Search

Abstract Dual cognitive-walking treadmill training (DTT), designed to replicate real-life walking conditions, has shown promise effect in individuals with Parkinson’s disease (PD). This study aims to compare the effects of DTT versus single treadmill training (STT) on cognitive and walking performance under both single and dual task conditions, as well as on fall, patients’ subjective feeling, and quality of life. Sixteen individuals with PD were randomly assigned to DTT or STT group and underwent 8 weeks of training. The DTT group received treadmill training with cognitive loads, while the STT group received treadmill training without cognitive load. Outcome measures included gait parameters (speed, step length) and cognitive performance (reaction time, accuracy, composite score) under both single and dual task conditions. Unified Parkinson’s Disease Rating Scale-part III (UPDRS-III), Falls Efficacy Scale (FES), Patient Global Impression of Change (PGIC), and Parkinson’s Disease Questionnaire (PDQ-39) were also measured. Both DTT and STT groups showed increased comfortable walking speed and step length. Only the DTT group demonstrated significant improvements in cognitive composite score under both single and dual task conditions, as well as UPDRS-III, FES, and PDQ-39(p

Lung cancer patients suffer from numerous symptoms that impact their quality of life. This study aims to identify the symptom burden on quality of life in lung cancer patients. This survey used a structured questionnaire to collect data from 8 March 2021 to 12 May 2021. Patient demographic information was collected. The data on symptom burden and quality of life (QOL) of patients were obtained from the QLQ-C30 and the QLQ-LC13. The stepwise multiple regression analysis was used to estimate lung cancer-related symptom burden in relation to quality of life. The study included 159 patients with lung cancer who completed the questionnaire. The mean age of the patients was 63.12 ± 11.4 years, and 64.8% of them were female. The Global Quality of Life score of the QLQ-C30 was 67.87 ± 22.24, and the top five lung cancer-related symptoms were insomnia, dyspnea, and fatigue from the QLQ-C30, and coughing and dyspnea from the QLQ-LC13. The multiple regression analysis showed that appetite loss was the most frequently associated factor for global QOL (β = −0.32; adjusted R2: 27%) and cognitive function (β = −0.15; adjusted R2: 11%), while fatigue was associated with role function (β = −0.35; adjusted R2: 43%), emotional function (β = −0.26; adjusted R2: 9%), and social function (β = −0.26; adjusted R2: 27%). Dyspnea was associated with physical function (β = −0.45; adjusted R2: 42%). Appetite loss, fatigue, and dyspnea were the main reasons causing symptom burdens on quality of life for lung cancer patients. Decreasing these symptoms can improve the quality of life and survival for patients with lung cancer.

Abstract Objective As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited. Methods Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses. Results The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p

Abstract Glutaraldehyde (GTA) crosslinking is commonly used to improve the thermal stability and mechanical strength of collagen casings. The aim of this research was to determine the optimal pH of the crosslinking between GTA and collagen as well as the crosslinking mechanisms. The weakly alkaline environment could facilitate the generation of GTA polymerization through the rapid generation of -C = C-C = O and -N = C-C = C- conjugated structures, and enhance the crosslinking reaction of GTA polymers with collagen amino groups. In the pH range of 8–10, the fibril diameter and d-space value declined significantly in the self-assembled collagen fibril-GTA system. Meanwhile, collagen casing films crosslinked with GTA in weakly alkaline conditions exhibited higher mechanical strength and thermal stability. These results suggest that the crosslinking of collagen casings and GTA can be improved by adjusting the pH. Possible crosslinking mechanisms related to the formation of conjugated long chains have also been proposed. This study could provide guidance on the appropriate use of GTA in the production process of collagen casings. Graphical Abstract

Abstract Background Sarcopenia, a group of muscle‐related disorders, leads to the gradual decline and weakening of skeletal muscle over time. Recognizing the pivotal role of gastrointestinal conditions in maintaining metabolic homeostasis within skeletal muscle, we hypothesize that the effectiveness of the myogenic programme is influenced by the levels of gastrointestinal hormones in the bloodstream, and this connection is associated with the onset of sarcopenia. Methods We first categorized 145 individuals from the Emergency Room of Taipei Veterans General Hospital into sarcopenia and non‐sarcopenia groups, following the criteria established by the Asian Working Group for Sarcopenia. A thorough examination of specific gastrointestinal hormone levels in plasma was conducted to identify the one most closely associated with sarcopenia. Techniques, including immunofluorescence, western blotting, glucose uptake assays, seahorse real‐time cell metabolic analysis, flow cytometry analysis, kinesin‐1 activity assays and qPCR analysis, were applied to investigate its impacts and mechanisms on myogenic differentiation. Results Individuals in the sarcopenia group exhibited elevated plasma levels of glucagon‐like peptide 1 (GLP‐1) at 1021.5 ± 313.5 pg/mL, in contrast to non‐sarcopenic individuals with levels at 351.1 ± 39.0 pg/mL (P

Radiotherapy (RT) is one of the primary treatment modalities in managing cancer patients. Recently, combined RT and immunotherapy (IT) (i.e., radio-IT [RIT]) have been aggressively investigated in managing cancer patients. However, several issues in conducting RIT are challenging, such as incorporating advanced irradiation techniques, predictive/prognostic biomarkers, and other treatment modalities. Several clinical efforts and novel biomarkers have been introduced and developed to solve these challenges. For example, stereotactic radiosurgery/stereotactic radiotherapy, stereotactic body radiotherapy/stereotactic ablative body radiotherapy, and FLASH-RT have been applied for delivering precise irradiation to lung and liver tumors in conjunction with IT. Besides, several novel IT agents and incorporations of other therapies, such as targeted and thermal therapies, have been further investigated. The present study reviewed the emerging challenges of RIT in modern oncology. We also evaluated clinical practice, bench research, and multimodality treatments. In addition to several clinically applicable biomarkers, we emphasize the roles of advanced irradiation techniques and epigenetic modification as predictive/prognostic biomarkers and potential therapeutic targets. For example, 6(m) A-based epigenetic agents demonstrate the potential to enhance the treatment effects of RIT. However, further prospective randomized trials should be conducted to confirm their roles.

Abstract Background Dengue virus (DENV) causes the most significant mosquito-borne viral disease with a wide spectrum of clinical manifestation, including neurological symptoms associated with lethal dengue diseases. Dopamine receptors are expressed in central nervous system, and dopamine antagonists have been reported to exhibit antiviral activity against DENV infection in vivo and in vitro. Although identification of host-cell receptor is critical to understand dengue neuropathogenesis and neurotropism, the involvement of dopamine receptors in DENV infection remains unclear. Results We exploited the sensitivity and precision of force spectroscopy to address whether dopamine type-2 receptors (D2R) directly interact with DENV particles at the first step of infection. Using optical tweezers, we quantified and characterized DENV binding to D2R expressed on Chinese hamster ovary (CHO) cells. Our finding suggested that the binding was D2R- and DENV-dependent, and that the binding force was in the range of 50–60 pN. We showed that dopamine antagonists prochlorperazine (PCZ) and trifluoperazine (TFP), previously reported to inhibit dengue infection, interrupt the DENV-D2R specific binding. Conclusions This study demonstrates that D2R could specifically recognize DENV particles and function as an attachment factor on cell surfaces for DENV. We propose D2R as a host receptor for DENV and as a potential therapeutic target for anti-DENV drugs. Graphical abstract

Background: Previous research has indicated a negative correlation between exclusive breastfeeding and the incidence of Kawasaki disease (KD). However, the validation of this discovery through meta-analytical studies has been lacking. Furthermore, uncertainties persist regarding whether breastfeeding reduces the risk of coronary artery lesions (CAL) or resistance to intravenous immunoglobulin (IVIG). Methods: A systematic exploration of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ClinicalTrials.gov databases was conducted to identify longitudinal or randomized controlled trials investigating the efficacy of breastfeeding in preventing KD. The primary focus was on the incidence of KD, with secondary emphasis placed on the incidence of CAL and IVIG resistance. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. Results: Of the 179 potentially eligible studies identified, five (n = 1,982,634) were included. The analysis revealed a significantly lower risk of KD (expressed as odds ratio, with 95% confidence intervals and p-values) in comparisons between exclusive breastfeeding and formula feeding (0.62, 0.43−0.91, p = 0.014), exclusive breastfeeding/partial breastfeeding and formula feeding (0.66, 0.46− 0.96, p = 0.03), and exclusive breastfeeding and partial breastfeeding/formula feeding (0.81, 0.74− 0.90, p

In online shopping for consumer electronics, information and physical flows are crucial determinants of consumer purchase intentions. This study examines these factors by integrating the Technology Acceptance Model with logistics service quality, analyzing the relationship between retailers and consumers in e-commerce. The focus is on how information and physical flows, as critical supply chain elements, affect consumers' decisions to purchase online. A structural model and machine learning algorithm with SHapley Additive exPlanations are employed to analyze the data, providing a comprehensive analysis of the Technology Acceptance Model in conjunction with logistics service quality. The findings reveal that attitude, perceived usefulness, and informativeness are the most influential factors affecting consumers' purchase intention. This study contributes to the understanding of consumer behavior in the context of e-commerce platforms for consumer electronic products by integrating the Technology Acceptance Model and logistics service quality theoretical perspectives and analyzing the data using innovative techniques, specifically, Shapley Additive Explanations. This research offers valuable insights into the significant role of various features in shaping consumers' purchase intention in the context of online e-commerce platforms for consumer electrical products.

Objectives: Campylobacter is a significant zoonotic pathogen primarily transmitted through poultry. Our study aimed to assess antimicrobial resistance and genetic relationships among Campylobacter isolates from retail chicken meat and humans in Taiwan. Methods: Campylobacter isolates were analysed using whole-genome sequencing to investigate their antimicrobial resistance, genetic determinants of resistance, and genotypes. Results: Campylobacter coli and Campylobacter jejuni accounted for 44.9% and 55.1% of chicken meat isolates, and 11.4% and 88.6% of human isolates, respectively. C. coli displayed significantly higher resistance levels. Furthermore, isolates from chicken meat exhibited higher levels of resistance to most tested antimicrobials compared to isolates from humans. Multidrug resistance was observed in 96.3% of C. coli and 43.3% of C. jejuni isolates from chicken meat and 80.6% of C. coli and 15.8% of C. jejuni isolates from humans. Macrolide resistance was observed in 85.5% of C. coli isolates, primarily attributed to the erm(B) rather than the A2075G mutation in 23S rRNA. Among the 511 genomes, we identified 133 conventional MLST sequence types, indicating significant diversity among Campylobacter strains. Notably, hierarchical Core-genome multilocus sequence typing clustering, including HC0, HC5, and HC10, revealed a significant proportion of closely related isolates from chicken meat and humans. Conclusions: Our research highlights significant associations in antimicrobial resistance and genetic relatedness between Campylobacter isolates from chicken meat and humans in Taiwan. The genetic analysis data suggest that campylobacteriosis outbreaks may occur more frequently in Taiwan than previously assumed. Our study emphasizes the need for strategies to control multidrug-resistant strains and enhance outbreak prevention.

Computer-simulated experiments have been gaining popularity over hands-on experiments in science education, given the availability of technology and the trend of distance learning. Past studies have focused primarily on comparing the learning outcomes and user experiences of the two experiment modes. In this study, we used an eye tracker to investigate the learning processes involved in manipulating hands-on and computer-simulated experiments, and the effect of prior knowledge and experiment mode on eye movements. A total of 105 undergraduates completed either mode of experiment to learn about pulley mechanics. Participants were asked to read relevant concepts before conducting the experiments to ensure they had basic knowledge about the subject matter. Results showed that the learning outcome of experimentation was affected by prior knowledge but not experiment mode. As for eye movements, the two experiment workstations were divided into nine functional regions. The findings revealed that eye movements in most regions were affected by the experiment mode, but not prior knowledge. The simulation group had shorter total fixation durations and smaller pupil sizes than the hands-on group, implying a lower cognitive load in learning in computer-simulated experiments. Lag sequential analysis and entropy analysis were conducted on cross-regional fixation transitions. The results revealed that participants in hands-on experiments tended to make more diversified fixation transitions across regions, whereas those in simulated experiments showed a higher level of concentration in the spatial pattern of fixation transitions. While sequential analysis offers insights into important fixation transitions on a regional level, entropy analysis allows for a more macro perspective on the overall transition distribution and facilitates conventional statistical modeling that takes individual differences into account.

Abstract NK2 Homeobox 1 (NKX2‐1) is a well‐characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2‐1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2‐1 is observed in high‐grade LUAD. Meanwhile, single‐cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell‐cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2‐1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT‐PCR. ATAC‐seq revealed the restrictive regulation of NKX2‐1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2‐1 modulates the infiltration of tumor‐promoting neutrophils by inhibiting CXCLs/CXCR2‐dependent mechanisms. Hence, targeting CXCR2 in NKX2‐1‐low tumors is a potential antitumor therapy that may improve LUAD patient outcomes.

BACKGROUND: End-stage renal disease (ESRD) and renal transplant (RT) patients are known to have more perioperative and postoperative complications after arthroplasty surgeries when compared to patients without. We hypothesize that RT patients undergoing shoulder arthroplasty (SA) have fewer systemic and surgical complications when compared to ESRD patients undergoing SA. METHODS: This was a retrospective review from the PearlDiver Patient Record Database. International Classification of Diseases and Current Procedural Terminology codes were used to identify patients who had undergone primary total and reverse shoulder arthroplasty, respectively, and subsequent surgical revisions. Unadjusted univariate analysis of patient demographics, Charlson Cormorbidty Index, and surgical complications at 90 days, 1 year, and 2 years after was performed using chi-squared testing. Multivariate logistic regression analyses were subsequently performed for systemic complications and prosthesis outcomes at all time points. RESULTS: Of 1191 patients with ESRD or previous RT and who underwent either total shoulder arthroplasty or reverse total shoulder arthroplasty, 1042 (87.5%) had ESRD and 149 (12.5%) had a previous RT. ESRD SA patients were more likely to have hypertension, liver disease, coronary artery disease, and hypothyroidism. Interestingly no statistical significance was found in multivariate analysis for systemic complications at 90 days, nor for surgical complications at the 90-day, 1-year, or 2-year mark between ESRD and RT cohorts. CONCLUSION: SAs have comparable outcomes in ESRD and RT patients. The differing conclusions among studies might be partially accounted for by the demographic differences and comorbidities between these 2 patient populations. Providers should continue to provide appropriate counseling concerning risks, benefits, and timing of SA for these patients.

Purpose of reviewLipoprotein(a) is an independent risk factor for cardiovascular disease. We review the ongoing shifts in consensus guidelines for the testing and management of Lp(a) and provide insight into whether current evidence suggests that awareness and testing of Lp(a) is clinically actionable.Recent findingsGWAS and Mendelian randomization studies have established causal links between elevated Lp(a) and forms of CVD, including CAD and calcific aortic valve disease. Testing of Lp(a) identifies patients with similar risk to that of heterozygous FH, enhances risk stratification in patients with borderline/intermediate risk as determined through traditional factors, and facilitates the assessment of inherited CVD risk through cascade screening in patients with known family history of elevated Lp(a). Reductions in Lp(a) through non-targeted therapies including PCSK9 inhibition and lipoprotein apheresis have demonstrated reductions in ASCVD risk that are likely attributable to lowering Lp(a). Targeted therapies to potently lower Lp(a) are in clinical development. Lp(a) is actionable, and can be used to identify high risk patients for primary prevention and their family members through cascade screening, and to guide intensification of therapy in primary and secondary prevention of ASCVD.

Intracellular delivery technologies that are cost-effective, non-cytotoxic, efficient, and cargo-agnostic are needed to enable the manufacturing of cell-based therapies as well as gene manipulation for research applications. Current technologies capable of delivering large cargoes, such as plasmids and CRISPR-Cas9 ribonucleoproteins (RNPs), are plagued with high costs and/or cytotoxicity and often require substantial specialized equipment and reagents, which may not be available in resource-limited settings. Here, we report an intracellular delivery technology that can be assembled from materials available in most research laboratories, thus democratizing access to intracellular delivery for researchers and clinicians in low-resource areas of the world. These filtroporation devices permeabilize cells by pulling them through the pores of a cell culture insert by the application of vacuum available in biosafety cabinets. In a format that costs less than $10 in materials per experiment, we demonstrate the delivery of fluorescently labeled dextran, expression plasmids, and RNPs for gene knockout to Jurkat cells and human CD34+ hematopoietic stem and progenitor cell populations with delivery efficiencies of up to 40% for RNP knockout and viabilities of >80%. We show that functionalizing the surfaces of the filters with fluorinated silane moieties further enhances the delivery efficiency. These devices are capable of processing 500,000 to 4 million cells per experiment, and when combined with a 3D-printed vacuum application chamber, this throughput can be straightforwardly increased 6-12-fold in parallel experiments.

Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disease characterized by painful, recurrent, inflamed lesions most commonly occurring in the axillary, inguinal, and anogenital regions. HS can inflict immense physical and psychological impact on patients who suffer from this distressing disease. Management of HS generally requires combining various medical and procedural treatment modalities; however, the disease is often recalcitrant to conventional treatments. In light of recent evidence supporting the effectiveness of biologic agents in the treatment of HS, the Taiwanese Dermatological Association established an expert panel of nine dermatologists to develop consensus statements aimed to provide up-to-date evidence-based guidance in optimizing HS patient management in Taiwan. The recommendations described in the statements were summarized in a management algorithm in terms of general care, topical treatment, systemic treatment, and procedural treatment.

AbstractActinobacillus pleuropneumoniae infection causes a high mortality rate in porcine animals. Antimicrobial resistance poses global threats to public health. The current study aimed to determine the antimicrobial susceptibilities and probe the resistome of A. pleuropneumoniae in Taiwan. Herein, 133 isolates were retrospectively collected; upon initial screening, 38 samples were subjected to next-generation sequencing (NGS). Over the period 2017–2022, the lowest frequencies of resistant isolates were found for ceftiofur, cephalexin, cephalothin, and enrofloxacin, while the highest frequencies of resistant isolates were found for oxytetracycline, streptomycin, doxycycline, ampicillin, amoxicillin, kanamycin, and florfenicol. Furthermore, most isolates (71.4%) showed multiple drug resistance. NGS-based resistome analysis revealed aminoglycoside- and tetracycline-related genes at the highest prevalence, followed by genes related to beta-lactam, sulfamethoxazole, florphenicol, and macrolide. A plasmid replicon (repUS47) and insertion sequences (IS10R and ISVAp11) were identified in resistant isolates. Notably, the multiple resistance roles of the insertion sequence IS10R were widely proposed in human medicine; however, this is the first time IS10R has been reported in veterinary medicine. Concordance analysis revealed a high consistency of phenotypic and genotypic susceptibility to florphenicol, tilmicosin, doxycycline, and oxytetracycline. The current study reports the antimicrobial characterization of A. pleuropneumoniae for the first time in Taiwan using NGS.

Since its invention, photography has been imbued with the promise of providing a sense of fullness and has been believed to possess the unique capacity to capture the entirety of a moment. On the other hand, such assumed potentiality to capture all is yet found subject to the surface, and photography turns out to be a sort of art that lacks depth. This paper intends to focus on the tension between surface and depth in the representation of photographs in literature, a topic that is often neglected in literary studies. Through the theoretical lens of Walter Benjamin’s and Roland Barthes’s discourses on photography, this paper examines Joy Kogawa’s Obasan and Paul Auster’s The Invention of Solitude, both of which expose the discrepancy between what is visible on the surface and what lies beneath, as well as between what is within the frame and what exists beyond it. This paper is divided into two parts. The first part discusses how Benjamin’s and Barthes’s discourses on photography lead to the discussion of the surface and depth issues. The second part deals with the photographs in the two literary works, exploring how theoretical concepts of photography, including Benjamin’s “the optical unconscious” and Barthes’s “punctum,” will help shed light on them. By juxtaposing critical discourses on photography with these literary works, this paper concludes that their representation of photographs grapples with the tension between surface and depth and resonates with Benjamin’s and Barthes’s notions on photography.