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Ching Su,1 I-Ting Tsai,1,2 Chung-Hsu Lai,2,3 Kuo-Hsuan Lin,1 Chia‐Chi Chen,2,4 Yin-Chou Hsu1,2,5– 7 1Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, 82445, Taiwan; 2School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 3Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung City, 82445, Taiwan; 4Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung City, 82445, Taiwan; 5School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan; 6School of Medicine for International Student, I-Shou University, Kaohsiung, Taiwan; 7Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Yin-Chou Hsu, Department of Emergency Medicine, E-Da Hospital, No. 1, Yida Road, Jiao-Su Village, Yan-Chao District, Kaohsiung City, 82445, Taiwan, Tel +886-7-615-0011, Fax +886-7-615-5352, Email yinchou0406@gmail.comPurpose: Klebsiella pneumoniae is an important causative pathogen of nosocomial infections, resulting in poor prognosis owing to its hypervirulence and antibiotic resistance. A simplified quicker version of the Pitt bacteremia score (PBS) (qPitt) for acute illness severity measurement was developed recently. The goal of this study was to explore the prognostic value of qPitt in patients with K. pneumoniae infection.Patients and Methods: Demographic information and management strategies were retrospectively collected from the records of all adult patients who visited the emergency department between January 1, 2021, and December 31, 2021, with culture-positive K. pneumoniae. The qPitt score was calculated based on: temperature < 36°C, systolic blood pressure ≤ 90 mmHg or vasopressor administration, respiratory rate ≥ 25 times/min or need of mechanical ventilation, altered mental status, and cardiac arrest event. The 30-day mortality prediction abilities of the qPitt were compared with the PBS, the sequential organ failure assessment (SOFA), and the quick sequential organ failure assessment (qSOFA) using receiver operating characteristic curves.Results: Data from 867 patients (57.8% men) with a mean age of 66.9 were compiled. The 30-day mortality rate of the enrolled patients was 13.4%, and the area under the curve (AUC) of the scoring systems were as follows: SOFA, 0.91 (95% confidence interval [CI]=0.89– 0.93), qPitt, 0.87 (95% CI=0.84– 0.89), PBS, 0.87 (95% CI=0.85– 0.89), and qSOFA, 0.73 (95% CI=0.70– 0.76). The AUC of qPitt was significantly higher than that of qSOFA (p< 0.01) and similar to that of PBS (p=0.65).The qPitt also demonstrated excellent mortality discrimination ability in non-bacteremic patients, AUC= 0.85 (95% CI=0.82– 0.88).Conclusion: The qPitt revealed excellent 30-day mortality prediction ability and also predicted mortality in non-bacteremic patients with K. pneumoniae infection. Clinicians can use this simplified scoring system to stratify patients earlier and initiate prompt treatment in high-risk patients.Keywords: Klebsiella pneumoniae, organ dysfunction scores, bacteremia, prognosis

Tzu-Chi Teng,1,2 I-Hung Shao,1,2 Yu-Chao Hsu,1,2 Yu Chen,1,2 Shu-Han Tsao,1,2 Yen-Te Kang,1,2 Ming-Li Hsieh1,2 1Division of Urology, Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan City, 33302, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan City, 33302, TaiwanCorrespondence: Ming-Li Hsieh; I-Hung ShaoDivision of Urology, Department of Surgery, Linkou Chang Gung Memorial Hospital, No. 5, Fuxing Street, Guishan District, Taoyuan City, 333423, TaiwanTel +886 975 365 568; +886 975 361311Fax +886-3-3274541Email h0810@cgmh.org.tw; b8902068@cgmh.org.twPurpose: Transurethral procedures, including transurethral resection of the prostate (TURP) and laser prostatectomy, are often linked to emergency room (ER) visits for postoperative bleeding. Although some studies have been conducted, the risk factors associated with these ER visits are not completely understood. This retrospective cohort study identified potential risk factors associated with ER visits for postoperative bleeding.Patients and Methods: Preoperative assessment data and operational and postoperational parameters recorded at Chang Gung Memorial Hospital, Taiwan between December 2015 and January 2017 for patients who underwent elective transurethral procedures were analyzed to identify potential risk factors. The primary endpoint was ER visits for gross hematuria within three months following operation, and the secondary endpoint was ER visits for blood clot-induced urinary retention (clot retention) within three months following operation.Results: A total of 665 patients who underwent elective transurethral procedures were enrolled. The transurethral procedures included monopolar transurethral resection of the prostate (M-TURP), bipolar TURP (B-TURP), greenlight photoselective vaporization of the prostate (PVP), thulium laser enucleation of the prostate (ThuLEP) and thulium laser transurethral vaporesection of the prostate (ThuVARP). Regarding ER visits for clot retention within three months, multivariable logistic regression revealed significantly lower rates of clot retention in patients who received B-TURP than in those who underwent ThuVARP (AOR, 0.18; 95% confidence interval [CI], 0.04– 0.82, p = 0.027). Moreover, significantly higher clot retention was observed in patients who underwent two or more rounds of manual irrigation (AOR, 9.51; 95% CI, 1.66– 54.43, p = 0.011).Conclusion: Multiple manual irrigations shortly after operation can be considered a novel predictor of postoperative clot retention-related ER visits. Among the transurethral procedures, ThuVARP was associated with a higher risk of clot retention-related ER visits than was B-TURP.Keywords: transurethral resection of prostate, laser prostatectomy, hematuria, clot retention

Yi-Sin Wong, 1 Sheng-Feng Sung, 2 Chi-Shun Wu, 2 Yung-Chu Hsu, 2 Yu-Hsiang Su, 2 Ling-Chien Hung, 2 Cheung-Ter Ong 2 1Department of Family Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan; 2Department of Neurology, Chia-Yi Christian Hospital, Chia-Yi, TaiwanCorrespondence: Cheung-Ter OngDepartment of Neurology, Chia-Yi Christian Hospital, 539 Chung-Shao Road, Chia-Yi, TaiwanTel +886-5-2765041Email ctong98@yahoo.com.twBackground: Intravenous tissue plasminogen activator (tPA) (0.9 mg/kg, maximum 90 mg) with a bolus of 10% of the total dose given within 1– 2 mins is the standard therapy for patients receiving thrombolytic therapy. Low-dose (0.6 mg/kg) tPA is also approved for thrombolytic therapy for ischemic stroke patients. Low-dose tPA is associated with a low bolus dose. It is unknown whether increasing the bolus dose in patients receiving low-dose tPA thrombolysis may improve outcomes or increase the risk of hemorrhagic transformation (HT).Aim: This study investigated the impact of the bolus dose on the outcome in ischemic stroke patients receiving low-dose tPA thrombolytic therapy.Methods: In this retrospective, observational study, we enrolled 214 ischemic stroke patients receiving low-dose tPA thrombolytic therapy. Of these 214 patients, 107 patients received 10% of the total dose as a bolus dose, and 107 patients received 15% of the total dose as a bolus dose. The National Institutes of Health Stroke Score (NIHSS) were evaluated before tPA infusion, 24 h after thrombolytic therapy, and at discharge. Stroke severity was categorized as mild (0– 5), moderate (6– 14), severe (15– 24), or very severe (≥ 25). Neurological improvement (NI) was defined as an improvement of 6 or more points in the NIHSS, and no response (NR) was defined as an increase in the NIHSS of ≤ 4 points or a decrease ≤ 6 points. Neurological deterioration (ND) was defined as an increase in the NIHSS > 4 points. A good outcome was defined as a modified Ranking Score (mRS) of 0 or 1. We compared the NI, NR, and ND rates at 24 hrs after thrombolytic therapy and discharge between the 15% and 10% bolus dose groups.Results: In patients with mild and moderate stroke, there was no significant difference in the NI, NR, ND, and HT rates and 6-month outcomes between the 15% and 10% bolus groups. In patients with severe and very severe stroke, outcomes at 6 months were significantly better in the 15% bolus group than in the 10% bolus group. The factors affecting the outcomes of severe and very severe stroke patients are hypertension and bolus dose.Conclusion: In severe and very severe stroke patients receiving low-dose tPA thrombolytic therapy, a bolus dose of 15% of the total dose can improve outcomes.Keywords: ischemic stroke, tPA, thrombolysis, hypertension, outcome

Yu-Chun Hsu,1,* Wei-Ting Wu,2,* Ke-Vin Chang,2–4 Der-Sheng Han,2–4 Li-Wei Chou5–7 1Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, 2Department of Physical Medicine and Rehabilitation and Community and Geriatric Research Center, National Taiwan University Hospital, Bei-Hu Branch, 3National Taiwan University College of Medicine, 4Community and Geriatric Research Center, National Taiwan University Hospital, Bei-Hu Branch, Taipei, 5Department of Physical Medicine and Rehabilitation, China Medical University Hospital, 6Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, 7Department of Rehabilitation, Asia University Hospital, Taichung, Taiwan *These authors contributed equally to this work Abstract: Achilles tendinopathy is a common cause of posterior heel pain and can progress to partial tendon tear without adequate treatment. Effects of traditional treatments vary, and many recent reports focus on the use of extracorporeal shockwave therapy (ESWT) for Achilles tendinopathy but not for Achilles tendon partial tear. Here, we report the case of a 64-year-old female suffering from severe left heel pain for half a year. All treatment and rehabilitation were less effective until ESWT was applied. Each course of focused shockwave therapy included 2500 shots with energy flux density from 0.142 mJ/mm2 to 0.341 mJ/mm2. The visual analog scale decreased from nine to one degree. High-resolution musculoskeletal ultrasonography was performed before and 1 month after the treatment, which revealed healing of the torn region and decrease in inflammation. ESWT had shown to be an alternative treatment for Achilles tendon partial tear under safety procedure and ultrasound observation. Keywords: focused shockwave, Achilles tendon, partial tear, ultrasonography

Yi-Chien Hsu,1,2 Yu-Ching Chou,3 Hsin-An Chang,1,2,4 Yu-Chen Kao,1,2,5 San-Yuan Huang,1,2 Nian-Sheng Tzeng1,2,4 1Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan; 2School of Medicine, 3School of Public Health, 4Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 5Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, Taipei, Taiwan Objectives: Refractory major depressive disorder (MDD) is a serious problem leading to a heavy economic burden. Antipsychotic augmentation treatment with aripiprazole and quetiapine is approved for MDD patients and can achieve a high remission rate. This study aimed to examine how psychiatrists in Taiwan choose medications and how that choice is influenced by health insurance payments and administrative policy.Design: Descriptive study.Outcome measures: Eight questions about the choice of treatment strategy and atypical antipsychotics, and the reason to choose aripiprazole.Intervention: We designed an augmentation strategy questionnaire for psychiatrists whose patients had a poor response to antidepressants, and handed it out during the annual meeting of the Taiwanese Society of Psychiatry in October 2012. It included eight questions addressing the choice of treatment strategy and atypical antipsychotics, and the reason whether or not to choose aripiprazole as the augmentation antipsychotic.Results: Choosing antipsychotic augmentation therapy or switching to other antidepressant strategies for MDD patients with an inadequate response to antidepressants was common with a similar probability (76.1% vs 76.4%). The most frequently used antipsychotics were aripiprazole and quetiapine, however a substantial number of psychiatrists chose olanzapine, risperidone, and sulpiride. The major reason for not choosing aripiprazole was cost (52.1%), followed by insurance official policy audit and deletion in the claims review system (30.1%).Conclusion: The prescribing behavior of Taiwanese psychiatrists for augmentation antipsychotics is affected by health insurance policy. Keywords: major depressive disorder, aripiprazole, psychiatrists, prescribing behavior, anti­psychotic augmentation, National Health Insurance program

Chen-Pang Hou,1,* Tzu-Yu Chen,2,* Chia-Chi Chang,3 Yu-Hsiang Lin,1 Phei-Lang Chang,1 Chien-Lun Chen,1 Yu-Chao Hsu,1 Ke-Hung Tsui1 1Department of Urology, Chang Gung Memorial Hospital Linko, Chang Gung University, Taiwan, Republic of China; 2Department of Nursing, Chang Gung Memorial Hospital, Taipei, Republic of China; 3College of Nursing, Taipei Medical University, Taipei, Republic of China *These authors contributed equally to this work Purpose: We used the Short Form (SF)-36® Health Survey scale to assess the effect of pelvic floor muscle exercise (PFE) on aging males who received transurethral resection of the prostate (TUR-P). Methods: From April 2010 to December 2010, a total of 66 patients who underwent TUR-P were enrolled in this study. They were randomized into two groups (with 33 patients in each group) – an experimental group who performed postoperative PFE every day and a control groups. Data, including the International Prostate Symptom Score (IPSS), uroflowmetry study, and the SF-36 quality of life measure, were collected before the operation, and at 1, 4, 8, and 12 weeks after the operation. We analyzed the differences between the two groups with respect to their IPSS scores, maximal urinary flow rate, residual urine amount, and life quality. Results: A total of 61 patients (experimental group: 32 patients, and control group: 29 patients) completed this study. We found that at 12 weeks postop, patients who performed PFE every day had a better maximal urinary flow rate (16.41 ± 6.20 vs 12.41 ± 7.28 mL/min) (P = 0.026) compared with patients in the control group. The experimental group had a much greater decrease in IPSS score (P < 0.001). As for the SF-36 scale, the experimental group had higher scores than did the control group on both the physiological domain (54.86 vs 49.86) (P = 0.029) and the psychological domain (61.88 vs 52.69) (P = 0.005). However, there were no significant differences with respect to the postvoiding residual urine between the two groups (57.24 ± 52.95 vs 64.68 ± 50.63 mL) (P = 0.618). Conclusion: Compared with the control group, patients who performed PFE for 12 weeks after TUR-P showed improvement in their maximal urinary flow rate and lower urinary tract symptoms, and had a better quality of life. The immediate initiation of PFE is suggested for patients who undergo TUR-P. Keywords: benign prostatic hyperplasia, SF-36, pelvic floor exercise, prostatectomy, quality of life

Objectives: The efficacy of sequential therapy and the applicability of genotypic resistance to guide the selection of antibiotics in the third-line treatment of Helicobacter pylori have not been reported. We aimed to assess the efficacy of genotypic resistance-guided sequential therapy in third-line treatment.Methods: Genotypic and phenotypic resistances were determined in patients who failed at least two eradication therapies by PCR with direct sequencing and agar dilution test, respectively. The patients were retreated with sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole plus clarithromycin, levofloxacin or tetracycline for another 7 days (all twice daily), according to genotypic resistance determined using gastric biopsy specimens. Eradication status was determined by the (13)C-urea breath test. Trial registered at clinicaltrials.gov (identifier: NCT01032655).Results: The overall eradication rate was 80.7% (109/135, 95% CI 73.3%-86.5%) in the intention-to-treat analysis. The presence of amoxicillin resistance (OR 6.83, 95% CI 1.62-28.86, P = 0.009) and prior sequential therapy (OR 4.77, 95% CI 1.315-17.3, P = 0.017), but not tetracycline resistance (tetracycline group), were associated with treatment failure. The eradication rates in patients who received clarithromycin-, levofloxacin- and tetracycline-based sequential therapies were 78.9% (15/19), 92.2% (47/51) and 71.4% (25/35) in strains susceptible to clarithromycin, levofloxacin and tetracycline, respectively.Conclusions: A simple molecular method guiding sequential therapy can achieve a high eradication rate in the third-line treatment of refractory H. pylori infection. [ABSTRACT FROM AUTHOR]

Context: Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection.Objective: To investigate the association between nucleoside analogue use and risk of tumor recurrence in patients with hepatitis B virus (HBV)--related HCC after curative surgery.Design, Setting, and Participants: A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010.Main Outcome Measures: The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality.Results: The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 [20.5%] vs n = 1765 [43.6%]; P < .001), and lower overall death (n = 55 [10.6%] vs n = 1145 [28.3%]; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89).Conclusion: Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection. [ABSTRACT FROM AUTHOR]

Triptolide (C(38) H(42) O(6) N(2) , TP, a diterpene triepoxide derived from Tripterygium wilfordii Hook F.), is a potent immunosuppresive and antiinflammatory agent. The present study investigated whether TP exerted antihepatofibrotic effects in vitro and in vivo. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with tumor necrosis factor-[alpha] (TNF-[alpha]) or transforming growth factor (TGF)-[beta]1. The inhibitory effects of TP on the nuclear factor-[kappa]B (NF[kappa]B) signaling cascade and fibrosis markers, including [alpha]-smooth muscle actin ([alpha]-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats. The rats were randomly assigned to one of three groups: control rats, DMN rats receiving vehicle only and DMN rats receiving TP (20 [mu]g/kg). Treatment was given by gavage twice daily for 3 weeks starting 1 week after the start of DMN administration. TP (5-100 nm) concentration-dependently inhibited the NF[kappa]B transcriptional activity induced by TNF-[alpha], lipopolysaccharide and phorbol 12-myristate 13-acetate in HSC-T6 cells. In addition, TP also suppressed TNF-[alpha] and TGF-[beta]1-induced collagen deposition and [alpha]-SMA secretion in HSC-T6 cells. In vivo, TP treatment significantly reduced hepatic fibrosis scores, collagen contents, IL-6 and TNF-[alpha] levels, and the number of [alpha]-SMA and NF[kappa]B-positive cells in DMN rats. The results showed that TP exerted antifibrotic effects in both HSC-T6 cells and DMN rats. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma are involved in the tumorigenesis and regulation of cell metabolism via Akt signaling. F-18 fluorodeoxyglucose-positron emission tomography ([(18)F]FDG PET), a functional imaging modality, can be used to measure tumor cell metabolism. Thus, in this study, we hypothesize that there exist correlations between EGFR mutation status and [(18)F]FDG uptake of advanced lung adenocarcinoma.Methods: From May 2004 to April 2008, patients with stage IIIB or IV lung adenocarcinoma who underwent [(18)F]FDG PET and EGFR mutation analysis before receiving any treatment were eligible to participate in this study. The association of EGFR mutation status with patient characteristics and the SUV(MAX) from the [(18)F]FDG PET was evaluated. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations.Results: Seventy-seven lung adenocarcinoma patients were included in this study. EGFR mutations were identified in 49 (64%) of the patients. The [(18)F]FDG uptake was significantly higher in EGFR-mutant (mean SUV(MAX) = 10.5 +/- 4.7) than wild-type (8.0 +/- 3.3) lung adenocarcinoma patients (P = 0.008). The median SUV(MAX) was 9.5, and patients with an SUV(MAX) >or= 9.5 were more likely to harbor EGFR mutations (P = 0.009). In the multivariate analysis, an SUV(MAX) >or= 9.5 remained a statistically significant predictor of EGFR mutations (P = 0.005).Conclusions: Among Asian patients with advanced lung adenocarcinoma, those with higher SUV(MAX) on the [(18)F]FDG PET are more likely to carry EGFR mutations. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study was to evaluate the feasibility and effectiveness of correction for square jaw with low angle using mandibular 'V-line' ostectomy combined with outer cortex ostectomy. STUDY DESIGN: From July 2005 to November 2007, 31 patients who had square faces with low angles were treated with mandibular 'V-line' ostectomy combined with mandibular outer cortex ostectomy. All the patients had standard frontal and lateral cephalometric radiographs, panoramic radiographs, and were photographed preoperatively and postoperatively to assess their face contour. The alteration of mandibular angle and width of lower face was observed for 6 to 24 months postoperatively. RESULTS: Postoperative appearance of all 31 cases showed that the width of lower face was reduced expectedly; the gonial angle and the mandibular plane angle were increased effectively. The final aesthetic outcomes were quite satisfactory in all cases for both the surgeons and the patients. CONCLUSION: A slender oval facial outline as the fashionable aesthetics could be achieved by using mandibular 'V-line' ostectomy combined with mandibular outer cortex ostectomy. It might be a feasible and a reasonable surgical procedure for correction of square jaw with low angle. [ABSTRACT FROM AUTHOR]

RATIONALE: Gefitinib is effective in treating patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Deletions in exon 19 and L858R in exon 21 are the best-documented EGFR mutations that are associated with effective gefitinib responsiveness. OBJECTIVES: To clarify the influence of gefitinib timing, we conducted a study to compare the outcomes of different lines of gefitinib treatment in patients with exon 19 deletions or L858R. METHODS: We surveyed the clinical data and mutational studies of patients with NSCLC with EGFR mutations in the National Taiwan University Hospital (Taipei, Taiwan). MEASUREMENTS AND MAIN RESULTS: Three hundred and twenty-eight patients, who received gefitinib for stage IIIb or IV NSCLC, were adequately sequenced for EGFR mutations; 192 patients had mutant EGFR, including 77 patients with exon 19 deletions and 75 patients with L858R. The 152 patients with exon 19 deletions or L858R and who were receiving gefitinib were classified into a chemonaive group (91 patients) or a chemotherapy-treated group (61 patients). Chemonaive status before gefitinib and female sex were associated with clinical response to gefitinib (P = 0.006 and 0.053, respectively). Neither overall survival after the start of antitumor therapy nor progression-free survival after gefitinib therapy was significantly different between these two groups (P = 0.207 and 0.804, respectively). Clinical response to gefitinib was the only factor associated with better overall survival (P = 0.001). CONCLUSIONS: This study suggests that gefitinib is effective in patients with EGFR mutations. The gefitinib response rate in chemonaive patients is higher than in chemotherapy-treated patients; however, there is no difference in overall survival. [ABSTRACT FROM AUTHOR]

Purpose: The etiology and mechanism of nasal polyps are still not well known. A newly discovered transcriptional factor, hypoxia-inducible factor (HIF), is a DNA-binding protein. Hypoxia-inducible factor is demonstrated to associate with various neoplasms. We investigate the expression of HIF-1alpha protein in nasal polyps compared with inferior turbinate mucosa, further examining the correlation to the computed tomography (CT) scoring and duration of symptoms with HIF-1alpha expression. Materials and Methods: Surgical specimens of polyps from 38 patients undergoing endoscopic sinus surgery had immunohistochemical staining for HIF-1alpha and vascular endothelial growth factor. Thirty-six patients who had undergone septomeatoplasty were collected as a control group. The severity of the disease was judged by the Lund-Mackay scoring system by CT scanning. Result: The expression of HIF-1alpha and vascular endothelial growth factor were significantly increased in nasal polyps than in the control group. No correlation was found between the severity of CT scan and duration of symptoms to the HIF-1alpha expression. Conclusion: We suggest that HIF-1alpha may play a role in the pathogenesis of nasal polyps. [ABSTRACT FROM AUTHOR]

Summary 1. Free radicals mediate cerebral ischaemic injury associated with heatstroke. Magnolol, an active component of Magnolia officinalis , is 1000-fold more potent than α-tocopherol in inhibiting lipid peroxidation in rat mitochondria. The aim of the present study was to ascertain whether magnolol attenuated cerebral ischaemic injury and free radical formation associated with heatstroke. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 42°C) to induce heatstroke. Controlled rats were exposed to 24°C. Mean arterial pressure, cerebral perfusion pressure and cerebral blood flow after the onset of heatstroke were all significantly lower than in control rats. However, colonic temperature, intracranial pressure, heart rate, cerebral free radicals, lipid peroxidation and the neuronal damage score were greater after the onset of heatstroke. 3. Magnolol (20 or 40 mg/kg, i.v.) significantly attenuated the heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischaemia and neuronal damage and increased free radical formation and lipid peroxidation in the brain. The extracellular concentrations of ischaemic (e.g. glutamate and lactate/pyruvate ratio) and damage (e.g. glycerol) markers in the corpus striatum were increased after the onset of heatstroke. Magnolol significantly attenuated the increase in striatal ischaemia and damage markers associated with heatstroke. 4. Thus, it appears that magnolol has impressive effects against heatstroke reactions. [ABSTRACT FROM AUTHOR]

Zwitterionic materials, known for their high hydrophilicity, are widely used to minimize the nonspecific adsorption of biomolecules in complex biological solutions. However, these materials can also reduce the capture efficiency between targets and peptide probes. To demonstrate how antifouling surfaces affect capture efficiency, we utilize a poly(3,4-ethylenedioxythiophene) (PEDOT)-based surface incorporating varying ratios of phosphorylcholine (PEDOT-PC) and maleimide functional groups to achieve both antifouling properties and peptide-protein binding. As a model system, the peptide YWDKIKDFIGGSSSSC, attached via maleimide groups, is used to capture the target protein, calmodulin (CaM). By systematically monitoring protein binding on both antifouling and peptide-immobilized PEDOT surfaces using a quartz crystal microbalance with dissipation, the results reveal that PEDOT-PC reduces both the specific binding between peptides and target proteins as well as the rate of protein fouling on the electrode surface. From these findings, we propose an equation for quantitative analysis. Furthermore, electrochemical impedance spectroscopy and differential pulse voltammetry are performed to measure the changes in the impedance in CaM solutions. The data indicate that impedance increases with protein adsorption, confirming the practical utility of the designed electrode surface.

Counselling sessions have multiple stages, each with its themes and objectives. This study aimed to apply Hidden Markov Models (HMMs) to analyse counselling sessions from Open Up, an online text-based counselling platform in Hong Kong. The focus was on inferring latent stages over word distributions and identifying distinctive patterns of progression in more versus less satisfying sessions. Transcripts from 2589 sessions were categorized into more satisfying sessions ( n = 1993 ) and less satisfying sessions ( n = 596 ) based on post-session surveys. A message-level HMM identified five distinct stages: Rapport-building, Problem-identification, Problem-exploration, Problem-solving, and Wrap-up. Compared with less satisfying sessions, more satisfying sessions saw significantly more efficient initial rapport building (7.5% of session duration), problem introduction (20.2%), problem exploration (28.5%), elaborated solution development (46.6%), and concise conclusion (8.2%). This study offers insights for improving the efficiency and satisfaction of text-based counselling services through efficient initial engagement, thorough issue exploration, and focused problem-solving., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This study aimed to assess the characteristics of particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) from various stationary and mobile emission sources in Taiwan, with a focus on source apportionment and associated health risks. The northern power plant, equipped with bag filters operating at 150 °C, had significantly lower FPM and CPM levels (0.44 and 0.13 mg/m 3 , respectively) compared to the central and southern power plants, which used electrostatic precipitators operating at 250 °C (FPM, 1.45-8.35 mg/m 3 ; CPM, 2.37-3.73 mg/m 3 ). Additionally, emissions from diesel vehicles under both idle and high-speed conditions exhibited higher FPM levels (3.46-4.67 mg/m 3 ) than gasoline vehicles (0.19-0.40 mg/m 3 ). In terms of PAH toxicity, diesel vehicle emissions had significantly higher BaP-TEQ (87.3 ng/m 3 ) and BaP-MEQ (25.9 ng/m 3 ) levels compared to power plants (BaP-TEQ, 5.49 ng/m 3 ; BaP-MEQ, 2.65 ng/m 3 ). The highest ambient concentrations of PM2.5, BaP-TEQ, and BaP-MEQ were recorded at traffic sites, with values of 48 ± 36 µg/m 3 , 0.29 ng/m 3 , and 0.11 ng/m 3 , respectively. Differences in PAH distributions between stationary and mobile sources were influenced by factors such as pollution control technologies, combustion temperatures, and fuel types. Diesel vehicle emissions were dominated by benzo[g,h,i]perylene (BghiP), indeno[1,2,3-cd]pyrene (IND), benzo[a]pyrene (BaP), and benzo[b]fluoranthene (BbF) under idle conditions, while phenanthrene (PA), pyrene (Pyr), and BghiP were prevalent under high-speed conditions. Source apportionment conducted using principal component analysis (PCA) and positive matrix factorization (PMF) identified diesel and gasoline vehicles as the dominant contributors to atmospheric PAHs in Taiwan, accounting for 38% of the total, followed by coal-fired power plants at 35%. The highest lifetime excess cancer risk (ECR) of 2.5 × 10⁻ 5 was observed in traffic-dense areas, emphasizing the public health implications of vehicle emissions. The study adds credibility to the source apportionment findings, and the health risk analysis highlights variations across different regions, including traffic, urban, rural, and background zones., Competing Interests: Declarations Ethical approval Not applicable. Consent to participate All authors contributed to this work. Consent for publication All authors have approved authorship, read, and consented to publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aim: Computed tomography of the abdomen exhibits subtle and complex features of liver lesions, subjectively interpreted by physicians. We developed a deep learning-based localization and classification (DLLC) system for focal liver lesions (FLLs) in computed tomography imaging that could assist physicians in more robust clinical decision-making., Methods: We conducted a retrospective study (approval no. EMRP-109-058) on 1589 patients with 17 335 slices with 3195 FLLs using data from January 2004 to December 2020. The training set included 1272 patients (male: 776, mean age 62 ± 10.9), and the test set included 317 patients (male: 228, mean age 57 ± 11.8). The slices were annotated by annotators with different experience levels, and the DLLC system was developed using generative adversarial networks for data augmentation. A comparative analysis was performed for the DLLC system versus physicians using external data., Results: Our DLLC system demonstrated mean average precision at 0.81 for localization. The system's overall accuracy for multiclass classifications was 0.97 (95% confidence interval [CI]: 0.95-0.99). Considering FLLs ≤ 3 cm, the system achieved an accuracy of 0.83 (95% CI: 0.68-0.98), and for size > 3 cm, the accuracy was 0.87 (95% CI: 0.77-0.97) for localization. Furthermore, during classification, the accuracy was 0.95 (95% CI: 0.92-0.98) for FLLs ≤ 3 cm and 0.97 (95% CI: 0.94-1.00) for FLLs > 3 cm., Conclusion: This system can provide an accurate and non-invasive method for diagnosing liver conditions, making it a valuable tool for hepatologists and radiologists., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment., Design: We identified TLR8 -expressing cell types in the human liver using publicly available single-cell RNA-seq data and established a method to isolate Kupffer cells (KCs). We characterised transcriptomic and cytokine KC profiles in response to SLGN. SLGN's indirect effect was evaluated by RNA-seq in hepatocytes treated with SLGN-conditioned media (CM) and quantification of HBV parameters following infection. Pathways mediating SLGN's effect were validated using transcriptomic data from HBV-infected patients., Results: Hepatic TLR8 expression takes place in the myeloid compartment. SLGN treatment of KCs upregulated monocyte markers (eg, S100A12 ) and downregulated genes associated with the KC identity (eg, SPIC ). Treatment of hepatocytes with SLGN-CM downregulated NTCP and impaired HBV entry. Cotreatment with an interleukin 6-neutralising antibody reverted the HBV entry inhibition., Conclusion: Our transcriptomic characterisation of SLGN sheds light into the programmes regulating KC activation. Furthermore, in addition to its previously described effect on established HBV infection and adaptive immunity, we show that SLGN impairs HBV entry. Altogether, SLGN may contribute through KCs to remodelling the intrahepatic immune microenvironment and may thus represent an important component of future combinations to cure HBV infection., Competing Interests: Competing interests: FZ and BT received grants from Assembly, Beam Therapeutics, Blue Jay and JnJ; FZ had consulting activities with Assembly, Blue Jay and GSK. YCH receives grants from Gilead Sciences and Sysmex. FZ is an associate editor of the journal. SD, LL, NK, JJW, AHL, and SPF are or were employees of Gilead Sc., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Empathy is an important factor in the doctor-patient relationship, but mental illness is more difficult to understand than other diseases. Besides traditional skills, virtual reality (VR) has been identified as a promising tool in empathy education. This study aimed to investigate the ability of empathy enhancement, the feasibility of depression education, and the changes in thoughts and attitudes in medical students through a single VR experience., Methods: We recruited medical students and randomly assigned them to two groups based on their completed Interpersonal Response Index scores. Two sets of VR systems were provided; the intervention group experienced the daily life of the depressed medical student, while the control group experienced the general medical student scenario. The improvement of empathy was assessed using the Jefferson Scale of Empathy-Health Professional Students (JSE-HPS), and the change of attitude was assessed through the Implicit Association Test. In addition, other questionnaires were used to evaluate the user experience of this VR system, and correlation analysis was conducted to examine the association between the use of VR and changes in the JSE and IAT scores., Results: A total of 59 medical students were enrolled in this study. The intervention group showed a significant increase in the perspective-taking (pre: mean 5.817, SD 0.536; post: mean 5.947, SD 0.620; P = .03) and compassionate care (pre: mean 5.546, SD 0.581; post: mean 5.721, SD 0.629; P = .01) domains of the JSE score and a significant decrease in the standing in the patient's shoes (SP) domain (pre: mean 3.583, SD 1.253; post: mean 2.967, SD 1.252; P = .002). The Pearson correlation analysis found a significant positive correlation between the JSE score with immersion aspect (r = .308, P = .049) and presence aspect (r = .415, P = .01), and we also found a significant negative correlation between the IAT score and presence aspect (r=-.333, P = .04)., Conclusions: This study is the first randomized case-control study to investigate the effect of two different versions of VR on empathy development toward depression for medical students. Although the single VR experience was unable to induce a great improvement in empathy or attitude, the VR system could help medical students enhance their understanding of depressive disorders., Trial Registration: This trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (21/03/2024, ACTRN12624000297527). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386683&isReview=true ., (© 2024. The Author(s).)

Pain is a sensation that signals the presence of inflammation or injury. In this issue of Developmental Cell, Ben-Shaanan et al. 1 show that beyond its sensory function, pain can activate hair follicle stem cells (HFSCs) by controlling their niche., Competing Interests: Declaration of interests Y.-C.H. is an inventor on a patent filed by the President and Fellows of Harvard College for methods and compositions related to hair growth control., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/aim: Beta2-glycoprotein I (β2-GPI) is a plasma glycoprotein with multiple physiological functions, but its relationship with hepatocellular carcinoma (HCC) is still poorly understood. HCC is one of the most common forms of liver cancer and is a leading cause of cancer-related death worldwide. This study aimed to investigate the association between β2-GPI and liver cancer and further validate its potential as a biomarker for HCC., Patients and Methods: Thirty-six patients diagnosed with HCC at the Division of Gastroenterology and Hepatology, E-Da Hospital, Taiwan, were included in the study. The expression levels of β2-GPI in plasma specimens from patients with HCC were determined by enzyme immunoassay and analyzed in relation to clinicopathological variables using the Chi-square test or Fisher's exact test. The predictive significance of β2-GPI for both overall survival (OS) and disease-free survival (DFS) was assessed using Kaplan-Meier estimates, and the statistical significance of differences was evaluated through the log-rank test. Cox proportional hazards regression models were used to evaluate the association between OS/DFS time and clinicopathological characteristics., Results: Results: Plasma β2-GPI levels were significantly lower in patients with HCC compared to non-cancer controls and significantly correlated with aspartate aminotransferase (AST) levels of HCC. High plasma β2-GPI levels were significantly associated with better OS and DFS in HCC patients. Furthermore, in multiple variates analyses, OS was found to be significantly better in HCC patients with higher plasma β2-GPI expression., Conclusion: Elevated levels of β2-GPI protein in the plasma of HCC patients were identified as an independent factor predictive of improved OS and DFS. Activating β2-GPI in individuals at high risk could serve as a promising way for mitigating the progression of HCC., Competing Interests: The Authors declare that they have no conflicting interests., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Mutations in various type II transmembrane serine protease (TMPRSS) family members are associated with non-syndromic hearing loss, with some mechanisms still unclear. For instance, the mechanism underlying profound hearing loss and tectorial membrane (TM) malformations in hepsin/TMPRSS1 knockout (KO) mice remains elusive. In this study, we confirmed significantly elevated hearing thresholds and abnormal TM morphology in hepsin KO mice, characterized by enlarged TM with gaps and detachment from the spiral limbus. Transgenic mouse lines were created to express either wild-type or a serine protease-dead mutant of human hepsin in the KO background. The Tg68;KO line, expressing moderate levels of wild-type human hepsin in the cochlea, showed partial restoration of hearing function. Conversely, the Tg5;KO or TgRS;KO lines, with undetectable hepsin or protease-dead hepsin, did not show such improvement. Histological analyses revealed that Tg68;KO mice, but not Tg5;KO or TgRS;KO mice, had a more compact TM structure, partially attached to the spiral limbus. These results indicate that hepsin expression levels correlate with improvements in hearing and TM morphology, and its protease activity is critical for these effects. Hepsin's role was further examined by studying its relationship with α-tectorin (TECTA) and β-tectorin (TECTB), non-collagenous proteins crucial for TM formation. Hepsin was co-expressed with TECTA and TECTB in the developing cochlear epithelium. Immunostaining showed decreased levels of TECTA and TECTB in hepsin KO TM, partially restored in Tg68;KO mice. These findings suggest that hepsin is essential for proper TM morphogenesis and auditory function, potentially by proteolytic processing/maturation of TECTA and TECTB and their incorporation into the TM., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dysregulated protein homeostasis, characterized by abnormal protein accumulation and aggregation, is a key contributor to the progression of neurodegenerative disorders such as Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Previous studies have identified PIAS1 gene variants in patients with late-onset SCA3 and Huntington's disease. This study aims to elucidate the role of PIAS1 and its S510G variant in modulating the pathogenic mechanisms of SCA3. Through in vitro biochemical analyses and in vivo assays, we demonstrate that PIAS1 stabilizes both wild-type and mutant ataxin-3 (ATXN3). The PIAS1 S510G variant, however, selectively reduces the stability and SUMOylation of mutant ATXN3, thereby decreasing its aggregation and toxicity while maintaining the stability of wild-type ATXN3. This effect is mediated by a weakened interaction with the SUMO-conjugating enzyme UBC9 in the presence of mutant ATXN3. In Drosophila models, downregulation of dPIAS1 resulted in reduced levels of mutant ATXN3 and alleviated associated phenotypes, including retinal degeneration and motor dysfunction. Our findings suggest that the PIAS1 S510G variant acts as a genetic modifier of SCA3, highlighting the potential of targeting SUMOylation as a therapeutic strategy for this disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A rapid, sensitive and specific test for blood is reported based on a novel application of recombinase polymerase amplification integrated with CRISPR-Cas and lateral flow assay (LFA). The blood specific marker ALAS2 was used as the target to record the presence of blood. The assay used either RNA extracted from a body fluid as a template, or omitting this extraction step and using a direct approach where the questioned body fluid was added directly to the assay. The assay only detected blood (all peripheral blood and some menstrual blood samples) and no other body fluid (semen, saliva, or vaginal fluid). The limit of detection varied from an initial template of 0.195 ng extracted RNA (2 7 dilution) or 0.0218 μL (2 6 dilution) liquid peripheral blood. The assay gave the expected result when peripheral blood was mixed with saliva: ratios of peripheral blood/saliva at 19:1, 3:1, 1:1, 1:3 and 1:19 all gave a positive result using extracted RNA. By contrast, only three ratios of peripheral blood and saliva gave a positive result for blood (19:1, 3:1 and 1:1) when adding these two body fluids directly. When peripheral blood was mixed with semen there was a strong inhibition of the assay and ALAS2 could only be detected at ratio of 19:1 using RNA. Using reconstituted peripheral bloodstains gave comparable results to liquid peripheral blood. This is the first application of RT-RPA integrated CRISPR and combined with a LFA assay to detect body fluid-specific RNA. The proposed method opens up the potential to perform this method remote from laboratories such as at crime scenes., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Perfusion imaging is useful to assess tissue recovery in patients with acute ischemic stroke (AIS); however, it cannot reflect tissue metabolism. We postulated that amide proton transfer (APT) imaging can characterize the tissue status after reperfusion therapy, thus providing prognostic value for 90-day functional outcomes. We included 63 patients with AIS and large-vessel occlusion (LVO). The APT signals, including APT # and NOE # (nuclear Overhauser enhancement) were quantified. Ischemic lesions observed on APT # and diffusion-weighted imaging (DWI) were classified according to their mismatch patterns (APT #  < DWI; APT # ≥ DWI). Predictors of 90-day good outcomes (modified Rankin scale score 0-2) were evaluated. Patients with successful reperfusion exhibited higher APT # , smaller percentage change of APT # , and a greater likelihood of presenting APT #  < DWI compared to those with poor reperfusion (all P  < 0.05). The APT # (odds ratio [OR] = 11.48, P  = 0.046) and a mismatch pattern of APT #  < DWI (OR = 7.41, P  = 0.020) independently predicted good outcomes besides the clinical parameters. A mismatch pattern of APT # ≥ DWI was a significant marker of poor outcomes despite successful reperfusion ( P  = 0.002). Our study provides preliminary evidence that APT may reveal tissue recovery after reperfusion and predict good outcomes at 90 days in patients with AIS and LVO., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The bioactive compounds in burdock ( Arctium lappa L.) roots, including chlorogenic acid (CGA) and cynarin, are valuable for use in nutraceutical foods. The ultrasound-assisted extraction of bioactive substances from dried burdock root powder (DBR) was investigated with 95% ethanol to reduce the impact of polysaccharide inulin on the extraction of free CGA and cynarin. The ethanolic extraction of CGA and cynarin was evaluated under ultrasound (300 W) at 40 kHz (U40) and 120 kHz (U120) with shaking at 120 rpm (S120) for comparison. Using a 1/30 (g/mL-solvent) solid-to-liquid ratio at 30 °C in 120 min, amounts of CGA and cynarin with U40 were as high as 818.74 μg/g-DBR and 173.68 μg/g-DBR, respectively, being much higher than those with U120 and S120. Total phenolic content, total flavonoid content, and antioxidant activity of the extract using U40 were significantly better than using U120 and S120. For U40 and U120, CGA increased with a decreasing solid-to-liquid ratio, while cynarin showed a decrease with a decreasing solid-to-liquid ratio using U120. Moreover, no observable degradations of free CGA and cynarin in ethanol were detected. By combining ultrasound and ethanol, the extracts with high-content CGA and cynarin from burdock roots were effectively achieved for use in health foods.

Background & Aims: The epidemiology of adult primary liver cancer continues to evolve, related to the increasing prevalence of metabolic disease, rising alcohol consumption, advancements in vaccination for hepatitis B (HBV), and antiviral therapy for hepatitis C (HCV). Disparities in care and the burden of liver cancer between populations persist. We assess trends in the burden of liver cancer and contributions by various etiologies across 204 countries and territories from 2010 to 2021., Methods: Utilizing the methodological framework of the Global Burden of Disease Study 2021, we analyzed global and regional temporal trends in incidence and mortality, and the contributions of various etiologies of liver disease., Results: In 2021, there were an estimated 529202 incident cases and 483875 deaths related to liver cancer. From 2010 to 2021, global liver cancer incident cases and deaths increased by 26% and 25%, respectively. Global age-standardized incidence rates (ASIRs) and death rates (ASDRs) for liver cancer declined but rose in the Americas and Southeast Asia. HBV remained the dominant cause of global incident liver cancer cases and deaths. Metabolic dysfunction-associated steatotic liver disease (MASLD) was the only etiology of liver cancer with rising ASIRs and ASDRs. By contrast, ASIRs and ASDRs remained stable for alcohol-related liver cancer, and declined for HBV- and HCV-related liver cancer., Conclusions: While age-adjusted incidence and deaths from liver cancer have started to decline, the absolute number of incident cases and deaths continues to increase. Population growth and aging contribute to the observed disconnect in the temporal trends of absolute cases and rates. Disparities remain, and MASLD-related liver cancer continues to surge., (Copyright © 2024. Published by Elsevier B.V.)

Background: Increasingly, more evidence has shown that inflammation stress and the tumor microenvironment pose a negative effect on targeted therapy. The neutrophil-to-lymphocyte ratio is considered to be a surrogate biomarker of inflammation and can predict pazopanib treatment effect in non-adipocytic soft-tissue sarcoma (STS). The role of the pan-immune-inflammation value (PIV) in STS is still yet to be determined., Objectives: We sought whether the pre-treatment PIV could be applied to predict the response of pazopanib in STS., Design: We conducted a retrospective analysis of 75 patients who had been treated with pazopanib for recurrent or metastatic non-adipocytic STS., Methods: Our cohort was stratified into either a pre-treatment high PIV group with PIV ⩾310 ( n  = 45) or a low PIV group with PIV <310 ( n  = 30). We compared their clinical features and outcomes. Cox regression analysis was employed to determine the risk factors of disease progression and mortality. Kaplan-Meier survival curves were utilized to assess both the progression-free survival (PFS) and overall survival (OS)., Results: The results revealed that a pre-treatment high PIV (⩾310) is a risk factor for progression under pazopanib (hazard ratio: 1.91; 95% confidence interval: 1.08-3.36; p  = 0.025). The median PFS and OS of the pre-treatment high PIV group were found to be significantly lower than the low PIV group (0.33 vs 0.75 years; p  = 0.023, 0.46 vs 1.63 years; p  = 0.025)., Conclusion: High pre-treatment PIV in STS patients may indicate an elevated risk of disease progression and mortality. Pre-treatment PIV reflects inflammation stress and acts as a practical biomarker for STS patients treated with pazopanib., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: To identify the association between daytime activity with objectively monitor and subjective variables at a different time-zone of day as well as the sex differences., Methods: Participants aged 50 years and older living in the community in Taiwan were recruited. The activity was measured by wearable actigraphy devices, diaries, and self-reported questionnaires. The study used nonparametric analysis to examine the association between mean activity level and demographic and subjective measurement variables., Results: Among the 55 participants enrolled in the study, data of 34 (62 %) participants who meet the criteria that wore a wearable actigraphy device for at least 7 completed days were analyzed. There is no significant relationship between each demographics and subjective measurement variables. However, actigraphy counts are significantly related to female's nutrition (Z = -2.367, p = 0.017*), and male's retirement status (Z = -2.132, p = 0.033*)., Conclusions: The activity in morning is highest of the day with significant correlation to evening activities. Moreover, actigraphy counts that indicating objective measure of physical activity in female is significantly related to physiological variables (nutritional status), while male are predicted by social variables (retired status)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jia-Chian Hu reports financial support was provided by Ministry of Science and Technology. Jia-Chian Hu reports financial support was provided by National Cheng Kung University College of Medicine. Jia-Chian Hu reports a relationship with Ministry of Science and Technology that includes: funding grants. Jia-Chian Hu reports a relationship with National Cheng Kung University College of Medicine that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Interpreting genetic variants remains a challenge in prostate cancer (PCa). Although many annotation tools are available for prioritizing causal variants, the clinical relevance of these variants is rarely studied., Methods: We collected a cohort study that included 274 PCa patients from June 2017 to December 2020 and sequenced 19 DNA damage repair (DDR) genes in these patients and explored the clinical consequence of these different approaches. We also examined all-cause and PCa-specific survival in DDR gene mutation carriers compared to non-carriers after androgen receptor (AR)-directed therapy., Results: We identified 13 variants from 19 DDR genes in a total of 14 (5.1%) patients who had at least one presumed pathogenic mutation using different annotation methods. Four variants were annotated as pathogenic, 11 variants were predicted as protein-truncating variants (PTVs), four variants received proxy-deleterious (Combined Annotation-Dependent Depletion scores of > 30), and only one variant was identified as a pathogenic variant or as having a functional effect by all three methods. PCa patients with PTVs were significantly associated with early onset, high cancer stage, and a worse response to AR-directed treatment. However, patients carrying a proxy-deleterious variant were only associated with a higher T (tumor) stage and N (node) stage than those without such a variant, but not associated with other clinical characteristics. In patients treated with AR-directed therapy, patients with a PTV showed an increased risk of all-cause death (adjusted hazard ratio (aHR) = 3.51, 95% confidence interval (CI): 1.06 ~ 11.56) and PCa-specific death (aHR = 4.49, 95% CI: 1.87 ~ 10.77) compared to non-PTV carriers after adjustment. We were unable to examine gene-specific risks due to the small number of patients., Conclusions: PTVs may assist in guiding treatment and early screening in PCa, while population-specific data for pathogenic variants are still being amassed., (© 2024. The Author(s).)

Background: The global prevalence of ischemic stroke in young adults is increasing, leading to a significant social impact. Fabry disease is a recognized cause of ischemic stroke in young patients, and although disease-modifying treatments are available, further evidence is needed to confirm their effectiveness in reducing the incidence of ischemic strokes., Aims: This study aimed to identify undiagnosed Fabry disease in young adult patients with ischemic stroke in a Taiwanese cohort., Methods: This multicenter, prospective cohort study enrolled patients aged 20-55 years who had experienced an ischemic stroke or transient ischemic attack (TIA) within 10 days, from 1 January 2016 to 31 December 2020. Screening for Fabry disease was performed using a dry blood test to measure α-galactosidase activity in male patients and blood globotriaosylsphingosine (lyso-Gb3) levels in female patients. For patients with positive screen results, genetic diagnosis of Fabry disease was pursued through Sanger sequencing of the GLA gene, covering all exons and a segment of intron 4., Results: A total of 977 patients (659 male, 68%) were enrolled from seven hospitals across Taiwan. Four patients (0.4%, all male) had positive screening results, and two patients (0.2%) were genetically diagnosed with Fabry disease. Case 1 had the GLA c.658C>T mutation and experienced ischemic stroke in the bilateral occipital regions. Case 2 had the GLA c.640-801G>A mutation and experienced an ischemic stroke in the left superficial watershed area., Conclusion: The prevalence of undiagnosed Fabry disease in this cohort of Taiwanese young adults with ischemic stroke or TIA was 0.3% among the young male population. Understanding the prevalence of undiagnosed Fabry disease in young adults with ischemic stroke could help shape future Fabry disease screening policies., Data Access Statement: The collected data will be available upon reasonable request from the corresponding author., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population., Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019)., Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg., Conclusions: In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Purpose: Postoperative delirium (POD) is a syndrome that often occurs after surgery. Nursing staff are the first-line personnel who have the most time and close contact with postoperative patients. If delirium is not recognized immediately, it will affect the patient's prognosis and increase clinical care requirements and health care costs. This study explores postanesthesia care unit (PACU) nursing staff's knowledge and ability to recognize POD in patients., Design: A cross-sectional study was conducted with purposive sampling to recruit nurses from hospital PACUs in central and southern Taiwan. Data were collected from April to December 2019 using a questionnaire survey on knowledge of POD and videos to test delirium recognition abilities., Methods: A total of 178 nurses from 9 hospitals met the inclusion criteria for participation; 2 participants were unable to attend because of taking leave, resulting in 176 valid questionnaires., Findings: The percentage of correct answers for POD knowledge was 63.84%, and for recognizing POD was 59.1%, both at a moderate level. Nurses' advanced skills significantly influenced their POD knowledge and recognition abilities. There was a positive correlation between PACU nurses' POD knowledge and recognition abilities (r = 0.23, P < .01)., Conclusions: PACU nurses demonstrated a moderate level of knowledge and ability to recognize POD in patients. Those with higher-level nursing skills showed better POD knowledge and recognition abilities. Nurses with better POD knowledge exhibited higher recognition abilities., Competing Interests: Declaration of Competing Interest None to report., (Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Objectives: Given increasing research suggesting the utility of positron emission tomography/magnetic resonance imaging (PET/MRI) in identifying the pain generator of low back pain, our study aims to assess its effectiveness in evaluating the source of pain in patients with failed back surgery syndrome (FBSS) by comparing the performance of fluorine-18-labeled fluorodeoxyglucose ( 18 F-FDG) PET/MRI with conventional MRI., Methods: We retrospectively analyzed data from patients with FBSS who underwent 18 F-FDG PET and MRI of the lumbar vertebrae and lower extremities for undetermined sources of pain. We assessed 1) The diagnostic reliability and efficacy of MRI and 18 F-FDG PET/MRI according to correct differential diagnosis, affected level, and affected side of the pain source compared to the findings of selective root or peripheral nerve block or revision lumbar spine surgery; and 2) The association between standardized uptake value (SUV) and standardized uptake value ratio (SUVR) threshold and accuracy of the suspected pathology on 18 F-FDG PET/MRI., Results: Among 30 included patients, the diagnostic accuracy of pain source recognition was higher for 18 F-FDG PET/MRI than for MRI alone (1.0 vs. 0.4 in spinal disease and 0.8 vs. 0 in lower extremity disease, both p < 0.05). SUVR values of 1.4-1.5 showed the highest accuracy (0.93), higher than the accuracy obtained using the SUV threshold (0.87)., Conclusion: 18 F-FDG PET/MRI added value to MRI alone in detecting of hypermetabolic activity associated with pain from spinal and non-spinal sources., (© 2024. The Author(s) under exclusive licence to Japan Radiological Society.)

Background/Objectives: Luteolin (LUT) is a natural flavonoid with known anti-inflammatory, antioxidant, and anti-cancer properties. Cervical cancer, particularly prevalent in certain regions, remains a significant health challenge due to its high recurrence and poor response to treatment. This study aimed to investigate the anti-tumor effects of LUT on human cervical epidermoid carcinoma cells (Ca Ski), focusing on cell growth inhibition, apoptosis induction, and regulation of mitochondrial membrane potential. Methods: Ca Ski cells were treated with varying concentrations of LUT (0, 25, 50, 100 µM) for different time periods (24, 48, 72 hours). Cell viability was measured using the MTT assay, apoptosis was assessed by flow cytometry with annexin V-FITC/PI staining, and changes in mitochondrial membrane potential were evaluated using JC-1 staining. Caspase-3 activation was examined by flow cytometry, and expression of apoptosis-related proteins (caspase-3, -8, -9, AIF) was analyzed via Western blotting. Results: LUT significantly inhibited the growth of Ca Ski cells in a dose- and time-dependent manner, with the most pronounced effects observed at 100 µM over 72 hours. Flow cytometry confirmed that LUT induced apoptosis without causing necrosis. Mitochondrial membrane potential was reduced after LUT treatment, coinciding with increased caspase-3 activation. Western blot analysis revealed the upregulation of pro-apoptotic proteins caspase-3, -8, -9, and AIF, indicating that LUT induces apoptosis through the intrinsic mitochondrial pathway. Conclusions: Luteolin effectively inhibits cervical cancer cell proliferation and induces apoptosis by disrupting mitochondrial membrane potential and activating caspases. These findings suggest that LUT holds potential as a therapeutic agent for cervical cancer, with further studies needed to explore its in vivo efficacy and broader clinical applications.

Background: The combination of anti-angiogenic therapy and immune checkpoint inhibitors has revolutionized the management of unresectable hepatocellular carcinoma (uHCC). While an early-phase study demonstrated promising outcomes for lenvatinib plus pembrolizumab (L+P) in treating uHCC, the LEAP-002 trial did not meet its primary endpoint. However, the comparative efficacy between L+P and atezolizumab plus bevacizumab (A+B) as first-line treatment remains a topic of uncertainty. This study aimed to assess the effectiveness and safety of L+P in contrast to A+B among patients diagnosed with uHCC., Methods: We conducted a retrospective analysis of enrolled patients with uHCC who received L+P or A+B as initial systemic treatment at Chang Gung Memorial Hospital from June 2019 to December 2022. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by modified RECIST were compared., Results: 121 patients were recruited, with 37 receiving L+P and 84 receiving A+B. Among them, 95 (78.5%) patients were BCLC stage C, and 99 (81.8%) patients had viral etiology for HCC, predominantly chronic HBV (68.6%). Both the L+P and the A+B groups demonstrated comparable OS (18.2 months versus 14.6 months, p = 0.35) and PFS (7.3 months versus 8.9 months, p = 0.75). The ORR and DCR were similar. After propensity score matching, the results remained consistent between the matched patients. Treatment-related adverse events of any grade occurred in 30 (81.1%) in the L+P group and 62 (73.8%) in the A+B group., Conclusions: Our findings suggest that L+P and A+B exhibit comparable efficacy and safety profiles in real-world settings.

Background: The impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear., Objective: We aimed to characterise the effects of tenofovir disoproxil fumarate (TDF) on intrahepatic viral burden and the liver immune microenvironment in patients with CHB., Design: Core liver biopsies were collected at baseline and year 3 from patients with CHB with minimally raised serum alanine aminotransferase in a double-blind placebo-controlled trial (NCT01522625). Paired biopsies were analysed by RNA-sequencing (n=119 pairs), a custom multiplex immunofluorescence assay (n=30 pairs), and HBV-targeted long-read DNA sequencing (n=49 pairs)., Results: Both non-integrated and integrated HBV DNA were present in all patients at baseline, with >65% having interchromosomal translocations. Treatment significantly reduced the frequency of HBV core+ hepatocytes and intrahepatic (integrated and non-integrated) HBV DNA, but had no effect on HBsAg+ hepatocytes. Clonally expanded integrations were enriched for HBsAg coding regions and showed dysregulation of nearby genes. At baseline, there was significant enrichment of intrahepatic CD8+ T cell proximity to HBV core+ hepatocytes, but not to HBsAg+ cells. The densities of T cells and B cells were significantly reduced by TDF. Transcriptomic analyses found TDF induced widespread downregulation of immune-related genes including inhibitory and regulatory genes., Conclusion: TDF significantly reduced intrahepatic integrated and non-integrated HBV DNA, exerting disparate effects on HBV core+ and HBsAg+ cells and on different immune cell subsets. Our data suggest there may be differential cytotoxic T cell-mediated killing of HBV core+ versus HBsAg+ hepatocytes, providing insights for HBV cure strategies., Competing Interests: Competing interests: DZP, CMS, AA, DH, NvB, PW, BF, BD, LL, LD, HM, SPF, SB, RR and VS were employees and stockholders of Gilead Sciences, Inc. J-TL, C-HT and Y-CH have research support from Gilead Sciences. C-HT and Y-CH are paid lecturers for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme and Novartis. Y-CH is an advisory committee member for Gilead Sciences., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)