The compliance with TTM protocol may benefit outcomes in cardiac arrest survivors: A retrospective cohort study.

BACKGROUND: Established protocols for implementing high-quality targeted temperature management (TTM) provide guidance concerning the cooling rate, duration of maintenance, and rewarming speed. However, whether compliant to TTM protocols results in improved survival and better neurological recovery has not been examined. METHODS: A retrospective cohort study enrolled 1141 survivors of non-traumatic adult cardiac arrest with a pre-arrest cerebral performance category (CPC) score of 1-2 from 2015 to 2020 at a tertiary medical center. Of the survivors, 330 patients who underwent TTM were further included. Patients with spontaneous hypothermia (<35 °C) (n = 107) and expired during the TTM (n = 21) were excluded. A total of 202 patients were thus enrolled. One hundred and ten patients underwent TTM that completely complied with the protocol (protocol-complaint group), but 92 patients deviated in some manner from the protocol (protocol non-compliant group). RESULTS: Fifty patients (50%) and 46 patients (50%) in the protocol-compliant and non-compliant groups, respectively, did not survive to hospital discharge. In the protocol-compliant group, 42 patients (38.2%) had favorable neurological recovery, compared with 32 patients (34.8%) in the protocol non-compliant group. After adjusting for age, initial shockable rhythm, witnessed collapse, and cardiopulmonary resuscitation duration, protocol non-compliant was associated with the poor neurological outcomes (aOR 2.44, 95% CI = 1.13-5.25), but not with in-hospital mortality (aOR 1.31, 95% CI = 0.70-2.47). The most common reason for noncompliance was a prolonged duration reaching the target temperature (n = 33, 58.7%). The number of phases of non-compliant was not significantly associated with in-hospital mortality or poor neurological recovery. CONCLUSION: Among cardiac arrest survivors undergoing TTM, those who did not receive TTM that in compliance with the protocol were more likely to experience poor neurological recovery than those whose TTM fully complied with the protocols. The most frequently identified deviation was a prolonged duration to reaching the target temperature.

Harnessing the Power of Radiotherapy for Lung Cancer: A Narrative Review of the Evolving Role of Magnetic Resonance Imaging Guidance.

Compared with computed tomography (CT), magnetic resonance imaging (MRI) traditionally plays a very limited role in lung cancer management, although there is plenty of room for improvement in the current CT-based workflow, for example, in structures such as the brachial plexus and chest wall invasion, which are difficult to visualize with CT alone. Furthermore, in the treatment of high-risk tumors such as ultracentral lung cancer, treatment-associated toxicity currently still outweighs its benefits. The advent of MR-Linac, an MRI-guided radiotherapy (RT) that combines MRI with a linear accelerator, could potentially address these limitations. Compared with CT-based technologies, MR-Linac could offer superior soft tissue visualization, daily adaptive capability, real-time target tracking, and an early assessment of treatment response. Clinically, it could be especially advantageous in the treatment of central/ultracentral lung cancer, early-stage lung cancer, and locally advanced lung cancer. Increasing demands for stereotactic body radiotherapy (SBRT) for lung cancer have led to MR-Linac adoption in some cancer centers. In this review, a broad overview of the latest research on imaging-guided radiotherapy (IGRT) with MR-Linac for lung cancer management is provided, and development pertaining to artificial intelligence is also highlighted. New avenues of research are also discussed.

Regimen on Dnaja3 haploinsufficiency mediated sarcopenic obesity with imbalanced mitochondrial homeostasis and lipid metabolism.

BACKGROUND: Sarcopenic obesity is characterized by excess fat mass and diminished muscular mass/function. DNAJA3, a mitochondrial co-chaperone protein, plays a crucial role in skeletal muscle development. GMI, an immunomodulatory protein, promotes myogenic differentiation through DNAJA3 activation. This study aims to elucidate the physiological effects of muscular Dnaja3 haploinsufficiency on mitochondrial dysfunction and dysregulated lipid metabolism and to assess the efficacy of GMI in rescuing sarcopenic obesity both in vitro and in vivo. METHODS: We generated mouse strain with Dnaja3 heterozygosity (HSA-Dnaja3f/+) specifically in skeletal muscle. The body weight, body composition, and locomotor activity of WT and HSA-Dnaja3f/+ mice were examined. The isolated skeletal muscles and primary myoblasts from the WT and HSA-Dnaja3f/+ mice, at young or old age, were utilized to study the molecular mechanisms, mitochondrial respiration and ROS level, mitochondrial proteomes, and serological analyses, respectively. To evaluate the therapeutic efficacy of GMI, both short-term and long-term GMI treatment were administrated intraperitoneally to the HSA-Dnaja3f/+ young (4 weeks old) or adult (3 months old) mice for a duration of either 1 or 6 months, respectively. RESULTS: Muscular Dnaja3 heterozygosity resulted in impaired locomotor activity (P < 0.05), reduced muscular cross-sectional area (P < 0.0001), and up-regulation of lipogenesis (ACC2) and pro-inflammation (STAT3) in skeletal muscles (P < 0.05). Primary myoblasts from the HSA-Dnaja3f/+ mice displayed impaired mitochondrial respiration (P < 0.01) and imbalanced mitochondrial ROS levels. A systemic proteomic analysis of the purified mitochondria from the primary myoblasts was conducted to show the abnormalities in mitochondrial function and fatty acid metabolism (P < 0.0001). At age of 13 to 14 months, the HSA-Dnaja3f/+ mice displayed increased body fat mass (P < 0.001), reduced fat-free mass (P < 0.01), and impaired glucose and insulin tolerance (P < 0.01). The short-term GMI treatment improved locomotor activity (P < 0.01) and down-regulated the protein levels of STAT3 (P < 0.05), ACC2, and mitochondrial respiratory complex III (UQCRC2) (P < 0.01) via DNAJA3 activation. The long-term GMI treatment ameliorated fat mass accumulation, glucose intolerance, and systemic inflammation (AST) (P < 0.05) in skeletal muscle, while enhancing thermogenesis (UCP1) (P < 0.01) in eWAT. GMI treatment promoted myogenesis, enhanced oxygen consumption, and ameliorated STAT3 (P < 0.01) through DNAJA3 activation (P < 0.05) in vitro. CONCLUSIONS: Muscular Dnaja3 haploinsufficiency dysregulates mitochondrial function and lipid metabolism then leads to sarcopenic obesity. GMI emerges as a therapeutic regimen for sarcopenic obesity treatment through DNAJA3 activation.

Association of salivary gland cancer with human papillomavirus infections.

PURPOSE: The link between human papillomavirus (HPV) infections and salivary gland cancer is still a subject of ongoing debate. This study aimed to explore the association between HPV infections and salivary gland cancer in a Taiwanese cohort. We hypothesize that HPV infection is associated with an increased risk of developing salivary gland cancer. METHODS: This case-control study included 416 individuals aged ≥ 20 years who had received their first diagnosis of salivary gland cancer as cases, and 2080 propensity-score-matched controls. We performed multivariate logistic regressions to evaluate the association of salivary gland cancer with HPV infections while considering sociodemographic characteristics and medical comorbidities. RESULTS: Statistical analysis showed a significant difference in the prevalence of HPV infections between patients diagnosed with salivary gland cancer and the controls, with rates of 10.8% and 6.2%, respectively (p < 0.001). The odds ratio for having prior HPV infections among patients with salivary gland cancer compared to controls was 1.885, with a 95% confidence interval of 1.315 to 2.701 after adjusting for variables such as age, sex, monthly income, geographic location, urbanization level, diabetes, hypertension, hyperlipidemia, tobacco use, and alcohol abuse/alcohol dependence syndrome. CONCLUSIONS: Our study adds to the evidence suggesting an association between HPV infections and salivary gland cancer. Individuals with a history of HPV infection have an approximately 88% higher likelihood of developing salivary gland cancer.

Exposure-associated DNA methylation among people exposed to multiple industrial pollutants.

BACKGROUND: Current research on the epigenetic repercussions of exposure to a combination of pollutants is limited. This study aims to discern DNA methylation probes associated with exposure to multiple pollutants, serving as early effect markers, and single-nucleotide polymorphisms (SNPs) as surrogate indicators for population susceptibility. The investigation involved the analysis of urine exposure biomarkers for 11 heavy metals (vanadium, arsenic, mercury, cadmium, chromium, nickel, lead, manganese, copper, strontium, thallium), polycyclic aromatic hydrocarbon (PAHs) (1-hydroxypyrene), genome-wide DNA methylation sequencing, and SNPs array on all study participants. The data were integrated with metabolomics information and analyzed both at a community level based on proximity to home addresses relative to the complex and at an individual level based on exposure biomarker concentrations. RESULTS: On a community level, 67 exposure-related CpG probes were identified, while 70 CpG probes were associated with urine arsenic concentration, 2 with mercury, and 46 with vanadium on an individual level. These probes were annotated to genes implicated in cancers and chronic kidney disease. Weighted quantile sum regression analysis revealed that vanadium, mercury, and 1-hydroxypyrene contributed the most to cg08238319 hypomethylation. cg08238319 is annotated to the aryl hydrocarbon receptor repressor (AHRR) gene, and AHRR hypomethylation was correlated with an elevated risk of lung cancer. AHRR was further linked to deregulations in phenylalanine metabolism, alanine, aspartate, and glutamate metabolism, along with heightened oxidative stress. Additionally, three SNPs (rs11085020, rs199442, and rs10947050) corresponding to exposure-related CpG probes exhibited significant interaction effects with multiple heavy metals and PAHs exposure, and have been implicated in cancer progression and respiratory diseases. CONCLUSION: Our findings underscore the pivotal role of AHRR methylation in gene-environment interactions and highlight SNPs that could potentially serve as indicators of population susceptibility in regions exposed to multiple heavy metals and PAHs.

Inter-subject gamma oscillation synchronization as a biomarker of abnormal processing of social interaction in ADHD.

Children with attention-deficit hyperactivity disorder (ADHD) have difficulties in social interactions. Studying brain activity during social interactions is difficult with conventional artificial stimuli. This pioneering study examined the neural correlates of social perception in children with ADHD and matched controls using naturalistic stimuli. We presented 20 children with ADHD and 20 age-and-sex-matched controls with tailored movies featuring high- or low-level social interactions while recording electroencephalographic signals. Both groups exhibited synchronized gamma-band oscillations, but controls demonstrated greater inter-subject correlations. Additionally, the difference in inter-subject correlations between high- and low-interaction movies was significantly larger in controls compared to ADHD patients. Between 55 and 75 Hz comparing viewing high interaction movies with low interaction moves, controls had a significantly larger weighting in the right parietal lobe, while ADHD patients had a significantly smaller weighting in the left occipital lobe. These findings reveal distinct spatiotemporal neural signatures in social interaction processing among children with ADHD and controls using naturalistic stimuli. These neural markers offer potential for group differentiation and assessing intervention efficacy, advancing our understanding ADHD-related social interaction mechanisms.

Comparing clinical outcomes in patients with type 2 diabetes mellitus after ischaemic stroke: Sodium-glucose cotransporter 2 inhibitors users versus non-users. A propensity score matching National Cohort Study.

AIM: This nationwide cohort study evaluated the impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i-treated patients and those not receiving SGLT2i. MATERIALS AND METHODS: Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow-up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first. RESULTS: After propensity score matching, compared with the non-SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34-0.88; p = 0.0131) and a significant reduction in all-cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39-0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation. CONCLUSIONS: Our findings indicate significantly lower risks of recurrent IS and all-cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects.

Photothermal Temperature-Modulated Cancer Metastasis Harnessed Using Proteinase-Triggered Assembly of Near-Infrared II Photoacoustic/Photothermal Nanotheranostics.

Here we demonstrate that cancer metastasis could be modulated by the judicious tuning of physical parameters such as photothermal temperature in nanoparticle-mediated photothermal therapy (PTT). This is supported by theranostic nanosystem design and characterization, in vitro and in vivo analyses, and transcriptome-based gene profiling. In this work, the highly efficient near-infrared II (NIR-II) photoacoustic image (PA)-guided PTT are selectively activated using our developed matrix metalloproteinase (MMP)-triggered in situ assembly of gold nanodandelions (GNDs@gelatin). Unlike other "always-on" NIR PTT agents lacking specific bioactivation and suffering from the intrinsic nonspecific pseudosignals and treatment-related side effects such as metastasis, our GNDs@gelatin possesses important advantages while deployed in cancer PTT that include the following: (1) The theranostic effects could be "turned on" only after specific MMP-2/-9 activity and with acidity in the tumor microenvironment. (2) The quantitative PA diagnosis allows for precise PTT planning for better cancer treatment. (3) GNDs@gelatin could noninvasively quantify MMP activity and efficiently harness NIR-I (808 nm) and NIR-II (1064 nm) energies for tumor ablation. (4) The multibranched nanostructures reabsorb scattered laser photons, thus enhancing the surface plasmons for the pronounced photothermal conversion of aggregated GNDs@gelatin in situ. (5) It is noteworthy that in situ tumor eradication at higher PTT temperature (>55 °C) mediated by GNDs@gelatin could induce subsequent metastasis, which could be otherwise abolished at lower PTT temperatures (50 °C > T > 43 °C). (6) Furthermore, the gene profiling using transcriptome-based microarray including GO and KEGG analyses revealed that 315 differentially expressed genes were identified in higher PTT temperature treated tumors compared with lower PTT temperature ones. These were enriched into some well-known cancer-related pathways, such as cell migration pathway, signal transductions, cell proliferation, wound healing, PPAR signaling, and metabolic pathways. These observations suggest a new perspective of "moderate-is-better" in nanoparticle-mediated PTT for maximizing its therapeutic/prognosis benefits and translational potential with metastasis inhibition.

Application of Three-Dimensional Printing Technology in the Perioperative Management of Cardiac Tumours: A Review and Analysis.

Background: Multimodal imaging plays a crucial role in evaluating suspected cardiac tumours. In recent years, three-dimensional (3D) printing technology has continued to advance such that image-based 3D-printed models have been incorporated into the auxiliary diagnosis and treatment of cardiac tumour diseases. The purpose of this review is to analyze the existing literature on the application of 3D printing in cardiac tumour surgery to examine the current status of the application of this technology. Methods: By searching PubMed, Cochrane, Scopus and Google Scholar, as well as other resource databases, a completed review of the available literature was performed. Effect sizes from published studies were investigated, and results are presented concerning the use of 3D surgical planning in the management of cardiac tumours. Results: According to the reviewed literature, our study comes to the point that 3D printing is a valuable technique for planning surgery for cardiac tumours. As shown in the review report, Mucinous and sarcomatous tumours are the most commonly used tumours for 3D printing, magnetic resonance imaging (MRI) and computed tomography (CT) are the most commonly used technologies for preparing 3D printing models, the main printing technology is stereolithography, and the most used 3D modeling software is Mimics. The printing time and cost required for 3D printing are affected by factors such as the size of the type, complexity, the printed material and the 3D printing technology used. The reported research shows that 3D printing can understand the anatomy of complex tumour cases, virtual surgical simulation, as well as facilitate doctor-patient communication and clinical teaching. Conclusions: These results show that the development of 3D printing technology has brought more accurate and safe perioperative treatment options for patients with cardiac tumours. Therefore, 3D printing technology is expected to become a routine clinical diagnosis and treatment tool for cardiac tumours.

Evaluation of a 3D-Printed Writing Assistive Device for People With Brain Injury.

Three-dimensional-printed assistive devices hold promise for improving writing abilities, yet factors influencing device selection and their impact on satisfaction and effectiveness remain unclear, especially in adults, as they are typically tested on children. The aim of this article is to assess the efficacy and satisfaction with a writing assistive device at different angles among individuals with brain injury and explore device selection factors. Twenty-six participants with brain injuries selected their preferred device angle. Writing speed, quality, and satisfaction were recorded. Immediate speed improvements were significant at 5° and 30° (p = .006, .013, respectively). Satisfaction scores did not significantly differ among angles. Normotonia in elbow (p < .001; odds ratio: 3.403) and wrist (p ≤ .001; odds ratio: 2.695) muscles increased the likelihood of selecting the 5° device. Immediate speed improvements at specific angles highlight the influence of muscle normotonia on device selection, vital for tailored brain injury rehabilitation.

Evaluation of a 3D-Printed Writing Assistive Device for People With Brain InjuryThis study, titled "Evaluation of a 3D-Printed Writing Assistive Device for People with Brain Injury," aimed to understand how 3D-printed devices could improve writing for individuals with brain injuries. The researchers explored the effectiveness and satisfaction of using these devices at different angles (5°, 20°, and 30°) among 26 participants with brain injuries. Participants chose the device angle that felt most comfortable to them, and the study measured their writing speed, quality, and satisfaction. The findings revealed that using 3D-printed writing devices significantly improved writing speed immediately, regardless of the chosen angle (5° or 30°). Satisfaction scores were similar across all angles. Interestingly, individuals with normal elbow and wrist muscle tone were more likely to prefer the 5° device. In summary, this study concludes that 3D-printed writing devices can promptly enhance writing for people with brain injuries. The specific angle of the device significantly affect outcomes, and participants generally find satisfaction with their choice. If you have normal elbow and wrist muscle tone, the 5° angle may be the optimal choice for you.

Hsa-miR-134-5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells.

This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa-miR-134-5p was found up-regulated in senescent EPCs where overexpression improved angiogenic activity. Hsa-miR-134-5p, which targeted transforming growth factor ß-activated kinase 1-binding protein 1 (TAB1) gene, down-regulated TAB1 protein, and inhibited phosphorylation of p38 mitogen-activated protein kinase (p38) in hsa-miR-134-5p-overexpressed senescent EPCs. Treatment with siRNA specific to TAB1 (TAB1si) down-regulated TAB1 protein and subsequently inhibited p38 activation in senescent EPCs. Treatment with TAB1si and p38 inhibitor, respectively, showed angiogenic improvement. In parallel, transforming growth factor Beta 1 (TGF-ß1) was down-regulated in hsa-miR-134-5p-overexpressed senescent EPCs and addition of TGF-ß1 suppressed the angiogenic improvement. Analysis of peripheral blood mononuclear cells (PBMCs) disclosed expression levels of hsa-miR-134-5p altered in adult life, reaching a peak before 65 years, and then falling in advanced age. Calculation of the Framingham risk score showed the score inversely correlates with the hsa-miR-134-5p expression level. In summary, hsa-miR-134-5p is involved in the regulation of senescence-related change of angiogenic activity via TAB1-p38 signalling and via TGF-ß1 reduction. Hsa-miR-134-5p has a potential cellular rejuvenation effect in human senescent EPCs. Detection of human PBMC-derived hsa-miR-134-5p predicts cardiovascular risk.

Prediction of In-Hospital Cardiac Arrest in the Intensive Care Unit: Machine Learning-Based Multimodal Approach.

Background: Early identification of impending in-hospital cardiac arrest (IHCA) improves clinical outcomes but remains elusive for practicing clinicians. Objective: We aimed to develop a multimodal machine learning algorithm based on ensemble techniques to predict the occurrence of IHCA. Methods: Our model was developed by the Multiparameter Intelligent Monitoring of Intensive Care (MIMIC)-IV database and validated in the Electronic Intensive Care Unit Collaborative Research Database (eICU-CRD). Baseline features consisting of patient demographics, presenting illness, and comorbidities were collected to train a random forest model. Next, vital signs were extracted to train a long short-term memory model. A support vector machine algorithm then stacked the results to form the final prediction model. Results: Of 23,909 patients in the MIMIC-IV database and 10,049 patients in the eICU-CRD database, 452 and 85 patients, respectively, had IHCA. At 13 hours in advance of an IHCA event, our algorithm had already demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI 0.815-0.885) in the MIMIC-IV database. External validation with the eICU-CRD and National Taiwan University Hospital databases also presented satisfactory results, showing area under the receiver operating characteristic curve values of 0.81 (95% CI 0.763-0.851) and 0.945 (95% CI 0.934-0.956), respectively. Conclusions: Using only vital signs and information available in the electronic medical record, our model demonstrates it is possible to detect a trajectory of clinical deterioration up to 13 hours in advance. This predictive tool, which has undergone external validation, could forewarn and help clinicians identify patients in need of assessment to improve their overall prognosis.

Effects of nurse-led brief behavioral treatment for insomnia in adults: a randomized controlled trial.

STUDY OBJECTIVES: To examine the effects of nurse-led brief behavioral treatment for insomnia (BBTI) on insomnia severity, sleep status, daytime function, quality of life (QoL), psychological distress levels, treatment response, and insomnia remission in young and middle-aged Asian adults with insomnia symptoms. METHODS: This two-parallel, randomized controlled trial recruited 42 participants with insomnia symptoms randomly allocated to the nurse-led BBTI group or sleep hygiene (SH) group. The outcome measurements included the Insomnia Severity Index, sleep diary, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Brief Fatigue Inventory, RAND-36 Health Status Inventory, and the Depression, Anxiety and Stress Scale-21. The measurement time points included baseline, the end of each week of the intervention period, and one-month follow-up. RESULTS: Compared with the SH group, participants in the BBTI group significantly improved insomnia severity, sleep onset latency, sleep efficiency, sleep quality, daytime sleepiness, and the mental components of QoL after completing nurse-led BBTI immediately and one month later (p < 0.05). In addition, 52.4% and 71.4% of the participants achieved remission after completing nurse-led BBTI immediately and one month later, which were significantly higher than the SH group (14.3%, p = 0.02; 14.3%, p < 0.001, respectively). CONCLUSIONS: We suggested the relative effects of BBTI on declined insomnia severity and improved sleep status among young and middle-aged Asian adults with insomnia symptoms and confirmed the benefits of nurse-led BBTI in alleviating insomnia. Nurses should incorporate BBTI into insomnia care further to enhance the daytime function and quality of life of the population with insomnia symptoms. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Effects of Nurse-led Brief Behavioral Treatment for Insomnia: A Feasibility Randomized Controlled Trial; URL: https://clinicaltrials.gov/study/NCT05310136; Identifier: NCT05310136.

Unveiling Novel Structural Biomarkers for the Diagnosis of Glaucoma.

Glaucoma, a leading cause of irreversible blindness, poses a significant global health burden. Early detection is crucial for effective management and prevention of vision loss. This study presents a collection of novel structural biomarkers in glaucoma diagnosis. By employing advanced imaging techniques and data analysis algorithms, we now can recognize indicators of glaucomatous progression. Many research studies have revealed a correlation between the structural changes in the eye or brain, particularly in the optic nerve head and retinal nerve fiber layer, and the progression of glaucoma. These biomarkers demonstrate value in distinguishing glaucomatous eyes from healthy ones, even in the early stages of the disease. By facilitating timely detection and monitoring, they hold the potential to mitigate vision impairment and improve patient outcomes. This study marks an advancement in the field of glaucoma, offering a promising avenue for enhancing the diagnosis and possible management.

Development and evaluation of real-time quantitative PCR assays for detection of Phellinus noxius causing brown root rot disease.

Brown root rot disease (BRRD) is a highly destructive tree disease. Early diagnosis of BRRD has been challenging because the first symptoms and signs are often observed after extensive tissue colonization. Existing molecular detection methods, all based on the internal transcribed spacer (ITS) region, were developed without testing against global Phellinus noxius isolates, other wood decay fungi, or host plant tissues. This study developed SYBR Green real-time quantitative PCR (qPCR) assays for P. noxius. The primer pair Pn_ITS_F/Pn_ITS_R targets the ITS, and the primer pair Pn_NLR_F/Pn_NLR_R targets a P. noxius-unique group of homologous genes identified through a comparative genomics analysis. The homologous genes belong to the nucleotide-binding-oligomerization-domain-like receptor (NLR) superfamily. The new primer pairs and a previous primer pair G1F/G1R were optimized for qPCR conditions and tested for specificity using 61 global P. noxius isolates, five other Phellinus species, and 22 non-Phellinus wood decay fungal species. While all three primer pairs could detect as little as 100 fg (about 2.99 copies) of P. noxius genomic DNA, G1F/G1R had the highest specificity and Pn_NLR_F/Pn_NLR_R had the highest efficiency. To avoid false positives, the cutoff Cq values were determined as 34 for G1F/G1R, 29 for Pn_ITS_F/Pn_ITS_R, and 32 for Pn_NLR_F/Pn_NLR_R. We further validated these qPCR assays using Ficus benjamina seedlings artificially inoculated with P. noxius, six tree species naturally infected by P. noxius, rhizosphere soil, and bulk soil. The newly developed qPCR assays provide sensitive detection and quantification of P. noxius, which is useful for long-term monitoring of BRRD status.

Psychometric and structural properties of the traditional Chinese version of the sleep condition indicator for patients undergoing hemodialysis.

PURPOSE: Insomnia is a prevalent sleep disorder among patients undergoing hemodialysis for chronic kidney disease. This study aimed to translate the sleep condition indicator (SCI), an insomnia screening tool based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into a traditional Chinese version (SCI-TC) and evaluate the reliability and validity of this version for patients undergoing hemodialysis. METHODS: This cross-sectional study conducted from November 2022 to June 2023 involved 200 patients on hemodialysis (mean age, 65.56 years; 61.5% men). Participants completed a series of questionnaires, with insomnia diagnosed according to DSM-5 criteria as the gold standard. A receiver operating characteristic (ROC) curve analysis was conducted to examine the sensitivity and specificity of the SCI-TC. RESULTS: According to the DSM-5 criteria, 38% of the participants had insomnia. Cronbach's alpha for the SCI-TC was 0.92. The SCI-TC exhibited a good fit as a two-factor model, and its scores were significantly associated with those of the traditional Chinese versions of the Insomnia Severity Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, EuroQol 5-Dimensions scale, and EuroQol Visual Analogue Scale (r = - 0.94, - 0.53, - 0.38, 0.27, and 0.30, respectively; all p < 0.05). The ROC curve analysis revealed an optimal cutoff of 16 points, with the sensitivity, specificity, and area under curve of 88.2%, 84.7%, and 0.91(95% confidence interval, 0.87-0.95), respectively. CONCLUSION: The SCI-TC demonstrates robust reliability and validity in detecting insomnia among patients undergoing hemodialysis. These findings suggest that health-care providers should considering using the SCI as an easy-to-use tool for the timely detection of insomnia in this population.

The dynamic duo: A narrative review on the synergy between stereotactic body radiotherapy and immunotherapy in lung cancer treatment (Review).

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), is undoubtedly one of the major breakthroughs in lung cancer research. Patient survival and prognosis have all been improved as a result, although numerous patients do not respond to immunotherapy due to various immune escape mechanisms of the tumor cells. Recent preclinical and clinical evidence has shown that stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy, has a prominent immune priming effect that could elicit antitumor immunity against specific tumor antigens and destroy distant tumor cells, thereby achieving the elusive abscopal effect, with the resulting immuno­active tumor environment also being more conducive to ICIs. Some landmark trials have already demonstrated the survival benefit of the dynamic duo of SBRT plus immunotherapy in metastatic non­small­cell lung cancer, while others such as PEMBRO­RT further suggest that the addition of SBRT to immunotherapy could expand the current indication to those who have historically responded poorly to ICIs. In the present review, the biological mechanisms that drive the synergistic effect of SBRT and immunotherapy were first briefly outlined; then, the current understanding from clinical trials was summarized and new insight into the evolving role of immunotherapy and SBRT synergy in lung cancer treatment was provided. Finally, novel avenues for discovery were highlighted. The innovation of the present review lies in the inclusion of non­ICI immunotherapy in the discussion, which provides a more comprehensive view on the current development and future trend of SBRT + immunotherapy synergy.

Senescence induces miR-409 to down-regulate CCL5 and impairs angiogenesis in endothelial progenitor cells.

This study explores the impact of senescence on autocrine C-C motif chemokine ligand 5 (CCL5) in human endothelial progenitor cell (EPCs), addressing the poorly understood decline in number and function of EPCs during ageing. We examined the effects of replication-induced senescence on CCL5/CCL5 receptor (CCR5) signalling and angiogenic activity of EPCs in vitro and in vivo. We also explored microRNAs controlling CCL5 secretion in senescent EPCs, its impact on EPC angiogenic activity, and validated our findings in humans. CCL5 secretion and CCR5 levels in senescent EPCs were reduced, leading to attenuated angiogenic activity. CCL5 enhanced EPC proliferation via the CCR5/AKT/P70S6K axis and increased vascular endothelial growth factor (VEGF) secretion. Up-regulation of miR-409 in senescent EPCs resulted in decreased CCL5 secretion, inhibiting the angiogenic activity, though these negative effects were counteracted by the addition of CCL5 and VEGF. In a mouse hind limb ischemia model, CCL5 improved the angiogenic activity of senescent EPCs. Analysis involving 62 healthy donors revealed a negative association between CCL5 levels, age and Framingham Risk Score. These findings propose CCL5 as a potential biomarker for detection of EPC senescence and cardiovascular risk assessment, suggesting its therapeutic potential for age-related cardiovascular disorders.

A hierarchical model of accelerating factors to promote urban renewal and reconstruction of unsafe and old buildings.

The issue of urban renewal is complex and multifaceted. In this study, six specialists in the construction industry were invited to conduct audio interviews, which were compiled into verbatim text. The key phrases were extracted by Grounded theory, and three levels of coding were retrieved. The data were categorized into ten accelerating urban renewal factors in three constructs to establish an Analytic Hierarchy Process framework. Using institutional theory to construct outcomes based on grounded theory, transforming these into specific urban renewal relation issue elements. 113 AHP questionnaires were collected from five types of specialists, including practitioners, professionals, participants in urban renewal, academics, and government staff. The results show that relaxing the plot ratio control and incentives is ranked No. 1 by practitioners, participants in urban renewal, professionals, and academics, indicating that the factor is highly valued by specialists but neglected by government staff. Secondly, practitioners, academics, participants in urban renewal, and professionals identified incentives and rewards for urban renewal and enhancing the trust and credibility of urban renewal projects as crucial factors. However, the government staff showed a different weighting. This indicates that government staff is determined to accelerate urban renewal. Finally, the suggestion of this study is in line with the views of the specialists interviewed, who suggest that the government should hold public hearings regularly and seriously to listen to people and specialists. Only through public hearings can all parties reach a consensus. The government should consolidate the views of all parties to amend or enact a bill on urban renewal that is more in line with the changes of the times, including appropriately relaxing the control of building plot ratio and other accelerating factors, to promote urban renewal in Taiwan.

Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: A Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.