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Shih-Chieh Shao,1,2 Tzu-Chi Liao,1 Kai-Cheng Chang,1,3 Hui-Yu Chen,3 Swu-Jane Lin,4 Cheng-Yang Hsieh,1,5 Edward Chia-Cheng Lai1 1School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 3Department of Pharmacy, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 5Department of Neurology, Tainan Sin Lau Hospital, Tainan, TaiwanCorrespondence: Cheng-Yang Hsieh, Department of Neurology, Tainan Sin Lau Hospital, 57, Section 1, Dongmen Road, East District, Tainan, 70142, Taiwan, Tel +886-6-274-8316, Ext 4180, Fax +886-6-282-4178, Email chengyanghsieh@gmail.comBackground: The ChAdOx1 nCoV-19 vaccine is associated with vaccine-induced thrombosis and thrombocytopenia (VITT). Patients with end-stage renal disease (ESRD) under hemodialysis are at elevated risk of heparin-induced thrombocytopenia, which shares similar mechanisms with VITT. We aimed to examine the risk of VITT after the first dose of ChAdOx1 nCoV-19 vaccine using a self-controlled case series analysis (SCCS) in the hemodialyzed ESRD population.Methods: Drawing from the largest multi-center electronic medical records database in Taiwan, we identified adult patients, with or without hemodialysis, between 1st December, 2020, and 31st December, 2021, who received a first dose of ChAdOx1 nCoV-19 vaccine and had an outcome of thrombocytopenia, venous thrombosis, or arterial thrombosis. We calculated the incident rate ratios (IRRs) of outcomes in different periods at risk, compared to periods not at risk.Results: We identified 59 hemodialysis patients and 41 non-dialysis patients with an outcome. The SCCS analyses showed, for the hemodialysis group, a significantly increased risk of outcomes during the period 31 to 60 days post-exposure to ChAdOx1 nCoV-19 vaccine (IRR: 2.823; 95% CI: 1.423– 5.600). However, in non-dialysis patients there was no increase in risks during any of the post-exposure risk periods.Conclusion: For ESRD patients under hemodialysis, the first dose of ChAdOx1 nCoV-19 vaccine was associated with a 2.8-fold increase in risk of thrombosis.Keywords: thrombosis, thrombocytopenia, ChAdOx1 nCoV-19 vaccine, hemodialysis, end-stage renal disease

Yu-Syuan Wei,1 Yu-Liang Chen,2 Wei-Yun Li,1 Ya-Yi Yang,3 Sung-Jan Lin,4– 6 Ching-Ho Wu,7 Jiue-In Yang,8 Tse-En Wang,1 Jiashing Yu,2 Pei-Shiue Tsai1,3,4 1Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 2Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei, 106, Taiwan; 3Department of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 4Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 10617, Taiwan; 5Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, 10051, Taiwan; 6Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, 10002, Taiwan; 7Graduate Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 8Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, TaiwanCorrespondence: Jiashing Yu, Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33669477, Email jiayu@ntu.edu.tw Pei-Shiue Tsai, Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33661290, Fax +886 2 23661475, Email psjasontsai@ntu.edu.twIntroduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology.Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks.Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte.Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.Keywords: nanomedicine, antioxidant, cisplatin, reproduction, DNA repair, polyphenol

Miyuki Hsing-Chun Hsieh,1,2,* Hsun-Yin Liang,2,* Chih-Ying Tsai,2 Yu-Ting Tseng,2 Pi-Hui Chao,2 Wei-I Huang,2 Wen-Wen Chen,2 Swu-Jane Lin,3 Edward Chia-Cheng Lai1 1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Taiwan Drug Relief Foundation (TDRF), Taipei, Taiwan; 3Department of Pharmacy Systems, Outcomes & Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA*These authors contributed equally to this workCorrespondence: Edward Chia-Cheng Lai, Email edward_lai@mail.ncku.edu.twPurpose: Development and evaluation of a drug-safety signal detection system integrating data-mining tools in longitudinal data is essential. This study aimed to construct a new triage system using longitudinal data for drug-safety signal detection, integrating data-mining tools, and evaluate adaptability of such system.Patients and Methods: Based on relevant guidelines and structural frameworks in Taiwan’s pharmacovigilance system, we constructed a triage system integrating sequence symmetry analysis (SSA) and tree-based scan statistics (TreeScan) as data-mining tools for detecting safety signals. We conducted an exploratory analysis utilizing Taiwan’s National Health Insurance Database and selecting two drug classes (sodium-glucose co-transporter-2 inhibitors (SGLT2i) and non-fluorinated quinolones (NFQ)) as chronic and episodic treatment respectively, as examples to test feasibility of the system.Results: Under the proposed system, either cohort-based or self-controlled mining with SSA and TreeScan was selected, based on whether the screened drug had an appropriate comparator. All detected alerts were further classified as known adverse drug reactions (ADRs), events related to other causes or potential signals from the triage algorithm, building on existing drug labels and clinical judgement. Exploratory analysis revealed greater numbers of signals for NFQ with a relatively low proportion of known ADRs; most were related to indication, patient characteristics or bias. No safety signals were found. By contrast, most SGLT2i signals were known ADRs or events related to patient characteristics. Four were potential signals warranting further investigation.Conclusion: The proposed system facilitated active and systematic screening to detect and classify potential safety signals. Countries with real-world longitudinal data could adopt it to streamline drug-safety surveillance.Keywords: drug safety, signal detection, triage, sequence symmetry analysis, tree-based scan statistics

Shu-Chen Liao,1,2 Shih-Chieh Shao,3,4 Edward Chia-Cheng Lai,4 Swu-Jane Lin,5 Wei-I Huang,6 Cheng-Yang Hsieh4,7 1Department of Emergency Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 2Chang Gung University College of Medicine, Taoyuan, Taiwan; 3Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 4School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Pharmacy Systems, Outcomes and Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 6Taiwan Drug Relief Foundation, Taipei, Taiwan; 7Department of Neurology, Tainan Sin Lau Hospital, Tainan, TaiwanCorrespondence: Cheng-Yang HsiehDepartment of Neurology, Tainan Sin Lau Hospital, 57, Section 1, Dongmen Road, East District, Tainan, 70142, TaiwanTel +886-6-274-8316, ext. 4180Fax +886-6-282-4178Email chengyanghsieh@gmail.comObjective: This study aims to determine the positive predictive value (PPV) of case definitions for cerebral venous sinus thrombosis (CVST) in Taiwan’s National Health Insurance claims database based on the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnostic codes.Study Design and Setting: Inpatient records with ICD-10-CM codes of G08, I629, I636, or I676 were retrieved from the claims data of all hospital branches of Chang Gung Medical Foundation. Manual review of the medical records and images was performed in order to ascertain the diagnosis. The PPV of various case definitions for CVST was estimated.Results: Of the 380 hospitalizations, 166 and 214 were determined to be true-positive and false-positive episodes of acute CVST, respectively. The PPV of the ICD-10-CM codes of G08, I629, I636, and I676 was 88.2%, 2.0%, 100.0%, and 91.3%, respectively. The PPV generally increased when acute CVST was defined as a primary diagnosis or as ICD-10-CM codes plus anticoagulant use. Miscoding in other conditions, tentative diagnosis, and remote episode of CVST were determined as the main reasons for false-positive diagnosis of acute CVST.Conclusion: This study determined the PPV of ICD-10-CM codes for identifying CVST, which may offer a reference for future claims-based research.Keywords: hospitalization claims data, positive predictive value, diagnostic codes, ICD-10-CM, cerebral venous sinus thrombosis, Taiwan

Cheng-Yang Hsieh,1,2 Chien-Chou Su,1 Shih-Chieh Shao,1,3 Sheng-Feng Sung,4,5 Swu-Jane Lin,6 Yea-Huei Kao Yang,1 Edward Chia-Cheng Lai1,71School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Neurology, Tainan Sin Lau Hospital, Tainan, Taiwan; 3Department of Pharmacy, Chang Gung Memorial Hospital, Keelung, Taiwan; 4Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi City, Taiwan; 5Department of Information Management and Institute of Healthcare Information Management, National Chung Cheng University, Chiayi County, Taiwan; 6Department of Pharmacy Systems, Outcomes & Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 7Department of Pharmacy, National Cheng Kung University Hospital, Tainan, TaiwanAbstract: Taiwan’s National Health Insurance Research Database (NHIRD) exemplifies a population-level data source for generating real-world evidence to support clinical decisions and health care policy-making. Like with all claims databases, there have been some validity concerns of studies using the NHIRD, such as the accuracy of diagnosis codes and issues around unmeasured confounders. Endeavors to validate diagnosed codes or to develop methodologic approaches to address unmeasured confounders have largely increased the reliability of NHIRD studies. Recently, Taiwan’s Ministry of Health and Welfare (MOHW) established a Health and Welfare Data Center (HWDC), a data repository site that centralizes the NHIRD and about 70 other health-related databases for data management and analyses. To strengthen the protection of data privacy, investigators are required to conduct on-site analysis at an HWDC through remote connection to MOHW servers. Although the tight regulation of this on-site analysis has led to inconvenience for analysts and has increased time and costs required for research, the HWDC has created opportunities for enriched dimensions of study by linking across the NHIRD and other databases. In the near future, researchers will have greater opportunity to distill knowledge from the NHIRD linked to hospital-based electronic medical records databases containing unstructured patient-level information by using artificial intelligence techniques, including machine learning and natural language processes. We believe that NHIRD with multiple data sources could represent a powerful research engine with enriched dimensions and could serve as a guiding light for real-world evidence-based medicine in Taiwan.Keywords: Health and Welfare Data Center of Taiwan, real-world data, big data analysis, validation, database cross-linkage

Tianbiao Zhou,1 Shujun Lin,1 Shen Yang,2 Wenshan Lin1 1Department of Nephrology, The Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China; 2Department of Nephrology, Huadu District People’s Hospital of Guangzhou, Southern Medical University, Guangzhou 510800, China Background: The purpose of this study was to detect the efficacy and safety of tacrolimus (TAC) in induction therapy of patients with lupus nephritis. Methods: Associated studies were extracted from the PubMed and the Cochrane Library on July 10, 2018, and applicable investigations were pooled and analyzed by meta-analysis. Data on complete remission (CR), total remission (TR; complete plus partial remission), proteinuria levels, urine erythrocyte number, albumin, glomerular filtration rate, negative rate of ds-DNA, C3 levels, C4 levels, systemic lupus erythematosus disease activity index (SLE-DAI), etc, were extracted and pooled using RevMan 5.3. Results: In the therapeutic regimen of TAC + glucocorticoids (GC) vs cyclophosphamide (CYC) + GC, the results indicated that the TAC group had high values of CR, TR, albumin, and negative rate of ds-DNA, and low values of proteinuria levels and SLE-DAI when compared with those in CYC group (all P0.05). In the therapeutic regimen comprising TAC + MMF + GC vs CYC + GC, multitarget therapy group showed higher values of CR, TR, urinary protein decline, and rise of serum albumin when compared with CYC group (all P

Background - Oxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase - derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element - binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium. Methods and Results - Using cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II - infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell - specific SREBP2 transgenic mice, locked nucleic acid - modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II - induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell - dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1β. Conclusions - Our findings suggest that SREBP2 - miR-92a - inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.

Diabetic nephropathy is characterized by excessive deposition of extracellular matrix protein and disruption of the glomerular filtration barrier. Matrix metalloproteinases (MMPs) affect the breakdown and turnover of extracellular matrix protein, suggesting that altered expression of MMPs may contribute to diabetic nephropathy. Here we used an MMP-9 gene knockout mouse model, with in vitro experiments and clinical samples, to determine the possible role of MMP-9 in diabetic nephropathy. After 6 months of streptozotocin-induced diabetes, mice developed markedly increased albuminuria, glomerular and kidney hypertrophy, and thickening of the glomerular basement membrane. Gelatin zymographic analysis and western blotting showed that there was enhanced MMP-9 protein production and activity in the glomeruli. However, MMP-9 knockout in diabetic mice significantly attenuated these nephropathy changes. In cultured podocytes, various cytokines related to diabetic nephropathy including TGF-β1, TNF-α, and VEGF stimulated MMP-9 secretion. Overexpression of endogenous MMP-9 induced podocyte dedifferentiation. MMP-9 also interrupted podocyte cell integrity, promoted podocyte monolayer permeability to albumin, and extracellular matrix protein synthesis. In diabetic patients, the upregulation of urinary MMP-9 concentrations occurred earlier than the onset of microalbuminuria. Thus, MMP-9 seems to play a role in the development of diabetic nephropathy. © 2014 International Society of Nephrology.

There are many existing algorithms and damage indices that can effectively meet the engineering need in damage diagnosis. However, all of them (except those with an exact formulation) are based on certain assumptions with approximations, and their performances depend on the combination of test parameters, for example, type, number, and location of excitations and sensors; identification algorithm adopted; and environmental noise effect. Results obtained from different combinations of these test parameters are different and they may be mathematically biased or contradicting. Existing practice adopts the general indication of result for further maintenance decisions or by subjective screening the results with engineering sense. This article demonstrates the possibility to have a better design of the structural health monitoring system where the benefits of different damage indices and evaluation methodologies can be reaped via the fusion of the identified results. The scenario for discussion is the vibration-based damage localization problem. The change in mode shape in the modal domain and change in the covariance of impulse response function change in the time domain are selected as damage indices for the illustration. An exact form of the covariance of impulse response function is also proposed for this purpose. The demonstration is conducted via a simulated truss structure, an experimental beam, and 280 days valid recorded data from an in-service suspension bridge deck. Different measurements are analyzed to produce large number of identified results for reducing traffic excitation effect, the temperature effect, and so on, and to enhance the structural damage information in the final set of results. Experiences in handling the structural health monitoring data for monitoring the movement of a structural joint before and after a typhoon are also presented. The proposed strategy does not need a mathematical model of the structure, but this leads to heavy sensor requirement for a fine spatial resolution of the local damage. [ABSTRACT FROM AUTHOR]

SUMMARYPneumonia is an important cause of mortality and morbidity in infants. However, information of risk factors for pneumonia in children aged <6 months is limited. This study aimed to evaluate the risk factors and their contribution to infantile pneumonia in a large population-based survey. Of 24 200 randomly sampled main caregivers invited, 21 248 (87·8%) participated in this study. A structured questionnaire was used to interview the main caregivers. Information regarding whether hospitalization was required, family environment, and medical history were obtained. The prevalence of pneumonia was 0·62% in our study cohort. Multivariate logistic regression analysis showed that preterm birth, congenital cardiopulmonary disease, antibiotic use during pregnancy, maternal overweight, daily prenatal exposure to environmental tobacco smoke, maternal smoking during pregnancy, and visible mould on walls at home are risk factors associated with infantile pneumonia. Further study is warranted to investigate the causality and mechanisms of these novel factors. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT(3) RAs in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions.Methods: PharMetrics claims database was used to identify patients diagnosed with breast cancer (BC) who were initiated on cyclophosphamide-based adjuvant chemotherapy or with lung cancer (LC) initiated on carboplatin-based or cisplatin-based chemotherapy between 2005 and 2008. Patients were stratified in two groups: those initiated and maintained on palonosetron versus those treated with any other 5-HT(3) RA regimens in the 6-month post first chemotherapy. Risk for CINV events, identified by ICD-9-CM for nausea, vomiting, and/or dehydration, were estimated using logistic regressions, controlling for age, gender, comorbidity, and total chemotherapy doses or days.Results: Of the 4,868 cyclophosphamide-treated BC, 5,414 carboplatin-treated LC, and 1,692 cisplatin-treated LC identified, there were 1,864 BC (38.5%), 1,806 carboplatin-treated LC (33.4%), and 390 cisplatin-treated LC (23.0%) in the palonosetron-only group. Palonosetron-only group had significantly lower probability of CINV events associated with ED/hospital admissions in all three cohorts (3.5% vs. 6.3% in BC, 9.5% vs. 13.8% in carboplatin-treated LC, and 16.4% vs. 22.6% in cisplatin-treated LC, all at p < 0.05). Logistic regressions found palonosetron-only group had significantly lower risk of CINV events (odds ratios = 0.550, 0.653, and 0.689 in BC, carboplatin-treated LC and cisplatin-treated LC, respectively, p < 0.05).Conclusion: Patients with lung or breast cancer receiving MEC or HEC had significantly lower risk of CINV events associated with hospital/ED admissions if initiated and maintained on palonosetron relative to patients receiving 5-HT(3) RA regimens. [ABSTRACT FROM AUTHOR]

Abstract Objective: Data are limited on the use of adjuvant imatinib in patients with gastrointestinal stromal tumor (GIST) outside of clinical trials. This retrospective, population-based, matched-cohort study evaluated adjuvant imatinib treatment patterns, assessed impact on clinical outcomes, and estimated effectiveness based on number needed to treat (NNT). Research design and methods: GIST-related claims from the PharMetrics claims database were included (2000-2010). A stepwise identification algorithm identified appropriate patients based on GIST-related ICD-9-CM codes, who were classified as 'imatinib (IM) patients' receiving imatinib within 84 days post-surgery and 'non-imatinib (non-IM) patients' undergoing surgery but not receiving imatinib during the study period. The primary composite outcome was based on incidence of a second GIST-related surgery and long-term follow-up in the matched cohorts. IM patients were matched with up to eight non-IM patients on age, gender, ICD-9-CM code, and first surgery date. Results: A total of 118 IM and 4088 non-IM patients with possible GIST ICD-9s and surgery were included. The median duration between first and second surgeries was significantly longer in IM than non-IM patients (488 vs. 290 days; p = 0.0005). IM patients also had longer median follow-up from initial surgery to composite outcome (433 vs. 320 days; p = 0.002). Adherence to IM, measured by medication possession ratio, was 0.83 and 0.73 during the first and second years of treatment, respectively. IM patients were less likely to have the composite outcome compared with non-IM patients (hazard ratio = 0.501; p = 0.0005). The NNT to prevent one outcome was 4. Conclusions: Patients receiving adjuvant imatinib treatment were less likely to have second surgery or be lost to follow-up, and had a longer interval to second surgery. Although treatment with adjuvant imatinib in patients with primary GIST is effective, adherence to imatinib and treatment duration are less than recommended by current treatment guidelines. [ABSTRACT FROM AUTHOR]

Objective: To design a whole-body MR protocol using exclusively diffusion-weighted imaging (DWI) with respiratory gating and to assess its value for lesion detection and staging in patients with diffuse large B-cell lymphoma (DLBCL), with integrated FDG PET/CT as the reference standard.Methods: Fifteen patients underwent both whole-body DWI (b = 50, 400, 800 s/mm(2)) and PET/CT for pretreatment staging. Lymph node and organ involvement were evaluated by qualitative and quantitative image analysis, including measurement of the mean apparent diffusion coefficient (ADC).Results: A total of 296 lymph node regions in the 15 patients were analysed. Based on International Working Group size criteria alone, DWI findings matched PET/CT findings in 277 regions (94%) (kappa score = 0.85, P < 0.0001), yielding sensitivity and specificity for DWI lymph node involvement detection of 90% and 94%. Combining visual ADC analysis with size measurement increased DWI specificity to 100% with 81% sensitivity. For organ involvement, the two techniques agreed in all 20 recorded organs (100%). All involved organ lesions showed restricted diffusion. Ann Arbor stages agreed in 14 (93%) of the 15 patients.Conclusion: Whole-body DWI with ADC analysis can potentially be used for lesion detection and staging in patients with DLBCL. [ABSTRACT FROM AUTHOR]

Abstract Objective  To evaluate the outcome of free influenza vaccination for healthcare workers in Taiwan. Method  A retrospective observational study was conducted in a partially vaccinated sample of healthcare workers in a medical centre in the southern part of Taiwan. A convenience sample of 500 employees received a questionnaire. Main outcome measure  Incidence of influenza like- illness (ILI), rates of absenteeism and costs savings. Results  A final number of 407 returned questionnaires could be evaluated. Forty respondents were not vaccinated. The incidence of ILI was lower in the vaccinated group than the nonvaccinated group (13.6 vs. 15%). Fever was the most frequently occurring ILI. Rate of absenteeism because of ILI in the non-vaccinated employees was higher than in the group of vaccinated employees. The costs per saved lost working day was US $ 36. Conclusion  Free influenza vaccination may cause reductions in incidence, absenteeism, and costs associated with ILI in healthcare workers in Taiwan. [ABSTRACT FROM AUTHOR]

With the vigorous development of building structures and important infrastructure, structural health monitoring is necessary. Because there is no need to establish structural finite element modeling and train for various structural conditions, the data-driven and unsupervised learning method is very popular. Principal component analysis is a powerful signal analysis tool, but its lack of physical significance and the loss of sensitive information have hindered its wider application. Therefore, the improved principal component analysis based narrowband filtering is proposed to extract mode shapes and construct the structural state vectors, so that the damage index is more sensitive to damage and robust to the environmental factors. After the vibration response of the long-term monitoring is analyzed by the principal component analysis, the Gaussian mixture model clustering analysis is used to classify the structural states. Finally, the proposed method is applied to the analysis of the simulation data of ASCE Benchmark structure and the measured data of steel beams in the lab. The results show that the structural state vector is sensitive to structural damage. The clustering analysis of Gaussian mixture model can distinguish the structural states. The effectiveness of the proposed method is verified. [ABSTRACT FROM AUTHOR]

Delta-like ligand 3 (DLL3) is expressed in more than 70% of small cell lung cancers (SCLCs) and other neuroendocrine-derived tumor types. SCLC is highly aggressive, and limited therapeutic options lead to poor prognosis for patients. HPN328 is a trispecific T cell-activating construct (TriTAC) consisting of three binding domains: a CD3 binder for T-cell engagement, an albumin binder for half-life extension, and a DLL3 binder for tumor cell engagement. In vitro assays, rodent models, and non-human primates were used to assess the activity of HPN328. HPN328 induces potent dose-dependent killing of DLL3-expressing SCLC cell lines in vitro, concomitant with T-cell activation and cytokine release. In an NCI-H82 xenograft model with established tumors, HPN328 treatment led to T-cell recruitment and anti-tumor activity. In an immunocompetent mouse model expressing a human CD3ε epitope, mice previously treated with HPN328 withstood tumor rechallenge, demonstrating long-term anti-tumor immunity. When repeat doses were administered to cynomolgus monkeys, HPN328 was well tolerated up to 10 mg/kg. Pharmacodynamic changes, such as transient cytokine elevation, were observed, consistent with the expected mechanism of action of T-cell engagers. HPN328 exhibited linear pharmacokinetics in the given dose range with a serum half-life of 78 to 187 hours, supporting weekly or less frequent administration of HPN328 in humans. Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3-expressing malignancies., (©2024 The Authors; Published by the American Association for Cancer Research.)

This article addresses the management of dental implants in joint orthodontic-restorative cases, emphasising the role of temporary skeletal anchorage devices and interdisciplinary treatment. Focused on complex malocclusions that require dental implants, the article navigates through critical aspects such as diagnosis, treatment planning, implant positioning challenges and the strategic role of temporary skeletal anchorage devices in cases with compromised anchorage. Effective communication, collaborative efforts and strategic planning are highlighted in determining optimal implant numbers, locations and timing of placement. A collaborative, strategic approach to managing the complexities of joint orthodontic-restorative cases involving dental implants is recommended., (© 2024. The Author(s), under exclusive licence to the British Dental Association.)

Introduction: Patients with end-stage heart failure have limited options for medical treatment, and this ultimately necessitates heart transplantation. Patients undergoing heart transplant surgery are burdened with substantial costs related to finances, procedural risks, and postoperative quality of life. This report presents a case of heart failure in a patient whose limbs and heart were preserved through a collaboration between modern and traditional Chinese medicine (TCM)., Patient Presentation: A 47-year-old man was admitted to the emergency department with out-of-hospital cardiac arrest (OHCA) and was diagnosed with 3-vessel disease and acute decompensated heart failure on October 27, 2020. After extracorporeal membrane oxygenation (ECMO), the patient presented with cyanosis and gangrene in all four limbs. Cardiologists and plastic surgeons recommended heart transplantation and amputation. The patient wanted to keep his limbs and heart intact and requested to receive TCM. A TCM physician was consulted by visiting staff to provide combined care. After TCM intervention, both the ejection fraction (EF) and gangrene improved. Until now, the patient continues to receive TCM treatment, lives with preserved limbs and heart, and went through SARS-CoV2 infection smoothly in 2023., Conclusion: TCM met the expectations of the patient and reduced the high medical expenses. This approach may improve the outlook and be a more economical option for patients with end-stage heart failure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The literature on patient-reported outcomes (PROs) discussing dorsal preservation rhinoplasty (DPR) and component dorsal hump reduction (CDHR) is scarce. This study aims to fill the gap in PROs between these techniques., Methods: A systematic review was conducted to investigate PROs of DPR and CDHR. A proportion meta-analysis was conducted using Stata statistical software., Results: A total of 25 studies met our inclusion criteria, pooling 1706 participants, with 13 studies on CDHP and 12 studies on DPR. Overall satisfaction rates were high, varying from 84% to 100% across studies. A subgroup analysis revealed that both techniques exhibited equally high satisfaction with no statistical differences ( P = 0.18). A random-effects model revealed that about two of 100 treated patients underwent revisions across our cohort (95% interquartile range: 0-4). Notably, the CDHR technique was associated with a significant 53.7-point reduction in the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS)-cosmetic domain [95% confidence interval (CI): -62.7 to -44.8, P < 0.001], along with a meaningful improvement in SCHNOS-obstructive scores by -27.3 points (95% CI: -50.5 to -4.04, P = 0.02). Conversely, the DPR was linked to a 55.3-point reduction in the SCHNOS-cosmetic domain (95% CI: -60.7 to -49.9, P < 0.001), and a -19.5 point change in the SCHNOS-obstructive domain (95% CI: -27.9 to -11.1, P < 0.001)., Conclusion: Although PROs are comparable, the literature suggests that CDHR outcomes may be better than DPR in alleviating obstructive symptoms, potentially offering an evidence-based choice for addressing functional concerns in rhinoplasty., Competing Interests: Dr. Lin receives royalties from McGraw Hill. The other authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families., (© 2024. The Author(s).)

Competing Interests: The authors have no financial interest to declare in relation to the content of this article.

Introduction: Research in gender-affirming chest surgery has primarily compared cisgender versus transgender and gender-diverse (TGD) people, without specifically addressing nonbinary people. This study will assess surgical complications between cisgender, transgender, and nonbinary adults undergoing breast reductions., Methods: The National Surgical Quality Improvement Program databases from 2015 to 2021 were used to identify TGD patients who underwent breast reduction (Current Procedural Terminology code: 19318) and cisgender patients who underwent this procedure for cosmesis or cancer prophylaxis. Analysis of variance tests, chi-squared tests, unpaired t-tests, and regression models compared complications among cisgender, transgender, and nonbinary patients., Results: A total of 1222 patients met the inclusion criteria: 380 (31.1%) were cisgender, 769 (62.9%) were transgender, and 73 (6.0%) were nonbinary. The proportion of TGD patients grew significantly relative to cisgender patients over the study period (P < 0.001). The overall all-cause complication rate was 3.4%, with 4.2% of cisgender, 1.4% of nonbinary, and 3.1% of transgender patients experiencing surgical complications. After adjusting for confounding variables, no statistically significant difference was observed in all-cause complication rates between the cohorts. In the sample, 19 transgender patients (2.5%) underwent reoperation. Transgender patients had a lower likelihood of wound complications (odds ratio: 0.172; 95% confidence interval: 0.035-0.849; P = 0.031) compared to cisgender patients and nonbinary patients. None of the patients experienced a severe systemic complication., Conclusions: The findings emphasize the growing demand and safety of gender-affirming breast reductions. They underscore the importance of continued research and tailored approaches to delivering care to nonbinary and transgender patients, addressing their diverse needs and improving access to gender-affirming surgeries., (Copyright © 2024. Published by Elsevier Inc.)

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E&#95;{QG,1}>10 times the Planck energy E&#95;{Pl} for the linear LIV effect, and E&#95;{QG,2}>6×10^{-8}E&#95;{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

The prevalence of white matter disease increases with age and is associated with cerebrovascular disease, cognitive decline, and risk for dementia. MRI measures of abnormal signal in the white matter (AWM) provide estimates of damage, however, regional patterns of AWM may be differentially influenced by genetic or environmental factors. With our data-driven regional parcellation approach, we created a probability distribution atlas using Vietnam Era Twin Study of Aging (VETSA) data (n = 475, mean age 67.6 years) and applied a watershed algorithm to define separate regional parcellations. We report biometrical twin modeling for five anatomically distinct regions: (1) Posterior, (2) Superior frontal and parietal, (3) Anterior and inferior frontal with deep areas, (4) Occipital, and (5) Anterior periventricular. We tested competing multivariate hypotheses to identify unique influences and to explain sources of covariance among the parcellations. Family aggregation could be entirely explained by additive genetic influences, with additive genetic variance (heritability) ranging from 0.69 to 0.79. Most genetic correlations between parcellations ranged from moderate to high (r g  = 0.57-0.85), although two were small (r g  = 0.35-0.39), consistent with varying degrees of unique genetic influences. This proof-of-principle investigation demonstrated the value of our novel, data-driven parcellations, with identifiable genetic and environmental differences, for future exploration., (© 2024 Wiley Periodicals LLC.)

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.