Effectiveness of home-based cardiac telerehabilitation based on wearable ECG or heart rate monitoring devices in patients with heart disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices in patients with heart disease. METHODS: We searched eight electronic databases under the guidance of Cochrane Handbook and PRISMA recommendations. RESULTS: The meta-analysis included data from 14 articles (15 RCTs) representing 1314 participants. A significant improvement in left ventricular ejection fraction [MD = 2.12, 95 % CI (1.21, 3.04), P < 0.001], 6-minute walk distance [MD = 40.00, 95 % CI (21.72, 58.29), P < 0.001] and peak oxygen intake [MD = 2.24, 95 % CI (1.38, 3.10), P < 0.001] were observed in the home-based cardiac telerehabilitation group. But it had no difference in anxiety [SMD = -0.83, 95 % CI (-1.65, -0.02), P = 0.05] and depression [SMD = -0.59, 95 % CI (-1.26, 0.09), P = 0.09]. Subgroup analyses revealed that interventions of no less than 3 months improved anxiety [SMD = -1.11, 95 % CI (-2.05, -0.18), P = 0.02] and depression [SMD = -1.01, 95 % CI (-1.93, -0.08), P = 0.03]. CONCLUSION: Home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices has a positive effect on cardiac function. Long-term (≥ 3 months) cardiac rehabilitation might benefit individuals suffering from anxiety or depression.

Selective biodegradation of octylphenol polyethoxylates with different ethoxylate length chains by aerobic bacterial culture.

Octylphenol polyethoxylates (OPEOn) are composed of a hydrophobic octylphenol (OP) group and a hydrophilic polyethylene oxide (EO) chain and are widely used in commercial products. Shorter EO chains and OPEOn biometabolites have been identified as endocrine-disrupting contaminants and can threaten biotic factors in the ecosystem. In this study, OPEOn at three EO lengths (TX-45, TX-114, and TX-165) were selected in monomer (MN) or micelle (MC) state for batch experiments under aerobic conditions, with results showing biodegradation rates of 90 % within 35-70 h. The pseudo-first-order constant (k) of OPEOn biodegradation was observed in the order TX-45 (0.1414 h-1) > TX-114 (0.0556 h-1) > TX-165 (0.0485 h-1), with biomineralisation reaching at least 80 % for all OPEOn. The selective biodegradation of EO chains was also measured, with initial accumulation of OPEO3 observed along with the depletion of longer EO chains for TX-45 and TX-114 in both the MN and MC states. A similar trend was observed for the MN state of TX-165, with OPEO3-OPEO9 observed to accumulate and reduced after 70 h. MC biodegradation was accomplished via the initial accumulation of OPEO3-OPEO9. The amounts of OPEO3 increased and others reduced; however, OPEO3 remained high at the end of biodegradation for TX-165. Bacterial community analysis indicated that the genera Sphingobium spp., Pseudomonas spp., Flavobacterium spp., Comamonas spp., and Sphingopyxis spp. dominate OPEOn biodegradation, and they have their roles during biodegradation, and the community-level physiological profile (CLPP) was also changed by biodegradation in both the MN and MC states.

Clinical characteristics of SARS-CoV-2 Omicron BA.2 infection and its impact on pediatric emergency care in northern Taiwan.

BACKGROUND: The SARS-CoV-2 Omicron BA.2 outbreak started in Taiwan in April 2022. The pandemic posed a challenge to pediatric emergency departments (PEDs) because of increased PED visits and diverse clinical presentations. METHODS: We analyzed the clinical characteristics and impact of the Omicron BA.2 pandemic in patients who visited our PED from April 2022 to July 2022. The data from the Alpha variant pandemic during the same period in 2021 were compared with these findings. RESULTS: Overall, 10,878 children were enrolled, and 7047 (64.8%) children were positive for SARS-CoV-2 infection. They had a mean ± SD age of 5.3 ± 4.1 years. The rates of patients with Pediatric Taiwan Triage and Acuity Scale (Ped-TTAS) level 1 (most urgent) (12.3%) and level 2 (27.6%) increased. More children were triaged as most urgent during the Omicron BA.2 pandemic than during the Alpha variant pandemic (p < 0.001). Patients with SARS-CoV-2 infection were likely to present with high fever, croup, dyspnea, febrile seizures, headache, dizziness, and myalgia (all p < 0.001). Four hundred and eleven (5.8%) patients were admitted; 25 (0.4%) patients needed intensive care, including 11 (44.0%) with encephalopathy or encephalitis. Three (0.04%) patients died due to fulminant encephalitis, encephalitis with septic shock, and respiratory failure. CONCLUSIONS: The number of PED visits and the Ped-TTAS level of disease severity significantly increased during the SARS-CoV-2 Omicron BA.2 outbreak. The most common symptom was fever, and high fever was more common in patients with SARS-CoV-2 Omicron BA.2 infection. The rates of patients with croup and febrile seizures also increased.

Zinc hexacyanoferrate/g-C3N4 nanocomposites with enhanced photothermal and photodynamic properties for rapid sterilization and wound healing.

Photoactivated therapy has gradually emerged as a promising and rapid method for combating bacteria, aimed at overcoming the emergence of drug-resistant strains resulting from the inappropriate use of antibiotics and the subsequent health risks. In this work, we report the facile fabrication of Zn3[Fe(CN)6]/g-C3N4 nanocomposites (denoted as ZHF/g-C3N4) through the in-situ loading of zinc hexacyanoferrate nanospheres onto two-dimensional g-C3N4 sheets using a simple metal-organic frameworks construction method. The ZHF/g-C3N4 nanocomposite exhibits enhanced antibacterial activity through the synergistic combination of the excellent photothermal properties of ZHF and the photodynamic capabilities of g-C3N4. Under dual-light irradiation (420 nm + 808 nm NIR), the nanocomposites achieve remarkable bactericidal efficacy, eliminating 99.98% of Escherichia coli and 99.87% of Staphylococcus aureus within 10 minutes. Furthermore, in vivo animal experiments have demonstrated the outstanding capacity of the composite in promoting infected wound healing, achieving a remarkable wound closure rate of 99.22% after a 10-day treatment period. This study emphasizes the potential of the ZHF/g-C3N4 nanocomposite in effective antimicrobial applications, expanding the scope of synergistic photothermal/photodynamic therapy strategies.

Optic Neuritis After COVID-19 Vaccination: A Case Series and a Review of Literature.

BACKGROUND: The coronavirus disease (COVID-19) pandemic broke out in March 2020, causing tremendous damage to public health and more than 6 million deaths. After authorization for the emergency use of COVID-19 vaccines, various adverse events have been reported, including optic neuritis. COVID-19 vaccination was implemented in Taiwan in March 2021. METHODS: We report patients who developed optic neuritis after COVID-19 vaccination at one university-affiliated tertiary hospital, between March 2021 and December 2022. We also provided a literature review of optic neuritis cases after COVID-19 vaccination. RESULTS: Five patients who developed optic neuritis after COVID-19 vaccination have been identified. Four brands of vaccine used were as follows: Moderna, Pfizer-BioNTech, Medigen, and Oxford AstraZeneca. Optic neuritis developed after the first dose of vaccination in 4 patients, whereas in 1 patient, it developed after the second shot. In the 3 patients with poor initial visual acuity, intravenous methylprednisolone pulse therapy achieved substantial improvement. CONCLUSIONS: Optic neuritis is a rare but potentially vision-threatening adverse effect of COVID-19 vaccination. We suggest early diagnosis and treatment to maximize visual outcomes.

Evaluation of methamphetamine assist packs: As-needed antipsychotics for self-management of methamphetamine-associated psychiatric toxicity.

BACKGROUND: Methamphetamine frequently causes substance-induced psychosis and related symptoms. There are currently no interventions to prevent or assist in self-management of these symptoms. METHODS: We evaluated a program providing "Methamphetamine Assist Packs" to patients who were seen in a psychiatric emergency services program for methamphetamine-induced psychosis. Methamphetamine Assist Packs included a small number of tablets of an antipsychotic medication (olanzapine), administration instructions, and referral information. We reviewed medical charts of patients who received Methamphetamine Assist Packs from January 2022 through May 2023 for sociodemographic and emergency visit characteristics. We assessed the changes between the number of psychiatric emergency visits before and after Methamphetamine Assist Pack receipt at two, six, and 12 months using generalized estimating equations. RESULTS: Ninety-two patients received a Methamphetamine Assist Pack, with a mean age of 40 years; 79 % were male and 49 % Black/African American; 77 % experienced housing instability or homelessness. The most common symptoms were suicidal ideation (54 %), paranoia or delusions (45 %), and hallucinations (40 %); 55 % were on involuntary psychiatric hold, 38 % required medications for agitation, and 18 % required seclusion or physical restraints. The rate of psychiatric emergency visits after Methamphetamine Assist Pack receipt was 0.68 and 0.87 times the rate prior to receipt at two and six months, respectively (p < 0.001). There was no difference at 12 months. CONCLUSIONS: Methamphetamine Assist Packs were associated with fewer psychiatric emergency visits for six months after receipt, and represent a promising intervention to address acute psychiatric toxicity from methamphetamine in need of further research.

The implication of serum HLA-G in angiogenesis of multiple myeloma.

BACKGROUND: Despite the advances of therapies, multiple myeloma (MM) remains an incurable hematological cancer that most patients experience relapse. Tumor angiogenesis is strongly correlated with cancer relapse. Human leukocyte antigen G (HLA-G) has been known as a molecule to suppress angiogenesis. We aimed to investigate whether soluble HLA-G (sHLA-G) was involved in the relapse of MM. METHODS: We first investigated the dynamics of serum sHLA-G, vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in 57 successfully treated MM patients undergoing remission and relapse. The interactions among these angiogenesis-related targets (sHLA-G, VEGF and IL-6) were examined in vitro. Their expression at different oxygen concentrations was investigated using a xenograft animal model by intra-bone marrow and skin grafts with myeloma cells. RESULTS: We found that HLA-G protein degradation augmented angiogenesis. Soluble HLA-G directly inhibited vasculature formation in vitro. Mechanistically, HLA-G expression was regulated by hypoxia-inducible factor-1α (HIF-1α) in MM cells under hypoxia. We thus developed two mouse models of myeloma xenografts in intra-bone marrow (BM) and underneath the skin, and found a strong correlation between HLA-G and HIF-1α expressions in hypoxic BM, but not in oxygenated tissues. Yet when stimulated with IL-6, both HLA-G and HIF-1α could be targeted to ubiquitin-mediated degradation via PARKIN. CONCLUSION: These results highlight the importance of sHLA-G in angiogenesis at different phases of multiple myeloma. The experimental evidence that sHLA-G as an angiogenesis suppressor in MM may be useful for future development of novel therapies to prevent relapse.

Refining Euclidean Obfuscatory Nodes Helps: A Joint-Space Graph Learning Method for Graph Neural Networks.

Many graph neural networks (GNNs) are inapplicable when the graph structure representing the node relations is unavailable. Recent studies have shown that this problem can be effectively solved by jointly learning the graph structure and the parameters of GNNs. However, most of these methods learn graphs by using either a Euclidean or hyperbolic metric, which means that the space curvature is assumed to be either constant zero or constant negative. Graph embedding spaces usually have nonconstant curvatures, and thus, such an assumption may produce some obfuscatory nodes, which are improperly embedded and close to multiple categories. In this article, we propose a joint-space graph learning (JSGL) method for GNNs. JSGL learns a graph based on Euclidean embeddings and identifies Euclidean obfuscatory nodes. Then, the graph topology near the identified obfuscatory nodes is refined in hyperbolic space. We also present a theoretical justification of our method for identifying obfuscatory nodes and conduct a series of experiments to test the performance of JSGL. The results show that JSGL outperforms many baseline methods. To obtain more insights, we analyze potential reasons for this superior performance.

SLIVER: Unveiling large scale gene regulatory networks of single-cell transcriptomic data through causal structure learning and modules aggregation.

Prevalent Gene Regulatory Network (GRN) construction methods rely on generalized correlation analysis. However, in biological systems, regulation is essentially a causal relationship that cannot be adequately captured solely through correlation. Therefore, it is more reasonable to infer GRNs from a causal perspective. Existing causal discovery algorithms typically rely on Directed Acyclic Graphs (DAGs) to model causal relationships, but it often requires traversing the entire network, which result in computational demands skyrocketing as the number of nodes grows and make causal discovery algorithms only suitable for small networks with one or two hundred nodes or fewer. In this study, we propose the SLIVER (cauSaL dIscovery Via dimEnsionality Reduction) algorithm which integrates causal structural equation model and graph decomposition. SLIVER introduces a set of factor nodes, serving as abstractions of different functional modules to integrate the regulatory relationships between genes based on their respective functions or pathways, thus reducing the GRN to the product of two low-dimensional matrices. Subsequently, we employ the structural causal model (SCM) to learn the GRN within the gene node space, enforce the DAG constraint in the low-dimensional space, and guide each factor to aggregate various functions through cosine similarity. We evaluate the performance of the SLIVER algorithm on 12 real single cell transcriptomic datasets, and demonstrate it outperforms other 12 widely used methods both in GRN inference performance and computational resource usage. The analysis of the gene information integrated by factor nodes also demonstrate the biological explanation of factor nodes in GRNs. We apply it to scRNA-seq of Type 2 diabetes mellitus to capture the transcriptional regulatory structural changes of ß cells under high insulin demand.

Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin Attenuates Sorafenib-Induced Myocardial Inflammation and Toxicity.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1ß/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

Rule-based modulation of a sensorimotor transformation across cortical areas.

Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes and uses rule information to guide behavior. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task where they switched between two rules: licking in response to tactile stimuli while rejecting visual stimuli, or vice versa. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, single-neuron activity distinguished between the two rules both prior to and in response to the tactile stimulus. We hypothesized that neural populations in these areas would show rule-dependent preparatory states, which would shape the subsequent sensory processing and behavior. This hypothesis was supported for the motor cortical areas (MM and ALM) by findings that (1) the current task rule could be decoded from pre-stimulus population activity; (2) neural subspaces containing the population activity differed between the two rules; and (3) optogenetic disruption of pre-stimulus states impaired task performance. Our findings indicate that flexible action selection in response to sensory input can occur via configuration of preparatory states in the motor cortex.

Biomechanical evaluation of various rigid internal fixation modalities for condylar-base-associated multiple mandibular fractures: A finite element analysis.

Condylar-base-associated multiple mandibular fractures are more prevalent than single ones. Direct trauma to mandibular symphysis, body or angle are prone to induce indirect condylar fracture. However, little is known about the effects of various rigid internal fixation modalities in condylar base for relevant multiple mandibular fractures, especially when we are confused in the selection of operative approach. Within the finite element analysis, straight-titanium-plate implanting positions in condylar base contained posterolateral zone (I), anterolateral zone (II), and intermediate zone (III). Von Mises stress (SS) in devices and bone and mandibular displacement (DT) were solved, while maximum values (SSmax and DTmax) were documented. For rigid internal fixation in condylar-base-and-symphysis fractures, I + II modality exhibited least SSmax in screws and cortical bone and least DTmax, I + III modality exhibited least SSmax in plates. For rigid internal fixation in condylar-base-and-contralateral-body fractures, I + III modality exhibited least SSmax in screws and cortical bone, I + II modality exhibited least SSmax in plates and least DTmax. For rigid internal fixation in condylar-base-and-contralateral-angle fractures, I + III modality exhibited least DTmax. The findings suggest that either I + II or I + III modality is a valid guaranty for rigid internal fixation of condylar base fractures concomitant with symphysis, contralateral body or angle fractures.

Eplerenone reduces lymphangiogenesis in the contralateral kidneys of UUO rats.

Inflammation and fibrosis often occur in the kidney after acute injury, resulting in chronic kidney disease and consequent renal failure. Recent studies have indicated that lymphangiogenesis can drive renal inflammation and fibrosis in injured kidneys. However, whether and how this pathogenesis affects the contralateral kidney remain largely unknown. In our study, we uncovered a mechanism by which the contralateral kidney responded to injury. We found that the activation of mineralocorticoid receptors and the increase in vascular endothelial growth factor C in the contralateral kidney after unilateral ureteral obstruction could promote lymphangiogenesis. Furthermore, mineralocorticoid receptor activation in lymphatic endothelial cells resulted in the secretion of myofibroblast markers, thereby contributing to renal fibrosis. We observed that this process could be attenuated by administering the mineralocorticoid receptor blocker eplerenone, which, prevented the development of fibrotic injury in the contralateral kidneys of rats with unilateral ureteral obstruction. These findings offer valuable insights into the intricate mechanisms underlying kidney injury and may have implications for the development of therapeutic strategies to mitigate renal fibrosis in the context of kidney disease.

Heart Sound Abnormality Detection From Multi-Institutional Collaboration: Introducing a Federated Learning Framework.

OBJECTIVE: Early diagnosis of cardiovascular diseases is a crucial task in medical practice. With the application of computer audition in the healthcare field, artificial intelligence (AI) has been applied to clinical non-invasive intelligent auscultation of heart sounds to provide rapid and effective pre-screening. However, AI models generally require large amounts of data which may cause privacy issues. Unfortunately, it is difficult to collect large amounts of healthcare data from a single centre. METHODS: In this study, we propose federated learning (FL) optimisation strategies for the practical application in multi-centre institutional heart sound databases. The horizontal FL is mainly employed to tackle the privacy problem by aligning the feature spaces of FL participating institutions without information leakage. In addition, techniques based on deep learning have poor interpretability due to their "black-box" property, which limits the feasibility of AI in real medical data. To this end, vertical FL is utilised to address the issues of model interpretability and data scarcity. CONCLUSION: Experimental results demonstrate that, the proposed FL framework can achieve good performance for heart sound abnormality detection by taking the personal privacy protection into account. Moreover, using the federated feature space is beneficial to balance the interpretability of the vertical FL and the privacy of the data. SIGNIFICANCE: This work realises the potential of FL from research to clinical practice, and is expected to have extensive application in the federated smart medical system.

Esaxerenone Inhibits Interferon-γ Induced Pyroptosis of Macrophages in the Lungs of Aldosterone-treated Mice.

Lung immune cells such as lymphocytes and macrophages can induce an inflammatory response due to the activation of mineralocorticoid receptor (MR), which is manifested by the infiltration of inflammatory cells and the secretion of inflammatory cytokines and subsequent apoptosis, pyroptosis and necrosis of intrinsic lung cells and immune cells. Macrophages are immune cells that are abundant in the lung and act as the first line of defense against pathogens but are also aggravating factors of infection. The activation of the renin-angiotensin-aldosterone system (RAAS), especially aldosterone-stimulated MR activation, can induce macrophage and CD8+ T cell aggregation and the secretion of cytokines such as tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ). Increased IFN-γ secretion can induce macrophage pyroptosis and the release of interleukin 1-ß (IL-1ß), aggravating lung injury. In this study, lung injury in C57BL/6 mice was induced by subcutaneous micro-osmotic pump infusion of aldosterone. After 12 weeks of administration, the kidney, heart, blood vessels and lungs all showed obvious inflammatory injury, which manifested as rapid accumulation of macrophages. The overexpression of IFN-γ in the lungs of aldosterone-treated mice and the stimulation of MH-S and RAW264.7 alveolar macrophages (AMs) with aldosterone in vitro showed that IFN-γ induced pyroptosis of macrophages via the activation of the inflammasome, and the MR blocker esaxerenone effectively inhibited this effect and alleviated lung injury. In addition, IFN-γ secreted by CD8+ T cells is associated with macrophage pyroptosis. In conclusion, the inhibition of macrophage pyroptosis can effectively alleviate lung injury.

Clinical implications of dextrocardia based on four visceroatrial situs studies.

BACKGROUND: Previous studies on congenital heart diseases (CHD) associated with dextrocardia were based on selective patient databases and did not reflect the full spectrum of dextrocardia in the general population. Additionally, these studies had complex classification and presentation. Nor did these studies elaborate on the distribution of the associated CHD's complexity, the various segmental connections, and associated CHD among the four visceroatrial situs. METHODS: We retrospectively reviewed the medical records of 211 children with primary dextrocardia. We used a segmental approach to diagnose CHD. We then analyzed and compared the distribution of the above-mentioned issues among the four visceroatrial situs. RESULTS: Dextrocardia occurred most commonly with situs inversus (52.6%), followed by situs solitus (28.4%), asplenia (17.1%), and polysplenia (1.9%). Although some patients had a structurally normal heart (22.7%) or they were associated with simple CHD (17.5%), most patients had complex CHD (59.7%) consisting of a single ventricle (34.6%) or conotruncal anomaly (25.1%) (double-outlet right ventricle [7.6%], corrected transposition of the great arteries [6.2%], complete transposition of the great arteries [5.7%], tetralogy of Fallot [4.7%], etc.). Situs inversus or polysplenia had a higher prevalence of a structurally normal heart or associated with simple CHD, two patent atrioventricular (AV) valves connections, and biventricular AV connections. Situs solitus or asplenia had a higher prevalence of associated complex CHD, common AV valve connection, univentricular AV connection, pulmonary outflow tract obstruction, and anomalous pulmonary venous drainage. CONCLUSION: Our study finds that situs inversus is the most common visceroatrial situs in dextrocardia. Although some patients had a structurally normal heart or were associated with simple CHD, most patients have associated complex CHD consisting of a single ventricle or conotruncal anomaly. Dextrocardia is associated with a higher incidence of complex CHD in situs solitus and asplenia groups than in situs inversus and polysplenia groups.

A multi-trait GWAS identifies novel genes influencing albuminuria.

BACKGROUND: Albuminuria is common and associated with increased risks of end-stage kidney disease and cardiovascular diseases, yet its underlying mechanism remains obscure. Previous genome-wide association studies (GWAS) for albuminuria did not consider gene pleiotropy and primarily focused on European ancestry populations. This study adopted a multi-trait analysis of GWAS (MTAG) approach to jointly analyze two vital kidney traits, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) to identify and prioritize the genes associated with UACR. METHODS: Data from the Taiwan Biobank from 2012 to 2023 were analyzed. GWAS of UACR and eGFR were performed separately and the summary statistics from these GWAS were jointly analyzed using MTAG. The polygenic risk scores (PRS) of UACR were constructed for validation. The UACR-associated loci were further fine-mapped and prioritized based on their deleteriousness, eQTL associations, and relatedness to Mendelian kidney diseases. RESULTS: MTAG analysis of the UACR revealed 15 genetic loci, including 12 novel loci. The PRS for UACR was significantly associated with urinary albumin level (P < 0.001) and microalbuminuria (P = 0.001 ∼ 0.045). A list of priority genes was generated. Twelve genes with high priority included the albumin endocytic receptor gene LRP2 and ciliary genes  IFT172. CONCLUSIONS: The findings of this multi-trait GWAS suggest that primary cilia play a role in sensing mechanical stimuli, leading to albumin endocytosis. The priority list of genes warrants further translational investigation to reduce albuminuria.

Sex Disparity in the Association of Metabolic Syndrome with Cognitive Impairment.

Background/Objectives: Metabolic syndrome (MS) is a constellation of several cardiometabolic risk factors. We investigated sex disparity in the associations between MS and cognitive impairment using cross-sectional data from Taiwan Biobank. Methods: We determined the associations of MS and its five components with cognitive impairment (mini-mental state examination, MMSE < 24) and the five domains of MMSE using logistic regression analyses. Results: A total of 7399 men and 11,546 women were included, and MS was significantly associated with cognitive impairment only in women (adjusted OR 1.48, 95% CI 1.29-1.71, p = 0.001) (p for interaction 0.005). In women, the association with MS was significant in orientation (adjusted OR 1.21, 95% CI 1.07-1.37, p = 0.003), memory (adjusted OR 1.12, 95% CI 1.01-1.25, p = 0.034) and design copying (adjusted OR 1.41, 95% CI 1.23-1.62, p = 0.001) (p value for interaction 0.039, 0.023, and 0.093, respectively). Among the components of MS, a large waist circumference (adjusted OR 1.25, 95% CI 1.08-1.46, p = 0.003), high fasting glucose (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.046), and low HDL cholesterol (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.049) were significantly associated with cognitive impairment in women. Conclusions: Our findings suggest that sex has a significant influence on the association between MS and cognitive dysfunction, especially in orientation and memory.

Supplemental effects of different production methods of pine needle additives on growth performance, intestinal environment, meat quality and serum of broiler chickens.

Objective: Pine needles are rich in many nutrients and exhibit antibacterial and antioxidant biological activities; however, the effects of different production methods of pine needle additives on the growth performance and intestinal flora of broiler chickens are not known. Methods: Normal diets were supplemented with PNF (Pine Needle Fermentation juice), PNS (Pine Needle Soaking juice), or PNP (Pine Needle Powder), and the associated effects on growth performance, relative organ weights, intestinal development, intestinal histological morphology, intestinal flora, meat quality, and serum indicators in broiler chickens were observed. Results: The results showed that PNF, PNS, and PNP all significantly improved feed utilisation and promoted the growth and development of broilers. All three additives also significantly improved the structure of the intestinal flora, specifically increasing the diversity of bacteria; increasing the abundance of beneficial bacteria, such as Faecalibacterium, Rikenella, and Blautia; and decreasing the abundance of harmful bacteria, such as Staphylococcus. The antioxidant properties of pine needles were also found to intensify lipid metabolic reactions in the blood, thus leading to lower TG and TCHO. Meanwhile, high doses of PNF reduced jejunum and ileum weights and also increased meat yellowness. Lastly, none of PNF, PNS, or PNP had an effect on relative organ weights or intestinal histological morphology. Conclusion: In conclusion, the addition of pine needles to the diet of broiler chickens can effectively promote their growth performance as well as improve their intestinal flora and serum status without side effects; in particular, the dose of 0.2% of either PNF and PNS is expected to have the capacity to replace growth-promoting antibiotics as diet additives.

Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.