a transradial artery approach group (TRA) and a transfemoral artery approach group (TFA) according to a random number table. The postoperative efficacy and safety of the 2 groups were compared., Results: There was no statistically significant difference in puncture time and operation time between the 2 groups (p > 0.05). Postoperative bed rest time, hospitalization time, and X-ray exposure time in the TRA group were shorter than those in the TFA group, and the difference was statistically significant (p < 0.05). Before operation and 3 days after operation, there was no significant difference in left ventricle ejection fraction between the 2 groups (p > 0. 05). The overall incidence of complications in the TFA group was higher than that in the TRA group. The incidence between haematoma and pseudoaneurysm in the TFA group was higher, and the difference was statistically significant (p < 0.05)., Conclusions: For simultaneous heart-brain angiography, interventional therapy via radial artery and femoral artery has good curative effect and can improve cardiac function. However, interventional therapy through the radial artery can shorten the postoperative bed rest time and hospitalization time, and reduce the incidence of complications., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Fundacja Videochirurgii.)

Objectives: Various treatment options are available for degenerative joint disease (DJD). During clinical visits, patients and clinicians collaboratively make decisions regarding the optimal treatment for DJD; this is the essence of shared decision-making (SDM). Here, we collated and assessed the SDM-related experiences and perspectives of outpatients with DJD in Taiwan., Design: In-depth interviews and thematic analysis., Setting: Primary care clinics of a regional teaching hospital in Taiwan, October 2021-May 2022., Participants: 21 outpatients with at least three visits for DJD and who were aware of SDM., Results: Four main themes emerged in this study: first, equipping themselves with knowledge: outpatients obtained disease-related and treatment-related knowledge in various ways-seeking relevant information online, discussing with family and friends, learning from their own experiences or learning from professionals. Second, shared or not shared: physicians had different patterns for communicating with patients, particularly when demonstrating authority, performing mutual discussion, respecting patient preferences or responding perfunctorily. Third, seldom saying no to physician-prescribed treatment plans during clinical visits: most patients respected physicians' professionalism; however, some patients rejected physicians' recommendations indirectly, whereas some responded depending on their disease prognosis. Fourth, whose call?-participants decided to accept or reject a treatment plan independently or by discussing it with their families or by obeying their physicians' recommendations., Conclusions: In general, patients with DJD sought reliable medical information from various sources before visiting doctors; however, when having a conversation with patients, physicians dominated the discussion on treatment options. The patient-physician interaction dynamics during the SDM process determined the final medical decision, which was in accordance with either patients' original autonomy or physicians' recommendations. To alleviate medical paternalism and physician dominance, patients should be empowered to engage in medical decision-making and share their opinions or concerns with their physicians. Family members should also be included in SDM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Suicide remains an urgent public health crisis. Although some sociodemographic characteristics are associated with greater suicide risk in the general population, it is unclear whether individuals utilizing health care in the United States have similar suicide incidence patterns. The authors examined whether race-ethnicity is associated with suicide death among patients seeking health care and investigated health care utilization patterns., Methods: Data were collected from electronic health records and government mortality records for patients seeking health care across nine health care systems in the United States. Patients who died by suicide (N=1,935) were matched with patients in a control group (N=19,350) within each health care system., Results: Patients who died by suicide were significantly more likely to be White, older, male, living in low-education areas, living in rural areas, or diagnosed as having mental health conditions or were significantly less likely to have commercial insurance (p<0.05). Among most racial-ethnic groups, those who died by suicide had a higher number of past-year mental health, primary care, and total health care visits; for American Indian/Alaska Native patients, the number of health care visits tended to be lower among suicide decedents., Conclusions: These findings suggest that higher past-year health care utilization was associated with increased likelihood of suicide death across several racial-ethnic groups. This observation underscores the need for identifying and managing suicide risk in health care settings, including outside of mental health visits, among most racial-ethnic groups., Competing Interests: Dr. Rossom’s institution has received research grants from Otsuka, Adelphi, and Bioxcel. Dr. Daida reports receiving research grants from Vir Biotechnology, GSK, and Gilead. The other authors report no financial relationships with commercial interests.

Converting solar energy into hydrogen energy using conjugated polymers (CP) is a promising solution to the energy crisis. Improving water solubility plays one of the critical factors in enhancing the hydrogen evolution rate (HER) of CP photocatalysts. In this study, a novel concept of incorporating hydrophilic side chains to connect the backbones of CPs to improve their HER is proposed. This concept is realized through the polymerization of carbazole units bridged with octane, ethylene glycol, and penta-(ethylene glycol) to form three new side-chain-braided (SCB) CPs: PCz2S-OCt, PCz2S-EG, and PCz2S-PEG. Verified through transient absorption spectra, the enhanced capability of PCz2S-PEG for ultrafast electron transfer and reduced recombination effects has been demonstrated. Small- and wide-angle X-ray scattering (SAXS/WAXS) analyses reveal that these three SCB-CPs form cross-linking networks with different mass fractal dimensions (f) in aqueous solution. With the lowest f value of 2.64 and improved water/polymer interfaces, PCz2S-PEG demonstrates the best HER, reaching up to 126.9 µmol h -1 in pure water-based photocatalytic solution. Moreover, PCz2S-PEG exhibits comparable performance in seawater-based photocatalytic solution under natural sunlight. In situ SAXS analysis further reveals nucleation-dominated generation of hydrogen nanoclusters with a size of ≈1.5 nm in the HER of PCz2S-PEG under light illumination., (© 2023 Wiley-VCH GmbH.)

Bacteria contribute to many physiological functions of coral holobionts, including responses to bleaching. The bacterial genus, Endozoicomonas , dominates the microbial flora of many coral species and its abundance appears to be correlated with coral bleaching. However, evidences for decoupling of bleaching and Endozoicomonas abundance changes have also been reported. In 2020, a severe bleaching event was recorded at reefs in Taiwan, providing a unique opportunity to re-examine bleaching- Endozoicomonas association using multiple stony corals in natural environments. In this study, we monitored tissue color and microbiome changes in three coral species ( Montipora sp., Porites sp., and Stylophora pistillata ) in Kenting National Park, following the bleaching event. All tagged Montipora sp. and Porites sp. recovered from bleaching within 1 year, while high mortality occurred in S. pistillata . Microbiome analysis found no correlation of Endozoicomonas relative abundance and bleaching severity during the sampling period, but found a stronger correlation when the month in which bleaching occurred was excluded. Moreover, Endozoicomonas abundance increased during recovery months in Montipora sp. and Porites sp., whereas in S. pistillata it was nearly depleted. These results suggest that Endozoicomonas abundance may represent a gauge of coral health and reflect recovery of some corals from stress. Interestingly, even though different Endozoicomonas strains predominated in the three corals, these Endozoicomonas strains were also shared among coral taxa. Meanwhile, several Endozoicomonas strains showed secondary emergence during coral recovery, suggesting possible symbiont switching in Endozoicomonas. These findings indicate that it may be possible to introduce Endozoicomonas to non-native coral hosts as a coral probiotic., Competing Interests: On behalf of all authors, the corresponding author states that there are no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Background: Previous studies have identified COVID-19 risk factors, such as age and chronic health conditions, linked to severe outcomes and mortality. However, accurately predicting severe illness in COVID-19 patients remains challenging, lacking precise methods., Objective: This study aimed to leverage clinical real-world data and multiple machine-learning algorithms to formulate innovative predictive models for assessing the risk of severe outcomes or mortality in hospitalized patients with COVID-19., Methods: Data were obtained from the Taipei Medical University Clinical Research Database (TMUCRD) including electronic health records from three Taiwanese hospitals in Taiwan. This study included patients admitted to the hospitals who received an initial diagnosis of COVID-19 between January 1, 2021, and May 31, 2022. The primary outcome was defined as the composite of severe infection, including ventilator use, intubation, ICU admission, and mortality. Secondary outcomes consisted of individual indicators. The dataset encompassed demographic data, health status, COVID-19 specifics, comorbidities, medications, and laboratory results. Two modes (full mode and simplified mode) are used; the former includes all features, and the latter only includes the 30 most important features selected based on the algorithm used by the best model in full mode. Seven machine learning was employed algorithms the performance of the models was evaluated using metrics such as the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, and specificity., Results: The study encompassed 22,192 eligible in-patients diagnosed with COVID-19. In the full mode, the model using the light gradient boosting machine algorithm achieved the highest AUROC value (0.939), with an accuracy of 85.5%, a sensitivity of 0.897, and a specificity of 0.853. Age, vaccination status, neutrophil count, sodium levels, and platelet count were significant features. In the simplified mode, the extreme gradient boosting algorithm yielded an AUROC of 0.935, an accuracy of 89.9%, a sensitivity of 0.843, and a specificity of 0.902., Conclusion: This study illustrates the feasibility of constructing precise predictive models for severe outcomes or mortality in COVID-19 patients by leveraging significant predictors and advanced machine learning. These findings can aid healthcare practitioners in proactively predicting and monitoring severe outcomes or mortality among hospitalized COVID-19 patients, improving treatment and resource allocation., 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 Hien, Tsai, Chang, Burton, Phuc, Nguyen, Harnod, Lam, Lu, Chen, Hsu, Lu, Huang, Yang and Hsu.)

Electron ptychography has emerged as a popular technology for high-resolution imaging by combining the high coherence of electron sources with the ultra-fast scanning electron coil. However, the limitations of conventional pixelated detectors, including poor dynamic range and slow data readout speeds, have posed restrictions in the past on conducting electron ptychography experiments. We used the Gatan STELA pixelated detector to capture sequential diffraction data of monolayer two-dimensional (2D) materials for ptychographic reconstruction. By using the pixelated detector and electron ptychography, we demonstrate the observation of the radiation damage at atomic resolution in Transition Metal Dichalcogenides (TMDs)., (© 2024. The Author(s).)

An economical and stable single-shot pulse picker design without dispersion, nonlinear effect, and limitation on wavelength is proposed. This design is composed of a periodic pulse blocker (PPB), a control unit, and a mechanical shutter. It has successfully been applied to the commercial high-fluence femtosecond laser with 11-mm beam diameter, 2-mJ pulse energy, and 1-kHz repetition rate. Significantly, by incorporating commercial optical choppers equipped with custom-designed chopper blades in the PPB, this design can accommodate lasers with fluences reaching 610 mJ/cm2 and the standard 1 kHz repetition rate typical of high-fluence lasers. Furthermore, the proposed design provides a cost-effective substitute compared to using electro-optic modulators or acousto-optic modulators., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Lack of biomarkers for follow-up after treatment is a clinical challenge. DNA methylation has been proposed to be a potential biomarker in HCC. However, there is still a lack of evidence of its clinical use. This study aimed to evaluate the value of using plasma Adenomatous Polyposis Coli promoter methylation level (APC-MET) as a potential biomarker in HCC treatment., Method: A total of 96 patients with HCC at BCLC stage B who underwent local tumor ablation treatment were prospectively included in this study. APC-MET was examined in the plasma of each patient before and 1 month after treatment. The prediction value of APC-MET for survival outcome and disease status after treatment was analyzed and adjusted with alpha-fetoprotein and protein induced by vitamin K absence-II using Cox regression analysis., Results: Univariate Cox regression analysis showed preoperative APC-MET >0 (HR, 2.9, 95% CI: 1.05-8.05, p = 0.041) and postoperative APC-MET >0 (HR, 3.47, 95% CI: 1.16-10.4, p = 0.026) were both predictors of death, and preoperative APC-MET >0 was a predictor of disease progression after treatment (HR, 2.04, 95% CI: 1.21-3.44, p = 0.007). In multivariate models, preoperative APC-MET >0 was a significant predictor of disease progression after adjusting with the other two traditional biomarkers (HR, 1.82, 95% CI: 1.05-3.17, p = 0.034)., Conclusions: Hypermethylation of APC promoter appears to be a potential biomarker that could predict patient survival and disease progression outcomes in patients with intermediate-stage HCC after local ablation treatment., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: Examine how changes in sleep duration, objectively measured by activity trackers, impact weight gain in incoming college freshman. Participants: Incoming college freshmen, age ≥ 18. Methods: We measured weight and daily sleep duration before college entry and through the 1st college quarter. Additionally, we examined changes in sleep variability, activity levels and smartphone screen time use as possible predictors of weight gain. Results: 75 participants completed the study. Total sleep duration decreased from 437.9 ± SD 57.3 minutes at baseline to 416.5 ± SD 68.6 minutes by the end of the first quarter ( p  = 6.6 × 10 -3 ). (BMI) did not change significantly in this cohort. Higher sleep variability at baseline and an increase in sleep variability were associated with increases in BMI. Smartphone screen use was note to be high (235.2 ±  SD 110.3 minutes/day) at the end of the first quarter. Conclusions: College weight gain may be affected by factors other than sleep duration, including sleep variability., Supplemental data for this article can be accessed online at https://doi.org/10.1080/07448481.2022.2032720.

Docetaxel-based chemotherapy has generally been considered as one of the effective treatments for castration-resistant prostate cancer (PCa). However, clinical treatment with docetaxel often encounters a number of undesirable effects, including drug resistance. Tubulin isoforms have been previously examined for their resistance to docetaxel in many cancers, but their real mechanisms remained unclear. In this study, a series of docetaxel-resistant PC/DX cell sublines were established by chronically exposing PC3 to progressively increased concentrations of docetaxel. Western blotting results showed significantly higher expression of acetyl-tubulin, α-tubulin, β-tubulin, γ-tubulin, and βIII-tubulin in PC/DX25 than in parental PC3 cells. PC/DX25 with greater resistance to docetaxel had higher levels of acetyl-tubulin and mitotic centromere-associated kinesin (MCAK) than PC3 cells. This study found that docetaxel induced the expression of acetyl-tubulin and MCAK in PC3 cells at a dose- and time-dependent manner. Both mRNA and protein levels of histone deacetylase 6 (HDAC6) were significantly decreased in PC/DX25 compared with PC3 cells. PC3 increased the resistance to docetaxel by HDAC6 knockdown and Tubastatin A (HDAC6 inhibitor). Conversely, PC/DX25 reversed the sensitivity to docetaxel by MCAK knockdown. Notably, flow cytometry analysis revealed that MCAK knockdown induced significantly sub G1 fraction in PC/DX cells. Overexpression of polo-like kinase-1 increased the cell survival rate and resistance to docetaxel in PC3 cells. Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl-tubulin in docetaxel-resistant PCa cells. These findings demonstrated that the EGFR-mediated upregulated expression of acetyl-tubulin played an important role in docetaxel-resistant PCa., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Prostaglandin F2α (PGF2α) is a luteolytic hormone that promotes parturition in mammals at the end of pregnancy by reducing progesterone secretion from the corpus luteum (CL). In rodents and primates, PGF2α rapidly converts progesterone to 20α-hydroxyprogesterone (20α-OHP) by promoting 20α-hydroxysteroid dehydrogenase (20α-HSD) expression. However, the specific mechanism of 20α-HSD regulation by PGF2α remains unclear. Casein Kinase 1α (CK1α) is a CK1 family member that regulates a variety of physiological functions, including reproductive development. Here, we investigated the effects of CK1α on pregnancy in female mice. Our experiments showed that CK1α is expressed in mouse CL, and its inhibition enhanced progesterone metabolism, decreased progesterone levels, and affected mouse embryo implantation. Further, CK1α mediated the effect of PGF2α on 20α-HSD in mouse luteal cells in vitro. Our results are the first to show that CK1α affects the 20α-HSD mRNA level by affecting the ERK signalling pathway to regulate the expression of the transcription factor SP1. These findings improve our understanding of PGF2α regulation of 20α-HSD., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Boehmeria formosana, with its related species, demonstrates anti-glycemic effect, inhibition of HBV production, anti-cancer activities, etc. Some indolizidine alkaloids from the same genus are bioactive but sensitive to light. To overcome this problem and obtain more phenanthroindolizidine alkaloids, isolation was performed in darkness, yielding 10 new indolizidine alkaloids and 17 known compounds. Among them, seven enhanced glucagon-like receptor 1 (GLP-1) activity at 50 mM, especially 14 and 6 (3.5- and 2.3-fold than the negative control). This procedure yielded bioactive indolizidine alkaloids with novel structures.

Background: The association between obesity indicators and mortality in individuals with diabetes remains unclear, and data on cardiovascular mortality are scarce. Therefore, we investigated the associations between the five adiposity indices and both all-cause and cardiovascular mortality in patients with diabetes., Methods: This cohort study included 34,686 adults with diabetes who underwent a standard health-screening program between 1996 and 2017 in Taiwan. The dates and causes of death till January 2022 were retrieved from the National Death Registry. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cardiovascular mortality in relation to body mass index (BMI), waist circumference, waist-hip ratio (WHR), body fat percentage (BF%), and A Body Shape Index (ABSI), using the third quintile as the reference group., Results: During a median follow-up of 15 years, there were 8,324 deaths, of which 1,748 were attributed to cardiovascular disease. After adjusting for demographics, lifestyle factors and comorbidities, ABSI was associated with all-cause mortality in an exposure-response manner; the HR (95% CI) for first and fifth vs. third quintile was 0.78 (0.69-0.89) and 1.24 (1.14-1.35), respectively. A similar but weaker exposure-response relationship was found between WHR and mortality. People with a lower BMI and BF% had an increased risk of mortality (HR [95% CI] for the first vs. third quintiles, 1.33 [1.22, 1.44] and 1.42 [1.30, 1.56], respectively). No association was observed between waist circumference categories and risk of mortality. Similar results were observed for the association of BF%, waist circumference, and ABSI with cardiovascular mortality. However, no significant association was observed between BMI and cardiovascular mortality. The association between WHR and cardiovascular mortality was stronger than that between WHR and all-cause mortality., Conclusions: ABSI demonstrated a consistent exposure-response relationship with both all-cause and cardiovascular mortality in this Asian cohort with diabetes. Our findings highlight the importance of monitoring ABSI, a surrogate index of central adiposity, in patients with diabetes., (© 2023. The Author(s).)

Today, many epidemiological studies and biobanks are offering to disclose individual genetic results to their participants, including the National Institutes of Health's All of Us Research Program. Returning hereditary disease risks and pharmacogenetic test results to study participants from racial/ethnic groups that are historically underrepresented in biomedical research poses specific challenges to those participants and the health system writ large. For example, individuals of African descent are underrepresented in research about drug-gene interactions and have a relatively higher proportion of variants of unknown significance, affecting their ability to take clinical action following return of results. In this brief report, we summarize studies published to date concerning the perspectives and/or attitudes of African Americans engaged in genetic research programs to anticipate factors in disclosure protocols that would minimize risks and maximize benefits. A thematic analysis of studies identified ( n = 6) lends to themes centered on motivations to engage or disengage in the return of results and integrating research and care. Actionable strategies determined in reaction to these themes center on ensuring adequate system and health education support for participants and personalizing the process for participants engaging in return of results. Overall, we offer these themes and actionable strategies as early guidance to research programs, and provide recommendations to policy makers focused on fair and equitable return of genetic research results to underrepresented research participants., Competing Interests: Conflicts of interest Please see ICMJE form(s) for author conflicts of interest. These have been provided as supplementary materials., (© The Author(s) 2023. Published by Oxford University Press on behalf of Project HOPE - The People-To-People Health Foundation, Inc.)

Multicomponent biomolecular aggregates, i.e., systems consisting of more than one type of biomolecular component co-assembling into one aggregate, provide an interesting design space for engineering unique biomaterials. In this study, we examine the co-assembly of two lipomimetic oligopeptide block copolymers selected for their lipid-like amphiphilicity and highly similar architectures into nanofibers via coarse-grained MD simulations. We focus on the behavior of these peptides due to incremental differences in size by selecting two peptides that differ in length by exactly one amino acid residue. We find that the longer peptide sequence displays greater self-association properties., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Meenakshi Dutt reports financial support was provided by National Science Foundation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Campylobacteriosis is a common cause of bacterial gastroenteritis worldwide. This study aimed to investigate the potential risk factors, clinical and laboratory manifestations of children with campylobacteriosis under five years old in Taiwan., Methods: This retrospective case-control study was conducted in ten major hospitals in Taiwan from 2014 to 2017. Laboratory tests and stool specimen were collected and analyzed together with questionnaire survey. Multivariate stepwise logistic regression model was used for identification of risk factors., Results: A total of 64 campylobacteriosis cases were included with a median age of 25 months. We observed a less prolonged vomiting (p = 0.047), more bloody (p < 0.001) and mucoid (p = 0.005) stools, and lower AST levels (p = 0.020) in patients with campylobacteriosis. Lower parental educational attainment (p < 0.001), direct contact with acute gastroenteritis patients (p < 0.001), as well as diarrhea in the mutually cared children (p = 0.007) were linked to campylobacteriosis. Consumption of municipal water (p < 0.001), milk (OR 0.34, 95% CI 0.118-0.979), and soft beverages (OR 0.41, 95% CI 0.192-0.888) were identified as protective factors, while consuming takeout food (p = 0.032) and seafood (p = 0.019) increased risk of campylobacteriosis., Conclusions: Shorter vomiting duration, bloody and mucoid stool, and less elevated AST levels are manifestations suggestive of campylobacteriosis. Risk factors of campylobacteriosis were low parental educational attainment, direct contact with acute gastroenteritis patients, diarrhea in mutually cared children, takeout food and seafood intake. Potential protective factors include municipal water, milk, and soft beverage intake., Competing Interests: Declaration of competing interest None., (© 2023 Chang Gung University. Publishing services provided by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Chicken is a major source of dietary protein worldwide. The dispersion and movement of chickens constitute vital indicators of their health and status. This is especially evident in Taiwanese native chickens (TNCs), a local variety which is high in physical activity when healthy. Conventionally, the dispersion and movement of chicken flocks are observed in patrols. However, manual patrolling is laborious and time-consuming. Moreover, frequent patrols increase the risk of carrying pathogens into chicken farms. To address these issues, this study proposes an approach to develop an automatic warning system for anomalous dispersion and movement of chicken flocks in commercial chicken farms. Embendded systems were developed to acquire videos of chickens from overhead view in a chicken house, in which approximately 20,000 TNCs were raised for a period of 10 wk. Each video was 5-min in length. The videos were transmitted to a remote cloud server and were converted into images. A You Only Look Once-version 7 tiny (YOLOv7-tiny) object detection model was trained to detect chickens in the images. The dispersion of the chicken flocks in a 5-min long video was calculated using nearest neighbor index (NNI). The movement of the chicken flocks in a 5-min long video was quantified using simple online and real-time tracking algorithm (SORT). The normal ranges (i.e., 95% confidence intervals) of chicken dispersion and movement were established using an autoregressive integrated moving average (ARIMA) model and a seasonal autoregressive integrated moving average with exogenous factors (SARIMAX) model, respectively. The system allows farmers to check up on the chicken farm only when the dispersion or movement values were not in the normal ranges. Thus, labor time can be saved and the risk of carrying pathogens into chicken farms can be reduced. The trained YOLOv7-tiny model achieved an average precision of 98.2% in chicken detection. SORT achieved a multiple object tracking accuracy of 95.3%. The ARIMA and SARIMAX achieved a mean absolute percentage error 3.71% and 13.39%, respectively, in forecasting dispersion and movement. The proposed approach can serve as a solution for automatic monitoring of anomalous chicken dispersion and movement in chicken farming, alerting farmers of potential health risks and environmental hazards in chicken farms., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The safety of human papillomavirus (HPV) vaccines has been evaluated continuously in pre-licensure clinical trials, post-marketing surveillance systems, and observational studies. Most studies have found no significant association between serious adverse events and HPV vaccination. However, these studies have focused on Western populations; similar studies focusing on Asian populations are insufficient. Our retrospective cohort study used the HPV-vaccination records of junior high-school adolescent girls aged 12-15 years between 2013 and 2018 in Taiwan's National Immunization Information System and linked them to a registry for beneficiaries in Taiwan's National Health Insurance Database (NHID) to establish the vaccinated group. We selected 19 serious diseases as serious adverse events. We compared the incidence rates of these serious adverse events between the vaccinated group and girls in the same age group population, and we calculated the standardized incidence ratio (SIR) to evaluate the risk of serious adverse events after HPV vaccination. Because of the onset of different types of diseases, we set three periods after the subjects received HPV vaccination: within 3 months, within 1 year, and during the study period (2013-2018). The results showed the incidence rates and the SIRs of 19 selected adverse events. Among the 19 selected serious adverse events, the disease with the highest incidence rate during the study period was fibromyalgia (73.23 cases per million population), and the disease with the lowest incidence rate during the study period was Crohn's disease (0.15 cases per million population). The results showed no statistically significant increases in the risk of 19 selected serious adverse events and indicated no association between HPV vaccination and serious adverse events. Given the benefits and safety of HPV vaccination, our research can reduce concerns about vaccine side effects, inform health policies and improve public and clinician's acceptance of HPV vaccine policy., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Fault-tolerant quantum computing based on surface code has emerged as an attractive candidate for practical large-scale quantum computers to achieve robust noise resistance. To achieve universality, magic states preparation is a commonly approach for introducing non-Clifford gates. Here, we present a hardware-efficient and scalable protocol for arbitrary logical state preparation for the rotated surface code, and further experimentally implement it on the Zuchongzhi 2.1 superconducting quantum processor. An average of 0.8983±0.0002 logical fidelity at different logical states with distance three is achieved, taking into account both state preparation and measurement errors. In particular, the logical magic states |A^{π/4}⟩&#95;{L}, |H⟩&#95;{L}, and |T⟩&#95;{L} are prepared nondestructively with logical fidelities of 0.8771±0.0009, 0.9090±0.0009, and 0.8890±0.0010, respectively, which are higher than the state distillation protocol threshold, 0.859 (for H-type magic state) and 0.827 (for T-type magic state). Our work provides a viable and efficient avenue for generating high-fidelity raw logical magic states, which is essential for realizing non-Clifford logical gates in the surface code.