Risk of Keratitis and Keratopathy in Hidradenitis Suppurativa Patients: A Global Federated Health Network Analysis.

BACKGROUND/AIM: Hidradenitis suppurativa (HS) is linked to immune dysregulation and systemic inflammation. While previous studies indicate a higher prevalence of ocular manifestations in HS, the specific risk of keratopathy and keratitis remains unclear. The primary aim of this study was to assess the risk of keratitis and keratopathy in individuals with HS. PATIENTS AND METHODS: In this retrospective cohort study conducted with data from the TriNetX database, 53,716 patients with HS were matched to an equivalent number of non-HS controls using propensity score matching. The study covered the period from January 1st, 2005, to December 31st, 2017. Hazard ratios and their respective 95% confidence intervals (CIs), were computed to evaluate the occurrences of keratitis and keratopathy over a 5-year duration in patients with HS, compared to non-HS controls. RESULTS: HS was associated with a 1.52 times higher risk of keratitis over a 5-year period (95%CI=1.24-1.86) and a 1.47 times higher risk of keratopathy (95%CI=1.18-1.84). These risks remained consistent in sensitivity analyses. The elevated risk of keratitis was observed across both sexes. However, the risk of keratopathy was significantly higher in women with HS (HR=1.61, 95%CI=1.24-2.10) and individuals aged 18-64 years (HR=1.32, 95%CI=1.04-1.68). CONCLUSION: HS was linked to an elevated risk of both keratitis and keratopathy over a 5-year period. Ophthalmologic manifestations are recommended to be considered in HS standard care.

Additive Blending Effects on PEDOT:PSS Composite Films for Wearable Organic Electrochemical Transistors.

Organic electrochemical transistors (OECTs) employing conductive polymers (CPs) have gained remarkable prominence and have undergone extensive advancements in wearable and implantable bioelectronic applications in recent years. Among the diverse arrays of CPs, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a common choice for the active-layer channel in p-type OECTs, showing a remarkably high transconductance for the high amplification of signals in biosensing applications. This investigation focuses on the novel engineering of PEDOT:PSS composite materials by seamlessly integrating several additives, namely, dimethyl sulfoxide (DMSO), (3-glycidyloxypropyl)trimethoxysilane (GOPS), and a nonionic fluorosurfactant (NIFS), to fine-tune their electrical conductivity, self-healing capability, and stretchability. To elucidate the intricate influences of the DMSO, GOPS, and NIFS additives on the formation of PEDOT:PSS composite films, theoretical calculations were performed, encompassing the solubility parameters and surface energies of the constituent components of the NIFS, PEDOT, PSS, and PSS-GOPS polymers. Furthermore, we conducted a comprehensive array of material analyses, which reveal the intricacies of the phase separation phenomenon and its interaction with the materials' characteristics. Our research identified the optimal composition for the PEDOT:PSS composite films, characterized by outstanding self-healing and stretchable capabilities. This composition has proven to be highly effective for constructing an active-layer channel in the form of OECT-based biosensors fabricated onto polydimethylsiloxane substrates for detecting dopamine. Overall, these findings represent significant progress in the application of PEDOT:PSS composite films in wearable bioelectronics and pave the way for the development of state-of-the-art biosensing technologies.

The effect of a bone-preserving board game program on the knowledge, attitudes and preventive behaviors of osteoporosis in older adults.

Osteoporosis predisposes to fractures, which affect the quality of life and can be life-threatening. However, the knowledge, attitudes and preventive behaviors of osteoporosis in older adults are insufficient. The aim of this paper was to develop and test the effect of a bone-preserving board game program among older adults. A convenience sample of 85 older adults recruited from two community activity centers in southern Taiwan were assigned to either an experimental group or a control group. The experimental group played a bone-preserving board game for 4 weeks, and the control group participated in routine community center activities. The generalized estimating equation showed significantly larger improvements in knowledge, attitudes, and preventive behaviors in the experimental group than in the control group. Board games designed for older adults can support public health education and help prevent osteoporosis. Our results provide a reference for educators, clinical practitioners and researchers.

Deep-learning model to improve histological grading and predict upstaging of atypical ductal hyperplasia / ductal carcinoma in situ on breast biopsy.

AIMS: Risk stratification of atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), diagnosed using breast biopsy, has great clinical significance. Clinical trials are currently exploring the possibility of active surveillance for low-risk lesions, whereas axillary lymph node staging may be considered during surgical planning for high-risk lesions. We aimed to develop a machine-learning algorithm based on whole-slide images of breast biopsy specimens and clinical information to predict the risk of upstaging to invasive breast cancer after wide excision. METHODS AND RESULTS: Patients diagnosed with ADH/DCIS on breast biopsy were included in this study, comprising 592 (740 slides) and 141 (198 slides) patients in the development and independent testing cohorts, respectively. Histological grading of the lesions was independently evaluated by two pathologists. Clinical information, including biopsy method, lesion size, and Breast Imaging Reporting and Data System (BI-RADS) classification of ultrasound and mammograms, were collected. Deep DCIS consisted of three deep neural networks to evaluate nuclear grade, necrosis, and stromal reactivity. Deep DCIS output comprised five parameters: total patches, lesion extent, Deep Grade, Deep Necrosis, and Deep Stroma. Deep DCIS highly correlated with the pathologists' evaluations of both slide- and patient-level labels. All five parameters of Deep DCIS were significantly associated with upstaging to invasive carcinoma in subsequent wide excisional specimens. Using multivariate logistic regression, Deep DCIS predicted upstaging to invasive carcinoma with an area under the curve (AUC) of 0.81, outperforming pathologists' evaluation (AUC, 0.71 and 0.69). After including clinical and hormone receptor status information, performance further improved (AUC, 0.87). This combined model retained its predictive power in two subgroup analyses: the first subgroup included unequivocal DCIS (excluding cases of ADH and DCIS suspicious for microinvasion) (AUC, 0.83), while the second excluded cases of high-grade DCIS (AUC, 0.81). The model was validated in an independent testing cohort (AUC, 0.81). CONCLUSION: This study demonstrated that deep-learning models can refine histological evaluation of ADH and DCIS on breast biopsies, which may help guide future treatment planning.

Purple Napiergrass (Pennisetum purpureum Schumach) Hot Water Extracts Ameliorate High-Fat Diet-Induced Obesity and Metabolic Disorders in Mice.

Purple Pennisetum (Pennisetum purpureum Schumach), a hybrid between Taihucao No. 2 and the local wild species of purple Pennisetum, has dark red stems and leaves due to its anthocyanin content. This study explores the potential of purple napiergrass extracts (PNE) in alleviating obesity and metabolic disorders induced by a high-fat diet in mice, where 50% of the caloric content is derived from fat. Mice were orally administered low-dose or high-dose PNE alongside a high-fat diet. Experimental findings indicate that PNE attenuated weight gain, reduced liver, and adipose tissue weight, and lowered blood cholesterol, triglyceride, low-density lipoprotein, and blood sugar levels. Stained sections showed that PNE inhibited lipid accumulation and fat hypertrophy in the liver. Immunoblotting analysis suggested that PNE improved the inflammatory response associated with obesity, dyslipidemia, and hyperglycemia induced by a high-fat diet. Furthermore, PNE potentially functions as a PPAR-γ agonist, increasing the adiponectin (ADIPOQ) concentration and suppressing inflammatory factors, while elevating the anti-inflammatory factor interleukin-10 (IL-10) in the liver. PNE-treated mice showed enhanced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways and increased fatty acid oxidation and liver lipolysis. In conclusion, this study elucidated the mechanisms underlying the anti-inflammatory, PI3K/Akt, and AMPK pathways in a high-fat diet-induced obesity model. These findings highlight the potential of PNE in reducing weight, inhibiting inflammation, and improving blood sugar and lipid levels, showing the potential for addressing obesity-related metabolic disorders in humans.

A streamlined molecular-dynamics workflow for computing solubilities of molecular and ionic crystals.

Computing the solubility of crystals in a solvent using atomistic simulations is notoriously challenging due to the complexities and convergence issues associated with free-energy methods, as well as the slow equilibration in direct-coexistence simulations. This paper introduces a molecular-dynamics workflow that simplifies and robustly computes the solubility of molecular or ionic crystals. This method is considerably more straightforward than the state-of-the-art, as we have streamlined and optimised each step of the process. Specifically, we calculate the chemical potential of the crystal using the gas-phase molecule as a reference state, and employ the S0 method to determine the concentration dependence of the chemical potential of the solute. We use this workflow to predict the solubilities of sodium chloride in water, urea polymorphs in water, and paracetamol polymorphs in both water and ethanol. Our findings indicate that the predicted solubility is sensitive to the chosen potential energy surface. Furthermore, we note that the harmonic approximation often fails for both molecular crystals and gas molecules at or above room temperature, and that the assumption of an ideal solution becomes less valid for highly soluble substances.

Lunasin ameliorates glucose utilization in C2C12 myotubes and metabolites profile in diet-induced obese mice benefiting metabolic disorders.

AIMS: Obesity is the main cause of low-grade inflammation and oxidation, resulting in insulin resistance. This study aimed to investigate the effects of a seed peptide lunasin on glucose utilization in C2C12 myotubes and the metabolite profiles in obese mice. MAIN METHODS: C2C12 myotubes were challenged by palmitic acid (PA) to mimic the obese microenvironment and inflammation, cell vitality, and glucose utilization were determined. C57BL6/j mice were divided into low-fat diet (LF), high-fat diet (HF), and HF with intraperitoneally injected lunasin (HFL) groups. Glucose intolerance and metabolite profiles of the tissues were analyzed. KEY FINDINGS: In vitro, C2C12 myotubes treated with lunasin showed decreased proinflammatory cytokines and increased cell vitality under palmitic acid conditions. Lunasin improved glucose uptake and glucose transporter 4 expression by activating insulin receptor substrate-1 and AKT phosphorylation. Next-generation sequencing revealed that lunasin regulates genes expression by promoting insulin secretion and decreasing oxidative stress. In vivo, HF mice showed increased tricarboxylic acid cycle and uric acid metabolites but decreased bile acids metabolites and specific amino acids. Lunasin intervention improved glucose intolerance and modulated metabolites associated with increased insulin sensitivity and decreased metabolic disorders. SIGNIFICANCE: This study is the first to reveal that lunasin is a promising regulator of anti-inflammation, anti-oxidation, and glucose utilization in myotubes and ameliorating glucose uptake and metabolite profiles in obese mice, contributing to glucose homeostasis and benefiting metabolic disorders.

Principles of assembly and regulation of condensates of Polycomb repressive complex 1 through phase separation.

Polycomb repressive complex 1 (PRC1) undergoes phase separation to form Polycomb condensates that are multi-component hubs for silencing Polycomb target genes. In this study, we demonstrate that formation and regulation of PRC1 condensates are consistent with the scaffold-client model, where the Chromobox 2 (CBX2) protein behaves as the scaffold while the other PRC1 proteins are clients. Such clients induce a re-entrant phase transition of CBX2 condensates. The composition of the multi-component PRC1 condensates (1) determines the dynamic properties of the scaffold protein; (2) selectively promotes the formation of CBX4-PRC1 condensates while dissolving condensates of CBX6-, CBX7-, and CBX8-PRC1; and (3) controls the enrichment of CBX4-, CBX7-, and CBX8-PRC1 in CBX2-PRC1 condensates and the exclusion of CBX6-PRC1 from CBX2-PRC1 condensates. Our findings uncover how multi-component PRC1 condensates are assembled via an intricate scaffold-client mechanism whereby the properties of the PRC1 condensates are sensitively regulated by its composition and stoichiometry.

Long noncoding RNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in alveolar hemorrhage associated with systemic lupus erythematosus.

BACKGROUND: Dysregulated long noncoding RNA (lncRNA) expression with increased apoptosis has been demonstrated in systemic lupus erythematosus (SLE) patients with alveolar hemorrhage (AH). SNHG16, a lncRNA, can enhance pulmonary inflammation by sponging microRNAs, and upregulate toll-like receptor 4 (TLR4) expression via stabilizing its mRNAs. TRAF6, a TLR4 downstream signal transducer, can induce autophagy and NETosis formation. In this study, we investigated whether SNHG16 could regulate TLR4-mediated autophagy and NETosis formation in SLE-associated AH. METHODS: Expression of SNHG16, TLR4 and TRAF6 and cell death processes were examined in lung tissues and peripheral blood (PB) leukocytes from AH patients associated with SLE and other autoimmune diseases, and in the lungs and spleen from a pristane-induced C57BL/6 mouse AH model. SNHG16-overexpressed or -silenced alveolar and myelocytic cells were stimulated with lipopolysaccharide (LPS), a TLR4 agonist, for analyzing autophagy and NETosis, respectively. Pristane-injected mice received the intra-pulmonary delivery of lentivirus (LV)-SNHG16 for overexpression and prophylactic/therapeutic infusion of short hairpin RNA (shRNA) targeting SNHG16 to evaluate the effects on AH. Renal SNHG16 expression was also examined in lupus nephritis (LN) patients and a pristane-induced BALB/c mouse LN model. RESULTS: Up-regulated SNHG16, TLR4 and TRAF6 expression with increased autophagy and NETosis was demonstrated in the SLE-AH lungs. In such patients, up-regulated SNHG16, TLR4 and TRAF6 expression was found in PB mononuclear cells with increased autophagy and in PB neutrophils with increased NETosis. There were up-regulated TLR4 expression and increased LPS-induced autophagy and NETosis in SNHG16-overexpressed cells, while down-regulated TLR4 expression and decreased LPS-induced autophagy and NETosis in SNHG16-silenced cells. Pristane-injected lung tissues had up-regulated SNHG16, TLR4/TRAF6 levels and increased in situ autophagy and NETosis formation. Intra-pulmonary LV-SNHG16 delivery enhanced AH through up-regulating TLR4/TRAF6 expression with increased cell death processes, while intra-pulmonary prophylactic and early therapeutic sh-SNHG16 delivery suppressed AH by down-regulating TLR4/TRAF6 expression with reduced such processes. In addition, there was decreased renal SNHG16 expression in LN patients and mice. CONCLUSIONS: Our results demonstrate that lncRNA SNHG16 regulates TLR4-mediated autophagy and NETosis formation in the human and mouse AH lungs, and provide a therapeutic potential of intra-pulmonary delivery of shRNA targeting SNHG16 in this SLE-related lethal manifestation.

Detecting schizophrenia with 3D structural brain MRI using deep learning.

Schizophrenia is a chronic neuropsychiatric disorder that causes distinct structural alterations within the brain. We hypothesize that deep learning applied to a structural neuroimaging dataset could detect disease-related alteration and improve classification and diagnostic accuracy. We tested this hypothesis using a single, widely available, and conventional T1-weighted MRI scan, from which we extracted the 3D whole-brain structure using standard post-processing methods. A deep learning model was then developed, optimized, and evaluated on three open datasets with T1-weighted MRI scans of patients with schizophrenia. Our proposed model outperformed the benchmark model, which was also trained with structural MR images using a 3D CNN architecture. Our model is capable of almost perfectly (area under the ROC curve = 0.987) distinguishing schizophrenia patients from healthy controls on unseen structural MRI scans. Regional analysis localized subcortical regions and ventricles as the most predictive brain regions. Subcortical structures serve a pivotal role in cognitive, affective, and social functions in humans, and structural abnormalities of these regions have been associated with schizophrenia. Our finding corroborates that schizophrenia is associated with widespread alterations in subcortical brain structure and the subcortical structural information provides prominent features in diagnostic classification. Together, these results further demonstrate the potential of deep learning to improve schizophrenia diagnosis and identify its structural neuroimaging signatures from a single, standard T1-weighted brain MRI.

Regulation of Xenobiotic-Metabolizing Enzymes by 5-Demethylnobiletin and Nobiletin to Mitigate Benzo[a]pyrene-Induced DNA Damage In Vitro and In Vivo.

Benzo[a]pyrene (B[a]P) is a genotoxic polycyclic aromatic hydrocarbon that is metabolized by cytochrome P450 family 1 enzymes (CYP 1s) and can bind to DNA to form DNA adducts, leading to DNA damage and increased colorectal cancer risk. Previous studies have shown polymethoxyflavones to have a high potential for anticancer effects by regulating CYP 1s, especially nobiletin (NBT) and 5-demethylnobiletin (5-DMNB). However, the effects of NBT and 5-DMNB on B[a]P metabolism remain unclear. Therefore, this study aimed to clarify the effects of NBT and 5-DMNB on B[a]P-induced DNA damage in vitro and in vivo. In NCM460 cells, 5-DMNB and NBT appeared to reduce the metabolic conversion of B[a]P by regulating the aryl hydrocarbon receptor (AhR)/CYP 1s signaling pathway. This process protected NCM460 cells from B[a]P's cytotoxic effects by decreasing DNA damage and suppressing B[a]P diol-epoxide-DNA adduct formation. In BALB/c mice, 5-DMNB and NBT also protected against B[a]P-induced DNA damage. Altogether, these findings indicate that 5-DMNB and NBT attenuate B[a]P-induced DNA damage by modulating biotransformation, highlighting their chemopreventive potential against B[a]P-induced carcinogenesis. Therefore, 5-DMNB and NBT are promising agents for colorectal cancer chemoprevention in the future.

Comparing the effectiveness of board game-based and drill-based education programs in improving Taiwanese nurses' fire safety knowledge, attitudes, and behavior: A quasi-experimental study.

BACKGROUND: Fire education is currently dominated by drill-based programs, however only a limited number of participants may take part in fire drills. This gap could be addressed by the development of innovative board game-based educational programs. OBJECTIVE: This study sought to compare the effectiveness of board game-based and drill-based fire safety education programs in improving nurses' fire safety knowledge, attitudes, and behavior. METHODS: In this quasi-experimental study, 122 nurses were purposively sampled from a hospital in southern Taiwan. The participants were divided into two groups based on their willingness. Sixty-two nurses in the game-based group took part in an hour-long educational board game for fire safety; and 60 in the drill-based group took part in an hour-long fire drill organized by the hospital. The participants' pre- (T0) and post-intervention (T1) questionnaire scores on fire safety knowledge, attitudes, and behavior were recorded. The statistical methods included descriptive statistics and t-tests. RESULTS: After the interventions, both groups had improved safety knowledge, attitudes, and behavior. However, from T0 to T1, only fire safety knowledge was significantly higher in the game-based group than in the drill-based group, and there were no significant differences in fire safety attitudes and behavior between the two groups. CONCLUSIONS: A board game-based fire education program is similar to a tabletop exercise, and drill-based programs more accurately reflect actual circumstances. Both methods can be applied based on the educational objectives and actual educational settings. The results of this study may function as a reference for designing clinical, educational, and academic interventions for fire safety in healthcare settings.

Aromatic and arginine content drives multiphasic condensation of protein-RNA mixtures.

Multiphasic architectures are found ubiquitously in biomolecular condensates and are thought to have important implications for the organization of multiple chemical reactions within the same compartment. Many of these multiphasic condensates contain RNA in addition to proteins. Here, we investigate the importance of different interactions in multiphasic condensates comprising two different proteins and RNA using computer simulations with a residue-resolution coarse-grained model of proteins and RNA. We find that in multilayered condensates containing RNA in both phases, protein-RNA interactions dominate, with aromatic residues and arginine forming the key stabilizing interactions. The total aromatic and arginine content of the two proteins must be appreciably different for distinct phases to form, and we show that this difference increases as the system is driven toward greater multiphasicity. Using the trends observed in the different interaction energies of this system, we demonstrate that we can also construct multilayered condensates with RNA preferentially concentrated in one phase. The "rules" identified can thus enable the design of synthetic multiphasic condensates to facilitate further study of their organization and function.

Necrosis in lymph nodes and their differential diagnoses: application of reticulin staining.

This study aimed to enhance the histopathological diagnosis of necrotic lymph node specimens. A chart review was conducted, revealing that the most common causes of lymph node necrosis were Kikuchi disease (33%), granulomatous inflammation (25%), metastasis (17%), and lymphomas (12%). Histological analysis of necrotic tissue in 333 specimens demonstrated significant differences between the four diseases. The necrotic tissue of Kikuchi disease was amorphous, and hypercellular, and exhibited karyorrhexis and congestion. Granulomatous inflammation presented amorphous necrotic tissue with a nodular-like pattern. Metastasis exhibited heterogeneous morphology that varied between cancer types. Lymphomas displayed extensive necrosis with ghost cells, congestion, and bubbles. Reticulin staining patterns also differed between diseases. Kikuchi disease and lymphomas exhibited preserved reticular fiber networks in the necrotic tissue, resembling the viable tissue. Granulomatous inflammation and metastasis showed disrupted reticular fiber networks in the necrotic tissue. Based on these findings, histological features and reticulin staining patterns can aid in diagnosing Kikuchi disease, granulomatous inflammation, metastasis, and lymphomas in necrotic lymph node specimens.

Dual-task multicomponent exercise-cognitive intervention improved cognitive function and functional fitness in older adults.

BACKGROUND: Maintaining cognitive and physical function is essential to healthy aging. AIM: This study aims to investigate the effect of an exercise-cognitive dual-task program in Chinese language on cognitive function and functional fitness in older adults. METHODS: Seventy adults aged 60-84 years were conveniently assigned to one of the three groups: exercise-cognitive dual-task (EC) group (n = 28), exercise group (n = 22), and control group (n = 20). The EC group received a 90-min class including multicomponent exercise-cognitive dual-task twice a week. The exercise group received a 90-min class including multicomponent exercise twice a week. The control group maintained their regular level of physical activity and general lifestyle. Cognitive functions and functional fitness were measured before and after the 12-week intervention. RESULTS: The participants in the EC and exercise group significantly improved scores in Taiwanese Frontal Assessment Battery, the Chang Gung University Orthographical Fluency Test, and the Mini-Mental State Examination; however, those in the control group did not. The participants in the EC and exercise group showed significant increases in almost all functional fitness tests. The participants in the EC group showed significantly higher improvements in Chang Gung University Orthographical Fluency Test score and aerobic endurance than the exercise group and in Chang Gung University Orthographical Fluency Test score and lower body strength than the control group. In addition, the changes in Taiwanese Frontal Assessment Battery and Mini-Mental State Examination scores were significantly correlated with the changes in functional fitness. CONCLUSION: The dual-task intervention resulted in greater improvements in verbal fluency, endurance, and muscular strength than exercise alone and control.

Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds.

The investigation of the effects of electrical and mechanical stimulations on chondrogenesis in tissue engineering scaffolds is essential for realizing successful cartilage repair and regeneration. The aim of articular cartilage tissue engineering is to enhance the function of damaged or diseased articular cartilage, which has limited regenerative capacity. Studies have shown that electrical stimulation (ES) promotes mesenchymal stem cell (MSC) chondrogenesis, while mechanical stimulation (MS) enhances the chondrogenic differentiation capacity of MSCs. Therefore, understanding the impact of these stimuli on chondrogenesis is crucial for researchers to develop more effective tissue engineering strategies for cartilage repair and regeneration. This study focuses on the preparation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive polymer (CP) scaffolds using the freeze-drying method. The scaffolds were fabricated with varying concentrations (0, 1, 3, and 10 wt %) of (3-glycidyloxypropyl) trimethoxysilane (GOPS) as a crosslinker and an additive to tailor the scaffold properties. To gain a comprehensive understanding of the material characteristics and the phase aggregation phenomenon of PEDOT:PSS scaffolds, the researchers performed theoretical calculations of solubility parameters and surface energies of PSS, PSS-GOPS, and PEDOT polymers, as well as conducted material analyses. Additionally, the study investigated the potential of promoting chondrogenic differentiation of human adipose stem cells by applying external ES or MS on a PEDOT:PSS CP scaffold. Compared to the group without stimulation, the group that underwent stimulation exhibited significantly up-regulated expression levels of chondrogenic characteristic genes, such as SOX9 and COL2A1. Moreover, the immunofluorescence staining images exhibited a more vigorous fluorescence intensity of SOX9 and COL II proteins that was consistent with the trend of the gene expression results. In the MS experiment, the strain excitation exerted on the scaffold was simulated and transformed into stress. The simulated stress response showed that the peak gradually decreased with time and approached a constant value, with the negative value of stress representing the generation of tensile stress. This stress response quantification could aid researchers in determining specific MS conditions for various materials in tissue engineering, and the applied stress conditions could be further optimized. Overall, these findings are significant contributions to future research on cartilage repair and biophysical ES/MS in tissue engineering.

Investigation of New Psychoactive Substances (NPS), Other Illicit Drugs, and Drug-Related Compounds in a Taiwanese Wastewater Sample Using High-Resolution Mass-Spectrometry-Based Targeted and Suspect Screening.

The proliferation of new psychoactive substances (NPSs) in recent years has posed a significant challenge to public health. Traditional monitoring methods have proven insufficient in tracking these constantly evolving substances, leading to the development of alternative approaches such as wastewater-based epidemiology (WBE). The present study aims to utilize high-resolution mass spectrometry (HRMS)-based targeted and suspect screening to profile NPS, other illicit drugs, and drug-related compounds in a Taiwanese wastewater sample. For the targeted analysis, 8 out 18 standards of illicit drugs have been identified. The suspect screening approach based on approximately 3600 substances in the SWGDRUG library can further identify 92 compounds, including opiate analgesics, synthetic cathinones, phenylalkylamines derivatives, phenethylamine derivatives, tryptamine derivatives, steroids, and ephedrine-related compounds. Additionally, the presence of 5-methoxy-2-aminoindane (MEAI) in the wastewater indicates that drug dealers have recently sold this potential NPS to evade drug regulations. This study firstly reports the HRMS-based comprehensive profile of NPS, other illicit drugs, and drug-related compounds in Taiwan, which could be applied as biomarkers for estimating the consumption of drugs.

Galectin-3 Mediates NETosis and Acts as an Autoantigen in Systemic Lupus Erythematosus-Associated Diffuse Alveolar Haemorrhage.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with enhanced NETosis and impaired degradation of neutrophil extracellular traps (NETs). Galectin-3 is a ß-galactoside binding protein and is associated with neutrophil functions as well as involved in mediating autoimmune disorders. In this study, we plan to examine the associations of galectin-3 with the pathogenesis of SLE and NETosis. Galectin-3 expression levels were determined in peripheral blood mononuclear cells (PBMCs) of SLE patients for the association with lupus nephritis (LN) or correlation of SLE disease activity index 2000 (SLEDAI-2K). NETosis was observed in human normal and SLE and murine galectin-3 knockout (Gal-3 KO) neutrophils. Gal-3 KO and wild-type (WT) mice induced by pristane were used to evaluate disease signs, including diffuse alveolar haemorrhage (DAH), LN, proteinuria, anti-ribonucleoprotein (RNP) antibody, citrullinated histone 3 (CitH3) levels, and NETosis. Galectin-3 levels are higher in PBMCs of SLE patients compared with normal donors and positively correlated with LN or SLEDAI-2K. Gal-3 KO mice have higher percent survival and lower DAH, LN proteinuria, and anti-RNP antibody levels than WT mice induced by pristane. NETosis and citH3 levels are reduced in Gal-3 KO neutrophils. Furthermore, galectin-3 resides in NETs while human neutrophils undergo NETosis. Galectin-3-associated immune complex deposition can be observed in NETs from spontaneously NETotic cells of SLE patients. In this study, we provide clinical relevance of galectin-3 to the lupus phenotypes and the underlying mechanisms of galectin-3-mediated NETosis for developing novel therapeutic strategies targeting galectin-3 for SLE.

Assessing the Resilience of Machine Learning Classification Algorithms on SARS-CoV-2 Genome Sequences Generated with Long-Read Specific Errors.

The emergence of third-generation single-molecule sequencing (TGS) technology has revolutionized the generation of long reads, which are essential for genome assembly and have been widely employed in sequencing the SARS-CoV-2 virus during the COVID-19 pandemic. Although long-read sequencing has been crucial in understanding the evolution and transmission of the virus, the high error rate associated with these reads can lead to inadequate genome assembly and downstream biological interpretation. In this study, we evaluate the accuracy and robustness of machine learning (ML) models using six different embedding techniques on SARS-CoV-2 error-incorporated genome sequences. Our analysis includes two types of error-incorporated genome sequences: those generated using simulation tools to emulate error profiles of long-read sequencing platforms and those generated by introducing random errors. We show that the spaced k-mers embedding method achieves high accuracy in classifying error-free SARS-CoV-2 genome sequences, and the spaced k-mers and weighted k-mers embedding methods are highly accurate in predicting error-incorporated sequences. The fixed-length vectors generated by these methods contribute to the high accuracy achieved. Our study provides valuable insights for researchers to effectively evaluate ML models and gain a better understanding of the approach for accurate identification of critical SARS-CoV-2 genome sequences.