Silibinin attenuates TGF-ß2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways.

Transforming growth factor-ß2 (TGF-ß2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-ß2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-ß2-induced cell migration, and mitigated TGF-ß2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-ß2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-ß2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-ß2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-ß2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-ß2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.

Clarity on the blazing trail: clearing the way for amyloid-removing therapies for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis. Senile plaques composed of the amyloid-ß (Aß) peptide in the brain are the core hallmarks of AD and a promising target for the development of disease-modifying therapies. However, over the past 20 years, the failures of clinical trials directed at Aß clearance have fueled a debate as to whether Aß is the principal pathogenic factor in AD and a valid therapeutic target. The success of the recent phase 3 trials of lecanemab (Clarity AD) and donanemab (Trailblazer Alz2), and lessons from previous Aß clearance trials provide critical evidence to support the role of Aß in AD pathogenesis and suggest that targeting Aß clearance is heading in the right direction for AD treatment. Here, we analyze key questions relating to the efficacy of Aß targeting therapies, and provide perspectives on early intervention, adequate Aß removal, sufficient treatment period, and combinatory therapeutics, which may be required to achieve the best cognitive benefits in future trials in the real world.

Diaphragmatic ultrasonography as a predictor of respiratory muscle fatigue in myasthenia gravis.

INTRODUCTION/AIMS: Easy fatigability, the clinical hallmark of generalized myasthenia gravis (GMG), cannot be detected in a dynamic way. The aim of this study was to assess respiratory function dynamically through diaphragmatic ultrasonography (DUS) in GMG patients. METHODS: GMG patients and controls were recruited in a 1:1 ratio. DUS was performed during one quiet breath and 15 consecutive deep breaths. The diaphragm thicknesses were measured at different positions. Diaphragm thickening fraction (TFdi) and the maximal change in diaphragm thickness (Tmax) during 15 consecutive deep breaths were calculated and transformed to normality, named N-TFdi and N-Tmax, respectively. The percentages of changes in TFdi and Tmax compared with baseline were named ΔTFdi and ΔTmax, respectively. The diagnostic parameter for respiratory muscle fatigue was chosen from ΔTFdi and ΔTmax at different deep breath times according to their ability to distinguish GMG patients from controls and the interrater reliability of TFdi and Tmax. RESULTS: Thirty-four GMG patients and 30 healthy controls were enrolled. N-TFdi and N-Tmax significantly changed as the number of deep breaths increased (p < .001) in GMG patients, but not in controls. ΔTmax of the 15th deep breath (ΔTmax15) was selected as the diagnostic parameter for respiratory muscle fatigue. There were no significant differences in percentage of predicted values of forced vital capacity and arterial partial pressure of carbon dioxide between patients with normal and abnormal ΔTmax15. DISCUSSION: DUS could identify diaphragm fatiguability in GMG patients, which may be more reliable and sensitive in assessment of diaphragm fatigue than conventional methods.

Relative frequencies and clinical features of Guillain-Barré Syndrome before and during the COVID-19 pandemic in North China.

OBJECTIVE: Most studies investigated the relationship between COVID-19 and Guillain-Barré syndrome (GBS) by comparing the incidence of GBS before and during the pandemic of COVID-19. However, the findings were inconsistent, probably owing to varying degrees of the lockdown policy. The quarantine requirements and travel restrictions in China were lifted around December 7, 2022. This study aimed to explore whether the relative frequency of GBS increased during the major outbreak in the absence of COVID-19-mandated social restrictions in China. METHODS: GBS patients admitted to the First Hospital, Shanxi Medical University, from December 7, 2022 to February 20, 2023, and from June, 2017 to August, 2019 were included. The relative frequencies of GBS in hospitalized patients during different periods were compared. The patients with and without SARS-CoV-2 infection within six weeks prior to GBS onset formed the COVID-GBS group and non-COVID-GBS group, respectively. RESULTS: The relative frequency of GBS among hospitalized patients during the major outbreak of COVID-19 (13/14,408) was significantly higher than that before the COVID-19 epidemic (29/160,669, P < 0.001). More COVID-GBS patients (11/13) presented AIDP subtype than non-COVID-GBS cases (10/27, P = 0.003). The mean interval between onset of infective symptoms and GBS was longer in COVID-GBS (21.54 ± 11.56 days) than in non-COVID-GBS (5.76 ± 3.18 days, P < 0.001). CONCLUSIONS: COVID-19 significantly increased the incidence of GBS. Most COVID-GBS patients fell into the category of AIDP, responded well to IVIg, and had a favorable prognosis.

Causal Relationship between Sex Hormones and Risk of Developing Common Neurodegenerative Diseases: A Mendelian Randomization Study.

BACKGROUND: Neurodegenerative diseases are a group of unexplained disorders of the central nervous system, and studies have shown that a large number of genetic and environmental factors are associated with these diseases. Since these diseases show significant gender differences in epidemiology, sex hormones are thought to be strongly associated with these diseases. In this study, we used Mendelian randomization to explore the causal relationship between sex hormones and the risk of developing neurodegenerative diseases. METHODS: We obtained genetic instrumental variables for sex hormones (sex hormone-binding globulin [SHBG], estradiol levels [EL], and bioavailable testosterone [BT]) separately through the Integrative Epidemiology Unit (IEU) database (https://gwas.mrcieu.ac.uk/). We analyzed the causal relationship of each with the risk of developing neurodegenerative diseases (Amyotrophic Lateral Sclerosis [ALS], Parkinson's disease [PD], and Alzheimer's disease [AD]) using inverse variance weighted (IVW) in Mendelian randomization. Data were then analyzed for sensitivity. RESULTS: BT was negatively associated with the risk of developing ALS (odds ratio [OR] = 0.794; 95% confidence interval [95% CI] = 0.672-0.938; p = 0.006). EL and SHBG were not associated with a risk for developing neurodegenerative diseases (ALS, PD, AD). CONCLUSIONS: Elevated BT is associated with a reduced risk of developing ALS. Further research is needed to investigate the underlying mechanisms of action for this correlation and how it can be used as a potential target of action to reduce the risk of developing ALS.

Establishment of a Homologous Silencing System with Intact-Plant Infiltration and Minimized Operation for Studying Gene Function in Herbaceous Peonies.

Gene function verification is a crucial step in studying the molecular mechanisms regulating various plant life activities. However, a stable and efficient homologous genetic transgenic system for herbaceous peonies has not been established. In this study, using virus-induced gene silencing technology (VIGS), a highly efficient homologous transient verification system with distinctive advantages was proposed, which not only achieves true "intact-plant" infiltration but also minimizes the operation. One-year-old roots of the representative species, Paeonia lactiflora Pall., were used as the materials; prechilling (4 °C) treatment for 3-5 weeks was applied as a critical precondition for P. lactiflora to acquire a certain chilling accumulation. A dormancy-related gene named HOMEOBOX PROTEIN 31 (PlHB31), believed to negatively regulate bud endodormancy release (BER), was chosen as the target gene in this study. GFP fluorescence was detected in directly infiltrated and newly developed roots and buds; the transgenic plantlets exhibited remarkably earlier budbreak, and PlHB31 was significantly downregulated in silenced plantlets. This study established a homologous transient silencing system featuring intact-plant infiltration and minimized manipulation for gene function research, and also offers technical support and serves as a theoretical basis for gene function discovery in numerous other geophytes.

Assessing PET/CT's diagnostic accuracy in idiopathic myopathies.

OBJECTIVE: Recent studies have utilized fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) specifically to diagnose cases of idiopathic inflammatory myopathies (IIM), excluding inclusion body myositis (IBM). Conversely, carbon-11 (11C) labeled Pittsburgh compound B (PIB)-PET imaging is exclusively used for the detection of IBM. This research is designed to evaluate the diagnostic accuracy of PET/CT in identifying IIM by employing rigorous diagnostic accuracy testing methodologies. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted across multiple databases including PubMed, and Embase. We focused on the diagnostic utility of PET/CT in IIM, assessing sensitivities, specificities, and deriving likelihood ratios (LR+ and LR-). The study was registered with PROSPERO (CRD42022343222). RESULTS: This systematic review identified 635 citations, of which 10 eligible trials were included, with a total of 419 participants. The results indicated a sensitivity of 0.86 (0.81-0.90), and a specificity of 0.93 (0.88-0.96). The synthesis of LR revealed the LR+ of 10.35 (6.31-16.98), and LR-of 0.15 (0.07-0.32). The summary receiver operating characteristic curve (SROC) showed an area under the curve (AUC) of 0.9658. Regarding IBM, the sensitivity was 0.84 (0.60-0.97), and the specificity was 1 (0.69-1). The synthesis of LR showed the LR+ of 9.61 (1.46-63.15) and an LR- of 0.21 (0.09-0.51). For disease activity, the sensitivity was 0.96 (0.92-0.99), and the specificity was 0.91 (0.084-0.96). The synthesis of LR showed an LR+ of 9.43 (5.39-16.51) and an LR- of 0.05 (0.02-0.11). CONCLUSION: Positron emission tomography/CT has great potential for accurately diagnosing and monitoring patients with IIM, and may have implications for their clinical management.

Identification of essential proteins based on edge features and the fusion of multiple-source biological information.

BACKGROUND: A major current focus in the analysis of protein-protein interaction (PPI) data is how to identify essential proteins. As massive PPI data are available, this warrants the design of efficient computing methods for identifying essential proteins. Previous studies have achieved considerable performance. However, as a consequence of the features of high noise and structural complexity in PPIs, it is still a challenge to further upgrade the performance of the identification methods. METHODS: This paper proposes an identification method, named CTF, which identifies essential proteins based on edge features including h-quasi-cliques and uv-triangle graphs and the fusion of multiple-source information. We first design an edge-weight function, named EWCT, for computing the topological scores of proteins based on quasi-cliques and triangle graphs. Then, we generate an edge-weighted PPI network using EWCT and dynamic PPI data. Finally, we compute the essentiality of proteins by the fusion of topological scores and three scores of biological information. RESULTS: We evaluated the performance of the CTF method by comparison with 16 other methods, such as MON, PeC, TEGS, and LBCC, the experiment results on three datasets of Saccharomyces cerevisiae show that CTF outperforms the state-of-the-art methods. Moreover, our method indicates that the fusion of other biological information is beneficial to improve the accuracy of identification.

Whole-exome and targeted gene sequencing of large-cell lung carcinoma reveals recurrent mutations in the PI3K pathway.

BACKGROUND: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC. METHODS: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway. RESULTS: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007). CONCLUSIONS: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC.

Achieving Ultra-Stable All-Solid-State Sodium Metal Batteries with Anion-Trapping 3D Fiber Network Enhanced Polymer Electrolyte.

All-solid-state sodium metal batteries paired with solid polymer electrolytes (SPEs) are considered a promising candidate for high energy-density, low-cost, and high-safety energy storage systems. However, the low ionic conductivity and inferior interfacial stability with Na metal anode of SPEs severely hinder their practical applications. Herein, an anion-trapping 3D fiber network enhanced polymer electrolyte (ATFPE) is developed by infusing poly(ethylene oxide) matrix into an electrostatic spun fiber framework loading with an orderly arranged metal-organic framework (MOF). The 3D continuous channel provides a fast Na+ transport path leading to high ionic conductivity, and simultaneously the rich coordinated unsaturated cation sites exposed on MOF can effectively trap anions, thus regulating Na+ concentration distribution for constructing stable electrolyte/Na anode interface. Based on such advantages, the ATFPE exhibits high ionic conductivity and considerable Na+ transference number, as well as enhanced interfacial stability. Consequently, Na/Na symmetric cells using this ATFPE possess cyclability over 600 h at 0.1 mA cm-2 without discernable Na dendrites. Cooperated with Na3 V2 (PO4 )3 cathode, the all-solid-state sodium metal batteries (ASSMBs) demonstrate significantly improved rate and cycle performances, delivering a high discharge capacity of 117.5 mAh g-1 under 0.1 C and rendering high capacity retention of 78.2% after 1000 cycles even at 1 C.

Major pathological response exhibited distinct prognostic significance for lung adenocarcinoma post different modalities of neoadjuvant therapy.

AIMS: For non-small-cell lung cancer (NSCLC) patients receiving neoadjuvant therapy, the major pathological response (MPR) is defined as the percentage of residual viable tumour cells (%RVT) in the tumour bed of no more than 10%. It has been proposed as a predictor of survival in neoadjuvant therapy-treated cohorts. Nonetheless, the significance of %RVT in the pathological assessment of lung adenocarcinoma cohorts remains undetermined. METHODS AND RESULTS: Overall, 152 lung adenocarcinoma patients were included in this retrospective study, among whom 67 received neoadjuvant targeted therapy and 85 received neoadjuvant chemotherapy. Clinicopathological characteristics, neoadjuvant treatment response and survival status were investigated. The routinely adopted standard for MPR (%RVT ≤ 10%) failed to differentiate prognosis in the lung adenocarcinoma population. For the neoadjuvant chemotherapy cohort, the optimal %RVT cut-off value of RFS was 60%. However, this cut-off value was clinically insignificant in the neoadjuvant targeted-therapy cohort. Hence, for these patients, we built a nomogram model including high-grade patterns and ypN stage to predict disease recurrence, demonstrating high efficacy (a bootstrap-corrected C-index of 0.731). CONCLUSIONS: %RVT served as a strong indicator of the prognosis of lung adenocarcinoma in patients receiving neoadjuvant chemotherapy but not neoadjuvant targeted therapy. Residual high-grade pathological patterns might substitute MPR in prognostic evaluation of lung adenocarcinoma post-targeted therapy.

Niclosamide inhibits TGF-ß1-induced fibrosis of human Tenon's fibroblasts by regulating the MAPK-ERK1/2 pathway.

Preventing postoperative bleb scar formation is an effective way of improving glaucoma filtration surgery (GFS) outcome. Use of more effective antifibrotic drugs with fewer adverse effects may be a good way to address the problem. In the present study, we use a primary cell model, consisting of Tenon's fibroblasts obtained from patients with glaucoma, which were stimulated with TGF-ß1 to induce the fibrotic phenotype. We explored the effects of niclosamide on TGF-ß1-induced fibrosis in these cells and examined its underlying mechanism of action. A transcriptome sequencing assay was used to explore possible signaling pathways involved. Niclosamide inhibited cell proliferation and migration, and decreased the levels of alpha-smooth muscle actin, type I and type III collagen in human Tenon's fibroblasts induced by TGF-ß1. Niclosamide also induced apoptosis and counteracted TGF-ß1-induced cytoskeletal changes and extracellular matrix accumulation. Moreover, niclosamide decreased TGF-ß1-induced phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) protein expression in human Tenon's fibroblasts. The results indicate that niclosamide inhibits TGF-ß1-induced fibrosis in human Tenon's fibroblasts by blocking the MAPK-ERK1/2 signaling pathway. Thus, niclosamide is a potentially promising antifibrotic drug that could improve glaucoma filtration surgery success rate.

Hyperhomocysteinemia in patients with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.

INTRODUCTION/AIMS: Riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) is an autosomal recessive disease chiefly caused by variants of ETFDH affecting fatty acid metabolism. In our cohort, hyperhomocysteinemia (HHcy) was common. In this study we aimed to identify the association between RR-MADD and HHcy. METHODS: We performed a retrospective review of 13 patients with RR-MADD. Thirty-three healthy controls were recruited, and logistic regression was used to investigate the association between RR-MADD and HHcy. Muscle tissues from six patients and six controls without myopathies were collected to measure the levels of flavin adenine dinucleotide (FAD), an active form of riboflavin. Whole-exome sequencing was performed to identify the disease-associated variants. RESULTS: The RR-MADD patients had a higher prevalence of HHcy (9 of 12) than controls (6 of 33, P < .001). In the multivariate analysis, RR-MADD was positively related to HHcy (P = .014). Muscular FAD levels were decreased in RR-MADD patients (P = .006). Thirteen variants (8 reported and 5 novel) were identified in ETFDH. Of these, c.250G > A was the most common pathogenic variant with an allelic frequency of 4 of 20. DISCUSSION: HHcy was associated with RR-MADD and may aid in the diagnosis of the disease. Our findings expand the mutational spectrum of RR-MADD.

Diagnostic utility of different dysphagia screening tools to detect dysphagia in individuals with amyotrophic lateral sclerosis.

OBJECTIVE: Dysphagia is a common and serious clinical symptom of amyotrophic lateral sclerosis (ALS). The study aimed to evaluate the diagnostic utility of four dysphagia screening tools in ALS, including the ALS Functional Rating Scale-Revised (ALSFRS-R) bulbar subscale, water-swallowing test (WST), Eating Assessment Tool-10 (EAT-10) and Sydney Swallow Questionnaire (SSQ). METHODS: A total of 68 individuals from First Hospital, Shanxi medical university, were recruited in the study. The ALSFRS-R, WST, EAT-10, SSQ and the gold standard video fluoroscopic swallowing study (VFSS) were performed. The Penetration Aspiration Scale (PAS) during VFSS was assessed to identify unsafe swallowing (PAS ≥ 3) and aspiration (PAS ≥ 6). Receiver operator characteristic curve (ROC) analyses were performed to evaluate the accuracy of the 4 tools. Youden index was used to determine the ideal cut-off value for each tool. RESULTS: Of the patients, 20.59% (14/68) presented unsafety swallowing and 16.18% (11/68) had aspiration. The four tools could effectively identify patients with unsafe swallowing and aspiration. The EAT-10 had the maximum AUC (0.873 and 0.963, respectively) among the tools in the diagnosis of unsafe swallowing and aspiration. To detect unsafe swallowing and aspiration, an EAT-10 score of 6 (sensitivity: 78.6%, specificity: 87.0%) and an EAT-10 score of 8 (sensitivity: 90.9%, specificity: 91.2%), were the most appropriate cut-off points, respectively. CONCLUSIONS: The ALSFRS-R bulbar subscale, WST, EAT-10, and SSQ could effectively identify unsafe swallowing and aspiration in patients with ALS. Of the four tools, the EAT-10 was relatively accurate, safe, and convenient. Further studies including more patients should be conducted to verify the conclusions.

A two-stage partial fixing approach for solving the residency block scheduling problem.

We consider constructing feasible annual block schedules for residents in a medical training program. We must satisfy coverage requirements to guarantee an acceptable staffing level for different services in the hospital as well as education requirements to ensure residents receive appropriate training to pursue their individual (sub-)specialty interests. The complex requirement structure makes this resident block scheduling problem a complicated combinatorial optimization problem. Solving a conventional integer program formulation for certain practical instances directly using traditional solution techniques will result in unacceptably slow performance. To address this, we propose a partial fixing approach, which completes the schedule construction iteratively through two sequential stages. The first stage focuses on the resident assignments for a small set of predetermined services through solving a much smaller and easier problem relaxation, while the second stage completes the rest of the schedule construction after fixing those assignments specified by the first stage's solution. We develop cut generation mechanisms to prune off the bad decisions made by the first stage if infeasibility arises in the second stage. We additionally propose a network-based model to assist us with an effective service selection for the first stage to work on the corresponding resident assignments to achieve an efficient and robust performance of the proposed two-stage iterative approach. Experiments using real-world inputs from our clinical collaborator show that our approach can speed up the schedule construction at least 5 times for all instances and even over 100 times for some huge-size instances compared to applying traditional techniques directly.

Abscisic Acid Regulates Carbohydrate Metabolism, Redox Homeostasis and Hormonal Regulation to Enhance Cold Tolerance in Spring Barley.

Abscisic acid (ABA) plays a vital role in the induction of low temperature tolerance in plants. To understand the molecular basis of this phenomenon, we performed a proteomic analysis on an ABA-deficit mutant barley (Az34) and its wild type (cv Steptoe) under control conditions (25/18 °C) and after exposure to 0 °C for 24 h. Most of the differentially abundant proteins were involved in the processes of photosynthesis and metabolisms of starch, sucrose, carbon, and glutathione. The chloroplasts in Az34 leaves were more severely damaged, and the decrease in Fv/Fm was larger in Az34 plants compared with WT under low temperature. Under low temperature, Az34 plants possessed significantly higher activities of ADP-glucose pyrophosphorylase, fructokinase, monodehydroascorbate reductase, and three invertases, but lower UDP-glucose pyrophosphorylase activity than WT. In addition, concentrations of proline and soluble protein were lower, while concentration of H2O2 was higher in Az34 plants compared to WT under low temperature. Collectively, the results indicated that ABA deficiency induced modifications in starch and sucrose biosynthesis and sucrolytic pathway and overaccumulation of reactive oxygen species were the main reason for depressed low temperature tolerance in barley, which provide novel insights to the response of barley to low temperature under future climate change.

Verification of a clinical decision support system for the diagnosis of headache disorders based on patient-computer interactions: a multi-center study.

BACKGROUND: Although headache disorders are common, the current diagnostic approach is unsatisfactory. Previously, we designed a guideline-based clinical decision support system (CDSS 1.0) for diagnosing headache disorders. However, the system requires doctors to enter electronic information, which may limit widespread use. METHODS: In this study, we developed the updated CDSS 2.0, which handles clinical information acquisition via human-computer conversations conducted on personal mobile devices in an outpatient setting. We tested CDSS 2.0 at headache clinics in 16 hospitals in 14 provinces of China. RESULTS: Of the 653 patients recruited, 18.68% (122/652) were suspected by specialists to have secondary headaches. According to "red-flag" responses, all these participants were warned of potential secondary risks by CDSS 2.0. For the remaining 531 patients, we compared the diagnostic accuracy of assessments made using only electronic data firstly. In Comparison A, the system correctly recognized 115/129 (89.15%) cases of migraine without aura (MO), 32/32 (100%) cases of migraine with aura (MA), 10/10 (100%) cases of chronic migraine (CM), 77/95 (81.05%) cases of probable migraine (PM), 11/11 (100%) cases of infrequent episodic tension-type headache (iETTH), 36/45 (80.00%) cases of frequent episodic tension-type headache (fETTH), 23/25 (92.00%) cases of chronic tension-type headache (CTTH), 53/60 (88.33%) cases of probable tension-type headache (PTTH), 8/9 (88.89%) cases of cluster headache (CH), 5/5 (100%) cases of new daily persistent headache (NDPH), and 28/29 (96.55%) cases of medication overuse headache (MOH). In Comparison B, after combining outpatient medical records, the correct recognition rates of MO (76.03%), MA (96.15%), CM (90%), PM (75.29%), iETTH (88.89%), fETTH (72.73%), CTTH (95.65%), PTTH (79.66%), CH (77.78%), NDPH (80%), and MOH (84.85%) were still satisfactory. A patient satisfaction survey indicated that the conversational questionnaire was very well accepted, with high levels of satisfaction reported by 852 patients. CONCLUSIONS: The CDSS 2.0 achieved high diagnostic accuracy for most primary and some secondary headaches. Human-computer conversation data were well integrated into the diagnostic process, and the system was well accepted by patients. The follow-up process and doctor-client interactions will be future areas of research for the development of CDSS for headaches.

Neurofilament markers in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

This study aims to determine the serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) in amyotrophic lateral sclerosis (ALS) patients, and to explore their feasibility as valid biomarkers for quantifying disease progression and predicting individual prognosis. 52 patients with ALS and 30 controls with noninflammatory neurological diseases were included. NFL and pNFH levels in serum and CSF were measured by enzyme-linked immunosorbent assay. Our findings showed that serum and CSF levels of NFL and pNFH in ALS patients were significantly increased. These values were negatively correlated with disease duration (except CSF NFL with disease duration) and ALSFRS-r score, and positively correlated with disease progression rate (DPR) and upper motor neuron (UMN) score, but did not correlate with bilateral median and ulnar nerve compound muscle action potential (cMAP) amplitudes (except a weak correlation between CSF NFL and cMAP amplitudes). The optimal cut-off values with high sensitivity and specificity were obtained in ROC curve analysis to discriminate ALS from controls. Kaplan-Meier survival curves illustrated that survival was significantly shorter for patients with higher neurofilament levels at diagnosis. The Cox proportional hazards regressions confirmed that NFL and pNFH were significant predictors of survival. Overall, NFL and pNFH in serum and CSF can be used as reliable biomarkers in ALS.

Ultrasensitive optofluidic coupled Fabry-Perot capillary sensors.

Refractive index (RI) measurements are pertinent in concentration and biomolecular detection. Accordingly, an ultrasensitive optofluidic coupled Fabry-Perot (FP) capillary sensor based on the Vernier effect for RI sensing is proposed. Square capillaries integrated with the coupled FP microcavity provide multiple microfluidic channels while reducing the complexity of the fabrication process. The incoherent light source and spectrometer used during measurement facilitate the development of a low-cost sensing system. An ultrahigh RI sensitivity of 51709.0 nm/RIU and detection limit of 2.84 × 10-5 RIU are experimentally demonstrated, indicating acceptable RI sensing performance. The proposed sensor has significant potential for practical and low-cost applications such as RI, concentration, or biomolecular sensing.

Tunable optofluidic microbubble lens.

Optofluidic microlenses are one of the crucial components in many miniature lab-on-chip systems. However, many optofluidic microlenses are fabricated through complex micromachining and tuned by high-precision actuators. We propose a kind of tunable optofluidic microbubble lens that is made by the fuse-and-blow method with a fiber fusion splicer. The optical focusing properties of the microlens can be tuned by changing the refractive index of the liquid inside. The focal spot size is 2.8 µm and the focal length is 13.7 µm, which are better than those of other tunable optofluidic microlenses. The imaging capability of the optofluidic microbubble lens is demonstrated under a resolution test target and the imaging resolution can reach 1 µm. The results indicate that the optofluidic microbubble lens possesses good focusing properties and imaging capability for many applications, such as cell counting, optical trapping, spatial light coupling, beam shaping and imaging.