Precision probiotics supplement strategy in aging population based on gut microbiome composition.

With the increasing prevalence of age-related chronic diseases burdening healthcare systems, there is a pressing need for innovative management strategies. Our study focuses on the gut microbiota, essential for metabolic, nutritional, and immune functions, which undergoes significant changes with aging. These changes can impair intestinal function, leading to altered microbial diversity and composition that potentially influence health outcomes and disease progression. Using advanced metagenomic sequencing, we explore the potential of personalized probiotic supplements in 297 older adults by analyzing their gut microbiota. We identified distinctive Lactobacillus and Bifidobacterium signatures in the gut microbiota of older adults, revealing probiotic patterns associated with various population characteristics, microbial compositions, cognitive functions, and neuroimaging results. These insights suggest that tailored probiotic supplements, designed to match individual probiotic profile, could offer an innovative method for addressing age-related diseases and functional declines. Our findings enhance the existing evidence base for probiotic use among older adults, highlighting the opportunity to create more targeted and effective probiotic strategies. However, additional research is required to validate our results and further assess the impact of precision probiotics on aging populations. Future studies should employ longitudinal designs and larger cohorts to conclusively demonstrate the benefits of tailored probiotic treatments.

Overexpression of malic enzyme is involved in breast cancer growth and is correlated with poor prognosis.

Malic enzyme (ME) genes are key functional metabolic enzymes playing a crucial role in carcinogenesis. However, the detailed effects of ME gene expression on breast cancer progression remain unclear. Here, our results revealed ME1 expression was significantly upregulated in breast cancer, especially in patients with oestrogen receptor/progesterone receptor-negative and human epidermal growth factor receptor 2-positive breast cancer. Furthermore, upregulation of ME1 was significantly associated with more advanced pathological stages (p < 0.001), pT stage (p < 0.001) and tumour grade (p < 0.001). Kaplan-Meier analysis revealed ME1 upregulation was associated with poor disease-specific survival (DSS: p = 0.002) and disease-free survival (DFS: p = 0.003). Multivariate Cox regression analysis revealed ME1 upregulation was significantly correlated with poor DSS (adjusted hazard ratio [AHR] = 1.65; 95% CI: 1.08-2.52; p = 0.021) and DFS (AHR, 1.57; 95% CI: 1.03-2.41; p = 0.038). Stratification analysis indicated ME1 upregulation was significantly associated with poor DSS (p = 0.039) and DFS (p = 0.038) in patients with non-triple-negative breast cancer (TNBC). However, ME1 expression did not affect the DSS of patients with TNBC. Biological function analysis revealed ME1 knockdown could significantly suppress the growth of breast cancer cells and influence its migration ability. Furthermore, the infiltration of immune cells was significantly reduced when they were co-cultured with breast cancer cells with ME1 knockdown. In summary, ME1 plays an oncogenic role in the growth of breast cancer; it may serve as a potential biomarker of progression and constitute a therapeutic target in patients with breast cancer.

circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC).

BACKGROUND: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC. METHODS: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis. RESULTS: The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance. CONCLUSIONS: Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

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.

PD-L1-positive circulating endothelial progenitor cells associated with immune response to PD-1 blockade in patients with head and neck squamous cell carcinoma.

A number of the inhibitors against programmed death protein 1 (PD-1) have been approved to treat recurrent or metastatic squamous cell carcinoma of head and neck (HNSCC). The interaction between PD-1 and its ligand (PD-L1) serves as an immune checkpoint that governs cytotoxic immune effectors against tumors. Numerous clinical trials of PD-1/PD-L1 inhibitors have so far been discordant about having sufficient PD-L1 expression in the tumor as a prerequisite for a successful anti-PD-1 treatment. On the other hand, vascular endothelial cells modulate immune activities through PD-L1 expression, and thus it is possible that the expressions of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CPCs) could affect antitumor immunity as well as neoangiogenesis. Here we investigated the potential involvement of PD-L1+ CECs and PD-L1+ CPCs in PD-1 blockade treatments for HNSCC patients. We measured CD8+ T cells, CECs, and CPCs in the peripheral blood of the HNSCC patients treated by anti-PD-1 therapies. We found that their PD-L1+ CPC expression before anti-PD1 therapies was strongly correlated with treatment responses and overall survival. Moreover, if the first infusion of PD-1 inhibitors reduced ≥ 50% PD-L1+ CPCs, a significantly better outcome could be predicted. In these patients as well as in an animal model of oral cancer, Pd-l1+ CPC expression was associated with limited CD8+ T-cell infiltration into the tumors, and anti-PD-1 treatments also targeted Pd-l1+ CPCs and increased CD8+ T-cell infiltration. Our results highlight PD-L1+ CPC as a potential regulator in the anti-PD-1 treatments for HNSCC.

ZmPHR1 contributes to drought resistance by modulating phosphate homeostasis in maize.

As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought.

Single-cell transcriptomics dissects the transcriptome alterations of hematopoietic stem cells in myelodysplastic neoplasms.

BACKGROUND: Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. METHODS: In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients. RESULTS: Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro. CONCLUSION: This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.

Analysis of mutation profiles in extranodal NK/T-cell lymphoma: clinical and prognostic correlations.

The molecular pathogenesis of extranodal NK/T-cell lymphoma (NKTCL) remains obscured despite the next-generation sequencing (NGS) studies explored on ever larger cohorts in the last decade. We addressed the highly variable mutation frequencies reported among previous studies with comprehensive amplicon coverage and enhanced sequencing depth to achieve higher genomic resolution for novel genetic discovery and comparative mutational profiling of the oncogenesis of NKTCL. Targeted exome sequencing was conducted to interrogate 415 cancer-related genes in a cohort of 36 patients with NKTCL, and a total of 548 single nucleotide variants (SNVs) and 600 Copy number variances (CNVs) were identified. Recurrent amplification of the MCL1 (67%) and PIM1 (56%) genes was detected in a dominant majority of patients in our cohort. Functional mapping of genetic aberrations revealed that an enrichment of mutations in the JAK-STAT signaling pathway, including the cytokine receptor LIFR (copy number loss) upstream of JAK3, STAT3 (activating SNVs), and downstream effectors of MYC, PIM1 and MCL1 (copy number gains). RNA in situ hybridization showed the significant consistence of MCL1 RNA level and copy number of MCL1 gene. We further correlated molecular and clinical parameters with overall survival (OS) of these patients. When correlations were analyzed by univariate followed by multivariate modelling, only copy number loss of LIFR gene and stage (III-IV) were independent prognostic factors of reduced OS. Our findings identified that novel loss of LIFR gene significantly correlated with the adverse clinical outcome of NKTCL patients and provided therapeutic opportunities for this disease through manipulating LIFR.

Abortive reaction leads to selective adsorbate rotation.

Electron-induced dissociation of a fluorocarbon adsorbate CF3 (ad) at 4.6 K is shown by Scanning Tunnelling Microscopy (STM) to form directed energetic F-atom 'projectiles' on Cu(110). The outcome of a collision between these directed projectiles and stationary co-adsorbed allyl 'target' molecules was found through STM to give rotational excitation of the target allyl, clockwise or anti-clockwise, depending on the chosen collision geometry. Molecular dynamics computation linked the collisional excitation of the allyl target to an 'abortive chemical reaction', in which the approach of the F-projectile stretched an H-C bond lifting the allyl above the surface, facilitating isomerization from 'Across' to 'Along' a Cu row.

Predicting the therapeutic response to valproic acid in childhood absence epilepsy through electroencephalogram analysis using machine learning.

Childhood absence epilepsy (CAE) is a common type of idiopathic generalized epilepsy, manifesting as daily multiple absence seizures. Although seizures in most patients can be adequately controlled with first-line antiseizure medication (ASM), approximately 25 % of patients respond poorly to first-line ASM. In addition, an accurate method for predicting first-line medication responsiveness is lacking. We used the quantitative electroencephalogram (QEEG) features of patients with CAE along with machine learning to predict the therapeutic effects of valproic acid in this population. We enrolled 25 patients with CAE from multiple medical centers. Twelve patients who required additional medication for seizure control or who were shifted to another ASM and 13 patients who achieved seizure freedom with valproic acid within 6 months served as the nonresponder and responder groups. Using machine learning, we analyzed the interictal background EEG data without epileptiform discharge before ASM. The following features were analyzed: EEG frequency bands, Hjorth parameters, detrended fluctuation analysis, Higuchi fractal dimension, Lempel-Ziv complexity (LZC), Petrosian fractal dimension, and sample entropy (SE). We applied leave-one-out cross-validation with support vector machine, K-nearest neighbor (KNN), random forest, decision tree, Ada boost, and extreme gradient boosting, and we tested the performance of these models. The responders had significantly higher alpha band power and lower delta band power than the nonresponders. The Hjorth mobility, LZC, and SE values in the temporal, parietal, and occipital lobes were higher in the responders than in the nonresponders. Hjorth complexity was higher in the nonresponders than in the responders in almost all the brain regions, except for the leads FP1 and FP2. Using KNN classification with theta band power in the temporal lobe yielded optimal performance, with sensitivity of 92.31 %, specificity of 76.92 %, accuracy of 84.62 %, and area under the curve of 88.46 %.We used various EEG features along with machine learning to accurately predict whether patients with CAE would respond to valproic acid. Our method could provide valuable assistance for pediatric neurologists in selecting suitable ASM.

Concealed firearm carrying laws and defensive firearm use in public locations of US metropolitan areas, 1986-2004.

OBJECTIVES: There has been extensive debate in the USA as to how laws regulating the carrying of concealed firearms affect crime and public safety. This study examines whether US state laws making it easier for civilians to obtain permits to carry concealed handguns in public increase defensive gun uses against violent threats and attacks in public. METHODS: We used National Crime Victimization Survey data from 39 metropolitan statistical areas (MSAs) in the USA over a 19-year period (1986-2004) to examine whether laws making it easier for civilians to obtain concealed carry permits are linked to higher levels of defensive gun use against violence in public spaces of metropolitan areas. Bivariate χ2 tests and multivariate logistic regression models (controlling for actor and situational characteristics) were used with 7196 public incidents to examine whether the likelihood of the victim using a gun against an attacker(s) varied based on the type of concealed carry law in the MSA at the time of the incident. RESULTS: The prevalence of self-defensive gun use in this sample was not clearly related to the passage of permissive gun carrying laws. Although defensive gun use was more common in MSAs with permissive gun carrying laws, this difference was not consistently related in magnitude or statistical significance to the passage of those laws or the length of time they had been in effect. CONCLUSIONS: Permissive concealed carry permit laws do not produce evident increases in self-defensive gun uses against crime in public locations.

A novel CPR-assist device vs. established chest compression techniques in infant CPR: A manikin study.

INTRODUCTION: Guidelines for infant CPR recommend the two-thumb encircling hands technique (TTT) and the two-finger technique (TFT) for chest compression. Some devices have been designed to assist with infant CPR, but are often not readily available. Syringe plungers may serve as an alternative infant CPR assist device given their availability in most hospitals. In this study, we aimed to determine whether CPR using a syringe plunger could improve CPR quality measurements on the Resusci-Baby manikin compared with traditional methods of infant CPR. METHODS: Compression area with a diameter of 1 to 2 cm is recommended in previous infant CPR device researches. In this is a randomized crossover manikin study, we examined the efficacy of the Syringe Plunger Technique (SPT) which uses the plunger of the 20 ml syringe with a 2 cm diameter flat piston, commonly available in hospital, for infant External Chest Compressions (ECC). Participants performed TTT, TFT and SPT ECC on Resusci® Baby QCPR® according to 2020 BLS guidelines. RESULTS: Sixty healthcare providers participated in this project. The median (IQR) ECC depths in the TTT, TFT and SPT in the first minute were 41 mm (40-42), 40 mm (38-41) and 40 mm (39-41), respectively, with p < 0.001. The median (IQR) ECC recoil in the TTT, TFT and SPT groups in the first minute was 15% (1-93), 64% (18-96) and 53% (8-95), respectively, with p = 0.003. The result in the second minute had similar findings. The SPT had the best QCPR score and less fatigue. CONCLUSION: The performance of chest compression depth and re-rebound ratio was statistically different among the three groups. TTT has good ECC depth and depth accuracy but poor recoil. TFT is the complete opposite. SPT can achieve a depth close to TTT and has a good recoil performance as TFT. Regarding comprehensive performance, SPT obtains the highest QCPR score, and SPT is also less fatigued. SPT may be an effective alternative technique for infant CPR.

Prevalence and disease burden of chronic cough in nine cities of China: an observational study.

BACKGROUND: Chronic cough (CC) is common in the general population of China, creating a difficult-to-ignore public health burden. However, there is a lack of research on the nationwide prevalence and disease burden of CC in the Chinese population. We aim to use an insurance claims database to assess the prevalence and the corresponding economic burden owing to CC in China. METHODS: This was a retrospective observational study based on an administrative medical insurance database in 2015, 2016 and 2017, from nine cities in North, South, East, South-West, and North-West regions of China. The study population was Chinese adults (≥ 18 years old) who had been identified as CC patients. Descriptive data analyses were used in statistical analysis. RESULTS: A total of 44,472, 55,565, and 56,439 patients with mean ages of 53.2 (16.3) years were identified as patients with CC in 2015, 2016, and 2017, respectively. Of these, 55.24% were women. In addition, 8.90%, 9.46%, and 8.37% of all patients in 2015, 2016, and 2017, who had applied for medical insurance, had CC, respectively, with a three-year average probability of 8.88%. The median number of outpatient visits within a calendar year was 27 per year due to any reason during the period of 2015-2017. The median medical cost of each patient per year increased from 935.30 USD to 1191.47 USD from 2015 to 2017. CONCLUSION: CC is common among medical insurance users, with a substantial utilization of medical resources, highlighting the huge burden of CC in China.

A mediation approach in resting-state connectivity between the medial prefrontal cortex and anterior cingulate in mild cognitive impairment.

Mild cognitive impairment (MCI) is recognized as the prodromal phase of dementia, a condition that can be either maintained or reversed through timely medical interventions to prevent cognitive decline. Considerable studies using functional magnetic resonance imaging (fMRI) have indicated that altered activity in the medial prefrontal cortex (mPFC) serves as an indicator of various cognitive stages of aging. However, the impacts of intrinsic functional connectivity in the mPFC as a mediator on cognitive performance in individuals with and without MCI have not been fully understood. In this study, we recruited 42 MCI patients and 57 healthy controls, assessing their cognitive abilities and functional brain connectivity patterns through neuropsychological evaluations and resting-state fMRI, respectively. The MCI patients exhibited poorer performance on multiple neuropsychological tests compared to the healthy controls. At the neural level, functional connectivity between the mPFC and the anterior cingulate cortex (ACC) was significantly weaker in the MCI group and correlated with multiple neuropsychological test scores. The result of the mediation analysis further demonstrated that functional connectivity between the mPFC and ACC notably mediated the relationship between the MCI and semantic fluency performance. These findings suggest that altered mPFC-ACC connectivity may have a plausible causal influence on cognitive decline and provide implications for early identifications of neurodegenerative diseases and precise monitoring of disease progression.

Dual-task performance and brain morphologic characteristics in Parkinson's disease.

Introduction Parkinson's disease (PD) reduces an individual's capacity for automaticity which limits their ability to perform two tasks simultaneously, negatively impacting daily function. Understanding the neural correlates of dual-tasks (DT) may pave the way for targeted therapies. To better understand automaticity in PD, we aimed to explore whether individuals with differing DT performances possessed differences in brain morphologic characteristics. Methods Data were obtained from 34 individuals with PD and 47 healthy older adults including: 1) demographics (age, sex), 2) disease severity (Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hoehn & Yahr, levodopa equivalent daily dose (LEDD)), 3) cognition (Montreal Cognitive Assessment), 4) Levodopa Equivalent Daily Dose, 5) single task- and DT- performance during a DT-Timed-Up-and-Go test utilizing a serial-subtraction task, and 6) Cortical thicknesses and subcortical volumes obtained from volumetric MRI. Participants were categorized as low or high DT performers if their combined DT-effect was greater than the previously determined mean value for healthy older adults (µ=74.2). Nonparametric testing using Quade's ANCOVA was conducted to compare cortical thicknesses and brain volumes between the highDT and lowDT groups while controlling for covariates: age, sex, MDS-UPDRS part III, LEDD, and intracranial volume. Secondarily, similar comparisons were made between the healthy older adult group the highDT and lowDT groups. Lastly, a hierarchical linear regression model was conducted regressing combined DT-effect on covariates (block one) and cortical thicknesses (block 2) in stepwise fashion. Results The highDT group had thicker cortices than the lowDT group in the right primary somatosensory (p=0.001), bilateral primary motor (p=<0.001, left; p=0.002, right), bilateral supplementary motor area (p=0.001, left; p<0.001, right), and mean of the bilateral hemispheres (p=0.001, left; p<0.001, right). Of note, left primary cortex thickness (p=0.002), left prefrontal cortex thickness (p<0.001), and right supplementary motor area thickness (p=0.003) differed when adding a healthy comparison group. Additionally, the regression analysis found that the left paracentral lobule thickness explained 20.8% of the variability in combined DT-effect (p=0.011) beyond the influence of covariates. Conclusions These results suggest regions underlying dual-task performance; specifically, a convergence of neural control relying sensorimotor integration, motor planning, and motor activation to achieve higher levels of DT performance for individuals with PD.

Clinicopathological characteristics and gene mutations in 11 patients with lipoprotein glomerulopathy.

OBJECTIVE: Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. METHODS: Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. RESULTS: The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. CONCLUSION: LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.

Development of a tool for monitoring the jaw-opening pace and preliminary comparison the pace between young and old ages.

OBJECTIVES: Studies have demonstrated that high-speed jaw-opening exercises are effective in improving swallowing function. However, there has been no objective tool available for monitoring jaw-opening pace. This study aimed to develop an objective tool for monitoring and validating jaw-opening pace and compare it between young and old ages from different age groups. MATERIALS AND METHODS: A load cell plug-in jaw pad connected to an automatic recording and analysis system was used to record jaw-opening motions for offline analysis. We recruited 58 healthy volunteers from different age groups (20-39 y/o; 40-59y/o; 60-79y/o). During a 2-min recording session, each participant was instructed to fully open and close their jaw as quickly as possible while wearing a sensor. Bland-Altman plot, paired t-test and Pearson's correlation test were used to compare the number of jaw-opening motions between manual counting and automatic software analysis. The number of jaw-opening motions during the 2-min recording was compared between the three age groups. RESULTS: Automated analysis of jaw-opening pace was efficient and equally comparable with the traditional manual counting method across the three age groups. A declining trend in jaw-opening pace among the old age group was found but with no statistically significant difference. CONCLUSIONS: A jaw-opening motion monitoring tool with reliable automatic pace analysis software was validated in young and old ages. The jaw-opening pace demonstrated a tendency to decline with age. CLINICAL RELEVANCE: This monitoring tool can also be used to provide visual feedback during jaw-opening motion training in pace control.

Multicenter registry of multisystem inflammatory syndrome in children (MIS-C) and Paired comparison with Kawasaki disease.

OBJECTIVES: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C. METHODS: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset. RESULTS: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors. CONCLUSIONS: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD.

Exploring the Potential Role of Oligodendrocyte-Associated PIP4K2A in Alzheimer's Disease Complicated with Type 2 Diabetes Mellitus via Multi-Omic Analysis.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two common diseases that affect the elderly population worldwide. The identification of common genes associated with AD and T2DM holds promise for potential biomarkers and intriguing pathogenesis of these two complicated diseases. This study utilized a comprehensive approach by integrating transcriptome data from multiple cohorts, encompassing both AD and T2DM. The analysis incorporated various data types, including blood and tissue samples as well as single-cell datasets, allowing for a detailed assessment of gene expression patterns. From the brain region-specific single-cell analysis, PIP4K2A, which encodes phosphatidylinositol-5-phosphate 4-kinase type 2 alpha, was found to be expressed mainly in oligodendrocytes compared to other cell types. Elevated levels of PIP4K2A in AD and T2DM patients' blood were found to be associated with key cellular processes such as vesicle-mediated transport, negative regulation of autophagosome assembly, and cytosolic transport. The identification of PIP4K2A's potential roles in the cellular processes of AD and T2DM offers valuable insights into the development of biomarkers for diagnosis and therapy, especially in the complication of these two diseases.

Genomic Alterations of Tumors in HER2-Low Breast Cancers.

The aim of this study was to elucidate molecular profiling in HER2-low tumors based on a promising dataset. A total of 615 consecutive HER2-negative breast cancer samples were assayed. The genomic mutations in the two groups with different HER2 expression levels (HER2-0 vs. HER2-low) were compared. The mutation types obtained via next-generation targeted sequencing were correlated with the clinicopathological features of the patients with HER2-0 and HER2-low breast cancer. The results showed that there was a significantly higher percentage of receptor-positive (ER/PR) tumors and more low-level Ki-67 tumors, but a lower incidence of stage I/II tumors in the HER2-low group compared to the HER2-0 group. There was a significantly higher frequency of 17.62% (65/369) for PIK3CA_SNA in the HER2-low group than in the HER2-0 group, which had a frequency of only 9.35% (23/246) (p = 0.006). When the called gene alterations in the triple-negative breast cancer (TNBC) group were compared with those in the luminal-like breast cancer group, there was a significantly high frequency of 28.17% (140/497) for ERBB2_SNA in a luminal-like group than in the TNBC group(16.95% (20/118)).We conclude that the early detection of PIK3CA mutations is likely to be important and might help therapeutic decision making in patients with HER2-low tumors.