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Previous studies have reported that tamoxifen use is associated with a decrease in mammographic breast density. This is a potentially valuable finding since mammographic sensitivity is limited by breast density. Anything that reduces breast density would theoretically enhance the sensitivity of mammography for the detection of breast cancer in women at an earlier stage when it is more curable. We performed a retrospective study investigating the potential effect of tamoxifen on breast density. The data for this retrospective study were collected from the records of 52 charts from a single medical oncologist. Patients with breast cancer were selected regardless of stage or age at the time of diagnosis or treatment, as long as their charts had records of bilateral mammograms. For each breast on each woman, both mediolateral oblique and craniocaudal views were reviewed independently by two radiologists on two separate occasions to obtain inter- and intraobserver variability. Two methods of classifying breast density were used: the Breast Imaging Reporting and Data System (BI-RADS), and measurements of percent density. Only age and menopausal status were found to be associated with breast density. There was no correlation between breast density and tamoxifen use (past or present). Our study shows no association between tamoxifen use and breast density. We confirm previous observations that breast density is inversely correlated with age and postmenopausal status. [ABSTRACT FROM AUTHOR]

The article talks about X-linked agammaglobulinemia (XLA), a genetic disorder that is caused due to deficiency of B Cells and low immunoglobulins. Rheumatological symptoms of arthritis are also observed in XLA. A case of two juvenile patients is discussed who were diagnosed with XLA due to bilateral knee swelling and arthralgia in first patient and bilateral knee, hip, and elbow arthritis in the second patient.

Background. We have recently shown that blockade of angiotensin II activity inhibits local macrophage and myofibroblast proliferation in progressive non-immune renal injury in the rat remnant kidney. However, it is not known whether this local proliferation contributes to macrophages and myofibroblast accumulation and the development of renal injury. Therefore, we examined this issue in a detailed time-course study of the rat remnant kidney. [ABSTRACT FROM PUBLISHER]

Background: It is important to find a comorbidity measure with better performance for use with administrative data. The new method proposed by Elixhauser et al. has never been validated and compared to the widely used Charlson method in the Asia region. The objective of this study was to compare the performance of three comorbidity measures using information from different data periods in predicting short- and long-term mortality among patients with acute myocardial infarction (AMI) and chronic obstructive pulmonary disease (COPD).Methods: We conducted a retrospective cohort study using National Health Insurance claims data (2001-2002) in Taiwan. We constructed the Elixhauser, the Charlson/Deyo, and the Charlson/Romano methods based on the International Classification of Disease, 9th Revision, Clinical Modification codes in the claims data. Two data periods, including the index hospitalization as well as the index and prior 1-year hospitalizations, were used in the analysis. The performances were compared using the c-statistics derived from multiple logistic regression models that included age, gender, race, and whether the patient received surgery or not. The outcomes of interest were in-hospital and 1-year mortality.Results: The performance was in the same rank order among both populations regardless of the outcome and data period: Elixhauser > Charlson/Romano > Charlson/Deyo. In predicting in-hospital mortality, the Elixhauser models using information from the index hospitalization performed best, even better than the Charlson/Deyo or Charlson/Romano models using information from the index and prior hospitalizations. Nevertheless, in predicting 1-year mortality, the Elixhauser models using information from the index and 1-year prior hospitalizations performed better than using information from the index hospitalization only.Conclusions: This is so far the first study to validate the Elixhauser method and compare it to other methods in the Asia region, and is the first to report its differences in data periods between short- and long-term outcomes. The comorbidity measurement developed by Elixhauser et al. has relatively good predictive validity, and researchers should consider its use in claims-based studies. [ABSTRACT FROM AUTHOR]

Infants with congenital heart disease (CHD) often undergo thymectomy during corrective cardiac surgery (CCS). The long-term immunological effects remain controversial, with concerns regarding increased susceptibility to infections, allergies, autoimmunity due to compromised immune tolerance mechanisms. This study aims to elucidate the long-term immunological effects of early thymectomy. We enrolled 22 patients who underwent thymectomy in infancy and were followed up in the Pediatric Allergy and Immunology Clinic at Marmara University. We performed demographic characteristics and detailed immunological evaluation, including immunoglobulins, vaccine responses, lymphocyte subset analyses, upregulation, proliferation of T cells and T-cell receptor excision circles (TRECs). Sixteen patients had a history of infection, including six serious infections, all in the first year. Lymphopenia was observed in 27% of patients, with a significant decrease in naive CD4 + and recent thymic emigrant T cells counts and an increase in the proportion of memory T-cells, indicating premature immune senescence. Low levels of IgG, IgA and IgM were found in 36%, 40% and 22% of patients respectively. Vaccine responses were positive in 90% of patients. TREC levels were low in all 10 patients analysed. Seven of nine patients had normal proliferation. Twenty-two percent of patients had allergic disease, and autoimmunity was not observed. Early thymectomy leads to permanent immunological changes that are indicative of early immunosenescence. It is recommended to preserve thymic tissue during surgery and requires long-term follow-up in terms of findings such as allergy and autoimmunity as well as infections due to impaired immune tolerance mechanisms., (© 2024 The Scandinavian Foundation for Immunology.)

A series of novel maleimide derivatives were synthesized, with various heterocyclic compounds serving as side chains in the synthesis process. The structural characteristics of these compounds were elucidated through the application of 1 H-NMR spectroscopy, 13 C-NMR (APT) spectroscopy, and high-resolution mass spectrometry (HRMS). The anti-cancer potential of these compounds was subsequently assessed in vitro, utilizing two distinct breast cancer cell lines, namely MDA-MB-231 and MCF-7, via MTT assay. Among the 12 newly synthesized compounds, 4 a, 4 b, 4 c, 4 d, 5 a, 5 b, 5 c and 5 d were determined to show the most promising anti-cancer activity against both breast cancer cell lines. Moreover, the morphological changes induced in the cells following a 24-hour incubation period with these compounds were observed using light microscopy. Additionally, molecular dynamics simulations were conducted to assess the stability of the bound conformations of the compounds to the target protein GSK-3β as obtained through molecular docking calculations., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)

Background: Bystander cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) has increased in Singapore, Japan, and South Korea following the implementation of several public health, bystander-focused interventions, such as dispatcher-assisted CPR and community CPR training. It is unclear whether bystander CPR prevalence will continue on this trajectory over time. This study aimed to investigate the temporal trends of bystander CPR prevalence over a ten-year period in these three Asian countries., Method: Using the national OHCA registries of Singapore, Japan and South Korea, we included witnessed, non-traumatic adult OHCA registered between 2010 and 2020 in Singapore and Japan, and between 2012 and 2020 in South Korea. We excluded those for whom resuscitation was not attempted or was terminated at scene. The study analysed the proportion of bystander CPR in the three countries, presenting the data annually and further breaking it down by age and gender., Results: This study included 491,067 patients in Japan [male 59 %, median, age 79 years (Q1-Q3, 69-87)], 13,143 patients in Singapore [male 66 %, median, age 69 years (Q1-Q3, 57-80)], and 87,997 patients in South Korea [male 64 %, median age 72 years (Q1-Q3, 59-81)]. The proportion of bystander CPR in each country had increased (Japan: 39 % in 2010 to 45 % in 2015, Singapore: 22 % in 2010 to 53 % in 2015, and South Korea: 37 % in 2012 to 56 % in 2015); however, these proportions have plateaued in 2020 (Japan: 46 %, Singapore: 54 %, and South Korea: 57 %) despite continued efforts. These trends were consistent across different age groups, gender and location., Conclusion: This study investigated the trend of bystander CPR over 10 years in three Asian countries. Although the proportion of bystander CPR has increased, it has now plateaued between 50-60 %. Further research is necessary to identify the contributing factors and advance beyond this "invisible ceiling"., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [YO has received a research grant from the ZOLL foundation and an overseas scholarship from the FUKUDA foundation for medical technology and the International medical research foundation. These organizations have no role in conducting this research. MEHO reports grants from the Laerdal Foundation, Laerdal Medical, and Ramsey Social Justice Foundation for funding of the Pan-Asian Resuscitation Outcomes Study an advisory relationship with Global Healthcare SG, a commercial entity that manufactures cooling devices; and funding from Laerdal Medical on an observation program to their Community CPR Training Centre Research Program in Norway. MEHO is a Scientific Advisor to TIIM Healthcare SG and Global Healthcare SG. SL Lim is supported by the National Medical Research Council Transitional Award; she has received research grants from National University Health System, National Kidney Foundation of Singapore and Singapore Heart Foundation. She is an Associate Editor for Resuscitation and a member of the Editorial Board for Resuscitation Plus]., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: The immune response in children elicited by SARS-CoV-2 Omicron infection alone or in combination with COVID-19 vaccination (hybrid immunity) is poorly understood. We examined the humoral and cellular immune response following SARS-CoV-2 Omicron infection in unvaccinated children and children who were previously vaccinated with COVID-19 mRNA vaccine., Methods: Participants were recruited as part of a household cohort study conducted during the Omicron predominant wave (Jan to July 2022) in Victoria, Australia. Blood samples were collected at 1, 3, 6 and 12 months following COVID-19 diagnosis. Humoral immune responses to SARS-CoV-2 Spike proteins from Wuhan, Omicron BA.1, BA.4/5 and JN.1, as well as cellular immune responses to Wuhan and BA.1 were assessed., Results: A total of 43 children and 113 samples were included in the analysis. Following Omicron infection, unvaccinated children generated low antibody responses but elicited Spike-specific CD4 and CD8 T-cell responses. In contrast, vaccinated children infected with the Omicron variant mounted robust humoral and cellular immune responses to both ancestral strain and Omicron subvariants. Hybrid immunity persisted for at least 6 months post infection, with cellular immune memory characterised by the generation of Spike-specific polyfunctional CD8 T-cell responses., Conclusion: SARS-CoV-2 hybrid immunity in children is characterised by persisting SARS-CoV-2 antibodies and robust CD4 and CD8 T-cell activation and polyfunctional responses. Our findings contribute to understanding hybrid immunity in children and may have implications regarding COVID-19 vaccination and SARS-CoV-2 re-infections., Competing Interests: NWC received funding from the National Institute of Health for influenza and COVID‐19 research. All other authors declare no conflict of interest., (© 2024 The Author(s). Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Background: Fecal incontinence has a devastating impact on quality of life and imposes a substantial socioeconomic burden. Best medical therapy, including biofeedback therapy, improves mild symptoms with minimal impact on moderate to severe symptoms. Surgical management for incontinence carries a degree of morbidity, resulting in low uptake and acceptability. Although acupuncture is common practice in Singapore for numerous medical conditions, its role in fecal incontinence is relatively novel. In our local context, however, acupuncture is accessible, inexpensive, and potentially well accepted as a treatment strategy., Objective: To determine the effectiveness of traditional Chinese medicine acupuncture, compared to biofeedback therapy, in the treatment of fecal incontinence. The secondary aim is to investigate the differences in quality of life after treatment., Design: Randomized controlled trial., Setting: Prospective, single-institution study., Patients: Patients with 2 or more episodes of fecal incontinence per week or St. Mark's incontinence score of 5 or higher were recruited. Patients were randomly assigned into biofeedback therapy, which included 3 sessions over 10 weeks, or 30 sessions of acupuncture over 10 weeks., Main Outcome Measures: Incontinence episodes, St. Mark's score, and fecal incontinence quality-of-life scale., Results: Eighty-five patients were randomly assigned to biofeedback therapy (n = 46) or acupuncture (n = 39). Demographics and baseline clinical characteristics were not different ( p > 0.05). Overall median incontinence episodes were reduced in both, with the acupuncture arm reporting significantly fewer episodes at week 15 ( p < 0.001). Acupuncture also improved quality of life, with improvement in lifestyle, coping, depression, and embarrassment at week 15 ( p < 0.05). Although the St. Mark's score was significantly reduced in both arms at week 15 ( p < 0.001), the acupuncture arm's score was significantly lower ( p = 0.002)., Limitations: Longer follow-up is required., Conclusions: Acupuncture is clinically effective and improves the quality of life in patients with fecal incontinence. See Video Abstract ., Clinical Trial Registration: Clinicaltrials.gov : NCT04276350., Eficacia De La Acupuntura Tradicional Comparada Con La Terapia De Biorretroalimentacin En La Incontinencia Fecal Un Ensayo Controlado Aleatorio: ANTECEDENTES:La incontinencia fecal tiene un impacto devastador en la calidad de vida e impone una carga socioeconómica sustancial. La mejor terapia médica, incluida la terapia de biorretroalimentación, mejora los síntomas leves, con un impacto mínimo sobre los síntomas moderados a graves. El tratamiento quirúrgico de la incontinencia conlleva un grado de morbilidad que resulta en una baja aceptación y aceptabilidad. Si bien la acupuntura es una práctica común en Singapur para numerosas afecciones médicas, su papel en la incontinencia fecal es relativamente novedoso. Sin embargo, en nuestro contexto local, la acupuntura es accesible, económica y potencialmente bien aceptada como estrategia de tratamiento.OBJETIVO:Determinar la efectividad de la acupuntura de la Medicina Tradicional China, en comparación con la terapia de biorretroalimentación en el tratamiento de la incontinencia fecal. El objetivo secundario es investigar las diferencias en la calidad de vida después del tratamiento.DISEÑO:Ensayo controlado aleatorio.AJUSTE:Estudio prospectivo de una sola institución.PACIENTES:Se reclutaron pacientes con >2 episodios de incontinencia fecal/semana o una puntuación de incontinencia de St. Mark's >5. Los pacientes fueron asignados aleatoriamente a una terapia de biorretroalimentación que incluyó 3 sesiones durante 10 semanas o 30 sesiones de acupuntura durante 10 semanas.PRINCIPALES MEDIDAS DE RESULTADO:Episodios de incontinencia, puntuación de St. Mark's y escala de calidad de vida de incontinencia fecal.RESULTADOS:Ochenta y cinco pacientes fueron asignados aleatoriamente a terapia de biorretroalimentación (n = 46) o acupuntura (n = 39). Las características demográficas y clínicas iniciales no fueron diferentes ( p > 0,05). La mediana general de episodios de incontinencia se redujo en ambos, y el grupo de acupuntura informó significativamente menos en la semana 15 ( p <0,001). La acupuntura también mejoró la calidad de vida, con mejoras en el estilo de vida, el afrontamiento, la depresión y la vergüenza en la semana 15 ( p <0,05). Mientras que la puntuación de St Mark se redujo significativamente en ambos brazos en la semana 15 ( p < 0,001), la puntuación del brazo de acupuntura fue significativamente menor (p = 0,002).LIMITACIONES:Se requiere un seguimiento más prolongado.CONCLUSIONES:La acupuntura es clínicamente efectiva y mejora la calidad de vida en pacientes con incontinencia fecal. (Traducción-Dr Yolanda Colorado )., (Copyright © The ASCRS 2024.)

Background: Medication-related problem is a concerning issue in older adults with multimorbidity due to complexity of disease conditions and polypharmacy, and may lead to increase in risk for adverse health outcomes. This study aims to investigate the prevalence and associated factors of potentially inappropriate medication use among the growing population of older adults with multimorbidity in Taiwan., Method: The study population was composed of patients who were aged 65 years or older with multimorbidity (two or more chronic diseases) and had at least one outpatient clinic visit with drug prescription in 2018 identified from the Taiwan National Health Insurance Research Database. Potentially inappropriate medication use was defined using the 2019 Beers criteria for drugs to be avoided for older adults. Multiple logistic regression model was conducted to examine patient-related and prescriber-related factors associated with PIM use., Results: A total of 2 432 416 patients (69.7% of the entire older adult population) had multimorbidity and received at least one drug prescription at the outpatient clinic in Taiwan in 2018. The prevalence of having at least one PIM in this population was found to be 85.6%. Patient-related factors (age, sex, specific chronic diseases, frequency of outpatient visits) and prescriber-related factors (physician characteristics, healthcare setting, total number of medications, prior PIM use) were found to be associated with use of PIM., Conclusion: High prevalence of PIM use was found in older patients with multimorbidity in Taiwan. Both patient-related and prescriber-related factors had been found to be predictors of PIM use, and should be addressed when trying to improve the medication quality in this population., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Historically in Singapore, all out-of-hospital cardiac arrests (OHCA) were transported to hospital for pronouncement of death. A 'Termination of Resuscitation' (TOR) protocol, implemented from 2019 onwards, enables emergency responders to pronounce death at-scene in Singapore. This study aims to evaluate the cost-effectiveness of the TOR protocol for OHCA management., Methods: Adopting a healthcare provider's perspective, a Markov model was developed to evaluate three competing options: No TOR, Observed TOR reflecting existing practice, and Full TOR if TOR is exercised fully. The model had a cycle duration of 30 days after the initial state of having a cardiac arrest, and was evaluated over a 10-year time horizon. Probabilistic sensitivity analysis was performed to account for uncertainties. The costs per quality adjusted life years (QALY) was calculated., Results: A total of 3,695 OHCA cases eligible for the TOR protocol were analysed; mean age of 73.0 ± 15.5 years. For every 10,000 hypothetical patients, Observed TOR and Full TOR had more deaths by approximately 19 and 31 patients, respectively, compared to No TOR. Full TOR had the least costs and QALYs at $19,633,369 (95% Uncertainty Interval (UI) 19,469,973 to 19,796,764) and 0 QALYs. If TOR is exercised for every eligible case, it could expect to save approximately $400,440 per QALY loss compared to No TOR, and $821,151 per QALY loss compared to Observed TOR., Conclusion: The application of the TOR protocol for the management of OHCA was found to be cost-effective within acceptable willingness-to-pay thresholds, providing some justification for sustainable adoption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Rapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy., Methods: A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in China (1980-2015). Literature searches were conducted in English and Chinese languages in six databases: Ovid MEDLINE, Global Health, EMBASE, Web of Science™ - Chinese Science Citation Database SM , The China National Knowledge Infrastructure (CNKI), and WanFang Med Online. Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. The number of published articles, reporting a given pathogen were presented, rather than incidence or prevalence of infection., Results: A total of 57,181 records from 13 provinces of China where malaria used to be endemic were screened, of which 392 met selection criteria and were included in this review. The review includes 60 (15.3%) records published from 1980 to 2000, 211 (53.8%) from 2001 to 2010 and 121 (30.9%) from 2011 to 2015;. Of the 392 records, 166 (42.3%) were from the eastern region of China, 120 (30.6%) were from the south-west, 102 (26.0%) from south-central, and four (1.0%) were multi-regional studies. Bacterial infections were reported in 154 (39.3%) records, viral infections in 219 (55.9%), parasitic infections in four (1.0%), fungal infections in one (0.3%), and 14 (3.6%) publications reported more than one pathogen group. Participants of all ages were included in 136 (34.7%) studies, only adults in 75 (19.1%), only children in 17 (4.3%), only neonates in two (0.5%) and the age distribution was not specified in 162 (41.3%) records. The most commonly reported bacterial pathogens included Typhoidal Salmonella (n = 30), Orientia/ Rickettsia tsutsugamushi (n = 31), Coxiella burnetii (n = 17), Leptospira spp. (n = 15) and Brucella spp. (n = 15). The most commonly reported viral pathogens included Hantavirus/Hantaan virus (n = 89), dengue virus (DENV) (n = 76 including those with unknown serovars), Japanese encephalitis virus (n = 21), and measles virus (n = 15). The relative lack of data in the western region of the country, as well as in in neonates and children, represented major gaps in the understanding of the aetiology of fever in China., Conclusions: This review presents a landscape of non-malaria pathogens causing febrile illness in China over 36 years as the country progressed toward malaria elimination. These findings can inform guidelines for clinical management of fever cases and infection surveillance and prevention, and highlight the need to standardize operational and reporting protocols for better understanding of fever aetiology in the country., (© 2024. The Author(s).)

Acute lung injury (ALI) is a difficult condition to manage, especially when it is complicated by bacterial sepsis. Hibifolin, a flavonoid glycoside, has anti-inflammatory properties that make it a potential treatment for ALI. However, more research is needed to determine its effectiveness in LPS-induced ALI. In this study, male ICR mice were treated with hibifolin before LPS-induced ALI. Protein content and neutrophil count in bronchoalveolar lavage (BAL) fluid were measured by BCA assay and Giemsa staining method, respectively. The levels of proinflammatory cytokines and adhesive molecules were detected by ELISA assay. The expression of NFκB p65 phosphorylation, IκB degradation, and Akt phosphorylation was assessed by western blot assay. Hibifolin pre-treatment significantly reduced pulmonary vascular barrier dysfunction and neutrophil infiltration into the BAL fluid in LPS-induced ALI mice. In addition, LPS-induced expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and adhesive molecules (ICAM-1, VCAM-1) within the BAL fluid were markedly reduced by hibifolin in LPS-induced ALI mice. More, hibifolin inhibited LPS-induced phosphorylation of NFκB p65, degradation of IκB, and phosphorylation of Akt in lungs with ALI mice. In conclusion, hibifolin shows promise in improving the pathophysiological features and proinflammatory responses of LPS-induced ALI in mice through the NFκB pathway and its upstream factor, Akt phosphorylation., (© 2024 Wiley Periodicals LLC.)

Machine learning (ML) methods are increasingly used to assess variable importance, but such black box models lack stability when limited in sample sizes, and do not formally indicate non-important factors. The Shapley variable importance cloud (ShapleyVIC) addresses these limitations by assessing variable importance from an ensemble of regression models, which enhances robustness while maintaining interpretability, and estimates uncertainty of overall importance to formally test its significance. In a clinical study, ShapleyVIC reasonably identified important variables when the random forest and XGBoost failed to, and generally reproduced the findings from smaller subsamples (n = 2500 and 500) when statistical power of the logistic regression became attenuated. Moreover, ShapleyVIC reasonably estimated non-significant importance of race to justify its exclusion from the final prediction model, as opposed to the race-dependent model from the conventional stepwise model building. Hence, ShapleyVIC is robust and interpretable for variable importance assessment, with potential contribution to fairer clinical risk prediction., Competing Interests: MEH Ong reports an advisory relationship with Global Healthcare SG, a commercial entity that manufactures cooling devices. MEH Ong has a licensing agreement and a patent filed (Application no: 13/047,348) with ZOLL Medical Corporation for a study titled "Method of predicting acute cardiopulmonary events and survivability of a patient". All other authors have no conflict of interests to declare., (Copyright: © 2024 Ning et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

ALI is a grave medical ailment that manifests as abrupt inflammation of the lungs and diminished oxygen levels. It poses a considerable challenge to the medical fraternity, with elevated rates of morbidity and mortality. Our research endeavors to investigate the potential of hibifolin, a flavonoid glucuronide, imbued with potent antioxidant properties, and its molecular mechanism to combat LPS-induced ALI in mice. The study utilized ICR mice to create an ALI model induced by LPS. Prior to LPS administration, hibifolin was given at 10, 30, or 50 mg/kg, or dexamethasone was given at 1 mg/kg to assess its preventative impact. Changes in lung tissue, pulmonary edema, and lipid peroxidation were analyzed using H&E stain assay, lung wet/dry ratio assay, and MDA formation assay, respectively. Activity assay kits were used to measure MPO activity and antioxidative enzymes (SOD, CAT, GPx) activity in the lungs. Western blot assay was used to determine the phosphorylation of Nrf-2 and AMPK2 in the lungs. Hibifolin demonstrated a concentration-dependent improvement in LPS-induced histopathologic pulmonary changes. This treatment notably mitigated pulmonary edema, lipid peroxidation, and MPO activity in ALI mice. Additionally, hibifolin successfully restored antioxidative enzyme activity in the lungs of ALI mice. Moreover, hibifolin effectively promoted Nrf-2 phosphorylation and reinstated AMPK2 phosphorylation in the lungs of ALI mice. The results indicate that hibifolin could effectively alleviate the pathophysiological impact of LPS-induced ALI. This is likely due to its antioxidative properties, which help to restore antioxidative enzyme activity and activate the AMPK2/Nrf2 pathway. These findings are valuable in terms of enhancing our knowledge of ALI treatment and pave the way for further investigation into hibifolin as a potential therapeutic option for lung injuries., (© 2024 Wiley Periodicals LLC.)

Background: Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor., Methods: We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing., Findings: We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified., Interpretation: Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants., Funding: Murdoch Children's Research Institute Infection and Immunity theme grant., Competing Interests: Declaration of interests D.W receives funds from GSK to lead a study evaluating RSV testing in Australia. Payments are made to research funds. D.W also receives consultancy funds from Sanofi, MSD and Praxhub which are paid to research funds. D. W is a co-chair on TSANZ and a working group member of Therapeutic Guidelines Ltd, (Antibiotics, respiratory) Australian clinical guidelines. L.A.H.D receives grants from CEPI, PATH and BMGF where payments are made to the institution. P.V.L receives grants from CEPI where payments are made to the institution. M.L.K.T receives grants from NHMRC and Allergy and Immunology Foundation of Australasia. M.L.K.T receives royalties from the book “Food Allergies for Dummies”, and consultancy fees from the Abrocitinib advisory board of Pfizer. M.L.K.T has received flight support from APAAACI Congress and the CUHK Allergy conference. M.L.K.T has patents covering food allergy and pending patents from allergy treatments. M.L.K.T is the board director for AllergyPal, on the board of directors for APAAACI and an advisory board membership for AAA which are all unpaid. M.L.K.T has received probiotics from Metagenics for the PEAT study and is a CFAR3 investigator, associate editor for JACI global and on the editorial board of World Allergy Organisation Journal, Asia Pacific Allergy Journal and JACI In Practice. K.M received funding support from the BMGF, funding paid to the institute and is a member of the WHO SAGE committee. K.M is also an investigator on a observational study of adult pneumonia in Mongolia funded by Pfizer. K.M has received funding support to attend meetings by the WHO and Christian Medical College Vellore India. K.M has also participated on the data safety monitoring board of Novavax COVID-19 studies in an unpaid position., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Emergency departments (ED) are complex, triage is a main task in the ED to prioritize patient with limited medical resources who need them most. Machine learning (ML) based ED triage tool, Score for Emergency Risk Prediction (SERP), was previously developed using an interpretable ML framework with single center. We aimed to develop SERP with 3 Korean multicenter cohorts based on common data model (CDM) without data sharing and compare performance with inter-hospital validation design. This retrospective cohort study included all adult emergency visit patients of 3 hospitals in Korea from 2016 to 2017. We adopted CDM for the standardized multicenter research. The outcome of interest was 2-day mortality after the patients' ED visit. We developed each hospital SERP using interpretable ML framework and validated inter-hospital wisely. We accessed the performance of each hospital's score based on some metrics considering data imbalance strategy. The study population for each hospital included 87,670, 83,363 and 54,423 ED visits from 2016 to 2017. The 2-day mortality rate were 0.51%, 0.56% and 0.65%. Validation results showed accurate for inter hospital validation which has at least AUROC of 0.899 (0.858-0.940). We developed multicenter based Interpretable ML model using CDM for 2-day mortality prediction and executed Inter-hospital external validation which showed enough high accuracy., (© 2024. The Author(s).)

Background: Shock-refractory ventricular fibrillation (VF) or ventricular tachycardia (VT) is a treatment challenge in out-of-hospital cardiac arrest (OHCA). This study aimed to develop and validate machine learning models that could be implemented by emergency medical services (EMS) to predict refractory VF/VT in OHCA patients., Methods: This was a retrospective study examining adult non-traumatic OHCA patients brought into the emergency department by Singapore EMS from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Data from April 2010 to March 2020 were extracted for this study. Refractory VF/VT was defined as VF/VT persisting or recurring after at least one shock. Features were selected based on expert clinical opinion and availability to dispatch prior to arrival at scene. Multivariable logistic regression (MVR), LASSO and random forest (RF) models were investigated. Model performance was evaluated using receiver operator characteristic (ROC) area under curve (AUC) analysis and calibration plots., Results: 20,713 patients were included in this study, of which 860 (4.1%) fulfilled the criteria for refractory VF/VT. All models performed comparably and were moderately well-calibrated. ROC-AUC were 0.732 (95% CI, 0.695 - 0.769) for MVR, 0.738 (95% CI, 0.701 - 0.774) for LASSO, and 0.731 (95% CI, 0.690 - 0.773) for RF. The shared important predictors across all models included male gender and public location., Conclusion: The machine learning models developed have potential clinical utility to improve outcomes in cases of refractory VF/VT OHCA. Prediction of refractory VF/VT prior to arrival at patient's side may allow for increased options for intervention both by EMS and tertiary care centres., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YO has received a research grant from the ZOLL Foundation and an overseas scholarship from the FUKUDA Foundation for Medical Technology and the International Medical Research Foundation. MEHO reports grants from the Laerdal Foundation, Laerdal Medical, and Ramsey Social Justice Foundation for funding of the Pan-Asian Resuscitation Outcomes Study; an advisory relationship with Global Healthcare SG, a commercial entity that manufactures cooling devices; and funding from Laerdal Medical on an observation program to their Community CPR Training Centre Research Program in Norway. MEHO is a Scientific Advisor to TIIM Healthcare SG and Global Healthcare SG. These organizations have no role in the design of the study, the collection, analysis, or interpretation of data, or in writing the manuscript. All other authors reported no competing interests., (© 2024 The Authors.)

Objective: There is a lack of reliable and valid evidence-based practice (EBP) measures for physiotherapy students. This study validated EBP-student (EBP-S) measures for physiotherapy students., Methods: EBP measures developed from previous research were cross-culturally validated for use by physiotherapy students. The adapted EBP-S consisted of six measures: use of EBP, EBP activities, EBP knowledge, self-efficacy for EBP, attitudes towards EBP, and perceptions of the teaching and assessment of EBP in the curriculum. The final version was completed by physiotherapy students (n = 335). The psychometric properties for each EBP-S measure were estimated, including construct validity using Rasch model, internal consistency reliability using person separation index (PSI), test-retest reliability using intraclass correlation coefficient (ICC), and differential item functioning (DIF)., Results: Two formative measures (use of EBP and EBP activities) were only linguistically modified for use with students. A Rasch model was applied to the other four reflective measures. For knowledge, 55% (6/11) items fit the Rasch model with chi-square fit statistic (χ2) = 34.46, p = 0.08; PSI = 0.85. For self-efficacy, 89% (8/9) items fit the Rasch model with χ2 = 25.11, p = 0.80; PSI = 0.89. For attitudes, 62% (8/13) items fit the Rasch model with χ2 = 61.49, p = 0.00; PSI = 0.71. For perception of the teaching and assessment of EBP in the curriculum, 62% (8/13) items fit the Rasch model with χ2 = 80.99, p = 0.45; PSI = 0.92. perception of the teaching and assessment of EBP in the curriculum showed DIF in three items. The ICCs ranged between 0.80 and 0.98., Conclusions: The EBP-S measures were validated for physiotherapy students, including the testing of psychometric properties, which were not tested in the original studies. Further refinements should be considered for the use of the EBP-S with other groups of students or if changes are applied to the current curriculum., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Al Zoubi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Due to the narrow window of opportunity for stroke therapeutics to be employed, effectiveness of stroke care systems is predicated on the efficiency of prehospital stroke systems. A robust prehospital stroke system of care that provides a rapid and well-coordinated response maximises favourable poststroke outcomes, but achieving this presents a unique set of challenges dependent on demographic and geographical circumstances. Set in the context of a highly urbanised first-world nation with a rising burden of stroke, Singapore's prehospital stroke system has evolved to reflect the environment in which it operates. This review aims to characterise the current state of prehospital stroke care in Singapore, covering prehospital aspects of the stroke survival chain from symptom onset till arrival at the emergency department. We identify areas for improvement and innovation, as well as provide insights into the possible future of prehospital stroke care in Singapore., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)