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Abstract Background Staphylococcal enterotoxin and fungal sensitization can influence asthma severity; however, the effects on the clinical outcomes of asthma remain unclear. This study investigated the clinical outcomes of asthma in patients with or without staphylococcal enterotoxin sensitization and further analyzed the effects of fungal sensitization on the clinical outcomes of patients with staphylococcal enterotoxin sensitization. Methods This retrospective study included patients with asthma who had undergone a staphylococcal enterotoxin-specific immunoglobulin E test at our hospital between January and August 2021. Data on clinical manifestations, medication use, pulmonary function, clinic and emergency room visits and hospitalization were collected from 106 patients. Results The prevalence of staphylococcal enterotoxin sensitization was 27.3%. Among the patients with staphylococcal enterotoxin sensitization, 50% also presented with fungal sensitization. The risk of hospitalization and emergency room visits was higher among patients with staphylococcal enterotoxin sensitization than among those without, as was the need for high-level asthma treatment, including triple inhaler therapy and biologics. After the 12-month Program enrollment, the rates of emergency room visits and hospitalization were similar in the two cohorts. Patients with concomitant staphylococcal enterotoxin and fungal sensitization exhibited a notable post-treatment decline in pulmonary function. Conclusion Adherence to asthma treatment protocols was shown to improve clinical outcomes in patients with or without staphylococcal enterotoxin sensitization. Among patients with staphylococcal enterotoxin sensitization, those with concomitant fungal sensitization were more likely to exhibit a rapid decline in pulmonary function during a 1-year high-level treatment program.

Abstract Background Cardiovascular disease (CVD) remains the foremost cause of mortality globally. Taurine, an amino acid, holds promise for cardiovascular health through mechanisms such as calcium regulation, blood pressure reduction, and antioxidant and anti-inflammatory effects. Despite these potential benefits, previous studies have yielded inconsistent results. This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the existing evidence on the quantitative effects of taurine on hemodynamic parameters and cardiac function grading, which are indicative of overall cardiovascular health and performance. Methods We conducted an electronic search across multiple databases, including Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from their inception to January 2, 2024. Our analysis focused on key cardiovascular outcomes, such as heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) Functional Classification. Meta-regression was applied to explore dose-dependent relationships based on the total taurine dose administered during the treatment period. A subgroup analysis, stratified according to the baseline disease status of patients, was also conducted. Results The analysis included a pooled sample of 808 participants from 20 randomized controlled trials. Taurine demonstrated a significant reduction in HR (weighted mean difference [WMD] = -3.579 bpm, 95% confidence interval [CI] = -6.044 to -1.114, p = 0.004), SBP (WMD = -3.999 mm Hg, 95% CI = -7.293 to -0.706, p = 0.017), DBP (WMD: -1.435 mm Hg, 95% CI: -2.484 to -0.386, p = 0.007), NYHA (WMD: -0.403, 95% CI: -0.522 to -0.283, p

BackgroundAlthough biological plausibility suggests that fluoroquinolones could lead to rhegmatogenous retinal detachment (RRD) through collagen degradation, real-world evidence on their relative risk of RRD is inconsistent, with limited information on absolute risk estimates.ObjectiveThe study aimed to estimate the RRD risk associated with fluoroquinolones versus other antibiotics with similar indications (i.e., comparison antibiotics).MethodsWe conducted a retrospective cohort study analyzing claims data from adult patients who initiated fluoroquinolones or amoxicillin/clavulanate or ampicillin/sulbactam or extended-spectrum cephalosporins using the Taiwan National Health Insurance Research Database (2009–2018) and the United States IBM MarketScan Database (2011–2020). Patients were followed for up to 90 days after cohort entry. For each country’s data, after 1:1 propensity score (PS) matching, we used Cox regression models to estimate RRD risks, presented with hazard ratios (HR) with 95% confidence interval (95% CI). We used random-effects meta-analyses to derive pooled HRs across both counties.ResultsOf 24,172,032 eligible patients comprising 7,944,620 insured Taiwanese (mean age [SD], 46 [18] years; 45% male) and 16,227,412 United States commercially insured individuals (mean age [SD], 47 [16] years; 40% male), 10,137,468 patients initiated fluoroquinolones, 10,203,794 initiated amoxicillin/clavulanate or ampicillin/sulbactam, and 3,830,770 initiated extended-spectrum cephalosporins. After PS matching, similar RRD incidence rates were observed between fluoroquinolones and amoxicillin/clavulanate or ampicillin/sulbactam users (0.33 [95% CI, 0.19–0.56] versus 0.35 [95% CI, 0.26–0.46] per 1,000 person-years), yielding an HR of 0.97 (95% CI, 0.76–1.23). The RRD incidence rates were also similar comparing fluoroquinolones to extended-spectrum cephalosporins (0.36 [95% CI, 0.22–0.57] versus 0.34 [95% CI, 0.22–0.50] per 1,000 person-years; HR, 1.08 [95% CI, 0.92–1.27]). The comparative safety profiles remained consistent by country, various patient characteristic (e.g., diabetes or ophthalmic conditions), type of fluoroquinolones, follow-up duration, or treatment setting.ConclusionThis large-scale study, leveraging real-world data from Taiwan and the United States, showed a low and comparable RRD risk among adults who initiated fluoroquinolones or other antibiotics with similar indications. This suggests that the RRD risk should not deter the use of fluoroquinolone when clinically indicated.

ABSTRACT Background Eosinophil activation is associated with asthma. Whether air pollution affects the activation of blood eosinophils in patients with asthma remains unknown. In this study, we investigated the correlation between transcriptional activity in eosinophils and air pollutant exposure in patients receiving different levels of Global Initiative for Asthma (GINA) treatment. Methods We evaluated the expression levels of activation‐ and function‐related genes in eosinophils from patients with GINA 4 or 5 (n = 20), those with GINA 3 (n = 12), and normal individuals (n = 7); the eosinophils were activated with interleukin (IL)−5 or IL‐17. A land use regression model was used to estimate air pollutant exposure. The correlations between mRNA expression, lung function, and air pollutant exposure were investigated. Results The expression levels of TGFB1, IL7R, and TLR3 were significantly higher for patients with GINA 4 or 5 than for those with GINA 3 or normal individuals. The expression of certain genes, particularly in IL‐17‐activated eosinophils, was correlated with lung function decline in patients with GINA 4 or 5. For patients with GINA 4 or 5, NO2 exposure was correlated with upregulated TGFB1 expression in IL‐5‐activated eosinophils. For patients with GINA 3, O3 exposure was correlated with upregulated CCR5, IL5RA, IL7R, and TGFB1 expression in IL‐17‐activated eosinophils and upregulated IL7R expression in IL‐5‐activated eosinophils. Conclusion Patients with GINA 4 or 5 may exhibit elevated transcriptional activity in eosinophils; this elevation is correlated with lung function decline. Air pollution may affect eosinophil mRNA expression in patients with asthma.

Abstract Background Asia’s elderly Baby Boomer demographic (born between 1946 and 1964) faced a huge problem during the COVID-19 pandemic due to increased all-cause mortality. We aimed to provide a unique Taiwan situation regarding the impact of Baby Boomers on excess mortalities from all causes relative to non-Baby Boomers throughout distinct times of SARS-CoV-2 mutations during the COVID-19 pandemic. Methods We used the Poisson time series design with a Bayesian directed acyclic graphic approach to build the background mortality prior to the COVID-19 pandemic between 2015 and 2019. It was then used for predicting the expected all-cause deaths compared to the reported figures during the COVID-19 pandemic period based on Taiwan residents, an Omicron-naïve cohort. Results Baby Boomers experienced a 2% negative excess mortality in 2020 (Wuhan/D614G) and a 4% excess mortality in 2021 (Alpha/Delta) with a rising background mortality trend whereas non-Baby Boomers showed the corresponding figures of 4% negative excess and 1% excess with a stable trend. Baby Boomer and non-Baby Boomer excess mortality soared to 9% (95% CI: 7-10%) and 10% (95% CI: 9-11%), respectively, during the epidemic Omicron period from January to June 2022. Surprisingly, Baby Boomers aged 58–76 experienced the same 9% excess mortality as non-Baby Boomers aged 77 and beyond. Non-COVID-19 deaths were more prevalent among Baby Boomers than non-Baby Boomers (33% vs. 29%). Conclusion Baby Boomers were more likely to die from COVID-19 in early pandemic and had more non-COVID-19 deaths in late pandemic than older non-Baby Boomers demonstrated in Taiwan Omicron-naïve cohort. For this vulnerable population, adequate access to medical care and medical capacity require more consideration.

Background: The trajectories of all-cause deaths linked to omicron infections are rarely studied, especially in relation to the efficacy of booster shots. For assessing three epidemiological death trajectories, including dying from COVID-19, dying with COVID-19, and non-COVID-19 death, we offer a new COVID-19-and-death competing risk model that deals with the primary pathway (e.g., dying from COVID-19) competing with two other pathways. Methods: We applied this model to track three trajectories: deaths directly from COVID-19, deaths with COVID-19 as a contributing factor, and indirect non-COVID-19 deaths. The study used data from a Taiwanese cohort, covering periods of Omicron subvariants BA.2, BA.5, and BA.2.75. It focused on the effectiveness of monovalent and bivalent booster vaccines against these death trajectories. Results: The highest mortality was observed during the BA.2 phase, which decreased in the BA.5 period and increased again in the BA.2.75 period. Analyzing each trajectory, we noted similar trends in deaths directly from and with COVID-19, while non-COVID-19 deaths remained stable across subvariants. Booster vaccines reduced all-cause mortality by 58% (52%−62%) for BA.2, 70% (65%−75%) for BA.5%, and 75% (70%−80%) for BA.2.75, compared to incomplete vaccination. The reduction in deaths directly from COVID-19 was 66% (61%−72%) for BA.2, 78% (72%−84%) for BA.5%, and 85% (76%−93%) for BA.2.75. For deaths with COVID-19, the figures were 46% (36%−55%), 76% (68%−84%), and 90% (86%−95%). Additionally, the booster shots decreased non-COVID-19 deaths by 64% (63%−66%) for BA.2, 38% (36%−40%) for BA.5, and 19% (17%−21%) for BA.2.75. Conclusion: Our competing risk analysis is effective for monitoring all-cause death trajectories amidst various Omicron infections. It provides insights into the impact of booster vaccines, especially bivalent ones, and highlights the consequences of inadequate healthcare for vulnerable groups.

Surgical repair of rotator cuff tears is performed routinely; however, the risks of re-tears and the associated consequences are significant. Sonoelastography, an imaging modality that evaluates the mechanical properties of tissues, can examine the dynamic transitions in rotator cuff stiffness following retear and investigate the relationship between these changes and the occurrences of retears. This systematic review aimed to summarize the role of perioperative sonoelastography in repaired rotator cuffs. A comprehensive search of the PubMed, Embase, and Cochrane databases was conducted, covering studies published until June 19, 2023. The Newcastle-Ottawa scale was used for quality assessment. The key information extracted from each study included the injury/surgery type, follow-up duration, sonoelastography mode, and main sonoelastographic findings. Eleven eligible studies comprising 355 patients were included. All studies focused on supraspinatus muscles and tendons with previous arthroscopic repairs. During the postoperative 1st - 6th months, muscle stiffness increased in the supraspinatus and decreased in the ipsilateral deltoid. Failure to recover supraspinatus muscle elasticity might be indicative of potential tendon re-tear; however, it is imperative to first establish correlations with other imaging modalities. Conflicting findings have been observed regarding stiffening or softening of the supraspinatus tendon after surgical repair. The preoperative stiffness of the supraspinatus tendon did not correlate with postoperative tendon integrity or function.

Abstract tRNA modifications affect ribosomal elongation speed and co-translational folding dynamics. The Elongator complex is responsible for introducing 5-carboxymethyl at wobble uridine bases (cm5U34) in eukaryotic tRNAs. However, the structure and function of human Elongator remain poorly understood. In this study, we present a series of cryo-EM structures of human ELP123 in complex with tRNA and cofactors at four different stages of the reaction. The structures at resolutions of up to 2.9 Å together with complementary functional analyses reveal the molecular mechanism of the modification reaction. Our results show that tRNA binding exposes a universally conserved uridine at position 33 (U33), which triggers acetyl-CoA hydrolysis. We identify a series of conserved residues that are crucial for the radical-based acetylation of U34 and profile the molecular effects of patient-derived mutations. Together, we provide the high-resolution view of human Elongator and reveal its detailed mechanism of action.

Abstract Background Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters. Methods We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control. Results Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = −3.999 mmHg, 95% confidence interval [CI] = −7.293 to −0.706, p = 0.017), DBP (WMD = −1.509 mmHg, 95% CI = −2.479 to −0.539, p = 0.002), FBG (WMD: −5.882 mg/dL, 95% CI: −10.747 to −1.018, p = 0.018), TG (WMD: −18.315 mg/dL, 95% CI: −25.628 to −11.002, p

BackgroundPatients with prolonged mechanical ventilation (PMV) is usually associated with muscle wasting and diaphragm weakness, resulting in high medical costs and mortality. Adequate energy and protein intake were beneficial in sarcopenia patients. We aimed to investigate the impact of protein intake in weaning parameters in patients with PMV.Materials and methodsWe enrolled patients with PMV (mechanical ventilation ≥6 h/day for ≥21 days) from a respiratory care center (RCC) of a tertiary medical center from December 2020 to October 2022, and classified them into weaning success and weaning failure groups. The patients’ characteristics, nutrition records, weaning parameters and outcomes were analyzed.ResultsA total of 289 patients were included (mean age 73.5 years). Of the 289 patients, 149 were weaned successfully and 140 were not. The average protein intake was higher in the weaning success group than in the weaning failure group (1.22 ± 0.320 versus 0.99 ± 0.332 g/kg/day, p

BackgroundPrevious studies have highlighted the importance of viral shedding using cycle threshold (Ct) values obtained via reverse transcription polymerase chain reaction to understand the epidemic trajectories of SARS-CoV-2 infections. However, it is rare to elucidate the transition kinetics of Ct values from the asymptomatic or presymptomatic phase to the symptomatic phase before recovery using individual repeated Ct values. ObjectiveThis study proposes a novel Ct-enshrined compartment model to provide a series of quantitative measures for delineating the full trajectories of the dynamics of viral load from infection until recovery. MethodsThis Ct-enshrined compartment model was constructed by leveraging Ct-classified states within and between presymptomatic and symptomatic compartments before recovery or death among people with infections. A series of recovery indices were developed to assess the net kinetic movement of Ct-up toward and Ct-down off recovery. The model was applied to (1) a small-scale community-acquired Alpha variant outbreak under the “zero-COVID-19” policy without vaccines in May 2021 and (2) a large-scale community-acquired Omicron variant outbreak with high booster vaccination rates following the lifting of the “zero-COVID-19” policy in April 2022 in Taiwan. The model used Bayesian Markov chain Monte Carlo methods with the Metropolis-Hastings algorithm for parameter estimation. Sensitivity analyses were conducted by varying Ct cutoff values to assess the robustness of the model. ResultsThe kinetic indicators revealed a marked difference in viral shedding dynamics between the Alpha and Omicron variants. The Alpha variant exhibited slower viral shedding and lower recovery rates, but the Omicron variant demonstrated swifter viral shedding and higher recovery rates. Specifically, the Alpha variant showed gradual Ct-up transitions and moderate recovery rates, yielding a presymptomatic recovery index slightly higher than 1 (1.10), whereas the Omicron variant had remarkable Ct-up transitions and significantly higher asymptomatic recovery rates, resulting in a presymptomatic recovery index much higher than 1 (152.5). Sensitivity analysis confirmed the robustness of the chosen Ct values of 18 and 25 across different recovery phases. Regarding the impact of vaccination, individuals without booster vaccination had a 19% higher presymptomatic incidence rate compared to those with booster vaccination. Breakthrough infections in boosted individuals initially showed similar Ct-up transition rates but higher rates in later stages compared to nonboosted individuals. Overall, booster vaccination improved recovery rates, particularly during the symptomatic phase, although recovery rates for persistent asymptomatic infection were similar regardless of vaccination status once the Ct level exceeded 25. ConclusionsThe study provides new insights into dynamic Ct transitions, with the notable finding that Ct-up transitions toward recovery outpaced Ct-down and symptom-surfacing transitions during the presymptomatic phase. The Ct-up against Ct-down transition varies with variants and vaccination status. The proposed Ct-enshrined compartment model is useful for the surveillance of emerging infectious diseases in the future to prevent community-acquired outbreaks.

Objective: This umbrella review synthesizes systematic reviews and meta-analyses to reach a conclusion concerning the overall effectiveness of ultrasound-guided vs landmark-guided injections for treating musculoskeletal pain. Design: Umbrella review. Methods: PubMed, EMBASE, MEDLINE, and Web of Science were searched for relevant systematic reviews and meta-analyses from inception to March 2024. Critical appraisal, data extraction, and synthesis were performed in accordance with the criteria for conducting an umbrella review. Results: Seventeen articles, comprising 4 systematic reviews and 13 meta-analyses, were included. Using the AMSTAR2 instrument for quality assessment, 3 articles were rated as high quality, 1 as moderate, 7 as low, and 6 as critically low. Generally, ultrasound-guided injections were found to be more accurate than landmark-guided injections, particularly in the shoulder joint, though the results for pain relief and functional outcomes varied. Ultrasound guidance was notably effective for injections into the bicipital groove, wrist, hip, and knee – yielding greater accuracy and improved pain management. Both ultrasound-guided and landmark-guided techniques showed low incidence of adverse effects. Conclusion: This umbrella review offers an in-depth analysis of the comparative effectiveness of ultrasound-guided and landmark-guided injections across a range of musculoskeletal sites/conditions. The findings suggest that ultrasound-guided is a reliable method.

BackgroundThe role of routine intravascular imaging in percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) remains unclear. This study evaluated the clinical outcomes of PCI guided by different imaging modalities in AMI patients.Materials and methodsData from AMI patients who had undergone PCI between 2012 and 2022 were analyzed. The mean follow-up was 12.9 ± 1.73 months. The imaging modality-either intravascular ultrasound (IVUS), optical coherence tomography (OCT), or angiography alone-was selected at the operator's discretion. The primary endpoint was major adverse cardiac events (MACEs), including cardiovascular (CV) death, myocardial infarction (MI), target vessel revascularization.ResultsOf the 1,304 PCIs performed, 47.5% (n = 620) were guided by angiography alone, 37.0% (n = 483) by IVUS, and 15.4% (n = 201) by OCT. PCI guided by intravascular imaging modalities was associated with lower 1-year rates of MI (1.3%, P = 0.001) and MACE (5.2%, P = 0.036). OCT-guided PCI was linked to lower rates of 1-year CV death (IVUS vs. OCT: 6.2% vs. 1.5%, P = 0.016) and MACE (IVUS vs. OCT: 6.4% vs. 2.5%, P = 0.032). Intravascular imaging modalities and diabetes were identified as predictors of better and worse 1-year MACE outcomes, respectively.ConclusionPCI guided by intravascular imaging modalities resulted in improved 1-year clinical outcomes compared to angiography-guided PCI alone in AMI patients. OCT-guided PCI was associated with lower 1-year MACE rates compared to IVUS-guided PCI. Therefore, intravascular imaging should be recommended for PCI in AMI, with OCT being particularly considered when appropriate.

Abstract Human papillomavirus (HPV) is a significant contributor to the global cancer burden, and its carcinogenic activity is facilitated in part by the HPV early protein 6 (E6), which interacts with the E3-ligase E6AP, also known as UBE3A, to promote degradation of the tumor suppressor, p53. In this study, we present a single-particle cryoEM structure of the full-length E6AP protein in complex with HPV16 E6 (16E6) and p53, determined at a resolution of ~3.3 Å. Our structure reveals extensive protein-protein interactions between 16E6 and E6AP, explaining their picomolar binding affinity. These findings shed light on the molecular basis of the ternary complex, which has been pursued as a potential therapeutic target for HPV-driven cervical, anal, and oropharyngeal cancers over the last two decades. Understanding the structural and mechanistic underpinnings of this complex is crucial for developing effective therapies to combat HPV-induced cancers. Our findings may help to explain why previous attempts to disrupt this complex have failed to generate therapeutic modalities and suggest that current strategies should be reevaluated.

Background: The objective of this study was to investigate the effect of ultrasound-guided corticosteroid injection to the subacromial-subdeltoid bursa (SSB) and coracohumeral ligament (CHL) in treating adhesive capsulitis, with a particular focus on evaluating the potential benefits of regular electrotherapy and conventional rehabilitation exercises. Methods: A total of 29 patients with unilateral shoulder pain and restricted shoulder range of motion (ROM) were included. Corticosteroids were delivered to the subacromial-subdeltoid bursa (SSB) and coracohumeral ligament (CHL) through a single percutaneous injection. Group 1 consisted of 18 patients who received injections only, while Group 2 comprised 11 patients who received injections in combination with regular physiotherapy. Shoulder Pain and Disability Index (SPADI) scores and ROM were assessed before the injection, and again at 4, 8, and 12 weeks following the intervention. A multivariate mixed-effects model with repeated measurements was conducted for the variables. Results: Electrotherapy and traditional rehabilitation exercises did not enhance the effectiveness of this injection approach. Pain, upper extremity function, and ROM in all planes were all significantly improved with a corticosteroid injection to the CHL and SSB. Conclusions: Physiotherapy did not offer additional benefits when combined with ultrasound-guided corticosteroid injection to the CHL and SSB. The injection alone significantly improved pain, disability, and ROM in patients with adhesive capsulitis. Further research is required to optimize current physiotherapy with electrotherapy and traditional rehabilitation exercises after ultrasound-guided corticosteroid injections.

Abstract Background The issues of replication and scientific transparency have been raised in exercise and sports science research. A potential means to address the replication crisis and enhance research reliability is to improve reporting quality and transparency. This study aims to formulate a reporting checklist as a supplement to the existing reporting guidelines, specifically for resistance exercise studies. Methods PubMed (which covers Medline) and Scopus (which covers Medline, EMBASE, Ei Compendex, World Textile Index, Fluidex, Geobase, Biobase, and most journals in Web of Science) were searched for systematic reviews that comprised the primary studies directly comparing different resistance training methods. Basic data on the selected reviews, including on authors, publication years, and objectives, were summarized. The reporting items for the checklist were identified based on the objective of the reviews. Additional items from an existing checklist, namely the Consensus on Exercise Reporting Template, a National Strength and Conditioning Association handbook, and an article from the EQUATOR library were incorporated into the final reporting checklist. Results Our database search retrieved 3595 relevant records. After automatic duplicate removal, the titles and abstracts of the remaining 2254 records were screened. The full texts of 137 records were then reviewed, and 88 systematic reviews that met the criteria were included in the umbrella review. Conclusion Developed primarily by an umbrella review method, this checklist covers the research questions which have been systematically studied and is expected to improve the reporting completeness of future resistance exercise studies. The PRIRES checklist comprises 26 reporting items (39 subitems) that cover four major topics in resistance exercise intervention: 1) exercise selection, performance, and training parameters, 2) training program and progression, 3) exercise setting, and 4) planned vs actual training. The PRIRES checklist was designed specifically for reporting resistance exercise intervention. It is expected to be used with other reporting guidelines such as Consolidated Standards of Reporting Trials and Standard Protocol Items: Recommendations for Interventional Trials. This article presents only the development process and resulting items of the checklist. An accompanying article detailing the rationale for, the importance of, and examples of each item is being prepared. Registration This study is registered with the EQUATOR Network under the title “Preferred Reporting Items for Resistance Exercise Studies (PRIRES).” PROSPERO registration number: CRD42021235259.

Background: Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection relies on immunity generated after primary infection. However, humoral immunity following primary infection with the Omicron variant is not well understood. Methods: We prospectively recruited children

Abstract Long-term wind power forecasting is a challenging endeavor that requires predictions that span years into the future. Accurate forecasting is crucial for optimizing energy production, grid integration, maintenance scheduling, and financial planning. This study attempts to first develop the long short-term memory networks (LSTM) with a seasonal wavelet transform forecasting model for practical long-term wind power forecasting problems with seasonal and regional influences on wind power and the instability of data signals. This model encapsulates wavelet transformation and seasonal decomposition, and employs LSTM for forecasting. The new prediction model adopted seasonal decompositions and two LSTMs to approach low- and high-frequency series datasets, as well as the wavelet synthesis prediction values. Furthermore, the parameters of the LSTM models are selected using stochastic optimization. For a comprehensive evaluation, the proposed LSTM with seasonal wavelet transform is compared with seven methods, including seasonal LSTM (SLSTM), wavelet LSTM (WLSTM), and the seasonal auto-regressive integrated moving average (SARIMA), back propagation neural network (BPNN), generalized regression neural network (GRNN), least square support vector regression (LSSVR), and support vector regression (SVR) were employed for long-term wind power output forecasting of wind farms. The empirical results underscore that the performance of the proposed forecasting model is better than other methods in terms of forecasting accuracy, which could efficiently provide reliable long-term predictions for long-term wind power output forecasting.

Patellofemoral pain syndrome (PFPS) is one of the most common etiologies of knee pain and might be relieved with lumbopelvic manipulation (LPM). This meta-analysis aimed to investigate the effects of LPM on pain reduction in patients with PFPS. Electronic databases were searched from inception to December 2023 for randomized controlled trials (RCTs) investigating the effects of LPM on PFPS. The primary outcome was the change in visual analog or numeric rating scale scores assessing pain. Ten studies comprising 346 participants were included. Significant pain reduction was noted in the LPM group (Hedges’ g = −0.706, 95% confidence interval [CI] = −1.197 to −0.214, p = 0.005, I2 = 79.624%) compared with the control group. Moreover, pain relief was more pronounced when LPM was combined with other physical therapies (Hedges’ g = −0.701, 95% CI = −1.386 to −0.017, p = 0.045, I2 = 73.537%). No adverse events were reported during the LPM. The LPM appears to be a safe and effective adjuvant therapy for pain reduction in patients with PFPS. Clinicians should consider adding LPM to other physical therapies (e.g., quadriceps muscle strengthening) during the management of these patients.

Summary: The phosphoinositide 3-kinase p110α is an essential mediator of insulin signaling and glucose homeostasis. We interrogated the human serine, threonine, and tyrosine kinome to search for novel regulators of p110α and found that the Hippo kinases phosphorylate p110α at T1061, which inhibits its activity. This inhibitory state corresponds to a conformational change of a membrane-binding domain on p110α, which impairs its ability to engage membranes. In human primary hepatocytes, cancer cell lines, and rodent tissues, activation of the Hippo kinases MST1/2 using forskolin or epinephrine is associated with phosphorylation of T1061 and inhibition of p110α, impairment of downstream insulin signaling, and suppression of glycolysis and glycogen synthesis. These changes are abrogated when MST1/2 are genetically deleted or inhibited with small molecules or if the T1061 is mutated to alanine. Our study defines an inhibitory pathway of PI3K signaling and a link between epinephrine and insulin signaling.

BackgroundContact tracing for containing emerging infectious diseases such as COVID-19 is resource intensive and requires digital transformation to enable timely decision-making. ObjectiveThis study demonstrates the design and implementation of digital contact tracing using multimodal health informatics to efficiently collect personal information and contain community outbreaks. The implementation of digital contact tracing was further illustrated by 3 empirical SARS-CoV-2 infection clusters. MethodsThe implementation in Changhua, Taiwan, served as a demonstration of the multisectoral informatics and connectivity between electronic health systems needed for digital contact tracing. The framework incorporates traditional travel, occupation, contact, and cluster approaches and a dynamic contact process enabled by digital technology. A centralized registry system, accessible only to authorized health personnel, ensures privacy and data security. The efficiency of the digital contact tracing system was evaluated through a field study in Changhua. ResultsThe digital contact tracing system integrates the immigration registry, communicable disease report system, and national health records to provide real-time information about travel, occupation, contact, and clusters for potential contacts and to facilitate a timely assessment of the risk of COVID-19 transmission. The digitalized system allows for informed decision-making regarding quarantine, isolation, and treatment, with a focus on personal privacy. In the first cluster infection, the system monitored 665 contacts and isolated 4 (0.6%) cases; none of the contacts (0/665, 0%) were infected during quarantine. The estimated reproduction number of 0.92 suggests an effective containment strategy for preventing community-acquired outbreak. The system was also used in a cluster investigation involving foreign workers, where none of the 462 contacts (0/462, 0%) tested positive for SARS-CoV-2. ConclusionsBy integrating the multisectoral database, the contact tracing process can be digitalized to provide the information required for risk assessment and decision-making in a timely manner to contain a community-acquired outbreak when facing the outbreak of emerging infectious disease.

Background: To investigate the effectiveness of muscle energy technique (MET) for treatment of non-specific neck pain (NSNP). Methods: A literature search was performed using electronic databases from their inception until October 2023 for randomized controlled trials (RCTs) that investigated the effects of MET on NSNP. A change in pain intensity and reduced disability were the primary and secondary outcomes, respectively, standardized using Hedges’ g. A random effects model was used for data pooling. Results: This study included 26 RCTs comprising 1170 participants. The results showed that MET significantly reduced pain intensity (Hedges' g = −0.967 95 % CI = −1.417 to −0.517, p

Abstract Background Heart failure with reduced ejection fraction (HFrEF) can coexist with chronic obstructive pulmonary disease (COPD), which complicates the clinical situation and worsens quality of life. The study used standard diagnostic criteria for detecting COPD in hospitalized HFrEF patients and to survey the influence of other comorbidities and medications on the long-term outcomes of HFrEF + COPD patients. Methods We retrospectively recruited patients hospitalized due to HFrEF in a tertiary medical center and examined and followed up clinical outcomes, including length of hospital stay, mortality, and readmission episodes, for a 5-year period. Risk factors for mortality were analyzed using multivariate analysis. Results Of the 118 hospitalized HFrEF study participants, 68 had concurrent COPD whereas 50 did not. There was a significant increase in the male predominance, smoking history, higher hemoglobin level and increased length of hospital stay in the HF + COPD group than in the HF-only group. Lower left ventricular ejection fraction was found in the HF and COPD comorbidity group. In multivariate analysis, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) use independently associated with a beneficial effect on survival in HF patients with COPD. Oral corticosteroid uses and stroke as a comorbidity were independently associated with a shorter time to the first readmission episode. Conclusion In HFrEF patients, COPD was associated with a prolonged length of hospital stay. ACEI/ARB use might relate to a beneficial effect on survival in HF patients with COPD. The use of maintenance oral corticosteroid in patients with both HF and COPD should be crucially evaluated to determine the clinical benefit and disadvantages.

Abstract Evaluating the magnitude of overdiagnosis associated with stool-based service screening for colorectal cancer (CRC) beyond a randomized controlled trial is often intractable and understudied. We aim to estimate the proportion of overdiagnosis in population-based service screening programs for CRC with the fecal immunochemical test (FIT). The natural process of overdiagnosis-embedded disease was first built up to learn transition parameters that quantify the pathway of non-progressive and progressive screen-detected cases calibrated with sensitivity, while also taking competing mortality into account. The Markov algorithms were then developed for estimating these transition parameters based on Taiwan FIT service CRC screening data on 5,417,699 residents aged 50–69 years from 2004 to 2014. Following the digital twin design with the parallel universe structure for emulating the randomized controlled trial, the screened twin, mirroring the control group without screening, was virtually recreated by the application of the above-mentioned trained parameters to predict CRC cases containing overdiagnosis. The ratio of the predicted CRCs derived from the screened twin to the observed CRCs of the control group minus 1 was imputed to measure the extent of overdiagnosis. The extent of overdiagnosis for invasive CRCs resulting from FIT screening is 4.16% (95% CI: 2.61–5.78%). The corresponding figure is increased to 9.90% (95% CI: 8.41–11.42%) for including high grade dysplasia (HGD) and further inflated to 15.83% (95% CI: 15.23–16.46%) when the removal adenoma is considered. The modest proportion of overdiagnosis modelled by the digital twin method, dispensing with the randomized controlled trial design, suggests the harm done to population-based FIT service screening is negligible.

Background: Little is known about long-term effectiveness of COVID-19 vaccine in reducing severity and deaths associated with Omicron VOC not perturbed by prior infection and independent of oral anti-viral therapy and non-pharmaceutical (NPI). Methods: A retrospective observational cohort study was applied to Taiwan community during the unprecedent large-scale outbreaks of Omicron BA.2 between April and August, 2022. Primary vaccination since March, 2021 and booster vaccination since January, 2022 were offered on population level. Oral Anti-viral therapy was also offered as of mid-May 2022. The population-based effectiveness of vaccination in reducing the risk of moderate and severe cases of and death from Omicron BA.2 with the consideration of NPI and oral anti-viral therapy were assessed by using Bayesian hierarchical models. Results: The risks of three clinical outcomes associated with Omicron VOC infection were lowest for booster vaccination, followed by primary vaccination, and highest for incomplete vaccination with the consistent trends of being at increased risk for three outcomes from the young people aged 12 years or below until the elderly people aged 75 years or older with 7 age groups. Before the period using oral anti-viral therapy, complete primary vaccination with the duration more than 9 months before outbreaks conferred the statistically significant 47 % (23–64 %) reduction of death, 48 % (30–61 %) of severe disease, and 46 % (95 % CI: 37–54 %) of moderate disease after adjusting for 10–20 % independent effect of NPI. The benefits of booster vaccination within three months were further enhanced to 76 % (95 % CI: 67–86 %), 74 % (95 % CI: 67–80 %), and 61 % (95 % CI: 56–65 %) for three corresponding outcomes. The additional effectiveness of oral anti-viral therapy in reducing moderate disease was 13 % for the booster group and 5.8 % for primary vaccination. Conclusions: We corroborated population effectiveness of primary vaccination and its booster vaccination, independent of oral anti-viral therapy and NPI, in reducing severe clinical outcomes associated with Omicron BA.2 naïve infection population.

Background: The regional respiratory syncytial virus (RSV) outbreak in southern Taiwan in late 2020 followed the surge of RSV cases in the national surveillance data and displayed distinct clinical features. This study investigated RSV epidemiology in the most recent five years and compared the clinical manifestations of this outbreak with non-outbreak period. Methods: Medical records of RSV-infected children at the National Cheng Kung University Hospital from January 2016 to December 2020 were retrospectively retrieved from hospital-based electronic medical database. Cases of RSV infection were identified by RSV antigen positive and/or RSV isolated from respiratory specimens. The demographic, clinical presentations, and laboratory data were recorded. The RSV isolates in 2020 was sequenced for phylogenetic analysis. Results: Overall, 442 RSV-infected cases were retrieved and 42.1% (186 cases) clustered in late 2020. The 2020 outbreak started in September, peaked in November, and lasted for 3 months. 2020 RSV-infected children were older (2.3 ± 2.2 years vs. 1.0 ± 1.0 years), more likely to be diagnosed with bronchopneumonia (57.5% vs. 31.6%), but also had a lower hospitalization rate, shorter hospital stay, less oxygen use, and less respiratory distress than those in 2016–2019 (all p value

Cardiorenal syndrome type I (CRS I) is defined as the development of acute kidney injury (AKI) following acute decompensated heart failure (ADHF). The clinical significance of endothelial markers in ADHF-associated AKI has yet to be clarified. This study therefore investigated the biological processes linking ADHF and AKI with the aim of determining whether the plasma markers of endothelial injury and activation are associated with AKI in patients with ADHF. The study prospectively recruited 125 consecutive patients admitted to a coronary critical unit due to ADHF. Patients with and without AKI were compared in terms of soluble thrombomodulin (sTM), angiopoietin (Ang)-1 and −2 plasma levels as well as baseline characteristics. Among the study population, 14 (11.2%) patients developed CRS within 7 days after admission. The hemoglobin levels (median [IQR]11.3[10.8–12.6] vs. 13.5 [12.2–15.0] g/dL, p = 0.003) and baseline eGFR (66.5[35.7–87.9] vs. 78.5 [64.9–107.5] mL/minute/1.73m2, p = 0.044) of patients with CRS were lower than those of patients without CRS. Patients with CRS also presented elevated plasma levels of BNP (1317.5 [222.6–3375.5] vs. 258.2 [63.2–925.8] pg/mL, p = 0.008), Ang-2 (3993.0 [1561.3–15722.7] vs. 1805.9 [1196.9–3302.3] pg/mL, p = 0.006), and sTM (6665.7 [4707.1–11947.3] vs. 4132.2 [3338.0–5531.8] ng/mL, p cutoff value of 4,855.2 pg/mL as an independent factor associated with the development of AKI. sTM could potentially be used as a biomarker to predict the development of AKI in patients with heart failure.These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI.

Objective: Post-stroke shoulder pain is a serious challenge for stroke survivors. The aim of this meta-analysis was to review the literature to confirm information on structural changes in post-stroke shoulders detected by ultrasound examination. Methods: PubMed, Embase, Web of Science and ClinicalTrials.gov were searched until 7 December 2022, for studies describing shoulder sonographic findings in stroke patients. Two independent authors selected the studies, extracted the data, and performed the critical appraisal. Results: A total of 23 clinical studies were included. The most prevalent pathologies in hemiplegic shoulders pertained to the biceps long head tendon (41.4%), followed by the supraspinatus tendon (33.2%), subdeltoid bursa (29.3%), acromioclavicular joint (15.0%), and subscapularis tendon (9.2%). The common pathological findings encompassed bicipital peritendinous effusion (39.2%), biceps tendinopathy (35.5%), subdeltoid bursitis (29.3%) and supraspinatus tendinopathy (24.6%). Biceps long head tendon and supraspinatus tendon abnormalities were observed significantly more in the hemiplegic (vs contralateral) shoulders, with odds ratios of 3.814 (95% confidence interval 2.044–7.117) and 2.101 (95% confidence interval 1.257–3.512), respectively. No correlation was observed between motor function and shoulder pathology. Conclusion: Ultrasonography enabled the identification of common shoulder pathologies after stroke. Further research is needed to establish the association between these changes and the clinical course of stroke patients.

Abstract Background Lung cancer is the leading cause of cancer-related mortality worldwide. Sarcopenia, defined as the loss of muscle mass and function, is known to cause adverse health outcomes. The purpose of this umbrella review was to integrate published systematic reviews and meta-analyses exploring sarcopenia and lung cancer to provide comprehensive knowledge on their relationship. Methods Eligible studies were searched from scientific databases until June 28, 2022. Critical appraisal was performed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. The impact of sarcopenia on the pathophysiology, prevalence, and prognosis of lung cancer is summarized at the level of systematic reviews or meta-analyses. Results Fourteen reviews and meta-analyses were conducted. The methodological quality was high for one review, low for nine, and critically low for four. The most common standard for diagnosing sarcopenia in the lung cancer population is computed tomography (CT) to measure the skeletal muscle index at the third lumbar vertebra (L3). Sarcopenia was highly prevalent among patients with lung cancer, with a pooled prevalence ranging from 42.8% to 45.0%. The association between sarcopenia and increased postoperative complications and decreased disease control rates with immune checkpoint inhibitors has been demonstrated. Mortality was significantly higher in sarcopenic patients than in non-sarcopenic patients with lung cancer, regardless of the stage of disease or type of treatment. Conclusions Sarcopenia is a poor prognostic factor for lung cancer. Future studies are necessary to clarify the pathophysiology of sarcopenia and develop effective interventions for sarcopenia in patients with lung cancer.

Objective. This study aims to assess the effectiveness of lumbar segmental stabilization exercise (LSSE) in managing spondylolysis and spondylolisthesis. Summary of Background Data. Spondylolysis and spondylolisthesis are spinal disorders associated with lumbar segmental instability. LSSE has shown positive effects in treating these conditions; however, systematic reviews and meta-analyses are lacking. Materials and Methods. A systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines, including studies from the inception of the databases used up to January 2024, was conducted. Disability improvement and pain intensity change were the primary and secondary outcomes, respectively, standardized using Hedges g. Eligible articles underwent independent scrutiny by two authors, who also performed data extraction and quality assessment. Data pooling was accomplished using a random-effects model. Results. In total, five randomized controlled trials comprising 198 participants were included, revealing a trend effect toward disability improvement in the LSSE group (Hedges g =-0.598, 95% CI: -1.211 to 0.016, P=0.056, I2=75.447%). When the LSSE was administered as a single treatment, disability improvement became significant (Hedge g= -1.325, 95% CI: -2.598 to -0.053, P=0.041, I2= 80.020%). No significant effect of LSSE on pain reduction was observed (Hedges g =-0.496, 95% CI: -1.082 to 0.090, P=0.097, I2=73.935%). Conclusions. In summary, our meta-analysis suggests that LSSE can potentially improve disability, especially when used as a single treatment. LSSE appears more beneficial in reducing disability than alleviating pain. Future research on different patient groups is needed to understand comprehensively LSSE's effects on other musculoskeletal disorders. [ABSTRACT FROM AUTHOR]

Lumbar radiculopathy causes lower back and lower extremity pain that may be managed with neural mobilization (NM) techniques. This meta-analysis aims to evaluate the effectiveness of NM in alleviating pain and reducing disability in patients with lumbar radiculopathy. We hypothesized that NM would reduce pain and improve disability in the lumbar radiculopathy population, leveraging the statistical power of multiple studies. Electronic databases from their inception up to October 2023 were searched for randomized controlled trials (RCTs) that explored the impact of NM on lumbar radiculopathy. Our primary outcome measure was the alteration in pain intensity, while the secondary one was the improvement of disability, standardized using Hedges’ g. To combine the data, we employed a random-effects model. A total of 20 RCTs comprising 877 participants were included. NM yielded a significant reduction in pain intensity (Hedges’ g = −1.097, 95% CI = −1.482 to −0.712, p < 0.001, I2 = 85.338%). Subgroup analyses indicated that NM effectively reduced pain, whether employed alone or in conjunction with other treatments. Furthermore, NM significantly alleviated disability, with a notable effect size (Hedges’ g = −0.964, 95% CI = −1.475 to −0.453, p < 0.001, I2 = 88.550%), particularly in chronic cases. The findings provide valuable insights for clinicians seeking evidence-based interventions for this patient population. This study has limitations, including heterogeneity, potential publication bias, varied causal factors in lumbar radiculopathy, overall study quality, and the inability to explore the impact of neural pathology on NM treatment effectiveness, suggesting opportunities for future research improvements.