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Jiu-Yang Liu,1,* Gui-Fang Yang,2,* Fang-Fang Chen,2 Chun-Wei Peng11Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan 430071, People’s Republic of China; 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China*These authors contributed equally to this workPurpose: Tumor-infiltrating lymphocytes (TILs) become increasingly relevant to tumor progression. This study aims to evaluate (a) methods of TILs assessment and (b) their prognostic significance in gastric cancer (GC).Methods: The percentage of stromal TILs (psTIL) was reported semi-quantitatively by H&E evaluation. Herein, we screened two independent cohorts of breast cancer (n=240) and GC (n=481) for psTIL characterization. Correlations between psTIL and clinic-pathological features, as well as overall survival (OS) were further explored. Additionally, the prediction role of psTIL in GC was evaluated by receiver operating characteristic curve (ROC) analysis.Results: TILs could be demonstrably distinguished from other stromal areas and surrounding tumor nests according to the assessment method. More importantly, it is reproducible, easily to determine, and quickly performed. In GC, a two-grade scale for psTIL was appropriate to be divided into low and high subgroups by using the median value of 10% as the threshold. High psTIL was correlated with no serosa invasion, earlier TNM stage and better survival state (P

Chunwei Peng,1 Jiuyang Liu,1 Guifang Yang,2 Yan Li3 1Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuchang District, Wuhan, 3Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital Affiliated to the Capital Medical University, Yangfangdian, Beijing, People’s Republic of China Purpose: Semiconductor quantum dots (QDs) are a promising alternative to organic fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have great advantages in holistically analyzing the complex interactions among cancer stromal components in situ.Patients and methods: A QD probe-based multiplexed spectral molecular imaging method was established for simultaneous imaging. Three tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were constructed for the study. Multispectral analyses were performed for quantifying stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including infiltrating of immune cells (high density of macrophages), angiogenesis (high density of microvessel density [MVD], low neovessel maturation) and extracellular matrix (ECM) remodeling (low density of type IV collagen, intense expression of matrix metalloproteinase 9 [MMP-9]) was evaluated.Results: This study compared the imaging features of the QD probe-based single molecular imaging method, immunohistochemistry, and organic dye-based immunofluorescent methods, and showed the advantages of the QD probe-based multiple molecular imaging method for simultaneously visualizing complex components of cancer stroma. The risk of macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9 expression and low type IV collagen was significantly increased for the expression of LOX. With the advantages of the established QD probe-based multiplexed molecular imaging method, the spatial relationship between LOX and stromal essential events could be simultaneously evaluated histologically. Stromal activation was defined and then evaluated. Survival analysis showed that the stromal activation was correlated with overall survival and disease-free survival (P

Wei-Juan Zeng,1 Chun-Wei Peng,1 Jing-Ping Yuan,1 Ran Cui,2 Yan Li11Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, People’s Republic of China; 2Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education) and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, People’s Republic of China Purpose: The aims of this study are to establish a new method for simultaneously detecting the interactions between cancer cells and immunocytes in malignant ascites (MA) and to propose a new model for MA classification.Methods: A quantum dot (QD)-based multiplexed imaging technique was developed for simultaneous in situ imaging of cancer cells, lymphocytes, and macrophages. This method was first validated in gastric cancer tissues, and then was applied to MA samples from 20 patients with peritoneal carcinomatosis from gastrointestinal and gynecological origins. The staining features of MA and the interactions between cancer cells and immunocytes in the ascites were further analyzed and correlated with clinical features.Results: The QD-based multiplexed imaging technique was able to simultaneously show gastric cancer cells, infiltrating macrophages, and lymphocytes in tumor tissue, and the technique revealed the distinctive features of the cancer tumor microenvironment. When this multiplexed imaging protocol was applied to MA cytology, different features of the interactions and quantitative relations between cancer cells and immunocytes were observed. On the basis of these features, MA could be classified into immunocyte-dominant type, immunocyte-reactive type, cancer cell-dominant type, and cell deletion type; the four categories were statistically different in terms of the ratio of cancer cells to immunocytes (P

Xue-Qin Yang1,2, Chuang Chen1, Chun-Wei Peng1, Jin-Xuan Hou1, Shao-Ping Liu1, Chu-Bo Qi3, Yi-Ping Gong4, Xiao-Bo Zhu5, Dai-Wen Pang6, Yan Li1 1Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory on Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan; 2Medical School of Jingchu University of Technology, Jingmen; 3Department of Pathology; 4Department of Breast Surgery, Hubei Cancer Hospital, Wuhan; 5Wuhan Jiayuan Quantum Dots Co Ltd and Wuhan Tumor Nanometer Diagnosis Engineering Research Center, Wuhan; 6Key Laboratory of Analytical Chemistry for Biology and Medicine, College of Chemistry and Molecular Sciences, and State Key Laboratory of Virology, Wuhan University, Wuhan, People's Republic of China Background: The epidermal growth factor receptor (EGFR) is a promising therapeutic target in cancer, but its clinical value in breast cancer remains controversial. Our previous studies have found that quantitative analysis of biomarkers with quantum dot-based nanotechnology had better detection performance than conventional immunohistochemistry. The present study was undertaken to investigate the prognostic value of EGFR in breast cancer using quantum dot-based quantitative spectral analysis. Methods: EGFR expression in 65 breast cancer specimens was detected by immunohistochemistry and quantum dot-immunohistochemistry, and comparisons were made between the two methods. EGFR expression in tissue microarrays of 240 breast cancer patients was then detected by quantum dot-immunohistochemistry and spectral analysis. The prognostic value of EGFR immunofluorescence area (EGFR area) for five-year recurrence-free survival was investigated. Results: The same antigen localization, high correlation of staining rates (r = 0.914), and high agreement of measurement (κ= 0.848) of EGFR expression in breast cancer were found by quantum dot-immunohistochemistry and immunohistochemistry. The EGFR area showed significant differences by tumor grade, lymph node status, HER2 status, and hormone receptor status (all P < 0.05). Patients in the large EGFR area (≥30.51) group had a significantly higher five-year recurrence rate (47.2% versus 27.4%, P = 0.002) and worse five-year recurrence-free survival (log-rank test, P = 0.0015) than those in the small EGFR area (

Background/purpose: This study examined the effects of a 5-HT(1A) receptor agonist (8-OH-DPAT) on external urethral sphincter (EUS) activity in urethane-anesthetized rats.Methods: An EUS electromyogram (EMG) and intravesical pressure (IVP) were simultaneously recorded during continuous cystometrographic monitoring, to provide a quantitative evaluation of EUS activity and urethral urodynamics of voiding.Results: When examining the EUS burst activity, durations of the active (AP) and silent periods (SP) as a function of the time axis, respectively, exhibited concave- and convex-shaped curves. The burst discharges of the EUS-EMG were divided into nonvoiding and voiding burst activities based on the oscillation waves of the IVP, which were located in Phases 1 and 2 of the IVP. After 8-OH-DPAT treatment, the entire burst period in Phases 1 to 2 of the IVP was significantly prolonged. The average SP in both Phases 1 and 2 significantly increased but the average APs were not affected. Urodynamic results showed decreases in the volume threshold, contraction amplitude, and residual volume as well as an increase in the contraction duration. In addition, the amplitude of bladder high-frequency oscillatory waves in the IVP and the average urethral flow rate were reduced, but the entire voiding efficiency increased.Conclusion: The influences of 8-OH-DPAT on EUS burst activity and urodynamics were exactly detected by the sophisticated EMG analytic design, and the results could be a reference for the pharmacological treatment of patients with lower urinary tract dysfunction. [ABSTRACT FROM AUTHOR]

This study examined a new emotional writing paradigm, that is PDDP. PDDP instructs participants to write diary in first-person pronoun first, and then narrate the same event from a different perspective using second-person pronoun. Finally, the participants write it again with third-person pronoun from yet another perspective. These three narrations were to be written in a consecutive sequential order. Results demonstrated that diary writers indeed benefited from features of PDDP. It also showed that highly anxious people received most long-term therapeutic effect from PDDP. We argue that PDDP enacts the needed mechanism to balance psychological distance prolonging and self-disclosure making in emotional writing. [ABSTRACT FROM AUTHOR]

Study Design: prospective study. Objective: present results of Prestige LP artificial cervical disc replacement (ADR). Summary Of Background Data: motion preservation with ADR can potentially reduce adjacent segment degeneration. METHODS.: Forty patients with 59 Prestige LP ADR were analyzed. Cervical range of motion, Neck Disability Index, Visual Analogue, Short Form-36, Modified American Academy of Orthopedic Surgeons, and Japanese Orthopedic Association scores and radiographs were evaluated. Clinical results were compared with anterior cervical discectomy and fusion. Results: there were 21 females and 19 males. Mean age was 43.9 years. Mean follow-up was 2.9 years. Of the patients, 62.5% had single level replacement-mainly C56 level (56%); 52.5% had myelopathy and 47.5% radiculopathy; 50% of neural compression was due to herniated disc, 45% due to spondylosis, and 5% due to both. There was significant improvement in the American Academy of Orthopedic Surgeons and Visual Analogue scores (P < 0.05) at 6 months and 2 years. There was significant improvement in the Neck Disability Index from a mean of 42.2 preoperation to 16.4 at 6 months and 15.2 at 2 years (P < 0.05). The mean Japanese Orthopedic Association score improved significantly from 14.7 preoperation to 15.7 at 6 months and 15.6 at 2 years (P < 0.05). There was significant improvement in all aspects of the Short Form-36 scores except general health (P < 0.05) at 6 months and 2 years. There was no significant difference in the clinical outcomes between ADR and anterior cervical discectomy and fusion. Segmental alignment (mean 8°, 14°, and 13° lordotic at preoperation, 6 months, and 2 years postoperation, respectively) and global alignment (mean 15.7°, 16.2°, and 17.3° lordotic at preoperation, 6 months, and 2 years postoperation, respectively) were maintained. Dynamic radiographs showed significant segmental motion with a 6 month's mean motion of 11.1° and a 2-year mean motion of 13.9° (P < 0.05). Conclusion: prestige LP ADR showed significant improvement in clinical outcomes at 2 years. It restores segmental lordosis and preserves segmental motion up to 2 years postoperation. [ABSTRACT FROM AUTHOR]

Transcranial temporal interference stimulation (tTIS) is a promising brain stimulation method that can target deep brain regions by delivering an interfering current from surface electrodes. Most instances of tTIS stimulate the brain with a single-frequency sinusoidal waveform generated by wave interference. Theta burst stimulation is an effective stimulation scheme that can modulate neuroplasticity by generating long-term potentiation- or depression-like effects. To broaden tTIS application, we developed a theta burst protocol using tTIS technique to modulate neuroplasticity in rats. Two cannula electrodes were unilaterally implanted into the intact skull over the primary motor cortex. Electrical field of temporal interference envelopes generated by tTIS through cannula electrodes were recorded from primary motor cortex. Theta burst schemes were characterized, and motor activation induced by the stimulation was also evaluated simultaneously by observing electromyographic signals from the corresponding brachioradialis muscle. After validating the stimulation scheme, we further tested the modulatory effects of theta burst stimulation delivered by tTIS and by conventional transcranial electrical stimulation on primary motor cortex excitability. Changes in the amplitude of motor evoked potentials, elicited when the primary motor cortex was activated by electrical pulses, were measured before and after theta burst stimulation by both techniques. Significant potentiation and suppression were found at 15 to 30 min after the intermittent and continuous theta burst stimulation delivered using tTIS, respectively. However, comparing to theta burst stimulations delivered using conventional form of transcranial electrical stimulation, using tTIS expressed no significant difference in modulating motor evoked potential amplitudes. Sham treatment from both methods had no effect on changing the motor evoked potential amplitude. The present study demonstrated the feasibility of using tTIS to achieve a theta burst stimulation scheme for motor cortical neuromodulation. These findings also indicated the future potential of using tTIS to carry out theta burst stimulation protocols in deep-brain networks for modulating neuroplasticity., (© 2024. The Author(s).)

Background: The current treatment options for overactive bladder (OAB) continue to pose challenges for refractory cases and may involve invasive procedures. To assess the potential benefit of non-invasive repetitive peripheral magnetic stimulation (rPMS) on sacral roots using intermittent theta burst stimulation (iTBS) as treatment option for OAB. The study involved a total of 33 rats, which were divided into three different experimental phases., Materials and Methods: To induce bladder overactivity rats were pretreated with a continuous transvesical infusion of 0.5% acetic acid (AA). During bladder infusion, the intravesical pressure was recorded using cystometrography (CMG) to investigate the effects of AA pretreatment and the therapeutic intervention of acute sacral rPMS using iTBS., Results: Pre-application of rPMS with iTBS at a 100% intensity significantly extended the mean first voiding time (Tv) in normal healthy rats to 132%. Acute rPMS iTBS at a 100% intensity resulted in a significant increase of the inter-contraction interval (ICI) to 121%. An AA model was established with continuous saline infusion after 0.5% AA treatment and resulted in significant reductions of Tv to 42% and ICI to 56% of the corresponding control values. Subsequently, rPMS iTBS at a 100% intensity on the sacral nerve effectively inhibited AA-induced bladder overactivity and significantly increased the ICI to 167%∼222%. No significant changes in maximum bladder pressure (Pmax) were found., Conclusions: Sacral nerve rPMS with iTBS demonstrated the ability to suppress AA-induced bladder overactivity. This promising modality could be developed as an alternative approach to enhance bladder continence in OAB syndrome patients., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have potentially influenced the research reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Most COVID-19 survivors are troubled with chronic persistent symptoms, which have currently no definitive treatments. Bufei Huoxue (BFHX) capsule exerts clinical benefit, while the material basis and molecular mechanism remain unclear., Aim: The study aimed to elucidate the protective mechanisms of BFHX capsules against COVID-19 convalescence. UHPLC-HRMS and various databases were employed to explore potential compounds and targets. PPI, MCODE, transcription factor (TF), and miRNA analyses were conducted to receive hub targets and corresponding upstream regulators., Method: Molecular docking was applied to verify the binding activity of compound and target. Further, GO, KEGG, WIKI, and Reactome analyses were performed, and compound-targetsymptom and gene-disease networks were constructed. A total of 127 compounds and 313 targets were acquired. A sum of 10 hub targets were screened and showed good binding affinities with critical compounds., Result: MLLT1, CBFB, and EZH2 were identified as key TFs, and hsa-mir-146a-5p, hsa-mir- 26b-5p, and hsa-mir-24-3p were predicted to be important miRNAs. BFHX capsule may alleviate the symptoms by targeting TNF, IL-6, IFNG, and TGF-β1. Besides, BFHX capsule may exert a therapeutic effect on respiratory disease (especially pulmonary fibrosis and lung infection) and multi-system damage during COVID-19 convalescence by regulating cytokine-cytokine receptor interaction, as well as TGF-β, TNF, and Toll-like receptor signaling pathways., Conclusion: In summary, BFHX capsule may exert a therapeutic effect on multi-system damages during COVID-19 convalescence through multiple compounds (such as albiflorin, isopsoralen, and neobavaisoflavone), multiple targets (such as TNF, IL-6, and EGF) and multiple pathways (TGF-β, TNF, and Toll-like receptor signaling pathways)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Various injectants are available for the treatment of carpal tunnel syndrome. This systematic review and network meta-analysis was conducted to investigate the effectiveness of different injection therapies in alleviating the symptoms of carpal tunnel syndrome. Various databases were searched for relevant studies from inception until May 10, 2023. Eligible studies were identified using the patient (P), intervention (I), comparison (C), and outcomes (O) model, which involved (P) participants with carpal tunnel syndrome, (I) an intervention based on injection therapy, (C) the use of placebo or another injectant as a control treatment, and (O) the measurement of clinical and electrodiagnostic outcomes of interest. A total of 18 studies were included in the analysis. The network meta-analysis revealed that platelet-rich plasma is effective in the treatment of carpal tunnel syndrome in terms of symptom and pain relief and functional improvement in both the short and long term, whereas steroids are effective only in the short term. Additionally, injections of dextrose solution may offer long-term pain relief as well as short- and long-term symptom alleviation and functional improvement. The study findings suggest that platelet-rich plasma should be used as the first-line treatment for carpal tunnel syndrome, with dextrose and steroids serving as alternative treatment options., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Managing chronic pelvic pain (CPP) remains a challenge due to its diverse range of causes. A newly identified anatomical entity known as the enthesis of the levator ani muscle (LAM) and its associated disorders might play a role. This paper describes a novel insight into CPP's origin, aiming to improve accurate diagnosis and treatment., Methods: Data were collected from medical records (paper or electronic) retrospectively. The study included 112 patients meeting the criteria, divided into CPP and non-CPP groups. Clinical symptoms, including location of LAM enthesis, referred pain from pain in LAM enthesis, and related lower urinary tract symptoms (LUTSs) were discussed. To identify differences in symptoms between the groups, a Chi-squared test and descriptive analyses were conducted., Results: Bimanual examination revealed tender sites in the attachment of the LAM to the pubic bone. LAM enthesis pain presumably caused referred pain in at least 10 areas, primarily in the lower abdominal quadrate (40.2%-47.3%) followed by the inguinal area (8.9%-15.1%). Multiple LUTSs were observed, including urinary frequency (72.3%), urgency (42.9%), nocturia (53.6%), residual urine sensation (64.3%), urinary incontinence (30.3%), painful bladder (34.8%), and weak urine stream (47.9%). Patients in the CPP groups experienced significant residual urine sensation (53.6%) and bearing-down sensation (42%) compared to the non-CPP group., Conclusion: Pain in LAM enthesis is a novel cause of pelvic pain and LUTSs that warrants attention for the evaluation and management of CPP., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: Genital nerve stimulation (GNS) is a promising, but under-researched, alternative treatment for neurogenic detrusor overactivity (NDO) in those with spinal cord injury (SCI)., Objectives: To investigate the urodynamic, quality-of-life (QOL) and carry-over effects of GNS when applied at home for 2 weeks by participants with incomplete SCI and NDO during activities of daily living., Methods: Seven men and 1 woman participated in this 1-month protocol study. Urodynamic and QOL data were gathered during week 1 (baseline measurements), followed by 2 weeks of daily GNS at home using a portable device. GNS was applied either on-demand or thrice daily, depending on the individual's sensation. At week 4, post-stimulation tests were repeated to record any carry-over effect from the GNS. Participants maintained voiding diaries throughout the study. Assessments were carried out at the end of each protocol period in a randomized order. Clinical procedures were conducted at Taipei Medical University Hospital (Taipei, Taiwan)., Results: Everyone completed the study but only 7 of the 8 participants completed their voiding diary. Two weeks after GNS, average cystometric bladder capacity was increased by 30 % compared to baseline (P< 0.05). A 1-week carry-over effect was demonstrated as this capacity remained, on average, 35 % greater than baseline in week 4 after GNS was stopped (P< 0.05). Incontinence frequency significantly decreased by the end of week 3 (P< 0.05) but no significant improvements were recorded for either detrusor pressure or bladder compliance., Conclusions: Chronic at-home GNS improved cystometric bladder capacity and reduced urinary incontinence for individuals with incomplete SCI and NDO. A carry-over effect of 1 week was observed following GNS treatment. The use of portable GNS treatment that can be applied by the individual at home merits further investigation as alternative treatment for NDO in those with SCI., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Quantitative hepatitis B surface antigen (qHBsAg) level at end-of-treatment (EOT) predict clinical relapse (CR) after nucleos(t)ide analogues (Nuc) in chronic hepatitis B(CHB) patients. It is unclear if higher EOT qHBsAg leads to earlier onset or more severe off-Nuc CR., Aim: This large cohort study investigates the association between EOT qHBsAg and CR onset/severity., Methods: This study enrolled HBeAg-negative CHB patients who had achieved undetectable HBV DNA for over 1 year after receiving Nuc therapy before discontinuation. The EOT qHBsAg level was categorised into three groups: <100, 100-999, ≥1000 IU/mL. The study assessed the predictability of qHBsAg levels for CR, and analysed and compared the incidence, time to onset and severity of CR among these three groups., Results: Patients with higher EOT qHBsAg showed a higher incidence of CR (≥1000, 100-999, <100 IU/mL: 73%, 65%, and 38%, p < 0.01) but a later onset of CR (median time to CR: 35, 33 and 27 weeks, p < 0.01). The predictabilities of EOT qHBsAg for CR were greater in patients aged <50-year-old or with genotype C than in those aged ≥50-year-old or with genotype B. There's no correlation between EOT qHBsAg level and ALT folds at CR (Pearson correlation coefficient: r = -0.03, p = 0.35). EOT qHBsAg was neither a predictor for severe hepatitis flare nor a predictor for hepatic decompensation., Conclusions: Predictability using EOT qHBsAg levels for CR differed in subgroups of age and genotypes. Higher EOT qHBsAg levels correlate with higher incidence but later onset of CR. No correlation between EOT qHBsAg and relapse severity was observed., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Long-term nucleos(t)ide analog (Nuc) treatment can reduce HCC in patients with HBV-related liver cirrhosis (HBV-LC). Earlier small cohort studies showed a comparable 5-year incidence of HCC in HBeAg-negative patients with HBV-LC who stopped and those continued Nuc therapy. This study aimed to validate these findings using a large cohort with 10-year follow-up., Approach and Results: From 2 centers, 494 HBeAg-negative patients with HBV-LC who stopped (finite group) and 593 who continued (continuous group) Nuc therapy were recruited. HCC, HBsAg loss, liver-related mortality/transplantation, and overall survival rates were compared between 2 groups with 1:1 propensity score matching of sex, treatment history, types of Nuc, age, transaminases, platelet count, and HBsAg levels at end of therapy in finite group or 3-year on-therapy in continuous groups. During a median follow-up of 6.2 (3.4-8.9) years, the annual and 10-year HCC incidence were lower in finite group (1.6 vs. 3.3%/y and 10-y 15.7% vs. 26.8%, respectively; log-rank test, p <0.0001). The finite group showed greater HBsAg decline/year (-0.116 vs. -0.095 log 10 IU/mL, p =0.0026) and 7.6 times higher 10-year incidence of HBsAg loss (22.7% vs. 3%, p <0.0001). Multivariate Cox regression showed finite therapy an independent factor for HBsAg loss (adjusted HR: 11.79) but protective against HCC (adjusted HR: 0.593), liver-related mortality/transplantation (adjusted HR: 0.312), and overall mortality (adjusted HR: 0.382)., Conclusions: Finite Nuc therapy in HBeAg-negative HBV-LC may reduce HCC incidence, increase HBsAg loss, and improve survival. Greater HBsAg decline/loss may reflect enhanced immunity and contribute to the reduction of hepatic carcinogenesis., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Our previous study showed that the Epstein-Barr virus (EBV) may be the etiology for some patients with interstitial cystitis/bladder pain syndrome (IC/BPS); hence, the current study aimed to investigate the urinary viral spectrum in patients with IC/BPS and the clinical efficacy of valacyclovir. Twenty-eight patients were prospectively enrolled for valacyclovir 500 mg twice a day for 4 weeks. Urine samples were collected from IC/BPS patients and 30 controls. The primary outcome was the difference in the visual analog scale (VAS) pain score, and secondary outcomes included changes in the urinary viral spectrum and urinary inflammatory cytokine level (ClinicalTrials.gov Identifier: NCT05094414). Urinary EBV was detected in 14.2% IC/BPS patients but not in the controls. Urinary John Cunningham virus and BK virus were detected in 18 (64.3%) and 2 (7.1%) patients with IC/BPS, respectively, with similar prevalences noted for the controls. No cytomegalovirus, varicella-zoster virus, or herpes simplex virus was detected in the urine samples. The VAS pain score in patients with IC/BPS significantly decreased after 4 weeks (from 7.5 [5.52-9.0] to 5 [1.5-6.0], p = 0.0003). Urinary EBV was undetectable in any sample after valacyclovir treatment, and the decreases in urinary interleukin (IL)-1β (from 0.66 [0.55-0.82] pg/mL to 0.58 [0.55-0.64] pg/mL, p = 0.0034), IL-8 (from 6.81 [2.38 to 29.1] pg/mL to 4.33 [1.53-11.04] pg/mL, p = 0.0361), IL-10 (from 1.06 [0.94-1.18] pg/mL to 0.92 [0.88-1.02], p = 0.0086), and tumor necrosis factor-α (from 1.61 [1.50-1.72] pg/mL to 1.50 [1.44-1.55] pg/mL, p = 0.0079) were significant. Valacyclovir could relieve bladder pain, eliminate urinary EBV, and reduce bladder inflammation.

The two-spotted spider mite (Tetranychus urticae) is one of the most well-known pesticide-resistant agricultural pests, with resistance often attributed to changes such as target-site mutations and detoxification activation. Recent studies show that pesticide resistance can also be influenced by symbionts, but their involvement in this process in spider mites remains uncertain. Here, we found that infection with Wolbachia, a well-known bacterial reproductive manipulator, significantly increased mite survival after exposure to the insecticides abamectin, cyflumetofen, and pyridaben. Wolbachia-infected (WI) mites showed higher expression of detoxification genes such as P450, glutathione-S-transferase (GST), ABC transporters, and carboxyl/cholinesterases. RNA interference experiments confirmed the role of the two above-mentioned detoxification genes, TuCYP392D2 and TuGSTd05, in pesticide resistance. Increased GST activities were also observed in abamectin-treated WI mites. In addition, when wild populations were treated with abamectin, WI mites generally showed better survival than uninfected mites. However, genetically homogeneous mites with different Wolbachia strains showed similar survival. Finally, abamectin treatment increased Wolbachia abundance without altering the mite's bacterial community. This finding highlights the role of Wolbachia in orchestrating pesticide resistance by modulating host detoxification. By unraveling the intricate interplay between symbionts and pesticide resistance, our study lays the groundwork for pioneering strategies to combat agricultural pests., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Kinetic chains (KCs) are primarily affected by the load of different activities that recruit muscles from different regions. We explored the effects of strengthening exercises on KCs through muscle activation. Four databases were searched from 1990 to 2019. The muscles of each KC, their surface electromyography (sEMG), and the exercises conducted were reported. We found 36 studies that presented muscle activation using the percent (%) maximal voluntary isometric contraction (MVIC) or average sEMG for nine KCs in different regions. The % MVIC is presented as the following four categories: low (≤20%), moderate (21~40%), high (41~60%), and very high (>60%). Only four studies mentioned muscle activation in more than three KCs, while the remaining studies reported inconsistent sEMG processing, lacked normalization, and muscle activation in one or two KCs. The roles of stabilizers and the base of support in overhead throwing mobility using balance exercises were examined, and the concentric phase of chin-up and lat pull-down activated the entire KC by recruiting multiple muscles. Also, deep-water running was shown to prevent the risk of falls and enhance balance and stability. In addition, low-load trunk rotations improved the muscles of the back and external oblique activation. Based on this study's findings, closed-chain exercises activate more groups of muscles in a kinetic chain than open-chain exercises. However, no closed or open chain exercise can activate optimal KCs.

Sleep staging serves as a fundamental assessment for sleep quality measurement and sleep disorder diagnosis. Although current deep learning approaches have successfully integrated multimodal sleep signals, enhancing the accuracy of automatic sleep staging, certain challenges remain, as follows: 1) optimizing the utilization of multi-modal information complementarity, 2) effectively extracting both long- and short-range temporal features of sleep information, and 3) addressing the class imbalance problem in sleep data. To address these challenges, this paper proposes a two-stream encode-decoder network, named TSEDSleepNet, which is inspired by the depth sensitive attention and automatic multi-modal fusion (DSA2F) framework. In TSEDSleepNet, a two-stream encoder is used to extract the multiscale features of electrooculogram (EOG) and electroencephalogram (EEG) signals. And a self-attention mechanism is utilized to fuse the multiscale features, generating multi-modal saliency features. Subsequently, the coarser-scale construction module (CSCM) is adopted to extract and construct multi-resolution features from the multiscale features and the salient features. Thereafter, a Transformer module is applied to capture both long- and short-range temporal features from the multi-resolution features. Finally, the long- and short-range temporal features are restored with low-layer details and mapped to the predicted classification results. Additionally, the Lovász loss function is applied to alleviate the class imbalance problem in sleep datasets. Our proposed method was tested on the Sleep-EDF-39 and Sleep-EDF-153 datasets, and it achieved classification accuracies of 88.9% and 85.2% and Macro-F1 scores of 84.8% and 79.7%, respectively, thus outperforming conventional traditional baseline models. These results highlight the efficacy of the proposed method in fusing multi-modal information. This method has potential for application as an adjunct tool for diagnosing sleep disorders.

Background and Objective: Transcranial Burst Electrical Stimulation (tBES) is an innovative non-invasive brain stimulation technique that combines direct current (DC) and theta burst stimulation (TBS) for brain neuromodulation. It has been suggested that the tBES protocol may efficiently induce neuroplasticity. However, few studies have systematically tested neuromodulatory effects and underlying neurophysiological mechanisms by manipulating the polarity of DC and TBS patterns. This study aimed to develop the platform and assess neuromodulatory effects and neuronal activity changes following tBES., Methods: Five groups of rats were exposed to anodal DC combined with intermittent TBS (tBES+), cathodal DC combined with continuous TBS (tBES-), anodal and cathodal transcranial direct current stimulation (tDCS+ and tDCS-), and sham groups. The neuromodulatory effects of each stimulation on motor cortical excitability were analyzed by motor-evoked potentials (MEPs) changes. We also investigated the effects of tBES on both excitatory and inhibitory neural biomarkers. We specifically examined c-Fos and glutamic acid decarboxylase (GAD-65) using immunohistochemistry staining techniques. Additionally, we evaluated the safety of tBES by analyzing glial fibrillary acidic protein (GFAP) expression., Results: Our findings demonstrated significant impacts of tBES on motor cortical excitability up to 30 min post-stimulation. Specifically, MEPs significantly increased after tBES (+) compared to pre-stimulation ( p  = 0.026) and sham condition ( p  = 0.025). Conversely, tBES (-) led to a notable decrease in MEPs relative to baseline ( p  = 0.04) and sham condition ( p  = 0.048). Although tBES showed a more favorable neuromodulatory effect than tDCS, statistical analysis revealed no significant differences between these two groups ( p  > 0.05). Additionally, tBES (+) exhibited a significant activation of excitatory neurons, indicated by increased c-Fos expression ( p  < 0.05), and a reduction in GAD-65 density (p < 0.05). tBES (-) promoted GAD-65 expression ( p  < 0.05) while inhibiting c-Fos activation ( p  < 0.05), suggesting the involvement of cortical inhibition with tBES (-). The expression of GFAP showed no significant difference between tBES and sham conditions ( p  > 0.05), indicating that tBES did not induce neural injury in the stimulated regions., Conclusion: Our study indicates that tBES effectively modulates motor cortical excitability. This research significantly contributes to a better understanding of the neuromodulatory effects of tBES, and could provide valuable evidence for its potential clinical applications in treating neurological disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nguyen, Kuo, Peng, Liu, Chang and Hsieh.)

Objective: The aim of the study is to evaluate the effect size of core stabilization exercise for prenatal and postnatal women through measures of urinary symptoms, voiding function, pelvic floor muscle strength and endurance, quality of life, and pain scores., Design: The PubMed, Embase, Cochrane Library, and Scopus databases were searched. Randomized controlled trials were selected and subjected to meta-analysis and risk of bias assessment., Results: Ten randomized controlled trials were selected, and 720 participants were included. Ten articles using seven outcomes were analyzed. Relative to the control groups, the core stabilization exercise groups exhibited superior results for urinary symptoms (standardized mean difference = -0.65, 95% confidence interval = -0.97 to 0.33), pelvic floor muscle strength (standardized mean difference = 0.96, 95% confidence interval = 0.53 to 1.39), pelvic floor muscle endurance (standardized mean difference = 0.71, 95% confidence interval = 0.26 to 1.16), quality of life (standardized mean difference = -0.9, 95% confidence interval = -1.23 to 0.58), transverse muscle strength (standardized mean difference = -0.45, 95% confidence interval = -0.9 to -0.01), and voiding function (standardized mean difference = -1.07, 95% confidence interval = -1.87 to 0.28)., Conclusions: Core stabilization exercises are safe and beneficial for alleviating urinary symptoms, improving quality of life, strengthening pelvic floor muscles, and improving transverse muscle function in prenatal and postnatal women with urinary incontinence., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We aim to study the association between spasticity and active range of motion (ROM) during four repetitive functional tasks such as cone stacking (CS), fast flexion-extension (FFE), fast ball squeezing (FBS), and slow ball squeezing (SBS), and predicted spasticity models., Methods: An experimental study with control and stroke groups was conducted in a Medical Center. A total of sixty-four participants, including healthy control ( n = 22; average age (years) = 54.68 ± 9.63; male/female = 12/10) and chronic stroke survivors ( n = 42; average age = 56.83 ± 11.74; male/female = 32/10) were recruited. We employed a previously developed smart glove device mounted with multiple inertial measurement unit (IMU) sensors on the upper limbs of healthy and chronic stroke individuals. The recorded ROMs were used to predict subjective spasticity through generalized estimating equations (GEE) for the affected side., Results: The models have significant ( p ≤ 0.05 *) prediction of spasticity for the elbow, thumb, index, middle, ring, and little fingers. Overall, during SBS and FFE activities, the maximum number of upper limb joints attained the greater average ROMs. For large joints, the elbow during CS and the wrist during FFE have the highest average ROMs, but smaller joints and the wrist have covered the highest average ROMs during FFE, FBS, and SBS activities., Conclusions: Thus, it is concluded that CS can be used for spasticity assessment of the elbow, FFE for the wrist, and SBS, FFE, and FBS activities for the thumb and finger joints in chronic stroke survivors.

Originally extracted from Momordica charantia seeds, the antiviral and anti-tumor activities of Momordica anti-HIV protein MAP30 have become well known. Although MAP30 has been reported to possess antiviral activity against several human viruses, the current understanding of the MAP30-mediated antiviral response is mainly derived from the previous research work on anti-HIV herbal medicines; the mechanistic insight of its effects on other viruses remains largely unknown. In this study, we showed that both ectopically expressed and purified recombinant MAP30 (rMAP30) impeded Epstein-Barr virus Nuclear Antigen 1 (EBNA1)-mediated transcription from the viral latent replication origin. Mechanistically, in vivo and in vitro studies revealed that MAP30 caused EBNA1 to dissociate from the cognate binding sites, which disrupted downstream EBNA1-dependent viral epigenome accumulation and cell maintenance of Epstein-Barr virus (EBV)-associated neoplastic cells. Finally, mutational analysis indicated that the N-terminal ricin A homologous domain shared by ricin-like proteins was implicated in the anti-EBV response. Our study provides evidence to support that MAP30 has a unique property to combat EBV latent infection, suggesting a potential to develop this herbal protein to be an alternative medicine for EBV associated diseases., Competing Interests: The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2023 The Authors.)

Bedside falls and pressure ulcers are crucial issues in geriatric care. Although many bedside monitoring systems have been proposed, they are limited by the computational complexity of their algorithms. Moreover, most of the data collected by the sensors of these systems must be transmitted to a back-end server for calculation. With an increase in the demand for the Internet of Things, problems such as higher cost of bandwidth and overload of server computing are faced when using the aforementioned systems. To reduce the server workload, certain computing tasks must be offloaded from cloud servers to edge computing platforms. In this study, a bedside monitoring system based on neuromorphic computing hardware was developed to detect bedside falls and sleeping posture. The artificial intelligence neural network executed on the back-end server was simplified and used on an edge computing platform. An integer 8-bit-precision neural network model was deployed on the edge computing platform to process the thermal image captured by the thermopile array sensing element to conduct sleep posture classification and bed position detection. The bounding box of the bed was then converted into the features for posture classification correction to correct the posture. In an experimental evaluation, the accuracy rate, inferencing speed, and power consumption of the developed system were 94.56%, 5.28 frames per second, and 1.5 W, respectively. All the calculations of the developed system are conducted on an edge computing platform, and the developed system only transmits fall events to the back-end server through Wi-Fi and protects user privacy.

Purpose: The anticoagulation activity of warfarin in populations with CYP2C9, VKORC1, and CYP4F2 variants differs between individuals and is correlated with poor international normalized ratio (INR) control. Pharmacogenetics-guided warfarin dosing has been successfully developed for patients with genetic variations in recent years. However, few real-world data have been used to investigate the INR and warfarin dosage and the time to target INR. This study examined the largest collection of genetic and clinical real-world data related to warfarin to provide further evidence supporting the benefits of pharmacogenetics in clinical outcomes., Methods: We retrieved a total of 69,610 INR-warfarin records after the index date from 2,613 patients in the China Medical University Hospital database between January 2003 and December 2019. Each INR reading was obtained from the latest laboratory data after the hospital visit date. Patients with a history of malignant neoplasms or pregnancy before the index date were excluded, as were patients without data on INR measurements after the fifth day of prescription, genetic information, or gender variables. The primary outcomes were the INR and warfarin dosage during days 7, 14, 28, 56, and 84 after prescription. The secondary outcome was the time required to reach the INR ranges of 1.5 to 3.0 and >4.0., Findings: A total of 59,643 INR-warfarin records from 2188 patients were retrieved. The average INR was higher for homozygous carriers of the minor allele at CYP2C9 and VKORC1 during the first 7 days (1.83 [1.03] [CYP2C9*1] and 2.46 [1.44] [CYP2C9*3], P < 0.001; 1.39 [0.36] [rs9923231 G/G], 1.55 [0.79] [rs9923231 G/A], and 1.96 [1.13] [rs9923231 A/A], P < 0.001) than for the wild-type allele. These patients with variants required lower warfarin doses than those with the wild-type allele during the first 28 days. CYP4F2 variant patients seemed to require higher doses of warfarin than those in the wild-type group; however, no significant difference in the average INR was observed (1.95 [1.14] [homozygous V433 carriers], 1.78 [0.98] [heterozygous V433M carriers], and 1.66 [0.91] [homozygous M433 carriers], P = 0.016)., Implications: Our study indicates that genetic variants in the Han population may enhance warfarin responsiveness, which holds clinical relevance. An increased warfarin dosage was not linked to a shorter time to therapeutic INR between CYP4F2 variant patients and those with a wild-type allele. Assessing CYP2C9 and VKORC1 genetic polymorphisms before initiating warfarin treatment in real-world practice is essential for potentially vulnerable patients and is likely to optimize therapeutic dosing., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background & Aims: Hepatitis B flare occurs earlier and is more severe in patients stopping tenofovir (TDF) compared with entecavir (ETV). This study investigated relationship between hepatitis B virus (HBV) kinetics, onset timing, and the severity of flares., Methods: Hepatitis B e antigen-negative chronic hepatitis B patients who developed off-ETV or off-TDF hepatitis flare were recruited. Their HBV kinetics and the severity of flares were compared between patients with early (<6 months) and late (between 6 and 24 months) flares. Propensity score matching was performed at 1:1 adjusting for age, sex, cirrhosis, and end-of-treatment (EOT) hepatitis B surface antigen between off-ETV and off-TDF flares., Results: After propensity score matching, 76% and 15% of each 107 off-TDF and off-ETV patients, respectively, developed early flare. A much steeper HBV DNA upsurge (ΔHBV DNA/month) was observed in off-TDF than off-ETV flares (2.12 vs 0.73 log 10 IU/mL; P < .01). Greater ΔHBV DNA/month correlated with earlier timing and higher peak alanine aminotransferase levels of flares. ΔHBV DNA/month ≥2.5 log 10 IU/mL was an independent factor for severe off-TDF flare, and ≥1 log 10 IU/mL was a predictor for severe off-ETV flares., Conclusions: Greater HBV DNA upsurge rate (ΔHBV DNA/month) ≥1 log 10 IU/mL is a key factor for an earlier onset and more severe flare. More frequent ΔHBV DNA/month ≥1 log 10 IU/mL in off-TDF than off-ETV flares may explain why off-TDF flare mostly occurred early and was more severe. More stringent monitoring in those with ΔHBV DNA/month ≥1 log 10 IU/mL at flare, especially ≥2.5 log 10 IU/mL in early off-TDF flares, is important for timely retreatment to prevent decompensation., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Drinking water safety is threatened by numerous toxic organic pollutants difficult to chemically monitor. This study aimed to determine the toxicological profiles of organic extracts (OEs) of water samples from source to tap in two drinking water supply systems in a metropolitan city, Central China, during different hydrological periods. Mortality, DNA damage, growth, and development of Caenorhabditis elegans were evaluated following exposure to OEs. The median lethal doses of OEs of drinking water samples (n = 48) ranged from 266 REF (relative enrichment factor) to > 1563 REF. When tested at a dose of 100 REF, 56.25% (27/48) of OEs induced genotoxicity, 4.17% (2/48) inhibited the growth, and 45.83% (22/48) decreased the offspring number in C. elegans. No clear temporal-spatial variation patterns of the OEs toxicity indicators were observed. The correlations among the toxicity indicators were generally poor. The observed toxicities were not closely related to the level of dissolved organic carbon in drinking water. These findings support using multiple endpoint bioassays, such as C. elegans-based approaches, as complementary tools to conventional chemical analysis for drinking water quality monitoring., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In recent meta-analyses, robot-assisted gait training for patients with multiple sclerosis (MS) have yielded limited clinical benefits compared with conventional overground gait training., Objective: To investigate the effect of robot-assisted gait training for patients with MS on clinical outcomes through a systematic review and meta-analysis., Methods: We searched for relevant studies in the PubMed, EMBASE, Cochrane Library, and Physiotherapy Evidence Database databases from their inception to April 7, 2022. We selected studies that (1) included participants with MS, (2) used robot-assisted gait training as the intervention, (3) included conventional overground gait training or another gait training protocol as control treatment, and (4) reported clinical outcomes. Continuous variables are expressed as standardized mean differences with 95% confidence intervals. Statistical analyses were performed using RevMan 5.4 software., Results: We included 16 studies enrolling 536 participants. Significant improvement was observed in the intervention group, with low heterogeneity at the end of the intervention with regard to walking velocity (standardized mean difference [SMD]: 0.38, 95% confidence interval [CI]: [0.15, 0.60]), walking endurance (SMD: 0.26, 95% CI [0.04, 0.48]), mobility (SMD: -0.37, 95% CI [-0.60, -0.14]), balance (SMD: 0.26, 95% CI [0.04, 0.48]), and fatigue (SMD: -0.27, 95% CI [-0.49, -0.04]). The results of subgroup analyses revealed improvements in these outcomes for the intervention group using grounded exoskeletons. No significant differences were noted in all the outcomes between the groups at follow-up., Conclusions: Robot-assisted gait training with grounded exoskeletons exerts a positive short-term effect and is an adequate treatment option for patients with MS.

Ras opposite (Rop) is known to play an essential role in regulating vesicle trafficking, including synaptic transmission and general secretion. The fundamental roles of Rop have been confirmed by the observation that null mutations in many organisms generate lethal phenotypes during embryogenesis. However, the effects of Rop during the postembryonic stages, especially in non-model organisms, remain largely unknown. Here, we provide new data that enhance our understanding of Rop's roles in the adults of multiple species of Tetranychus spider mites (Acari: Tetranychidae), a class of notorious agricultural pests. Our in silico and experimental evidence demonstrated that Rop is under purifying selection and is highly conserved in Tetranychus spp. RNA interference experiments showed that Rop is required for maintaining normal fecundity but has no significant effect on survival. We further demonstrate that knockdown of Rop darkens the body color of spider mites and blocks the excretion of fecal pellets, which is likely to be related to an abnormality in the excretion of food waste in the digestive system. Overall, our findings clarify novel functions of a vesicle trafficking-related gene in the adult stage of multiple Tetranychus species and highlight the need to evaluate the roles of essential genes in various organisms., (© 2022 Institute of Zoology, Chinese Academy of Sciences.)

After a stroke, sustained gait impairment can restrict participation in the activities listed in the International Classification of Functioning, Disability, and Health model and cause poor quality of life. The present study investigated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and visual feedback training (VF) training in improving lower limb motor performance, gait, and corticospinal excitability in patients with chronic stroke. Thirty patients were randomized into three groups that received either rTMS or sham stimulation over the contralesional leg region accompanied by VF training groups in addition to the conventional rehabilitation group. All participants underwent intervention sessions three times per week for four weeks. Outcome measures included the motor-evoked potential (MEP) of the anterior tibialis muscle, Berg Balance Scale (BBS) scores, Timed Up and Go (TUG) test scores, and Fugl-Meyer Assessment of Lower Extremity scores. After the intervention, the rTMS and VF group had significantly improved in MEP latency ( p = 0.011), TUG scores ( p = 0.008), and BBS scores ( p = 0.011). The sham rTMS and VF group had improved MEP latency ( p = 0.027). The rTMS and VF training may enhance the cortical excitability and walking ability of individuals with chronic stroke. The potential benefits encourage a larger trial to determine the efficacy in stroke patients.

Due to the popularity of different high bandwidth applications, it is becoming increasingly difficult to satisfy the huge data capacity requirements, since the traditional electrical interconnects suffer significantly from limited bandwidth and huge power consumption. Silicon photonics (SiPh) is one of the important technologies for increasing interconnect capacity and decreasing power consumption. Mode-division multiplexing (MDM) allows signals to be transmitted simultaneously, at different modes, in a single waveguide. Wavelength-division multiplexing (WDM), non-orthogonal multiple access (NOMA) and orthogonal-frequency-division multiplexing (OFDM) can also be utilized to further increase the optical interconnect capacity. In SiPh integrated circuits, waveguide bends are usually inevitable. However, for an MDM system with a multimode bus waveguide, the modal fields will become asymmetric when the waveguide bend is sharp. This will introduce inter-mode coupling and inter-mode crosstalk. One simple approach to achieve sharp bends in multimode bus waveguide is to use a Euler curve. Although it has been reported in the literature that sharp bends based on a Euler curve allow high performance and low inter-mode crosstalk multimode transmissions, we discover, by simulation and experiment, that the transmission performance between two Euler bends is length dependent, particularly when the bends are sharp. We investigate the length dependency of the straight multimode bus waveguide between two Euler bends. High transmission performance can be achieved by a proper design of the waveguide length, width, and bend radius. By using the optimized MDM bus waveguide length with sharp Euler bends, proof-of-concept NOMA-OFDM experimental transmissions, supporting two MDM modes and two NOMA users, are performed.

Interstitial cystitis/bladder pain syndrome with Hunner's lesion (HIC) is characterized by chronic inflammation and nerve hyperplasia; however, the pathogenesis of HIC remains a mystery. In this study, we detected both Epstein-Barr virus (EBV) latency infection genes EBNA-1 and LMP-1 and EBV lytic infection BZLF-1 and BRLF-1 expression in the HIC bladders, indicating the coexistence of EBV persistence and reactivation in the B cells in HIC bladders. Upregulation of EBV-associated inflammatory genes in HIC bladders, such as TNF-α and IL-6, suggests EBV infection is implicated in the pathogenesis of bladder inflammation. Nerve hyperplasia and upregulation of brain-derived neurotrophic factor (BDNF) were noted in the HIC bladders. Double immunochemical staining and flow cytometry revealed the origin of BDNF to be EBV-infected B cells. Inducible BDNF expression was noted in B cells upon EBV infection, but not in the T cells. A chromatin immunoprecipitation study revealed BDNF transcription could be promoted by cooperation between EBV nuclear antigens, chromatin modifiers, and B-cell-specific transcription. Knockdown of BDNF in EBV-infected B cells resulted in the inhibition of cell proliferation and viability. Downregulation of phosphorylated SMAD2 and STAT3 after BDNF knockdown may play a role in the mechanism. Implantation of latent EBV-infected B cells into rat bladder walls resulted in a higher expression level of CD45 and PGP9.5, suggesting tissue inflammation and nerve hyperplasia. In contrast, implantation of BDNF depleted EBV-infected B cells abrogated these effects. This is the first study to provide insights into the mechanisms underlying the involvement of EBV-infected B cells in HIC pathogenesis. © 2022 The Pathological Society of Great Britain and Ireland., (© 2022 The Pathological Society of Great Britain and Ireland.)

Background: Bladder dysfunction is a common non-motor disorder in Parkinson's disease (PD). This study attempted to determine the bladder dysfunction with disease progression in the PD rat model produced from unilateral/bilateral injections of 6-hydroxydopamine (6-OHDA)., Methods: Cystometrographic (CMG) and external urethral sphincter electromyographic (EUS-EMG) measurements were scheduled in a time-course manner to determine the disease timing, onset, and severity. Animals were allotted into normal control, unilateral, bilateral 6-OHDA injected groups and subjected to scheduled CMG, EUS-EMG analyses at weeks 1, 2, and 4., Results: The urodynamic results concluded that voiding efficiency (VE) was reduced in both unilateral and bilateral PD rats at all-time points. VE had decreased from 57 ± 11% to 31 ± 7% in unilateral PD rats and in bilateral PD rats, a decreased VE of 20 ± 6% was observed compared to control and unilateral PD rats. The EMG results in unilateral PD rats indicated declines in bursting period (BP) (3.78-2.94 s), active period (AP) (93.38-88.75 ms), and silent period (SP) (161.62-114.30 ms). A sudden reduction was noticed in BP (3.62-2.82 s), AP (92.21-86.01 ms), and SP (128.61-60.16 ms) of bilateral PD rats than in control and unilateral PD rats. Histological evidence exhibited a progressive dopaminergic neurons (DA) depletion in the substantia nigra (SN) region in 6-OHDA lesioned rats., Conclusion: The experimental outcomes strongly implied that significant variations in bladder function and VE decline were due to the depletion of DA neurons in the SN region of the brain., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Behavioral flexibility (or set-shifting), which is regulated by the prefrontal cortex (PFC), is often impaired in patients with attention-deficit/hyperactivity disorder (ADHD), which is characterized by poor inhibitory control and reinforcement learning. Transcranial direct current stimulation (tDCS) has been proposed as a means of noninvasive brain stimulation and a potential therapeutic tool for modulating behavioral flexibility. Animal studies can pave the way to know if tDCS application can potentially benefit rule- and goal-based activities in ADHD. Spontaneously hypertensive rats (SHRs) and inbred Wistar-Kyoto (WKY) rats were used as an animal model of ADHD and controls, respectively, and their strategy set-shifting abilities, including initial discrimination, set-shifting, and reversal learning tasks under 0-s or 15-s reinforcer delivery delay conditions, were evaluated. The tDCS treatment had a limited effect on the performance of the SHRs and WKY rats in initial discrimination task under 0-s delay condition. Under the 15-s delay condition, the SHRs had longer lever-press reaction times and/or more trial omissions than the WKY rats did when completing set-shifting and reversal-learning tasks. Among the SHRs, tDCS treatment improved the rats' reaction times and/or reduced their trial omissions in the set-shifting and reversal-learning tasks. Although tDCS may improve delayed reinforcement learning set-shifting performance in SHRs, further studies are required to clarify the responsible mechanism., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Silicon photonics (SiPh) are considered a promising technology for increasing interconnect speed and capacity while decreasing power consumption. Mode division multiplexing (MDM) enables signals to be transmitted in different orthogonal modes in a single waveguide core. Wideband MDM components simultaneously supporting wavelength division multiplexing (WDM) and orthogonal frequency-division multiplexing (OFDM) can significantly increase the transmission capacity for optical interconnects. In this work, we propose, fabricate and demonstrate a wideband and channel switchable MDM optical power divider on an SOI platform, supporting single, dual and triple modes. The switchable MDM power divider consists of two parts. The first part is a cascaded Mach-Zehnder interferometer (MZI) for switching the data from their original TE 0 , TE 1 and TE 2 modes to different modes among themselves. After the target modes are identified, mode up-conversion and Y-branch are utilized in the second part for the MDM power division. Here, 48 WDM wavelength channels carrying OFDM data are successfully switched and power divided. An aggregated capacity of 7.682 Tbit/s is achieved, satisfying the pre-forward error correction (pre-FEC) threshold (bit-error-rate, BER = 3.8 × 10 -3 ). Although up to three MDM modes are presented in the proof-of-concept demonstration here, the proposed scheme can be scaled to higher order modes operation.

Repetitive Transcranial Magnetic Stimulation (rTMS) and transspinal electrical stimulation (tsES) have been proposed as a novel neurostimulation modality for individuals with incomplete spinal cord injury (iSCI). In this study, we integrated magnetic and electrical stimulators to provide neuromodulation therapy to individuals with incomplete spinal cord injury (iSCI). We designed a clinical trial comprising an 8-week treatment period and a 4-week treatment-free observation period. Cortical excitability, clinical features, inertial measurement unit and surface electromyography were assessed every 4 weeks. Twelve individuals with iSCI were recruited and randomly divided into a combined therapy group, a magnetic stimulation group, an electrical stimulation group, or a sham stimulation group. The magnetic and electric stimulations provided in this study were intermittent theta-burst stimulation (iTBS) and 2.5-mA direct current (DC) stimulation, respectively. Combined therapy, which involves iTBS and transspinal DC stimulation (tsDCS), was more effective than was iTBS alone or tsDCS alone in terms of increasing corticospinal excitability. In conclusion, the effectiveness of 8-week combined therapy in increasing corticospinal excitability faded 4 weeks after the cessation of treatment. According to the results, combination of iTBS rTMS and tsDCS treatment was more effective than was iTBS rTMS alone or tsDCS alone in enhancing corticospinal excitability. Although promising, the results of this study must be validated by studies with longer interventions and larger sample sizes.

Background: The endosymbiont Wolbachia is known for manipulating host reproduction. Wolbachia also can affect host fitness by mediating interactions between plant and herbivores. However, it remains unclear whether saliva proteins are involved in this process., Results: We found that Wolbachia infection decreased the number of deposited eggs but increased the egg hatching rate in the spider mite Tetranychus urticae Koch (Acari: Tetranychidae), a cosmopolitan pest that infects >1000 species of plants. Transcriptomic and proteomic analyses revealed that Wolbachia-infected mites upregulated the gene expression levels of many T. urticae salivary proteins including a cluster of Tetranychidae-specific, functionally uncharacterized SHOT1s (secreted host-responsive proteins of Tetranychidae). The SHOT1 genes were expressed more in the feeding stages (nymphs and adults) of mites than in eggs and highly enriched in the proterosomas. RNA interference experiments showed that knockdown of SHOT1s significantly decreased Wolbachia density, increased the number of deposited eggs and decreased the egg hatching rate., Conclusion: Together, these results indicate that SHOT1s are positively correlated with Wolbachia density and account for Wolbachia-mediated phenotypes. Our results provide new evidence that herbivore salivary proteins are related to Wolbachia-mediated manipulations of host performance on plants. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Foot drop is a common clinical gait impairment characterized by the inability to raise the foot or toes during walking due to the weakness of the dorsiflexors of the foot. Lumbar spine disorders are common neurogenic causes of foot drop. The accurate prognosis and treatment protocols of foot drop are not well delineated in the scientific literature due to the heterogeneity of the underlying lumbar spine disorders, different severities, and distinct definitions of the disease. For translational purposes, the use of animal disease models could be the best way to investigate the pathogenesis of foot drop and help develop effective therapeutic strategies for foot drops. However, no relevant and reproducible foot drop animal models with a suitable gait analysis method were developed for the observation of foot drop symptoms. Therefore, the present study aimed to develop a ventral root avulsion (VRA)-induced foot drop rat model and record detailed time-course changes of gait pattern following L5, L6, or L5 + L6 VRA surgery. Our results suggested that L5 + L6 VRA rats exhibited changes in gait patterns, as compared to sham lesion rats, including a significant reduction of walking speed, step length, toe spread, and swing phase time, as well as an increased duration of the stance phase time. The ankle kinematic data exhibited that the ankle joint angle increased during the mid-swing stage, indicating a significant foot drop pattern during locomotion. Time-course observations displayed that these gait impairments occurred as early as the first-day post-lesion and gradually recovered 7-14 days post-injury. We conclude that the proposed foot drop rat model with a video-based gait analysis approach can precisely detect the foot drop pattern induced by VRA in rats, which can provide insight into the compensatory changes and recovery in gait patterns and might be useful for serving as a translational platform bridging human and animal studies for developing novel therapeutic strategies for foot drop., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Kuo, Liao, Peng, Hsieh and Chang.)

Background and Aim: In HBeAg negative chronic hepatitis B (CHB) patients, clinical relapse (CR) occurs more frequently, much earlier and often more severely after stopping tenofovir (TDF) and other nucleos(t)ide analogues (Nucs) than after stopping entecavir (ETV). It is unknown whether off-Nuc hepatitis flare can be alleviated by switching from one Nuc to another., Methods: HBeAg-negative CHB patients who had stopped Nuc according to the APASL stopping rule and had been followed-up for > 48 weeks after Nuc cessation were recruited. Patients were classified as four groups: ETV monotherapy (mono-ETV), TDF monotherapy (mono-TDF), switched to ETV (switch-ETV), and switched to TDF (switch-TDF). Both switch groups had switched to the replacement Nuc > 12 weeks prior to end of therapy. Propensity score matching (PSM) was performed to minimize confounders among groups. Cox regression analysis was used to identify risks factors for off-Nuc CR and flares., Results: A total of 1309 patients (1022 mono-ETV, 219 mono-TDF, 40 switch-ETV and 28 switch-TDF) were enrolled. The median time to CR was 39, 13, 38 and 14 weeks in mono-ETV, mono-TDF, switch-ETV and switch-TDF respectively (P < 0.001). After PSM, the mono-ETV (adjusted HR: 0.39, P < 0.001) and switch-ETV patients (adjusted HR: 0.41, P = 0.003) had both significantly later occurrence and lower rates of CR and flare., Conclusion: In summary, the incidence and timing of CR was determined by ETV or TDF in the last 3 months prior to end of treatment. Patients treated with non-ETV-Nuc switched to ETV > 12 weeks before end of the original Nuc therapy may reduce/defer CR., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Hepatocellular carcinoma (HCC) can be potentially discovered from abdominal computed tomography (CT) studies under varied clinical scenarios (e.g., fully dynamic contrast-enhanced [DCE] studies, noncontrast [NC] plus venous phase [VP] abdominal studies, or NC-only studies). Each scenario presents its own clinical challenges that could benefit from computer-aided detection (CADe) tools. We investigate whether a single CADe model can be made flexible enough to handle different contrast protocols and whether this flexibility imparts performance gains. We developed a flexible three-dimensional deep algorithm, called heterophase volumetric detection (HPVD), that can accept any combination of contrast-phase inputs with adjustable sensitivity depending on the clinical purpose. We trained HPVD on 771 DCE CT scans to detect HCCs and evaluated it on 164 positives and 206 controls. We compared performance against six clinical readers, including two radiologists, two hepatopancreaticobiliary surgeons, and two hepatologists. The area under the curve of the localization receiver operating characteristic for NC-only, NC plus VP, and full DCE CT yielded 0.71 (95% confidence interval [CI], 0.64-0.77), 0.81 (95% CI, 0.75-0.87), and 0.89 (95% CI, 0.84-0.93), respectively. At a high-sensitivity operating point of 80% on DCE CT, HPVD achieved 97% specificity, which is comparable to measured physician performance. We also demonstrated performance improvements over more typical and less flexible nonheterophase detectors. Conclusion: A single deep-learning algorithm can be effectively applied to diverse HCC detection clinical scenarios, indicating that HPVD could serve as a useful clinical aid for at-risk and opportunistic HCC surveillance., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background/purpose: Paired stimulation can cause neuroplasticity in corticospinal and spinal pathways in subjects with a chronic spinal cord injury (SCI). We aimed to know the effects of different waveforms using paired stimulations with bicycling in subjects with a chronic SCI., Methods: Recruited subjects with an SCI underwent three treatment interventions in random order for 4-20 min followed by 30 min of bicycling (control, repetitive transcranial magnetic stimulation (TMS; rTMS) at 20 Hz with transspinal direct current stimulation (tsDCS), and intermittent theta burst stimulation (iTBS) with tsDCS with a 1-week gap period. A TMS method was employed to record the resting motor threshold (RMT), the 90% values of which was used as the stimulation intensity, and the Hoffman (H)-reflex was measured by stimulating the tibial nerve in the popliteal fossa. The RMT, motor evoked potential (MEP) latency, MEP peak-to-peak amplitude, and H-reflex latency as primary variables and lower extremity motor scale (LEMS) and modified Ashworth spasticity scale (MAS) as secondary variables were analyzed before and after the interventions., Results: The MEP latency, MEP amplitude, and LEMS significantly improved with the rTMS-iTBS/tsDCS or the rTMS-20 Hz/tsDCS (p < 0.050) protocols compared to the control intervention. All other outcome measures, including RMT, H-reflex latency, and MAS score showed some changes but did not fully attain a level of significance., Conclusion: The paired stimulation with rTMS-iTBS/tsDCS was equally effective to produce neuroplastic effect in subjects with chronic SCI compared to the conventional TMS-20 Hz/tsDCS intervention., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Various infarct sizes induced by middle cerebral artery occlusion (MCAO) generate inconsistent outcomes for stroke preclinical study. Monitoring cerebral hemodynamics may help to verify the outcome of MCAO. The aim of this study was to investigate the changes in brain tissue optical properties by frequency-domain near-infrared spectroscopy (FD-NIRS), and establish the relationship between cerebral hemodynamics and infarct variation in MCAO model. The rats were undergone transient MCAO using intraluminal filament. The optical properties and hemodynamics were measured by placing the FD-NIRS probes on the scalp of the head before, during, and at various time-courses after MCAO. Bimodal infarction severities were observed after the same 90-min MCAO condition. Significant decreases in concentrations of oxygenated hemoglobin ([HbO]) and total hemoglobin ([HbT]), tissue oxygenation saturation (StO 2 ), absorption coefficient (μa) at 830 nm, and reduced scattering coefficient (μs') at both 690 and 830 nm were detected during the occlusion in the severe infarction but not the mild one. Of note, the significant increases in [HbO], [HbT], StO 2 , and μa at both 690 and 830 nm were found on day 3; and increases in μs' at both 690 and 830 nm were found on day 2 and day 3 after MCAO, respectively. The interhemispheric correlation coefficient (IHCC) was computed from low-frequency hemodynamic oscillation of both hemispheres. Lower IHCCs standing for interhemispheric desynchronizations were found in both mild and severe infarction during occlusion, and only in severe infarction after reperfusion. Our finding supports that sequential FD-NIRS parameters may associated with the severity of the infarction in MCAO model, and the consequent pathologies such as vascular dysfunction and brain edema. Further study is required to validate the potential use of FD-NIRS as a monitor for MCAO verification.

Background: High-definition transcranial electrical theta burst superimposing direct current stimulation (HD-tDCS-eTBS) not only incorporates the therapeutic advantages of tDCS and TBS but enhances stimulation focality and practicality. However, the applicability of this innovative neuromodulatory device in post-stroke rehabilitation remains uncertain., Objective: This study aimed to assess the efficacy and safety of the HD-tDCS-eTBS on upper extremity (UE) motor function in patients with chronic stroke., Methods: A patient-blinded, randomized controlled study was conducted. Twenty-four participants were randomly assigned into either the active HD-tDCS-eTBS group or sham HD-tDCS-eTBS group. Both groups received 20 minutes of active/sham HD-tDCS-eTBS combined with 30 minutes of conventional UE rehabilitation each time, 3 times a week for 4 weeks. Outcome measures including the Fugl-Meyer Assessment of Upper Extremity, Wolf Motor Function Test, Jebsen-Taylor Hand Function Test, Finger-Nose Test, and Modified Ashworth Scale were assessed before and immediately after the intervention period., Results: Spasticity of shoulder adductor ( P  = .05), elbow extensor ( P  = .04), and thumb flexor ( P  < .01) were significantly reduced in the active HD-tDCS-eTBS group versus the sham group. Nonsignificant trends in the improvements of most other outcome measures were in favor of the active HD-tDCS-eTBS group with moderate to large effect sizes ( P  = .06-.26, η p 2  = 0.06-0.16). No severe adverse events except for slight skin redness under the stimulus electrode was detected after the HD-tDCS-eTBS., Conclusions: Our findings support that HD-tDCS-eTBS is safe and has therapeutic potential for post-stroke UE motor rehabilitation., Trial Registration: ClinicalTrials.gov (ID: NCT04278105).

Almost one-fifth of the people in the world experience a decrease in quality of life due to overactive bladder (OAB) syndrome. The main bothersome symptoms are urgency accompanied by urinary frequency and nocturia. This chronic, disabling condition is first managed by reducing fluid intake and pelvic floor muscle training, supplemented with antimuscarinic drugs, if necessary. However, refractory cases often still occur. In more severe cases, invasive surgical interventions can be considered; yet, the success rate is still inconsistent, and there is a high complication rate. This condition is frustrating for patients and challenging for the medical staff involved. Although its pathophysiology has not been fully elucidated, peripheral autonomic somatic and sensory afferent receptors are considered to be involved in this condition. Hence, currently, physical agent-based treatments such as neuromodulation have taken a significant place in the third-line therapy of OAB. The efficacy and safety profiles of electrical and magnetic stimulation continue to evolve. Physical-based agents provide an appealing option owing to their effectiveness and minimal side effects. In addition, more physical therapies using light and shock energy are currently being investigated. Thus, a comprehensive understanding of these modalities is an extremely important aspect to provide the most suitable modalities for patients.

Paired stimulation of the brain and spinal cord can remodel the central nervous tissue circuitry in an animal model to induce motor neuroplasticity. The effects of simultaneous stimulation vary according to the extent and severity of spinal cord injury. Therefore, our study aimed to determine the significant effects on an incomplete SCI rat brain and spinal cord through 3 min and 20 min stimulations after 4 weeks of intervention. Thirty-three Sprague Dawley rats were classified into six groups: (1) normal, (2) sham, (3) iTBS/tsDCS, (4) iTBS/ts-iTBS, (5) rTMS/tsDCS, and (6) rTMS/ts-iTBS. Paired stimulation of the brain cortex and spinal cord thoracic (T10) level was applied simultaneously for 3−20 min. The motor evoked potential (MEP) and Basso, Beattie, and Bresnahan (BBB) scores were recorded after every week of intervention for four weeks along with wheel training for 20 min. Three-minute stimulation with the iTBS/tsDCS intervention induced a significant (p < 0.050 *) increase in MEP after week 2 and week 4 treatments, while 3 min iTBS/ts-iTBS significantly improved MEP (p < 0.050 *) only after the week 3 intervention. The 20 min rTMS/ts-iTBS intervention showed a significant change only in post&#95;5 min after week 4. The BBB score also changed significantly in all groups except for the 20 min rTMS/tsDCS intervention. iTBS/tsDCS and rTMS/ts-iTBS interventions induce neuroplasticity in an incomplete SCI animal model by significantly changing electrophysiological (MEP) and locomotion (BBB) outcomes.