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Abstract Background and purpose Radiomics offers little explainability. This study aims to develop a radiomics model (Rad-Score) using diffusion-weighted imaging (DWI) to predict high-risk patients for nodal metastasis or recurrence in endometrial cancer (EC) and corroborate with choline metabolism. Materials and methods From August 2015 to July 2018, 356 EC patients were enrolled. Rad-Score was developed using LASSO regression in a training cohort (n = 287) and validated in an independent test cohort (n = 69). MR spectroscopy (MRS) was also used in 230 patients. Nuclear MRS measured choline metabolites in 70 tissue samples. The performance was compared against European Society for Medical Oncology (ESMO) risk groups. A P

Pancreatic cancer (PC) is a highly lethal malignancy due to the cancer routinely being diagnosed late and having a limited response to chemotherapy. Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic malignant tumor, representing more than 85% of all pancreatic cancers. In the present study, we characterized the phenotypes of concomitant P53 and APC mutations in pancreatic neoplasms driven by the oncogene KRAS in genetically modified mice (GEMM). In this GEMM setting, APC haploinsufficiency coupled with P53 deletion and KRASG12D activation resulted in an earlier appearance of pancreatic intraepithelial neoplasia (PanIN) lesions and progressed rapidly to highly invasive and metastatic PDAC. Through a microarray analysis of murine PDAC cells derived from our APC-deficient PDAC model, we observed that APC loss leads to upregulated CD34 expression in PDAC. CD34 is a member of a family of single-pass transmembrane proteins and is selectively expressed in hematopoietic progenitor cells, vascular endothelial cells, interstitial precursor cells, and various interstitial tumor cells. However, the functional roles of CD34 in pancreatic cancer remain unclear. Thus, in this study, we explored the mechanisms regarding how CD34 promotes the deterioration of pancreatic malignancy. Our results demonstrated that the increased expression of CD34 induced by APC inactivation promotes the invasion and migration of PDAC cells, which may relate to PDAC metastasis in vivo. Collectively, our study provides first-line evidence to delineate the association between CD34 and the APC/Wnt pathway in PDAC, and reveals the potential roles of CD34 in PDAC progression.

Abstract PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot–Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSC M70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSC M70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

Objectives: Task-Technology Fit (TTF) is mainly used to determine the users’ performance based on the tasks and technological attributes. This study integrated and evaluated TTF with the Technology Acceptance Model (TAM) and the Unified Theory of Acceptance and Use of Technology 2 (UTAUT2). This paper aims to compile and analyze the literature on task-technology fit (TTF) since 2000. Method: Through the meta-analytic structural equation modeling (MASEM) approach, understand the application of TTF in the last 20 years and explore future research directions. In addition, this paper employs subgroup analysis and sample sub-grouping to better understand the differences between these studies. The samples were divided into two categories: identity groups (employee, individual, and student) and voluntary groups (voluntary and non-voluntary). Findings: The relationship between the variables belonging to the original TTF model (including TASK, TEC, TTF, PI, and UT) was found to be relatively stable. After combining the variables of UTAUT2 (including PEOU, BI, and PE) and IC, all paths were also found to have a medium or high effect. The TTF-BI path was significant in the identity-based subgroup analysis, and the IC-TTF path was significant in the voluntary-based subgroup analysis. Novelty:Given that the traditional TTF literature is too subjective, this paper adopts MASEM as applied in management research. There are few similar studies so far. Therefore, this paper not only analyzes TTF objectively through MASEM but also provides some directions and suggestions for expanding the TTF model and hopes to give a stronger explanation for future research. Doi: 10.28991/ESJ-2024-08-01-06 Full Text: PDF

With COVID-19 spreading around the world, schools have switched classes from in-person to online courses. At the same time, research on the intention to switch learning styles has received attention. Therefore, this study is based on decomposed planned behavior theory, adding perceived COVID-19 risk and infectivity, to explore the factors that influence students’ intention to switch to distance learning during the COVID-19 period. This study distributed online questionnaires to students with distance learning experience during the epidemic, collected 290 valid samples, and then applied the partial least squares method to analyze. The results show that (1) attitude, subjective norm, perceived behavior control, and perceived risk significantly affect switching intention; (2) perceived usefulness and satisfaction are important factors for attitude; (3) peer influence is the most important factor for subjective norm; (4) digital competence and facilitating conditions significantly affect perceived behavior control; (5) perceived risk is the most critical factor affecting switching intention. Finally, this study provides management implications, strategic recommendations, and future research directions for educators and educational institutions in the process of transitioning students from classes in person to distance learning during the COVID-19 pandemic.

Purpose: This study aimed to investigate differences in cervical lymph node image quality on dual-energy computed tomography (CT) scan with datasets reconstructed using filter back projection (FBP), hybrid iterative reconstruction (IR), and deep learning–based image reconstruction (DLIR) in patients with head and neck cancer. Method: Seventy patients with head and neck cancer underwent follow-up contrast-enhanced dual-energy CT examinations. All datasets were reconstructed using FBP, hybrid IR with 30 % adaptive statistical IR (ASiR-V), and DLIR with three selectable levels (low, medium, and high) at 2.5- and 0.625-mm slice thicknesses. Herein, signal, image noise, signal-to-noise ratio, and contrast-to-noise ratio of lymph nodes and overall image quality, artifact, and noise of selected regions of interest were evaluated by two radiologists. Next, cervical lymph node sharpness was evaluated using full width at half maximum. Results: DLIR exhibited significantly reduced noise, ranging from 3.8 % to 35.9 % with improved signal-to-noise ratio (11.5–105.6 %) and contrast-to-noise ratio (10.5–107.5 %) compared with FBP and ASiR-V, for cervical lymph nodes (p

Environmental aflatoxin B1 (AFB1) exposure has been proposed to contribute to hepatocellular carcinoma by promoting liver fibrosis, but the potential mechanisms remain to be further elucidated. Extracellular vesicles (EVs) were recognized as crucial traffickers for hepatic intercellular communication and play a vital role in the pathological process of liver fibrosis. The AFB1-exposed hepatocyte-derived EVs (AFB1-EVs) were extracted, and the functional effects of AFB1-EVs on the activation of hepatic stellate cells (HSCs) were explored to investigate the molecular mechanism of AFB1 exposure-induced liver fibrogenesis. Our results revealed that an environment-level AFB1 exposure induced liver fibrosis via HSCs activation in mice, while the AFB1-EVs mediated hepatotoxicity and liver fibrogenesis in vitro and in vivo. AFB1 exposure in vitro increased PINK1/Parkin-dependent mitophagy in hepatocytes, where upregulated transcription of the PARK2 gene via p53 nuclear translocation and mitochondrial recruitment of Parkin, and promoted AFB1-EVs-mediated mitochondria-trafficking communication between hepatocytes and HSCs. The knockdown of Parkin in HepaRG cells reversed HSCs activation by blocking the mitophagy-related AFB1-EVs trafficking. This study further revealed that the hepatic fibrogenesis of AFB1 exposure was rescued by genetic intervention with siPARK2 or p53's Pifithrin-α (PFTα) inhibitors. Furthermore, AFB1-EVs-induced HSCs activation was relieved by GW4869 pharmaceutic inhibition of EVs secretion. These results revealed a novel mechanism that AFB1 exposure-induced p53-Parkin signal axis regulated mitophagy-dependent hepatocyte-derived EVs to mediate the mitochondria-trafficking intercellular communication between hepatocytes and HSCs in the local hepatotoxic microenvironment to promote the activated HSCs-associated liver fibrogenesis. Our study provided insight into p53-Parkin-dependent pathway regulation and promised an advanced strategy targeting intervention to EVs-mediated mitochondria trafficking for preventing xenobiotics-induced liver fibrosis.

Background Few previous studies have established Snaith–Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. Aims To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. Method This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. Results The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. Conclusions Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.

The traditional visual prosthesis combines both a camera and an electrode array implanted on the visual neural networks. Here, we introduce a new design of artificial retina which integrate the transmission of image and the electrical stimulation of cortical neurons on a single PMMA micro fiber. It is comprised of multiple PMMA microfibers with both ends connected with one flexible and one rigid substrates. The flexible one is a PDMS mold of microrods and ready to conform to a curved image plane. The rigid one is in the form of a silica plate coated with a PMMA thin film and could be attached to a CMOS image sensor for the evaluation of its optical performance. The multiple PMMA microfibers were directly drawn from liquid PMMA thin film with PDMS rods. With arrayed PMMA microfibers, the image planes could be transferred from the flexible to rigid substrate. Each PMMA microfiber delivers a part of the image the PDMS mold transmits. Incorporated with O/E convertors, each micro fiber could function as an unit of electrical stimulation in accordance with part of the image the artificial retina delivered and is ready to function as a cortical neural prosthesis in the future application.

Abstract Background Dental film mounting is an essential but time-consuming task in dental radiography, with manual methods often prone to errors. This study aims to develop a deep learning (DL) model for accurate automated classification and mounting of both intraoral and extraoral dental radiography. Method The present study employed a total of 22,334 intraoral images and 1,035 extraoral images to train the model. The performance of the model was tested on an independent internal dataset and two external datasets from different institutes. Images were categorized into 32 tooth areas. The VGG-16, ResNet-18, and ResNet-101 architectures were used for pretraining, with the ResNet-101 ultimately being chosen as the final trained model. The model’s performance was evaluated using metrics of accuracy, precision, recall, and F1 score. Additionally, we evaluated the influence of misalignment on the model’s accuracy and time efficiency. Results The ResNet-101 model outperformed VGG-16 and ResNet-18 models, achieving the highest accuracy of 0.976, precision of 0.969, recall of 0.984, and F1-score of 0.977 (p

Abstract Abnormal polyglutamine (polyQ) expansion and fibrillization occur in Huntington’s disease (HD). Amyloid modifier SERF enhances amyloid formation, but the underlying mechanism is not revealed. Here, the fibrillization and toxicity effect of SERF1a on Htt-exon1 are examined. SERF1a enhances the fibrillization of and interacts with mutant thioredoxin (Trx)-fused Httex1. NMR studies with Htt peptides show that TrxHttex1-39Q interacts with the helical regions in SERF1a and SERF1a preferentially interacts with the N-terminal 17 residues of Htt. Time-course analysis shows that SERF1a induces mutant TrxHttex1 to a single conformation enriched of β-sheet. Co-expression of SERF1a and Httex1-polyQ in neuroblastoma and lentiviral infection of SERF1a in HD-induced polypotent stem cell (iPSC)-derived neurons demonstrates the detrimental effect of SERF1a in HD. Higher level of SERF1a transcript or protein is detected in HD iPSC, transgenic mice, and HD plasma. Overall, this study provides molecular mechanism for SERF1a and mutant Httex1 to facilitate therapeutic development for HD.

Abstract Background Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R. Methods The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure (pO2), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function. Results The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO2 level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury. Graphical Abstract

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.

The intestinal epithelial barrier can prevent the invasion of pathogenic microorganisms and food antigens to maintain a consistent intestinal homeostasis. However, an imbalance in this barrier can result in various diseases, such as inflammatory bowel disease, malnutrition, and metabolic disease. Thus, the aim of this study was to select probiotic strains with epithelial barrier-enhancing ability in cell-based model and further investigate them for their improving effects on colitis mouse and weaned piglet models. The results showed that selected specific cell-free fermentation supernatants (CFSs) from Ligilactobacillus salivarius P1, Lactobacillus gasseri P12, and Limosilactobacillus reuteri G7 promoted intestinal epithelial cell growth and proliferation, strengthening the intestinal barrier in an intestinal epithelial cell line Caco-2 model. Further, the administration of CFSs of L. salivarius P1, L. gasseri P12, and L. reuteri G7 were found to ameliorate DSS-induced colitis in mice. Additionally, spray-dried powders of CFS from the three strains were examined in a weaned piglet model, only CFS powder of L. reuteri G7 could ameliorate the feed/gain ratio and serum levels of D-lactate and endotoxin. In conclusion, a new potential probiotic strain, L. reuteri G7, was selected and showed ameliorating effects in both colitis mouse and weaned piglet models.

A novel coagulase-negative Staphylococcus strain (H164T) was isolated from soymilk in Taiwan. Comparative sequence analysis of the 16S rRNA gene revealed that the H164T strain is a member of the genus Staphylococcus. We used multilocus sequence analysis (MLSA) and phylogenomic analyses to demonstrate that the novel strain was closely related to Staphylococcus gallinarum, Staphylococcus nepalensis, Staphylococcus cohnii, and Staphylococcus urealyuticus. The average nucleotide identity and digital DNA-DNA hybridization values between H164T and its closest relatives were T strain could also be distinguished from its closest relatives by the fermentation of d-fructose, d-maltose, d-trehalose, and d-mannitol, as well as by the activities of α-glucosidase and alkaline phosphatase. The major cellular fatty acids were C15:0 iso and C15:0 anteiso, and the predominant menaquinones were MK-7 and MK-8, respectively. The major cellular fatty acids and predominant menaquinones were C15:0 iso and C15:0 anteiso and MK-7 and MK-8, respectively. In conclusion, this strain represents a novel species, named Staphylococcus hsinchuensis sp. nov., with the type strain H164T (=BCRC 81404T = NBRC 116174T).

This article presents a novel bonding method for chip packaging applications in the semiconductor industry, with a focus on downsizing high-density and 3D-stacked interconnections to improve efficiency and performance. Microfluidic electroless interconnections have been identified as a potential solution for bonding pillar joints at low temperatures and pressures. However, the complex and time-consuming nature of their production process hinders their suitability for mass production. To overcome these challenges, we propose a tailored plating solution using an enhanced copper concentration and plating rate. By eliminating the need for fluid motion and reducing the process time, this method can be used for mass production. The Taguchi approach is first used to optimize the copper–quadrol complex solution with the plating rate and decomposition time. This solution exhibits a copper concentration that is over five times higher than that of conventional solutions, a plating rate of 22.2 μm/h, and a decomposition time of 8 min on a Cu layer substrate. This technique enables Cu pillars to be successfully bonded within 7 min at 35 °C. Planarizing the pillar surface yields a high bonding percentage of 99%. Mechanical shear testing shows a significant fracture strength of 76 MPa.

In recent years, investing in cryptocurrencies has become a fad worldwide. However, fewer studies have explored the intention of using cryptocurrencies. Different from traditional financial commodities, cryptocurrencies have a unique appeal. Therefore, this study uses technology mindfulness, technology readiness, and financial literacy, and through perceived trust and perceived risk, to understand users’ intentions to use cryptocurrencies. The respondents to this study were cryptocurrency owners or those having financial investment experience. A total of 337 valid samples were obtained and analyzed by the partial least square-structural equation model (PLS-SEM) method. The results showed that technology mindfulness and negative technology readiness significantly impacted perceived trust and perceived risk. On the other hand, perceived trust and perceived risk significantly impacted the intention to use. Finally, this study proposes theoretical and practical implications which can help cryptocurrency trading platforms understand the motivations of potential and existing users. Finally, this study can also serve as a reference for cryptocurrency trading service providers to develop marketing strategies.

Sonogenetics is an emerging approach that harnesses ultrasound for the manipulation of genetically modified cells. The great penetrability of ultrasound waves enables the non-invasive application of external stimuli to deep tissues, particularly advantageous for brain stimulation. Genetically encoded ultrasound mediators, a set of proteins that respond to ultrasound-induced bio-effects, play a critical role in determining the effectiveness and applications of sonogenetics. In this context, we will provide an overview of these ultrasound-responsive mediators, delve into the molecular mechanisms governing their response to ultrasound stimulation, and summarize their applications in neuromodulation.

Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α'β' mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α'β' MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α'β' MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α'β' MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α'β'-related MB output neurons (MBONs), MBON-α'3 and MBON-β'1, are necessary for the output of integrated hot avoidance information from α'β' MBn. Our results demonstrate the presence of dual insulin modulation pathways in α'β' MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states.

Abstract Background The prevalence of skin diseases among prisoners in Taiwan has rarely been investigated. This study aimed to estimate the prevalence of skin diseases by sex in a sample of prisoners in Taiwan. Methods We included 83,048 participants from the National Health Insurance Program. The outcomes were measured using the clinical version of the International Classification of Diseases, Ninth Revision. For prevalence, we presented absolute values as well as percentages. We also conducted an X 2 test to assess sex differences and age group differences in the percentages of skin and subcutaneous tissue diseases. Results The prevalence of skin diseases was 42.25%, higher than that in the general population. The prevalence of skin diseases among male prisoners was higher than that among female prisoners (p 40. Among all cases diagnosed with skin disease, the top three diseases were contact dermatitis and other types of eczema, cellulitis and abscess, pruritus, and related conditions. Male prisoners had a significantly higher prevalence of all types of skin diseases than female prisoners. Conclusions Skin diseases are common in prisoners in Taiwan. Therefore, early prevention and appropriate treatment are needed. Male-specific skin products are also needed, given the differences in the prevalence of skin diseases among male and female prisoners.

Key points 1. Transfer learning (TL) improves performance of tumor segmentation on diffusion-weighted imaging (DWI) especially in limited case numbers. 2. Training a model by combining sufficient data of different cancers exhibited the highest performance for segmenting mixed cervical and uterine datasets and also improved the pretrained cervical model. 3. The TL model with fine-tuning the early layers of the encoder part outperformed those by fine-tuning the other layers.

Frailty is a common geriatric syndrome. However, there is little information about the relationship between dietary sodium restriction (DSR) and frailty in later life. This study aimed to elucidate the relationship between DSR and frailty in middle-aged and older adults. The 8-year follow-up data from the Taiwan Longitudinal Study on Aging, including 5131 individuals aged ≥50 years, were analyzed using random-effects panel logit models. DSR was evaluated by assessing whether the participants were told by a physician to reduce or avoid sodium intake from food. Three indices were used to measure frailty: the Study of Osteoporotic Fractures (SOF) index, the Fried index, and the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) index. Individuals with DSR were more likely to report frailty compared with those with non-DSR (SOF: adjusted odds ratio [AOR] = 1.82, 95% confidence interval [CI] = 1.46–2.27; Fried: AOR = 2.55, 95% CI = 1.64–3.98; FRAIL: AOR = 2.66, 95% CI = 1.89–3.74). DSR was associated with a higher likelihood of SBF (AOR = 2.61, 95% CI = 1.61–4.22). We identified a temporal trajectory in our study, noting significant participant reactions to both short- and mid-term DSR. Future research should address the balance between frailty risk and cardiovascular risk related to DSR.

Purpose: This narrative review aims to explore the current status of facial scanning technology in the dental field; outlining the history, mechanisms, and current evidence regarding its use and limitations within digital dentistry. Methods: Subtopics within facial scanner technology in dentistry were identified and divided among four reviewers. Electronic searches of the Medline (PubMed) database were performed with the following search terms: facial scanner, dentistry, prosthodontics, virtual patient, sleep apnea, maxillofacial prosthetics, accuracy. For this review only studies or review papers evaluating facial scanning technology for dental or medical applications were included. A total of 44 articles were included. Due to the narrative nature of this review, no formal evidence-based quality assessment was performed and the search was limited to the English language. No further restrictions were applied. Results: The significance, applications, limitations, and future directions of facial scanning technology were reviewed. Specific subtopics include significant history of facial scanner use and development for dentistry, different types and mechanisms used in facial scanning technology, accuracy of scanning technology, use as a diagnostic tool, use in creating a virtual patient, virtual articulation, smile design, diagnosing and treating obstructive sleep apnea, limitations of scanning technology, and future directions with artificial intelligence. Conclusions: Despite limitations in scan quality and software operation, 3D facial scanners are rapid and non-invasive tools that can be utilized in multiple facets of dental care. Facial scanners can serve an invaluable role in the digital workflow by capturing facial records to facilitate interdisciplinary communication, virtual articulation, smile design, and obstructive sleep apnea diagnosis and treatment. Looking into the future, facial scanning technology has promising applications in the fields of craniofacial research, and prosthodontic diagnosis and treatment planning.

Abstract Background Frailty is a common issue in the aging population. Given that frailty syndrome is little discussed in the literature on the aging voice, the current study aims to examine the relationship between frailty and vocal biomarkers in older people. Methods Participants aged ≥ 60 years visiting geriatric outpatient clinics were recruited. They underwent frailty assessment (Cardiovascular Health Study [CHS] index; Study of Osteoporotic Fractures [SOF] index; and Fatigue, Resistance, Ambulation, Illness, and Loss of weight [FRAIL] index) and were asked to pronounce a sustained vowel /a/ for approximately 1 s. Four voice parameters were assessed: average number of zero crossings (A1), variations in local peaks and valleys (A2), variations in first and second formant frequencies (A3), and spectral energy ratio (A4). Results Among 277 older adults, increased A1 was associated with a lower likelihood of frailty as defined by SOF (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.74–0.96). Participants with larger A2 values were more likely to be frail, as defined by FRAIL and CHS (FRAIL: OR 1.41, 95% CI 1.12–1.79; CHS: OR 1.38, 95% CI 1.10–1.75). Sex differences were observed across the three frailty indices. In male participants, an increase in A3 by 10 points increased the odds of frailty by almost 7% (SOF: OR 1.07, 95% CI 1.02–1.12), 6% (FRAIL: OR 1.06, 95% CI 1.02–1.11), or 6% (CHS: OR 1.06, 95% CI 1.01–1.11). In female participants, an increase in A4 by 0.1 conferred a significant 2.8-fold (SOF: OR 2.81, 95% CI 1.71–4.62), 2.3-fold (FRAIL: OR 2.31, 95% CI 1.45–3.68), or 2.8-fold (CHS: OR 2.82, 95% CI 1.76–4.51, CHS) increased odds of frailty. Conclusions Vocal biomarkers, especially spectral-domain voice parameters, might have potential for estimating frailty, as a non-invasive, instantaneous, objective, and cost-effective estimation tool, and demonstrating sex differences for individualised treatment of frailty.

Temperature has a significant effect on all physiological processes of animals. Suitable temperatures promote responsiveness, movement, metabolism, growth, and reproduction in animals, whereas extreme temperatures can cause injury or even death. Thus, thermosensation is important for survival in all animals. However, mechanisms regulating thermosensation remain unexplored, mostly because of the complexity of mammalian neural circuits. The fruit fly Drosophila melanogaster achieves a desirable body temperature through ambient temperature fluctuations, sunlight exposure, and behavioral strategies. The availability of extensive genetic tools and resources for studying Drosophila have enabled scientists to unravel the mechanisms underlying their temperature preference. Over the past 20 years, Drosophila has become an ideal model for studying temperature-related genes and circuits. This review provides a comprehensive overview of our current understanding of thermosensation and temperature preference in Drosophila. It encompasses various aspects, such as the mechanisms by which flies sense temperature, the effects of internal and external factors on temperature preference, and the adaptive strategies employed by flies in extreme-temperature environments. Understanding the regulating mechanisms of thermosensation and temperature preference in Drosophila can provide fundamental insights into the underlying molecular and neural mechanisms that control body temperature and temperature-related behavioral changes in other animals.

Background: We aimed to develop and validate a preoperative CT-based radiomics signature for differentiating lymphoma versus benign splenomegaly. Methods: We retrospectively analyzed CT studies from 139 patients (age range 26–93 years, 43% female) between 2011 and 2019 with histopathological diagnosis of the spleen (19 lymphoma, 120 benign) and divided them into developing (n = 79) and testing (n = 60) datasets. The volumetric radiomic features were extracted from manual segmentation of the whole spleen on venous-phase CT imaging using PyRadiomics package. LASSO regression was applied for feature selection and development of the radiomic signature, which was interrogated with the complete blood cell count and differential count. All p values < 0.05 were considered to be significant. Results: Seven features were selected for constructing the radiomic signature after feature selection, including first-order statistics (10th percentile and Robust Mean Absolute Deviation), shape-based (Surface Area), and texture features (Correlation, MCC, Small Area Low Gray-level Emphasis and Low Gray-level Zone Emphasis). The radiomic signature achieved an excellent diagnostic accuracy of 97%, sensitivity of 89%, and specificity of 98%, distinguishing lymphoma versus benign splenomegaly in the testing dataset. The radiomic signature significantly correlated with the platelet and segmented neutrophil percentage. Conclusions: CT-based radiomics signature can be useful in distinguishing lymphoma versus benign splenomegaly and can reflect the changes in underlying blood profiles.

Abstract Tumor suppressor p53 plays a central role in preventing tumorigenesis. Here, we unravel how p53 modulates mitochondrial dynamics to restrain the metastatic properties of cancer cells. p53 inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling to attenuate the protein level of mitochondrial fission process 1 (MTFP1), which fosters the pro-fission dynamin-related protein 1 (Drp1) phosphorylation. This regulatory mechanism allows p53 to restrict cell migration and invasion governed by Drp1-mediated mitochondrial fission. Downregulating p53 expression or elevating the molecular signature of mitochondrial fission correlates with aggressive tumor phenotypes and poor prognosis in cancer patients. Upon p53 loss, exaggerated mitochondrial fragmentation stimulates the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling resulting in epithelial-to-mesenchymal transition (EMT)-like changes in cell morphology, accompanied by accelerated matrix metalloproteinase 9 (MMP9) expression and invasive cell migration. Notably, blocking the activation of mTORC1/MTFP1/Drp1/ERK1/2 axis completely abolishes the p53 deficiency-driven cellular morphological switch, MMP9 expression, and cancer cell dissemination. Our findings unveil a hitherto unrecognized mitochondria-dependent molecular mechanism underlying the metastatic phenotypes of p53-compromised cancers.

Summary: Sexual conflict over mating is costly to female physiology. Caenorhabditis elegans hermaphrodites generally produce self-progeny, but they can produce cross-progeny upon successfully mating with a male. We have uncovered that C. elegans hermaphrodites experience sexual conflict over mating, resulting in severe costs in terms of their fertility and longevity. We show that reactive oxygen species (ROS) accumulate on the apical surfaces of spermathecal bag cells after successful mating and induce cell damage, leading to ovulation defects and fertility suppression. To counteract these negative impacts, C. elegans hermaphrodites deploy the octopamine (OA) regulatory pathway to enhance glutathione (GSH) biosynthesis and protect spermathecae from mating-induced ROS. We show that the SER-3 receptor and mitogen-activated protein kinase (MAPK) KGB-1 cascade transduce the OA signal to transcription factor SKN-1/Nrf2 in the spermatheca to upregulate GSH biosynthesis.

We assessed the effects of a 12-week shoulder corrective training program for shoulder flexibility and strengthening on pitching loads and sonographic morphology of the elbow joints in youth baseball players. Seventeen subjects were recruited and underwent evaluations before and after the training program. We found that following training, subjects demonstrated significantly increased ranges of shoulder internal rotation (38.9 ± 12.9° vs. 69.2 ± 10.8°, p < 0.001), external rotation (91.2 ± 14.6° vs. 107.3 ± 9.5°, p = 0.004), and horizontal adduction (21.5 ± 8.0° vs. 32.7 ± 7.3°, p = 0.002); improved strength in the shoulder internal rotators (8.7 ± 1.6 kg vs. 9.8 ± 2.1 kg, p = 0.04), external rotators (6.5 ± 1.9 kg vs. 7.5 ± 2.8 kg, p = 0.04), middle trapezius (12.7 ± 2.1 kg vs. 14.3 ± 2.4 kg, p = 0.04), and middle deltoid muscles (10.8 ± 3.3 kg vs. 14.8 ± 3.2 kg, p = 0.001); and decreased thickness of the ulnar collateral ligament (6.1 ± 0.6 mm vs. 4.8 ± 0.7 mm, p = 0.002). Although there was no substantial change in elbow torque and arm speed, significantly increased ball speed (51.2 ± 4.6 mph vs. 54.1 ± 4.5 mph, p < 0.001) and decreased arm slot (63.8 ± 11.9° vs. 53.0 ± 12.7°, p = 0.02) were observed. We suggest that adequate corrective training should be performed regularly to minimize or mitigate adverse soft tissue changes at the elbow in youth baseball players. Balanced shoulder strength and flexibility may decrease medial elbow stress during pitching. Future studies should consider the kinetic and kinematic effects of other corrective training programs on the shoulder or elbow joint during pitching. [ABSTRACT FROM AUTHOR]

Adipocytes store a significant amount of cholesterol and triglycerides. However, whether cholesterol modulates adipocyte function remains largely unknown. We modulated the cholesterol level in adipocytes to examine its effect on the secretion of adiponectin, an important hormone specifically secreted by adipocytes. Treating differentiated 3T3-L1 adipocytes with 4 mM methyl-β-cyclodextrin (MβCD), a molecule with a high affinity for cholesterol, rapidly depleted cholesterol in adipocytes. Interestingly, MβCD treatment increased adiponectin in the medium without affecting its intracellular level, suggesting a modulation of secretion. By contrast, cholesterol addition did not affect adiponectin secretion, suggesting that cholesterol-depletion-induced intracellular cholesterol trafficking, but not reduced cholesterol level, accounted for MβCD-induced adiponectin secretion. MβCD-induced adiponectin secretion was reduced after 10 μg/mL U18666A treatment that suppressed cholesterol transport out of late endosomes/lysosomes. Depleting Niemann–Pick type C1 (NPC1) or NPC2 proteins, which mediate endosomal/lysosomal cholesterol export, consistently reduced MβCD-induced adiponectin secretion. Furthermore, treatment with 1 μM bafilomycin A1, which neutralized acidic endosomes/lysosomes, also attenuated MβCD-induced adiponectin secretion. Finally, MβCD treatment redistributed cellular adiponectin to lower-density fractions in sucrose gradient fractionation. Our results show that MβCD-mediated cholesterol depletion elevates the secretion of adiponectin, highlighting the involvement of endosomes and lysosomes in adiponectin secretion in adipocytes.

Background: The International Society of Urological Pathology (ISUP) grade and positive surgical margins (PSMs) after radical prostatectomy (RP) may reflect the prognosis of prostate cancer (PCa) patients. This study aimed to investigate whether DCE-MRI parameters (i.e., Ktrans, kep, and IAUC) could predict ISUP grade and PSMs after RP. Method: Forty-five PCa patients underwent preoperative DCE-MRI. The clinical characteristics and DCE-MRI parameters of the 45 patients were compared between the low- and high-risk (i.e., ISUP grades III-V) groups and between patients with or without PSMs after RP. Multivariate logistic regression analysis was used to identify the significant predictors of placement in the high-risk group and PSMs. Results: The DCE parameter Ktrans-max was significantly higher in the high-risk group than in the low-risk group (p = 0.028) and was also a significant predictor of placement in the high-risk group (odds ratio [OR] = 1.032, 95% confidence interval [CI] = 1.005–1.060, p = 0.021). Patients with PSMs had significantly higher prostate-specific antigen (PSA) titers, positive biopsy core percentages, Ktrans-max, kep-median, and kep-max than others (all p < 0.05). Of these, positive biopsy core percentage (OR = 1.035, 95% CI = 1.003–1.068, p = 0.032) and kep-max (OR = 1.078, 95% CI = 1.012–1.148, p = 0.020) were significant predictors of PSMs. Conclusion: Preoperative DCE-MRI parameters, specifically Ktrans-max and kep-max, could potentially serve as preoperative imaging biomarkers for postoperative PCa prognosis based on their predictability of PCa risk group and PSM on RP, respectively.

In addition to existing theories, this study proposes a new mechanism of Kuroshio Intrusion passing through the Luzon Strait (LSKI) on the basis of the satellite observed sea surface height anomaly from January 1993 to December 2018. First, 11 events of westward propagating cyclonic Eddy Impingement on the Kuroshio on the Eastern side of Taiwan (EIET) were recognized. Statistical results indicate that approximately 82% of EIET led to consequential LSKI. Systematic analysis indicates a reduction in northward inertial advection, which is responsible for connecting EIET to consequential LSKI. Dynamic diagnosis further unveils the detailed physical exchange processes therein. Squeezing of the planetary vorticity and advection of negative relative vorticity in response to the collision of the EIET with downstream Kuroshio current (KC) contribute to LSKI. Although the beta-term is relatively weak, for the left flank of LSKI, where the influences of advection and flow divergence largely reduce, it plays a dominant role in forcing the KC to intrude farther west into the northern SCS. Aforementioned results identify the possibility of the downstream Kuroshio changes might modify the upstream LSKI critically. More interestingly, this mechanism is a backward feedback sourcing from the Kuroshio downstream region (east of Taiwan) to the upstream region (Luzon Strait).

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.

Adaptive immune receptor repertoire (AIRR) is encoded by T cell receptor (TR) and immunoglobulin (IG) genes. Profiling these germline genes encoding AIRR (abbreviated as gAIRR) is important in understanding adaptive immune responses but is challenging due to the high genetic complexity. Our gAIRR Suite comprises three modules. gAIRR-seq, a probe capture-based targeted sequencing pipeline, profiles gAIRR from individual DNA samples. gAIRR-call and gAIRR-annotate call alleles from gAIRR-seq reads and annotate whole-genome assemblies, respectively. We gAIRR-seqed TRV and TRJ of seven Genome in a Bottle (GIAB) DNA samples with 100% accuracy and discovered novel alleles. We also gAIRR-seqed and gAIRR-called the TR and IG genes of a subject from both the peripheral blood mononuclear cells (PBMC) and oral mucosal cells. The calling results from these two cell types have a high concordance (99% for all known gAIRR alleles). We gAIRR-annotated 36 genomes to unearth 325 novel TRV alleles and 29 novel TRJ alleles. We could further profile the flanking sequences, including the recombination signal sequence (RSS). We validated two structural variants for HG002 and uncovered substantial differences of gAIRR genes in references GRCh37 and GRCh38. gAIRR Suite serves as a resource to sequence, analyze, and validate germline TR and IG genes to study various immune-related phenotypes.

(1) Background: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are common cognitive and behavioral disorders. Antibiotics are widely used in pregnant women and their newborns. The objective of this study was to examine the potential association between prenatal exposure to antibiotics and the risk of ADHD and ASD in childhood from a nationwide perspective. (2) Methods: The Taiwan National Health Insurance Research Database (NHIRD) was used as the primary data source. This nationwide cohort study included only first-time pregnancies. A total of 906,942 infants were enrolled. All infants were followed up for at least 6 years. The Cox regression model was applied for covariate control. (3) Results: Prenatal exposure to antibiotics was found to significantly increase the cumulative incidence of ADHD while having only a borderline effect on the cumulative incidence of ASD. Exposure to antibiotics during any of the three different gestational age ranges significantly increased the cumulative risk. However, only exposure after 34 weeks of gestation had a significant impact on the occurrence of ASD. The study also revealed a dose-dependent effect on the occurrence of ADHD but no effect on the occurrence of ASD. (4) Conclusions: This study suggests that prenatal exposure to antibiotics may increase the risk of developing ADHD and ASD later in life.

Human Cep57 is a coiled-coil scaffold at the pericentriolar matrix (PCM), controlling centriole duplication and centrosome maturation for faithful cell division. Genetic truncation mutations of Cep57 are associated with the mosaic-variegated aneuploidy (MVA) syndrome. During interphase, Cep57 forms a complex with Cep63 and Cep152, serving as regulators for centrosome maturation. However, the molecular interplay of Cep57 with these essential scaffolding proteins remains unclear. Here, we demonstrate that Cep57 undergoes liquid-liquid phase separation (LLPS) driven by three critical domains (NTD, CTD, and polybasic LMN). In vitro Cep57 condensates catalyze microtubule nucleation via the LMN motif-mediated tubulin concentration. In cells, the LMN motif is required for centrosomal microtubule aster formation. Moreover, Cep63 restricts Cep57 assembly, expansion, and microtubule polymerization activity. Overexpression of competitive constructs for multivalent interactions, including an MVA mutation, leads to excessive centrosome duplication. In Cep57-depleted cells, self-assembly mutants failed to rescue centriole disengagement and PCM disorganization. Thus, Cep57's multivalent interactions are pivotal for maintaining the accurate structural and functional integrity of human centrosomes. [ABSTRACT FROM AUTHOR]