Intraosseous versus intravenous vascular access in upper extremity among adults with out-of-hospital cardiac arrest: cluster randomised clinical trial (VICTOR trial).

OBJECTIVE: To compare the effectiveness of intraosseous versus intravenous vascular access in the treatment of adult patients with out-of-hospital cardiac arrest. DESIGN: Cluster randomised controlled trial. SETTING: The VICTOR (Venous Injection Compared To intraOsseous injection during resuscitation of patients with out-of-hospital cardiac arrest) trial involved emergency medical service agencies with all four advanced life support ambulance teams in Taipei City, Taiwan. The enrolment period spanned 6 July 2020 to 30 June 2023 and was temporarily suspended between 20 May 2021 and 31 July 2021 owing to the covid-19 pandemic. PARTICIPANTS: Adult (age 20-80 years) patients with non-traumatic out-of-hospital cardiac arrest. INTERVENTIONS: Biweekly randomised clusters of four participating advanced life support ambulance teams were assigned to insert either intravenous or intraosseous access. MAIN OUTCOME MEASURES: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation, sustained return of spontaneous circulation (≥2 hours), and survival with favourable neurological outcomes (cerebral performance category score ≤2) at hospital discharge. RESULTS: Among 1771 enrolled patients, 1732 (741 in the intraosseous group and 991 in the intravenous group) were included in the primary analysis (median age 65.0 years; 1234 (71.2%) men). In the intraosseous group, 79 (10.7%) patients were discharged alive, compared with 102 (10.3%) patients in the intravenous group (odds ratio 1.04, 95% confidence interval 0.76 to 1.42; P=0.81). The odds ratio of intraosseous versus intravenous access was 1.23 (0.89 to 1.69; P=0.21) for pre-hospital return of spontaneous circulation, 0.92 (0.75 to 1.13; P=0.44) for sustained return of spontaneous circulation, and 1.17 (0.82 to 1.66; P=0.39) for survival with favourable neurological outcomes. CONCLUSIONS: Among adults with non-traumatic out-of-hospital cardiac arrest, initial attempts to establish vascular access through the intraosseous route did not result in different outcomes compared with intravenous access in terms of the proportion of patients surviving to hospital discharge, pre-hospital return of spontaneous circulation, sustained return of spontaneous circulation, and favourable neurological outcomes. TRIAL REGISTRATION: NCT04135547ClinicalTrials.gov NCT04135547.

Effects of opioid drugs on immune function in cancer patients.

Opioid receptor agonists are often used when cancer patients undergo surgery or analgesic treatment. As analgesics in clinical care, opioids can provide intraoperative or to chronic cancer pain relief. Immune function plays an important role in anti-cancer therapy, with cellular immunity, comprised principally of T-lymphocytes and natural killer cells, representing the primary anti-cancer immune response. However, it remains unclear whether immune function is further affected with the use of opioids in already immunocompromised cancer patients. This article provides a review of the effects of commonly used clinical opioids, including morphine, oxycodone, fentanyl and tramadol, on immune function in cancer patients. It provides a summary of current evidence regarding the immunomodulatory effects of opioids in the cancer setting and mechanisms underlying these interactions.

A comparison between intraosseous and intravenous access in patients with out-of-hospital cardiac arrest: A retrospective cohort study.

INTRODUCTION: The optimal vascular access for patients with out-of-hospital cardiac arrest (OHCA) remains controversial. Increasing evidence supports intraosseous (IO) access due to faster medication administration and higher first-attempt success rates compared to intravenous (IV) access. However, the impact on patient outcomes has been inconclusive. METHODS: This retrospective cohort study in Taoyuan City, Taiwan, from January 1, 2019, to December 31, 2022, included patients aged ≥18 years with non-traumatic OHCA resuscitated by emergency medical technician paramedics (EMT-Ps) with either IVs or IOs for final vascular access. The exclusion criteria were cardiac arrest en route to the hospital and resuscitation during the coronavirus pandemic (from May 1, 2022, to October 31, 2022). The primary and secondary outcomes were sustained ROSC (≥2 h) and cerebral performance category (CPC) 1-2, respectively. Univariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for the primary analysis. Multivariable logistic regression was employed, with variables selected based on a p-value of <0.05 in the univariate analysis. The survival benefits of different insertion sites and subgroups like general ambulance teams (with a composition that includes fewer EMT-Ps and limited experience in using IO access) were also analyzed. RESULTS: A total of 2003 patients were enrolled; 1602 received IV access and 401 IO access. The median patient age was 70 years, and most were male (66.6%). Compared to patients receiving IV access, the adjusted odds ratios (aORs) for primary and secondary outcomes in patients with IOs were 0.83 (95% confidence interval [CI], 0.61-1.11; p = 0.20) and 0.96 (95% CI, 0.39-2.40; p = 0.93), respectively. Different insertion sites showed no outcome differences. In the subgroups of females and patients resuscitated by general ambulance teams, the aORs for sustained ROSC were 0.55 (95% CI, 0.33-0.92; p = 0.02) and 0.62 (95% CI, 0.41-0.94; p = 0.02), respectively. CONCLUSIONS: For patients with OHCA resuscitated by EMT-Ps, IO access was comparable to IV access regarding patient outcomes. However, in females and patients resuscitated by general ambulance teams, IV access might be favorable.

Association between Combustible Cigarettes and Noncombustible Nicotine or Tobacco Products and Generalized Anxiety Disorder Based on Data from the 8th Korea National Health and Nutrition Examination Survey 2021.

Background: Despite the increasing prevalence of anxiety disorders in Korea, there have been no nationwide studies on the association between tobacco status and generalized anxiety disorder (GAD). Furthermore, despite the increasing number of people using noncombustible nicotine or tobacco products (NNTPs), the association between NNTP use and GAD remains unclear. Therefore, this study investigated the association between tobacco use and GAD. Methods: This nationwide study used data from the 8th Korea National Health and Nutrition Examination Survey (2021) and included 5,454 adults aged ≥19 years who self-reported on the tobacco use and mental health sections. Multivariable logistic regression analysis was performed to investigate the odds ratios (ORs) of GAD (Generalized Anxiety Disorder-7 score ≥10) according to tobacco status among Korean adults. The severity of anxiety was assessed using the Generalized Anxiety Disorder-7 scale. Results: Compared to never tobacco users, the ORs of GAD for combustible cigarette smokers and NNTP users were 2.74 (95% confidence interval [CI], 1.66-4.50) and 2.11 (95% CI, 1.16-3.83), respectively. The OR of GAD for former tobacco users was 1.63 (95% CI, 0.98-2.72). Conclusion: Tobacco use (combustible cigarettes and NNTP) was positively associated with GAD. However, in former tobacco users, there was no significant association with GAD when compared with never tobacco users. Given the OR of GAD among tobacco users, it is crucial to pay attention to screening for GAD and implement appropriate early interventions.

Role of low-density lipoprotein electronegativity and sexual dimorphism in contributing early ventricular tachyarrhythmias following ST-elevation myocardial infarction.

Background: Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI. Methods: We analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE-/- mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF. Results: In 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P < 0.001), despite analogous action potential durations. Furthermore, isolated ventricular myocytes from male mice showed a distinctly lower sodium current density (-29.20 ± 3.04 pA/pF, n = 6) in comparison to female mice (-114.05 ± 6.41 pA/pF, n = 6, P < 0.001). This decreased sodium current density was paralleled by a reduced membrane expression of Nav1.5 protein (0.38 ± 0.06 vs. 0.89 ± 0.09 A.U., P < 0.001) and increased cytosolic Nav1.5 levels (0.59 ± 0.06 vs. 0.29 ± 0.04 A.U., P = 0.001) in male mice. Furthermore, it was observed that the overall expressions of sorting nexin 27 (SNX27) and vacuolar protein sorting 26 (VPS26) were significantly diminished in male mice as compared to female littermates (0.91 ± 0.15 vs. 1.70 ± 0.28, P = 0.02 and 0.74 ± 0.09 vs. 1.57 ± 0.13, P < 0.01, respectively). Conclusions: Our findings reveal that male STEMI patients with early VT/VF are associated with elevated L5 levels. The gender-based discrepancy in early VT/VF predisposition might be due to compromised sodium channel trafficking, possibly linked with increased LDL electronegativity.

Persistent hiccups as a rare presenting symptom of empyema: a case report.

BACKGROUND: Empyema is uncommon owing to antibiotic use but still affects patient health if not treated. Hiccups as the initial symptom of empyema are rare; however, empyema should be considered if a patient has persistent hiccups with unexplained fever. CASE PRESENTATION: We present a case of persistent hiccups, left upper quadrant abdominal pain, and fever on day 1, and total left lung white-out and empyema on day 3. The hiccups resolved gradually after antibiotic treatment and surgical decortication. CONCLUSIONS: Clinicians should consider the possibility of empyema and conduct a chest computed tomography study if unexplained fever and persistent hiccups coexist.

Investigation of the Therapeutic Potential of Organic Nitrates in Mortality Reduction Following Acute Myocardial Infarction in Hyperlipidemia Patients: A Population-Based Cohort Study.

BACKGROUND: Dyslipidemia is a known risk factor for cardiac dysfunction, and lipid-lowering therapy with statins reduces symptoms and reduces hospitalization related to left ventricular heart failure. Acute myocardial infarction (AMI) is a cause of morbidity and mortality worldwide. In this study, we aimed to determine the real-world AMI treatment drug combination used in Taiwan by using the NHI database to understand the treatment outcomes of current clinical medications prescribed for hyperlipidemia patients with AMI. METHODS: Using the NHI Research Database (NHIRD), we conducted a retrospective cohort study that compared different treatments for AMI in hyperlipidemia patients in the period from 2016 to 2018. We compared the survival outcomes between those treated with and without organic nitrates in this cohort. RESULTS: We determined that most hyperlipidemia patients were aged 61-70 y (29.95-31.46% from 2016 to 2018), and the annual AMI risk in these patients was <1% (0.42-0.68% from 2016 to 2018). The majority of hyperlipidemia patients with AMI were women, and 25.64% were aged 61-70 y. Receiving organic nitrates was associated with lower all-cause mortality rates (HR, 95% CI, p-value = 0.714, 0.674-0.756, p < 0.0001). After multivariate analysis, the overall survival in four groups (beta-blockers, beta-blocker + diuretics, diuretics, and others) receiving an organic nitrate treatment was significantly higher than in the groups that were not treated with organic nitrates (beta-blockers HR = 0.536, beta-blocker + diuretics HR = 0.620, diuretics HR = 0.715, and others HR = 0.690). CONCLUSIONS: The survival benefit was significantly greater in patients treated with organic nitrates than in those treated without organic nitrates, especially when combined with diuretics. A combination of organic nitrates could be a better treatment option for hyperlipidemia patients with AMI.

Laser Speckle Contrast Imaging Guides Needling Treatment of Vascular Complications from Dermal Fillers.

BACKGROUND: Although laser Doppler imaging (LDI) accurately delineates a hypoperfused area to help target hyaluronidase treatment, laser speckle contrast imaging (LSCI) is more appropriate for assessing microvascular hemodynamics and has greater reproducibility than LDI. This study investigated the use of LSCI in the evaluation and treatment of six patients who developed vascular complications after facial dermal filler injections. METHODS: The areas of vascular occlusion were accurately defined in real time by LSCI and were more precise than visual inspections or photographic evidence for guiding needling and hyaluronidase treatment. RESULTS: All patients had achieved satisfactory outcomes as early as Day 2 of treatment and no procedure-related complications were reported after a median follow-up of 9.5 (7-37) days. CONCLUSION: LSCI accurately and noninvasively delineated vascular occlusions in real time among patients experiencing complications of facial dermal filler injections. Moreover, LSCI was more accurate than visual and photographic evaluations. Clinicians can use LSCI to reliably follow-up therapeutic outcomes after salvage interventions for vascular occlusions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

An observational study on salivary conductivity for fluid status assessment and clinical relevance in acute ischemic stroke during intravenous fluid hydration.

The body fluid status in acute stroke is a crucial determinant in early stroke recovery but a real-time method to monitor body fluid status is not available. This study aims to evaluate the relationship between salivary conductivity and body fluid status during the period of intravenous fluid hydration. Between June 2020 to August 2022, patients presenting with clinical signs of stroke at the emergency department were enrolled. Salivary conductivities were measured before and 3 h after intravenous hydration. Patients were considered responsive if their salivary conductivities at 3 h decreased by more than 20% compared to their baseline values. Stroke severity was assessed using the National Institutes of Health Stroke Scale, and early neurological improvement was defined as a decrease of ≥ 2 points within 72 h of admission. Among 108 recruited patients, there were 35 of stroke mimics, 6 of transient ischemic attack and 67 of acute ischemic stroke. Salivary conductivity was significantly decreased after hydration in all patients (9008 versus 8118 µs/cm, p = 0.030). Among patients with acute ischemic stroke, the responsive group, showed a higher rate of early neurological improvement within 3 days compared to the non-responsive group (37% versus 10%, p = 0.009). In a multivariate logistic regression model, a decrease in salivary conductivity of 20% or more was found to be an independent factor associated with early neurological improvement (odds ratio 5.42, 95% confidence interval 1.31-22.5, p = 0.020). Real-time salivary conductivity might be a potential indicator of hydration status of the patient with acute ischemic stroke.

Emergency Medical Services in Taiwan: Past, Present, and Future.

This review assessed the development of Taiwan's emergency medical services (EMS) and focused on the optimizing initiatives of the EMS systems, the current state of Taiwan's EMS system, EMS benchmarks in different regions of Taiwan, EMS response during the coronavirus disease 2019 (COVID-19) pandemic, and future design. In the past decade, there has been a noticeable increase in prehospital services, numerous optimizing initiatives to improve patient prognosis, and the medical oversight model. Taiwan's current EMS system, including the dispatch system, out-of-hospital cardiac arrest (OHCA) patient management, time-sensitive critical illness in prehospital settings, and disaster response, has undergone significant improvements. These improvements have been demonstrated to have a measurable impact on patient outcomes, as supported by medical literature. Each region in Taiwan has developed a unique EMS system with local characteristics, such as the implementation of the Global Resuscitation Alliance 10 steps for OHCA-related quality control, hearing automated external defibrillator program, a five-level prehospital triage system, an island-hopping strategy for patients with major trauma, dispatcher-assisted teamwork for OHCA resuscitation, and optimized prehospital care for acute coronary syndrome patients. In response to the COVID-19 pandemic from 2019 to 2023, Taiwan's EMS implemented measures to combat the outbreak such as interagency collaboration to obtain patient's personal information, to optimize prehospital management initiatives, and to provide financial compensation and personal insurance for emergency medical technicians. The areas that need focus include integrating prehospital and in-hospital information to build a national-level database (One-Stop Emergency Management), increasing public awareness of first responders and emergency casualty care, and evolving the EMS system by incorporating private EMS system, initiating school-based education of paramedicine, and legally recognizing paramedics as medical and health care personnel. By improving these areas, we can better prepare for the future and ensure that Taiwan's EMS system continues to provide high-quality care to those in need.

Changing clinical manifestations of Gaucher disease in Taiwan.

BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder characterized by deficient glucocerebrosidase activity that results from biallelic mutations in the GBA1 gene. Its phenotypic variability allows GD to be classified into 3 subtypes based on the presence and extent of neurological manifestations. Enzyme replacement therapy (ERT) has been available for all patients with GD in Taiwan since 1998. Newborn screening (NBS) for GD has been available since 2015. This study attempted to unveil the clinical features of patients diagnosed with GD during different eras in Taiwan. MATERIALS AND METHODS: Data from the health records of two tertiary hospitals responsible for two-thirds of the patients with GD in Taiwan were used. The study population included all patients identified as having GD between 1998, and April 2022, in these two hospitals for review. A total of 42 individuals were included, six of whom were diagnosed by NBS. RESULTS: Our cohort presented a higher proportion of GD3 individuals, both by clinical suspicion and by NBS diagnosis, than that reported worldwide. The major subtypes that were recognized following NBS diagnosis were GD2 and GD3. The majority of GD patients carry at least one p.Leu483Pro variant. The 5-year survival rates were 0% for GD2 patients and 100% for patients with other subtypes. Patients diagnosed during the post-NBS era were free of symptoms on initial presentation, except for those with the GD2 subtype. For those diagnosed earlier, ERT was shown to be effective in terms of improved hemograms and prevented bone crises. However, the neurological symptoms in GD3 patients progressed despite ERT intervention. CONCLUSION: ERT is essential in reversing the hematological presentations and preventing the skeletal complications of GD. Timely diagnosis of GD with NBS allows for early intervention with ERT to prevent disease progression and complications. However, the need for effective intervention for neurological dysfunction remains unmet.

A Common East Asian aldehyde dehydrogenase 2*2 variant promotes ventricular arrhythmia with chronic light-to-moderate alcohol use in mice.

Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

The effect of point-of-care ultrasound on length of stay and mortality in patients with chest pain/dyspnea.

PURPOSE: This study aims to investigate the effects of point-of-care ultrasound (PoCUS) on length of stay (LOS) and mortality in hemodynamically stable patients with chest pain/dyspnea. MATERIALS AND METHODS: The prospective study was conducted from June 2020 to May 2021. A convenience sample of adult non-traumatic patients with chest pain/dyspnea was included and evaluated by PoCUS. The primary outcome was the relationship between the door-to-PoCUS time and LOS/mortality categorized by the ST-segment elevation (STE) and non-STE on the initial electrocardiogram. The diagnostic accuracy of PoCUS was computed, compared to the final diagnosis. RESULTS: A total of 465 patients were included. 3 of 18 patients with STE had unexpected cardiac tamponade and 1 had myocarditis with pulmonary edema. PoCUS had a minimal effect on LOS and mortality in patients with STE. In the non-STE group, the shorter door-to-PoCUS time was associated with a shorter LOS (coefficient, 1.26±0.47, p=0.008). After categorizing the timing of PoCUS as 30, 60, 90, and 120 minutes, PoCUS had a positive effect, especially when performed within 90 minutes of arrival, on LOS of less than 360 minutes (OR, 2.42, 95% CI, 1.61-3.64) and patient survival (OR, 3.32, 95% CI, 1.14-9.71). The overall diagnostic performance of PoCUS was 96.6% (95% CI, 94.9-98.2%), but lower efficacy occurred in pulmonary embolism and myocardial infarction. CONCLUSION: The use of PoCUS was associated with a shorter LOS and less mortality in patients with non-STE, especially when performed within 90 minutes of arrival. Although the effect on patients with STE was minimal, PoCUS played a role in discovering unexpected diagnoses.

Influence of Wobble-Based Scanning Strategy on Surface Morphology of Laser Powder Bed-Fabricated Permalloy.

Surface roughness quality is still a significant problem in the laser powder bed fusion (LPBF) process. This study proposes a wobble-based scanning strategy to improve the insufficiencies of the traditional scanning strategy with regard to surface roughness. A laboratory LPBF system with a self-developed controller was used to fabricate Permalloy (Fe-79Ni-4Mo) with two scanning methods: traditional line scanning (LS) and the proposed wobble-based scanning (WBS). This study investigates the influences of these two scanning strategies on porosity and surface roughness. The results imply that WBS can maintain higher surface accuracy than LS, and the surface roughness can be reduced by about 45%. Furthermore, WBS can produce periodic surface structures arranged in fish scales or parallelograms with appropriate parameters.

pH-driven continuous stem cell production with enhanced regenerative capacity from polyamide/chitosan surfaces.

Adipose-derived stem cells (ASCs) have raised significant interest for their potential therapeutic applications in regenerative medicine. However, ASCs usually suffer from decreased pluripotency and functional plasticity during in vitro expansion. Herein, this study sought to develop a continuous cell production system that can mass-produce ASCs with sustained regenerative capacity. The strategy was blending pH-responsive chitosan (CS) with polyamide-66 (PA) to generate combined surface properties with controllable cell growth/detachment ability to achieve a repeated cell production process. From the collected data, all the polymer blends were capable of completing a minimum of four consecutive production cycles, wherein the PA17CS blend (PA:CS = 1:7) outperformed with respect to the working effectiveness (average cell detachment ratio = 88%) and the cell viability. Compared to the trypsin-based method, ASCs harvested from PA17CS exhibited superior stemness characteristics along with SDF-1-mediated CXCR4 chemotactic response for stem cell homing. Moreover, injection of ASCs generated from PA17CS blend could more effectively induce neovascularization and protect skin flaps during an ischemic injury in a rat model.

Discriminative Ability of Left Ventricular Strain in Mildly Reduced Ejection Fraction Heart Failure.

Background: Left ventricular (LV) systolic strain is presumably a more sensitive myocardial indicator than LV ejection fraction (LVEF). Data regarding the use of LV strain in clinical risk stratification and in identifying angiotensin receptor-neprilysin inhibitor (ARNi) responders remain scarce in heart failure with mildly reduced ejection fraction (HFmrEF). Objectives: The authors aimed to examine whether assessing LV strain may provide prognostic insight beyond LVEF and help discriminate the therapeutic efficacy of ARNi in HFmrEF patients. Methods: LVEF and LV strain were quantified among 1,075 first-time hospitalized HFmrEF patients (mean age: 68.1 ± 15.1 years, 40% female). The MAGGIC (Meta-analysis Global Group in Chronic Heart Failure) risk score and its components were calculated. A Cox proportional hazard model was constructed for time-to-event analysis. Restrictive cubic spline curves were used to model the therapeutic effects of ARNi against renin-angiotensin system inhibitor according to baseline LVEF or LV strain. Results: LV strain showed a statistically significant inverse association with MAGGIC cardiac risk (coefficient: -0.14, P < 0.001). LV strain was independently associated with clinical outcomes after accounting for LVEF. MAGGIC-LV strain strata outperformed MAGGIC-LVEF strata in overall survival (Harrell's C-index: 0.71 and 0.56, P for difference <0.001; category-free net reclassification index: 0.44, P < 0.001). Lower LV strain but not LVEF consistently showed the beneficial therapeutic effects of ARNi against renin-angiotensin system inhibitor by Cox models and restrictive cubic spline (all P interaction <0.05). Conclusions: Among HFmrEF patients, LV strain may serve as an attractive systolic marker and provide a better prognostic and therapeutic discriminative measure for ARNi treatment than conventional LVEF.

PD-L1 and AKT Overexpressing Adipose-Derived Mesenchymal Stem Cells Enhance Myocardial Protection by Upregulating CD25+ T Cells in Acute Myocardial Infarction Rat Model.

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure-volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure-volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.

Quantifying calcium carbonate and organic carbon content in marine sediments from XRF-scanning spectra with a machine learning approach.

Geochemical variations of sedimentary records contain vital information for understanding paleoenvironment and paleoclimate. However, to obtain quantitative data in the laboratory is laborious, which ultimately restricts the temporal and spatial resolution. Quantification based on fast-acquisition and high-resolution provides a potential solution but is restricted to qualitative X-ray fluorescence (XRF) core scanning data. Here, we apply machine learning (ML) to advance the quantification progress and target calcium carbonate (CaCO3) and total organic carbon (TOC) for quantification to test the potential of such an XRF-ML approach. Raw XRF spectra are used as input data instead of software-based extraction of elemental intensities to avoid bias and increase information. Our dataset comprises Pacific and Southern Ocean marine sediment cores from high- to mid-latitudes to extend the applicability of quantification models from a site-specific to a multi-regional scale. ML-built models are carefully evaluated with a training set, a test set and a case study. The acquired ML-models provide better results with R2 of 0.96 for CaCO3 and 0.78 for TOC than conventional methods. In our case study, the ML-performance for TOC is comparably lower but still provides potential for future optimization. Altogether, this study allows to conveniently generate high-resolution bulk chemistry records without losing accuracy.

Development of a Multi-Layer Marking Toolkit for Layout-Printing Automation at Construction Sites.

In this study, the development of a multi-layer marking toolkit was investigated to improve construction quality and mitigate the problem of irregular designs in the layout-printing work performed at construction sites. The quality of conventional layout-printing work is dependent on the skill of the worker, and construction quality can suffer owing to inconsistencies in drawings resulting from human error. In this study, these problems were analyzed, and a construction-site-layout-marking toolkit apparatus and mechanical unit, with a structure that allowed for multi-layer installation for automated implementation at construction sites, were developed. The marking toolkit and mechanical unit with the multi-layer structure were developed in a modular form so that each module can operate independently. Furthermore, each module was developed in manual mode to improve the system by acquiring information on the movement of the marking toolkit and multi-layer structure. Additionally, data on the layout-printing method was developed by connecting the system via Ethernet and operating a wireless joystick. Finally, experiments were performed on a road surface covered with B4 paper and concrete panels to confirm the operational feasibility of the system, which was developed to operate manually.

PKD2 founder mutation is the most common mutation of polycystic kidney disease in Taiwan.

Autosomal Dominant polycystic kidney disease (ADPKD) is the most common inherited adult kidney disease. Although ADPKD is primarily caused by PKD1 and PKD2, the identification of several novel causative genes in recent years has revealed more complex genetic heterogeneity than previously thought. To study the disease-causing mutations of ADPKD, a total of 920 families were collected and their diagnoses were established via clinical and image studies by Taiwan PKD Consortium investigators. Amplicon-based library preparation with next-generation sequencing, variant calling, and bioinformatic analysis was used to identify disease-causing mutations in the cohort. Microsatellite analysis along with genotyping and haplotype analysis was performed in the PKD2 p.Arg803* family members. The age of mutation was calculated to estimate the time at which the mutation occurred or the founder arrived in Taiwan. Disease-causing mutations were identified in 634 families (68.9%) by detection of 364 PKD1, 239 PKD2, 18 PKHD1, 7 GANAB, and 6 ALG8 pathogenic variants. 162 families (17.6%) had likely causative but non-diagnostic variants of unknown significance (VUS). A single PKD2 p.Arg803* mutation was found in 17.8% (164/920) of the cohort in Taiwan. Microsatellite and array analysis showed that 80% of the PKD2 p.Arg803* families shared the same haplotype in a 250 kb region, indicating those families may originate from a common ancestor 300 years ago. Our findings provide a mutation landscape as well as evidence that a founder effect exists and has contributed to a major percentage of the ADPKD population in Taiwan.