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Zi-Qiang Li,1,&ast; Ye Qin,2,&ast; Wen-Peng Cai,1,&ast; Si-Qi Deng,3 Xiao-Fei Mao,1 Jian-Guo Zhang,1 Tian-Ya Hou,1 Yu Pan,4 Yi Cui,1 Ying-Nan Ge,5 Wei Dong,1,&ast; Yun-Xiang Tang1,&ast; 1Faculty of Psychology, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2The School of Mechanical Engineering, Changzhou University, Changzhou, 210046, People’s Republic of China; 3Department of Clinical Psychological Counseling, Shanghai Tongxinjici Health Couseling Center, Shanghai, 200433, People’s Republic of China; 4Department of Medical Psychology, Chinese PLA General Hospital, Beijing, 100830, People’s Republic of China; 5Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Dong; Yun-Xiang Tang, Faculty of Psychology, Naval Medical University, No. 800 Xiangyin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-13524435414 ; +86-13386271042, Email sophiedongwei@163.com; tangyun7633@sina.comPurpose: This study aims to examine the impact of sleep deprivation on individual cognitive reappraisal ability using a standardized behavioral paradigm.Methods: A randomized pretest-posttest control group design was conducted. Thirty-nine participants were eventually enrolled and randomly assigned to receive either the sleep control (SC: n = 17) or the sleep deprivation (SD: n = 22). Both of them were required to perform a standardized behavioral paradigm of measuring cognitive reappraisal ability one time under sleep-rested condition and another time under the condition of different sleep manipulation a week later.Results: Mean valence ratings of SD group were more negative than SC group’s (p < 0.05) and mean arousal ratings of SD group were higher than SC group’s (p < 0.01).Conclusion: Sleep deprivation may impair individual cognitive reappraisal ability and could potentially undermine the efficacy of cognitive therapy in terms of emotion regulation.Keywords: sleep deprivation, emotion regulation, cognitive reappraisal, IAPS, CRA

Jia-Yin Yeh,1 Tsai-Yu Hou,1 Wei-Ting Tseng,1 Vincent Chin-Hung Chen,2,3 Yao-Hsu Yang,4,5 Ting-Yu Kuo,4 Jun-Cheng Weng,6,7 Charles Tzu-Chi Lee,8 Yi-Lung Chen,9,10 Min-Jing Lee2,3 1Department of Psychiatry, Chang Gung Memorial Hospital, Kaohsiung Branch, Kaohsiung, Taiwan; 2Department of Psychiatry, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 3School of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 5Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan; 6Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan; 7Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 8Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan; 9Department of Healthcare Administration, Asia University, Taichung, Taiwan; 10Department of Psychology, Asia University, Taichung, TaiwanCorrespondence: Min-Jing LeeDepartment of Psychiatry, Chang Gung Memorial Hospital, Chiayi, Taiwan, No. 6, W. Sec., Jiapu Road, Puzi City, Chiayi County 613, TaiwanTel +886-5-3621000 ext2303Fax +886-5-3622188Email 8035c@cgmh.org.twPurpose: Literature suggests that attention deficit hyperactivity disorder (ADHD) is associated with a high risk of unintentional injury. However, few studies have focused on whether risk of burn injury is relatively high among patients with ADHD. The aim of this study was to investigate whether ADHD affects the risk of burn injury.Materials and Methods: Individuals aged < 18 years with a current diagnosis of ADHD (N = 52,705) and age-, sex-, and other comorbidity-matched controls were selected from Taiwan’s National Health Insurance Research Database for the period of January 1996 to December 2013. Burn injury was identified in both groups, and risk was evaluated using Cox proportional hazards models. We also explored the effects of age and sex on the association.Results: We determined that patients with ADHD had an increased probability of burn injury compared with the control group (ADHD vs controls, 4.6% vs 2.6%; adjusted hazard ratio [aHR] = 1.78; 95% confidence interval [CI] = 1.66– 1.90). The effect of ADHD on burn injury was more prominent among those aged < 6 years (aHR = 1.96; 95% CI = 1.75– 2.20) relative to those aged ≥ 6 years (aHR = 1.69; 95% CI = 1.56– 1.83). Both sexes had similar risk profiles.Conclusion: The study findings contribute to the increasing body of evidence that ADHD is associated with proneness to burn injury, particularly in children aged < 6 years.Keywords: ADHD, burn injury, propensity-matched, cohort

Background: Advanced glycation end products (AGEs) are compounds formed by non-enzymatic processes in the Maillard reaction and can cause various chronic diseases. This study explores the AGE formation process in a glucose-amino acid system under both wet- and dry-heating conditions, and analyzes the effect of cysteine in AGE formation., Results: Under wet-heating conditions, N ε -carboxymethyllysine (CML) and N ε -carboxyethyllysine (CEL) concentrations rose for the initial 90 min and subsequently declined after 120 min; after 90 min of heating, the maximum yields in the absence of cysteine were 1151.04 ± 14.01 and 3386.90 ± 26.55 ng mL -1 , respectively. The concentration of pyrraline (Pyr) increased after 30 min and then decreased after 60 min with a maximum yield of 777.68 ± 23.36 ng mL -1 . However, in dry-heating models, the AGE concentrations consistently increased with increasing heating time; the maximum yields for CML, CEL and Pyr were 468.66 ± 10.96, 1993.57 ± 14.81 and 1085.74 ± 58.06 ng mL -1 , respectively. The addition of cysteine showed an inhibitory effect on AGE formation, especially for Pyr in the dry-heating model, with inhibition rates ranging from 17.14% to 95.60%., Conclusion: Although wet-heating models produced more CML and CEL, they produced less Pyr than dry-heating models. The AGE formation in wet-heating models positively correlated with the reaction rate; however, the dry-heating reaction demonstrated a more complex relationship between reaction rate and reaction protocol. Moreover, cysteine exhibited a significant inhibitory effect on AGE production, and the degree of inhibition was proportional to the cysteine concentration. This study provides important insights into the mechanisms for AGE formation under various heating conditions, such as those representing baking (dry-heating) and steaming conditions (wet-heating). © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: To compare the surgical outcomes of the inverted internal limiting membrane (ILM) flap technique and ILM insertion for macular hole (MH) without retinal detachment in eyes with extremely high myopia., Methods: In this retrospective study, we analyzed 22 eyes with an axial length ≥ 30.0 mm that had underwent MH surgery between April 2015 and August 2021. The surgical procedures involved either an inverted ILM flap or ILM insertion. The outcomes were compared between the two techniques. Closure of the MH was confirmed by optical coherence tomography (OCT). The best-corrected visual acuity (BCVA) was measured before and after surgery. Associated complications were documented., Results: The median of axial length was 30.64 mm (range, 30.0-34.42). The MH closed in 100% (22/22) eyes and did not recur with a median follow-up of 12.5 months. For the inverted ILM flap technique, the median BCVA improved significantly from 0.80 logarithm of the minimum angle of resolution (logMAR) (range, 0.40-2.00) before surgery to 0.70 logMAR (range, 0.09-1.52) after surgery (p = 0.002). In addition, the median of final BCVA was better for the inverted ILM flap than ILM insertion (0.7 logMAR V.S. 1.00 logMAR; p = 0.016)., Conclusions: In eyes with extremely high myopia, despite comparable effects on MH closure for both ILM insertion and the inverted ILM flap, the later technique achieved significantly better visual outcomes., (© 2024. The Author(s).)

Background/purpose: The success of root canal treatments is influenced by the shape of the access opening and the outcomes of root canal enlargement. The aim of this study was to evaluate the impact of various rotary instruments on the maintenance of the root canal's central alignment post shaping, considering a range of access cavity designs., Materials and Methods: Using digital tooth simulation, 4 sets of 12 teeth underwent traditional (TradAC) or conservative (ConsAC) access cavity preparations. Root canals were enlarged with TruNatomy or ProTaper Ultimate rotary instruments. Canal transportation and centering ratio were separately measured. Statistical analysis was performed using JMP trial 17 software., Results: The analysis revealed no significant difference in buccal and lingual canal transportation among different rotary instruments or canal enlargement designs ( P  > 0.05). TradAC yielded higher centering ratios in MB and ML canals, while ConsAC excelled in the distal canal for the TruNatomy group. Conversely, in the ProTaper Ultimate group, ConsAC demonstrated higher ML canal ratios ( P  < 0.05)., Conclusion: TruNatomy maintained superior canal centering with ConsAC, while ProTaper performed better with TradAC., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background/aim: To investigate the treatment outcomes and determinants of prognosis in patients experiencing visual acuity (VA) deterioration due to inflammatory isolated sphenoid sinus disease (ISSD) who underwent endonasal endoscopic surgery (EES)., Patients and Methods: Thirteen patients with 14 lesions treated with EES between March 2010 and April 2022 were included. Evaluation included improvements in VA using the logarithm of the minimum angle of resolution (LogMAR) scale, resolution rates of associated symptoms, and identification of factors predicting VA recovery. A literature review was conducted to assess the outcomes for ISSD-related VA impairments., Results: The most common etiology is mycetoma (n=5), followed by an equal representation of mucocele and sphenoiditis (n=4). The mean interval from symptom onset to intervention was 4.7 months, with an average follow-up duration of 14.4 months. Seven eyes exhibited preoperative VA of 2.1 LogMAR or worse, with diplopia/ptosis (n=8) and headache (n=5) being the predominant co-occurring symptoms. After surgery, all ancillary symptoms improved, with an overall VA recovery rate of 87.5% (improvement more than 0.2 logMAR units). Mucocele exhibited the best improvements, whereas sphenoiditis showed the least progress (p=0.021). Poor baseline VA (p=0.026) and combined diplopia/ptosis (p=0.029) were identified as negative prognostic factors for VA recovery., Conclusion: Our findings suggest a favorable prognosis for VA recovery following EES in patients with inflammatory ISSDs, with response variations based on disease entity. However, further research is needed to personalize therapeutic strategies for enhanced outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Uncontrolled massive bleeding and bowel edema are critical issues during liver transplantation. Temporal intra-abdominal packing with staged biliary reconstruction (SBR) yields acceptable outcomes in deceased donor liver transplantation; however, data on living donor liver transplantation (LDLT) are scarce., Methods: A retrospective analysis of 1269 patients who underwent LDLT was performed. After one-to-two propensity score matching, patients who underwent LDLT with SBR were compared with those who underwent LDLT with one-stage biliary reconstruction (OSBR). The primary outcomes were graft survival (GS) and overall survival (OS), and the secondary outcomes were postoperative biliary complications., Results: There were 55 and 110 patients in the SBR and OSBR groups, respectively. The median blood loss was 6500 mL in the SBR and 4875 mL in the OSBR group. Patients receiving SBR-LDLT had higher incidence of sepsis (69.0% vs. 43.6%; P < 0.01) and intra-abdominal infections (60.0% vs. 30.9%; P < 0.01). Biliary complication rates (14.5% vs. 19.1%; P = 0.47) and 1-and 5-year GS (87.27%, 74.60% vs. 83.64%, 72.71%; P = 0.98) and OS (89.09%, 78.44% vs. 84.55%, 73.70%; P = 0.752) rates were comparable between the two groups., Conclusions: SBR could serve as a life-saving procedure for patients undergoing complex critical LDLT, with GS, OS, and biliary outcomes comparable to those of OSBR., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Malnutrition is not uncommon among the elderly undergoing pancreatoduodenectomy (PD) and is related to increased complications. Previous studies have shown that the Geriatric Nutritional Risk Index (GNRI) predicts outcomes in various populations. Nevertheless, the research exploring the correlation between GNRI and postoperative outcomes in PD is scarce. This study aimed to investigate the preoperative malnutrition, as measured by GNRI, on outcomes in elderly patients undergoing PD., Materials and Methods: This retrospective analysis enrolled 144 elderly patients underwent PD for periampullary tumors from November 2016 to December 2021. Patients were stratified based on the GNRI value: high/moderate nutrition risk (GNRI ≤ 92, N = 54), low nutrition risk (92 < GNRI ≤ 98, N = 35), and no nutrition risk (GNRI > 98, N = 55). Perioperative outcomes and postoperative surgical complications were compared between these groups. Univariate and multivariate analyses were performed on major postoperative complications and prolonged postoperative length of stay (PLOS)., Results: Patients in the high/moderate risk group were significantly older, with lower BMI (P = 0.012), higher mortality rate (11.1%, P = 0.024), longer PLOS (P < 0.001), and higher incidence of over grade IIIB complications (37.0%, P = 0.001), Univariate and multivariate analyses showed the high/moderate risk GNRI group (OR 3.61, P = 0.032), increased age (OR 1.11, P = 0.014) and operative time over 8 h (OR 3.04, P = 0.027) were significantly associated with increased major postoperative complications. The high/moderate risk GNRI group was also a significant predictor for prolonged PLOS (OR 3.91, P = 0.002)., Conclusions: Preoperative GNRI has the potential to be a predictive tool for identifying high-risk elderly patients and monitoring nutritional status preoperatively to improve postoperative surgical outcomes following PD., (© 2024. The Author(s).)

The study aims to perform alkali-induced covalent modification of perilla seed meal protein (PSMP) using different polyphenols: gallic acid (GA), protocatechuic acid (PCA), caffeic acid (CA), apigenin (API) and luteolin (LU). Covalent binding between different polyphenols and PSMP was found to occur, with PSMP-LU showing the highest binding rate of 90.89 ± 1.37 mg/g; the fluorescence spectrum of PSMP-CA showed a maximum blue shift of Δ13.4 nm; the solubility increased from 69.626 ± 1.39 % to 83.102 ± 0.98 %. In order to better understand how these covalent conjugates, stabilize -carotene in emulsions, they were utilized as emulsifiers in an emulsion delivery method. The work further reveals the formation of PSMP-polyphenol conjugates and develops a novel emulsification system to deliver readily decomposable functional factors, providing a potential scenario for the application of PSMP and bioactive conjugates., 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 © 2023 Elsevier Ltd. All rights reserved.)

The multidisciplinary treatment model led by surgery has become a comprehensive strategy and overall concept for the treatment of spinal metastatic tumors. But the surgical treatment of spinal metastatic tumors is different from primary malignant tumors of the spine. Surgery is only a part of the multidisciplinary comprehensive treatment. Therefore, the following aspects need to be evaluated comprehensively based on the survival assessment, evaluation of spinal stability damage, nerve dysfunction, and oncological characteristics of the metastatic tumors with a reasonable surgical intervention. The attention should be paid to the minimally invasive treatment of spinal metastases, progress of new radiotherapy technology, neoadjuvant chemotherapy, targeted drug therapy and other medical treatment to make a comprehensive and individualization decision which is benefit to relieve patients ' pain, reconstruct spinal stability and avoid paralysis. While improving patient survival, increasing local tumor control rate and possibly prolonging survival time, avoiding excessive surgery as much as possible.

Background: Several techniques have been developed to reduce blood loss in liver resection. The half-Pringle and Pringle maneuvers are commonly used for inflow control. This study compared the outcomes of different inflow control techniques in laparoscopic subsegmentectomy., Methods: From October 2010 to December 2020, a total of 362 laparoscopic liver resections were performed by a single surgeon (C.C. Yong) in our institute. We retrospectively enrolled 133 patients who underwent laparoscopic subsegmentectomy during the same period. Perioperative and long-term outcomes were analyzed., Results: The 133 patients were divided into 3 groups: no inflow control (n = 49), half-Pringle maneuver (n = 46), and Pringle maneuver (n = 38). A lower proportion of patients with cirrhosis were included in the half-Pringle maneuver group (P = .02). Fewer patients in the half-Pringle maneuver group had undergone previous abdominal (P = .01) or liver (P = .02) surgery. The no inflow control group had more patients with tumors located in the anterolateral segments (P = .001). The no inflow control group had a shorter operation time (P < .001) and less blood loss (P = .03). The need for blood transfusion, morbidity, and hospital days did not differ among the 3 groups. The overall survival did not significantly differ among the 3 groups (P = .89)., Conclusions: The half-Pringle and Pringle maneuvers did not affect perioperative or long-term outcomes during laparoscopic subsegmentectomy. The inflow control maneuvers could be safely performed in laparoscopic subsegmentectomy., (© 2023. The Author(s).)

Fresnel zone plates (FZPs) are widely used in integrated optical systems to meet new cutting-edge demands for photonic integration and device miniaturizing. However, their use in applications of cross-scale fabrication still faces several obstacles, such as low efficiency, fixed focal length, single wavelength, large size, and complicated fabrication. Here, we first examine a novel adaptive focal length in white light focusing by using reflective-type and phase-only spatial light modulator (RLC-SLM) based on a liquid crystal on silicon. The device achieves a maximum diffraction efficiency of approximately 38% at primary focal points of binary phase-type FZPs throughout the visible range (red, green, and blue wavelengths). The RLC-SLM focuses the light of the desired wavelength while other sources are defocused. White light focusing and color separation are demonstrated by sequentially and additively switching different FZPs. These recent advances show that optically tunable FRZs are promising potential candidates to enhance adaptive camera systems, microscopes, holograms, and portable and wearable devices, thereby opening up novel possibilities in optical communications and sensing., (© 2023. Springer Nature Limited.)

Allergic asthma is an inflammatory lung disorder, and mast cells play crucial roles in the development of this allergic disease. Norisoboldine (NOR), the major isoquinoline alkaloid present in Radix Linderae, has received considerable attention because it has anti-inflammatory effects. Herein, the aim of this study was to explore the antiallergic effects of NOR on allergic asthma in mice and mast cell activation. In a murine model of ovalbumin (OVA)-induced allergic asthma, oral administration at 5 mg/kg body weight (BW) of NOR produced strong reductions in serum OVA-specific immunoglobulin E (IgE) levels, airway hyperresponsiveness, and bronchoalveolar lavage fluid (BALF) eosinophilia, while an increase in CD4 + Foxp3 + T cells of the spleen was detected. Histological studies demonstrated that NOR treatment significantly ameliorated the progression of airway inflammation including the recruitment of inflammatory cells and mucus production by decreasing levels of histamine, prostaglandin D 2 (PGD 2 ), interleukin (IL)-4, IL-5, IL-6, and IL-13 in BALF. Furthermore, our results revealed that NOR (3 ∼ 30 μM) dose-dependently reduced expression of the high-affinity receptor for IgE (FcεRI) and the production of PGD 2 and inflammatory cytokines (IL-4, IL-6, IL-13, and TNF-α), and also decreased degranulation of bone marrow-derived mast cells (BMMCs) activated by IgE/OVA. In addition, a similar suppressive effect on BMMC activation was observed by inhibition of the FcεRI-mediated c-Jun N-terminal kinase (JNK) signaling pathway using SP600125, a selective JNK inhibitor. Collectively, these results suggest that NOR may have therapeutic potential for allergic asthma at least in part through regulating the degranulation and the release of mediators by mast cells., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: The treatment of common bile duct (CBD) stones with minimally invasive surgery (MIS) is more technical demanding than laparoscopic cholecystectomy (LC), especially in patients with history of previous abdominal surgery, cholangitis or cholecystitis. Near-infrared (NIR) cholangiography via systemic or biliary tree administration of indocyanine green (ICG), which enhances the visualization of the biliary tree anatomy, may increase the reassurance of CBD localization. The aim of this study was to identify the benefit of near-infrared cholangiography for laparoscopic common bile duct exploration (LCBDE)., Methods: Three groups of CBD stone patients were included in this retrospective study depending on the surgical methods: 1) open choledocholithotomy (OCC), 2) laparoscopic choledocholithotomy (LCC), and 3) near-infrared cholangiography-assisted laparoscopic choledocholithotomy (NIR-CC). For the NIR-CC group, either 3 ml (concentration: 2.5 mg/mL) of ICG were intravenously administered or 10 ml (concentration: 0.125 mg/mL) of ICG were injected directly into the biliary tree. The enhancement rate of the cystic duct (CD), CBD, the upper and lower margin of the CBD were compared using white light image., Results: A total of 187 patients with a mean age of 68.3 years were included (OCC, n = 56; LCC, n = 110; NIR-CC, n = 21). The rate of previous abdominal surgery was significantly lower in the LCC group. The conversion rate was similar between the LCC and the NIR CC groups (p = 0.746). The postoperative hospital stay was significantly longer in the OCC group. No differences in morbidity and mortality were found between the three groups. In the NIR-CC group, the localization of CBD was as high as 85% compared to 24% with white light imaging., Conclusions: Near-infrared cholangiography helps increase the chance of success in minimally invasive approaches to CBD stones even in patients with previous abdominal surgeries, without increasing the rate of conversion., (© 2023. The Author(s).)

Objectives: To derive the paternity index (PI) calculation formula of the alleged father (AF) when the AF is a relative (parent/child, siblings, grandparent/grandchild, uncle/nephew, first cousins) of the child's biological mother., Methods: For the case when the AF is related to the child's biological mother, the existence of the relationship in the numerator and denominator hypothesis of PI was considered. The genotype frequency of the AF was calculated by using the frequency formula in which the mother's genotype was considered, while the random male in the denominator was substituted as another relative of the mother's same rank. The PI calculation formula was derived to eliminate the effect of the relationship between AF and the child's biological mother., Results: When the AF and the biological mother have first, second and tertiary kinship, a more conservative PI was obtained from the PI calculation formula derived in this study compared with the PI calculation method which did not consider kinship., Conclusions: The calculation method provided in this study can eliminate the effect of the relation of the AF and mother on the PI in incest cases, to obtain more accurate and conservative identification conclusions.

Wastewater-based epidemiology (WBE) represents an efficient approach for public pathogen surveillance as it provides early warning of disease outbreaks; however, it has not yet been applied to dengue virus (DENV), which might cause endemics via mosquito spread. In this study, a working platform was established to provide direct virus recovery and qPCR quantification from wastewater samples that were artificially loaded with target DENV serotypes I to IV and noncognate spike control viral particles. The results showed qPCR efficiencies of 91.2 %, 94.8 %, 92.6 % and 88.7 % for DENV I, II, III, and IV, respectively, and a broad working range over 6 orders of magnitude using the preferred primer sets. Next, the results revealed that the ultrafiltration method was superior to the skimmed milk flocculation method for recovering either DENV or control viral particles from wastewater. Finally, DENV-2 was loaded simultaneously with the noncognate spike control and could be recovered at comparable levels either in PBS or in wastewater, indicating the applicability of noncognate spike control particles to reflect the efficiency of experimental steps. In conclusion, our data suggest that DENV particles in wastewater could be recovered and quantitatively detected in absolute amounts, indicating the feasibility of DENV surveillance using the WBE approach., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: Collateral status is an important predictor for the outcome of acute ischemic stroke with large vessel occlusion. Multiphase computed-tomography angiography (mCTA) is useful to evaluate the collateral status, but visual evaluation of this examination is time-consuming. This study aims to use an artificial intelligence (AI) technique to develop an automatic AI prediction model for the collateral status of mCTA., Methods: This retrospective study enrolled subjects with acute ischemic stroke receiving endovascular thrombectomy between January 2015 and June 2020 in a tertiary referral hospital. The demographic data and images of mCTA were collected. The collateral status of all mCTA was visually evaluated. Images at the basal ganglion and supraganglion levels of mCTA were selected to produce AI models using the convolutional neural network (CNN) technique to automatically predict the collateral status of mCTA., Results: A total of 82 subjects were enrolled. There were 57 cases randomly selected for the training group and 25 cases for the validation group. In the training group, there were 40 cases with a positive collateral result (good or intermediate) and 17 cases with a negative collateral result (poor). In the validation group, there were 21 cases with a positive collateral result and 4 cases with a negative collateral result. During training for the CNN prediction model, the accuracy of the training group could reach 0.999 ± 0.015, whereas the prediction model had a performance of 0.746 ± 0.008 accuracy on the validation group. The area under the ROC curve was 0.7., Conclusions: This study suggests that the application of the AI model derived from mCTA images to automatically evaluate the collateral status is feasible.

The death triad, including coagulopathy, hypothermia, and acidosis, is shown to be a strong predictor of mortality in trauma patients. We aimed to investigate whether the inclusion of hypotension, defined as systolic blood pressure (SBP) < 60 mmHg, as a fourth factor in the death triad would comprise a death tetrad to help stratify mortality risk in trauma patients. A total of 3361 adult trauma patients between 1 January 2009 and 31 December 2019 were allocated into groups to investigate whether hypotension matters in determining the mortality outcome of trauma patients who possess 1−3 death triad components compared to those without any component. Hypotension was added to the death tetrad, and the adjusted mortality outcome was compared among groups with 0−4 death tetrad components. Herein, we showed that SBP < 60 mmHg could be used to identify patients at risk of mortality among patients with one or two death triad components. Patients with one, two, and three death tetrad components had respective adjusted mortality rates of 3.69-, 10.10-, and 40.18-fold, determined by sex, age, and comorbidities. The mortality rate of trauma patients with all the four death tetrad components was 100%. The study suggested that hypotension, defined as an SBP < 60 mmHg, may act as a proper death tetrad component to stratify the mortality risk of trauma patients.

Long noncoding RNAs have been implicated in many of the hallmarks of cancer. Herein, we found that the expression of lncRNA152 (lnc152; a.k.a. DRAIC), which we annotated previously, is highly upregulated in luminal breast cancer (LBC) and downregulated in triple-negative breast cancer (TNBC). Knockdown of lnc152 promotes cell migration and invasion in LBC cell lines. In contrast, ectopic expression of lnc152 inhibits growth, migration, invasion, and angiogenesis in TNBC cell lines. In mice, lnc152 inhibited the growth of TNBC cell xenografts, as well as metastasis of TNBC cells in an intracardiac injection model. Transcriptome analysis of the xenografts indicated that lnc152 downregulates genes controlling angiogenesis. Using pull down assays followed by LC/MS-MS, we identified RBM47, a known tumor suppressor in breast cancer, as a lnc152-interacting protein. The effects of lnc152 in TNBC cells are mediated, in part, by regulating the expression of RBM47. Collectively, our results demonstrate that lnc152 is an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC., Implications: This study identifies lncRNA152 as an angiogenesis-inhibiting tumor suppressor that attenuates the aggressive cancer-related phenotypes found in TNBC by upregulating the expression of the tumor suppressor RBM47. As such, lncRNA152 may serve as a biomarker to track aggressiveness of breast cancer, as well as therapeutic target for treating TNBC., (©2022 American Association for Cancer Research.)

This study developed a predictive model for cognitive degeneration in patients with Parkinson's disease (PD) using a machine learning method. The clinical data, plasma biomarkers, and neuropsychological test results of patients with PD were collected and utilized as model predictors. Machine learning methods comprising support vector machines (SVMs) and principal component analysis (PCA) were applied to obtain a cognitive classification model. Using 32 comprehensive predictive parameters, the PCA-SVM classifier reached 92.3% accuracy and 0.929 area under the receiver operating characteristic curve (AUC). Furthermore, the accuracy could be increased to 100% and the AUC to 1.0 in a PCA-SVM model using only 13 carefully chosen features.

Background: Tactile processing plays a pivotal role in the early stages of human development; however, little is known about tactile function in young children. An understanding of how tactile processing changes with age from early childhood to adulthood is fundamental in understanding altered tactile experiences in neurodevelopmental disorders, such as autism spectrum disorder., Methods: In this cross-sectional study, 142 children and adults aged 3-23 years completed a vibrotactile testing battery consisting of 5 tasks, which rely on different cortical and cognitive mechanisms. The battery was designed to be suitable for testing in young children to investigate how tactile processing changes from early childhood to adulthood., Results: Our results suggest a pattern of rapid, age-related changes in tactile processing toward lower discrimination thresholds (lower discrimination thresholds = greater sensitivity) across early childhood, though we acknowledge limitations with cross-sectional data. Differences in the rate of change across tasks were observed, with tactile performance reaching adult-like levels at a younger age on some tasks compared to others., Conclusions: While it is known that early childhood is a period of profound development including tactile processing, our data provides evidence for subtle differences in the developmental rate of the various underlying cortical, physical, and cognitive processes. Further, we are the first to show the feasibility of vibrotactile testing in early childhood (<6 years). The results of this work provide estimates of age-related differences in performance, which could have important implications as a reference for investigating altered tactile processing in developmental disorders., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

To better understand the functions of non-coding enhancer RNAs (eRNAs), we annotated the estrogen-regulated eRNA transcriptome in estrogen receptor α (ERα)-positive breast cancer cells using PRO-cap and RNA sequencing. We then cloned a subset of the eRNAs identified, fused them to single guide RNAs, and targeted them to their ERα enhancers of origin using CRISPR/dCas9. Some of the eRNAs tested modulated the expression of cognate, but not heterologous, target genes after estrogen treatment by increasing ERα recruitment and stimulating p300-catalyzed H3K27 acetylation at the enhancer. We identified a ∼40 nucleotide functional eRNA regulatory motif (FERM) present in many eRNAs that was necessary and sufficient to modulate gene expression, but not the specificity of activation, after estrogen treatment. The FERM interacted with BCAS2, an RNA-binding protein amplified in breast cancers. The ectopic expression of a targeted eRNA controlling the expression of an oncogene resulted in increased cell proliferation, demonstrating the regulatory potential of eRNAs in breast cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this paper, we propose and demonstrate a novel interferometer and signal process to retrieve two-dimensional signals with multilevel phases. The interferometer is based on a shearing interferometry with double-frequency grating, and phase-shifting interferometry is derived as a built-in function of the lateral displacement of the grating. The interferometer not only retrieves the multilevel phase signals but also eliminates slow-varying phase errors wherever they occur. Owing to the common path algorithm, the new interferometer is more robust in dynamic circumstances for optical testing and data processing. We propose a pre-integral signal process for two-dimensional (2D) data processing to prevent post-phase-integral due to shearing interferometry. The simulation and experiment showed that the proposed interferometer with a pre-integral process has various advantages in signal processing for multilevel phase retrieval, and will be useful for higher data rates in optical data storage and free-space communication., (© 2022. The Author(s).)

Clinical Relevance: Conjunctivitis, chalazion and blepharitis are routinely managed by optometrists. However, it is especially important to consider the diagnosis of canaliculitis in patients with chronic or recurrent conditions., Background: This study aimed to report the clinical features, radiological findings and treatment outcomes in patients with plug-related canaliculitis., Methods: This retrospective study included patients with canaliculitis secondary to plug insertion between 2007 and 2020. All data regarding epidemiological characteristics, clinical presentation, isolated microorganisms, computed tomography imaging findings, treatment, and outcomes were analysed., Results: A total of 20 plug-related canaliculitis from 19 patients (18.3%) among all 109 cases of canaliculitis were identified. All patients with plug-related canaliculitis were females with a past history of lacrimal plug insertion for dry eye (mean age: 58.2 years). Most patients were initially treated as conjunctivitis with the mean time lapse to a diagnosis of 5.2 months. The average time from plug insertion to onset of symptoms was 5.1 years. Eighteen patients underwent canaliculotomy, and one patient received lacrimal irrigation. Plugs were identified in 18 cases, with SmartPlug in 13 cases (72%), followed by EaglePlugTM (two cases), Herrick Lacrimal Plug (two cases), and migrated FCI Painless Plug (1 case). Cultures of discharge, concretions, and/or infected plugs mostly revealed Pseudomonas aeruginosa (42%). Orbital computed tomography in four cases with SmartPlug revealed central radiolucency with surrounding soft-tissue enhancement. No recurrent canaliculitis was observed throughout a mean follow-up period of 13.7 months. No patient needed re-plugging after canaliculotomy and plug removal, with only one required additional lubricants for recurrent dry eye., Conclusion: Plug-related canaliculitis is often underdiagnosed due to late onset and similar symptoms to common ocular diseases. Awareness of plug insertion history as well as meticulous removal of the plug, concretion and/or granulation tissue is important for early diagnosis and to ensure a good outcome.

Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in directing T-cell responses and are involved in the pathogenesis of allergic asthma. Acteoside, an active phenylethanoid glycoside, is widely distributed in many medicinal plants. Herein, we explored the immunomodulatory effects of acteoside on bone marrow-derived DCs in vitro, and further investigated the immunosuppressive ability of acteoside to manipulate T helper type 2 (Th2)-mediated allergic asthma in mice. Following lipopolysaccharide activation, 50 μM of acteoside significantly reduced the production of proinflammatory mediators, including interleukin (IL)-12 and tumor necrosis factor (TNF)-α, whereas it enhanced secretion of the anti-inflammatory cytokine, IL-10, by DCs. However, these effects of acteoside on DCs were reversed by pretreatment with CH223191, an aryl hydrocarbon receptor (AhR) antagonist. Additionally, coculture of acteoside-treated DCs with CD4 + T cells promoted the generation of forkhead box P3-positive (Foxp3 + ) regulatory T cells (Tregs) via AhR activation. Using a murine asthma model, our results demonstrated that oral administration of 50 mg/kg of acteoside decreased levels of Th2-type cytokines, such as IL-4, IL-5, and IL-13, whereas the level of IL-10 and the frequency of CD4 + Foxp3 + Tregs were augmented. Moreover, acteoside treatment markedly inhibited the elevated serum level of ovalbumin-specific immunoglobulin E, attenuated the development of airway hyperresponsiveness, and reduced inflammatory cell counts in bronchoalveolar lavage fluid. Additionally, histological results reveled that acteoside ameliorated pulmonary inflammation in asthmatic mice. Taken together, these results indicated that acteoside exhibits immunomodulatory effects on DCs and plays an anti-inflammatory role in the treatment of allergic asthma., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Allergic asthma is induced by T helper 2 (Th2) responses and allergen-specific immunoglobulin E (IgE). In asthma, regulatory T (Treg) cells play a crucial role in controlling immune homeostasis, and induction of Treg cells is a good strategy to treat Th2-mediated allergic asthma. Schisandrin B (Sch B), the main component isolated from Schisandra chinensis, reportedly possesses various pharmacological properties, but its immunomodulatory mechanism in allergic asthma remains unclear. In the present study, we explored whether Sch B exerts an antiallergic effect through modifying the function of dendritic cells (DCs) to regulate T-cell polarization and further investigated the immunomodulatory effects of Sch B in allergic asthma. Herein, an in vitro study revealed that 20 μM of Sch B-treated bone-marrow-derived DCs exhibited a semi-mature phenotype that secreted low amounts of proinflammatory cytokines including interleukin (IL)-12, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and expressed decreased levels of surface molecules of cluster of differentiation 80 (CD80) and CD86. Compared to fully mature DCs, these Sch B-treated DCs displayed a regulatory ability to promote CD4 + Foxp3 + Treg cell generation via upregulation of heme oxygenase (HO)-1 expression. Of note, in a murine model of ovalbumin (OVA)-induced asthma, levels of Th2-type cytokines such as IL-4, IL-5, and IL-13, and C-C motif chemokine 11 (CCL11) were dampened, whereas numbers of forkhead box P3 (Foxp3)-positive Treg cells were augmented in Sch B-treated mice. Moreover, administration of 5 mg/kg of Sch B alleviated the cardinal features of Th2-mediated allergic asthma, namely, serum OVA-specific IgE production, the development of airway hyperresponsiveness (AHR), and airway inflammation. Collectively, these findings indicate that the effectiveness of Sch B treatment against Th2-mediated allergic asthma was at least partially due to enhancement of DC induction of Treg cells, and Sch B can possibly be developed as an immunomodulatory adjuvant to treat allergic asthma., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Due to the critical roles of emotion and working memory in our daily activities, a great deal of attention has been given to how emotion influences working memory performance. Although the association between emotion and working memory is relatively well established, whether mood enhances or impairs working memory performance remains controversial. The present review provides a relatively representative overview of the research on the effect of different dimensions of emotion on working memory among healthy adults spanning a 30-year period. The findings show that the valence, arousal and motivational dimensions of emotion could all exert an impact on working memory performance. The impact of emotion on working memory might be modulated by task relevance, emotion type, working memory paradigms and individual differences. The vast majority of the studies regarding the effect of emotion on working memory performance focused on the impact of negatively valenced affect and yielded highly contradictory findings. The impacts of arousal and motivation on working memory have been less explored, and inconsistent findings have also been reported. Possible explanations are discussed. Considerable research on the effect of certain dimensions of emotion on working memory has suffered from a lack of control of other emotional dimensions, and different aspects of working memory have been investigated by various paradigms. Directions for further studies should include the exploration of specific dimensions of emotion on different aspects of working memory, with the other dimensions being well controlled., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest and approved to submit to your journal., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Graves' ophthalmopathy (GO) is the most common extrathyroidal manifestation of Graves' disease. It is characterized initially by an inflammatory process, followed by tissue remodeling and fibrosis, leading to proptosis, exposure keratopathy, ocular motility limitation, and compressive optic neuropathy. The pathogenic mechanism is complex and multifactorial. Accumulating evidence suggests the involvement of oxidative stress in the pathogenesis of GO. Cigarette smoking, a major risk factor for GO, has been shown to induce reactive oxygen species (ROS) generation and oxidative damage in GO orbital fibroblasts. In addition, an elevation in ROS and antioxidant enzymes is observed in tears, blood, and urine, as well as orbital fibroadipose tissues and fibroblasts from GO patients. In vitro and in vivo studies have examined the efficacy of various antioxidant supplements for GO. These findings suggest a therapeutic role of antioxidants in GO patients. This review summarizes the current understanding of oxidative stress in the pathogenesis and potential antioxidants for the treatment of GO.

Malignant melanoma can arise from melanocytes in various structures of the eye, orbit, and ocular adnexa. We reviewed the clinical features and long-term results of all subjects with histologically proved melanoma originating from any of the ocular and periocular structures in a tertiary referral center. Overall, 88 patients including 47 men were recruited. The tumor was primarily located in the uvea, followed by the conjunctiva, orbit, eyelid, and lacrimal sac. Patients with uveal melanoma were diagnosed at a relatively younger age (47.0 years), while those with orbital and eyelid melanomas were older at presentation (79.5 years and 78.5 years, respectively). The overall local recurrence rate was 9% at a median follow-up of 41.0 months, among which orbital and eyelid melanomas recurred most commonly. The overall mortality rate was 41% in a median duration of 27.2 months (IQR, 13-58 months) from diagnosis, with the highest for lacrimal sac melanoma, followed by melanoma of the orbit, uveal, conjunctiva, and eyelid. Despite prompt local control, the risk for metastasis and mortality was high. Therefore, efficient modalities for early diagnosis and treatment of ocular melanoma are necessary.

Microhaplotype loci (microhaplotype, MHs), defined by two or more closely linked single nucleotide polymorphisms, are a type of molecular marker within a short segment of DNA. As emerging forensic genetic markers, MHs have no stutter artefacts and higher polymorphism, and permit the design of smaller amplicons. In order to identify the markers from a genome wide perspective and explore their potential application further, we constructed the most comprehensive MH dataset to date, based on the whole genome sequencing data of 105 Han individuals in Southern China from 1000 Genomes Project. The results showed that there were 9,490,075 MH loci in the range of 350 bp in the human genome, and the distribution density of microhaplotypes suggests gene variation. Polymorphism analysis of MHs from various base spans showed that the polymorphism of MHs could reach or exceed common short tandem repeat sites. In addition, based on their flexible assembly, a scheme to build the public database of microhaplotypes was proposed.

Background: Previous study revealed proton pump inhibitors (PPIs) have an effect on gut microbiota. Alteration of the microbiome causes changes of the host immune system and then induces the development of autoimmune diseases (ADs). This study aimed to explore the possible association between PPIs use and ADs., Methods: This study was conducted using data from the Taiwan National Health Insurance Research Database in the period between 2002 and 2015. We performed multivariate and stratified analysis through the Kaplan-Meier method and Cox proportional hazard models to estimate the association between proton pump inhibitor use and the risk of autoimmune diseases., Results: Of the 297,099 patients treated with PPI identified, the overall mean (SD) age was 49.17 (15.63) years and 56.28% of the subjects was male. As compared with the non-PPI group, the adjusted hazard ratio (aHR) were higher for incident organ specific ADs such as Graves disease (aHR=3.28), Hashmoto thyroiditis (aHR=3.61), autoimmune hemolytic anemia (aHR=8.88), immune thrombocytopenic purpura (aHR=5.05) Henoch-Schonlein pupura (aHR=4.83) and Myasthenia gravis (aHR=8.73). Furthermore, the adjusted hazard ratio (aHR) were also higher for incident systemic ADs such as ankylosing spondylitis (aHR=3.67), rheumatoid arthritis (aHR=3.96), primary Sjogren syndrome (aHR=7.81), systemic lupus erythemtoasus (aHR=7.03). systemic vasculitis (aHR=5.10), psoriasis (aHR=2.57), systemic scleroderma (aHR=15.85) and inflammatory myopathy (aHR=37.40). Furthermore, we observed no dose-dependent effect between PPI use and the risk of ADs., Conclusions: Our retrospective population-based cohort study showed that the prescription of proton pump inhibitors is associated with a higher risk of ADs., 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 © 2021 Lin, Chang, Lin, Hu, Hou, Hsu, Shen, Kuo, Chen, Lin, Chen and Chang.)

Pirfenidone is a pyridinone derivative that has been shown to inhibit fibrosis in animal models and in patients with idiopathic pulmonary fibrosis. Its effect on orbital fibroblasts remains poorly understood. We investigated the in vitro effect of pirfenidone in transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation and extracellular matrix (ECM) homeostasis in primary cultured orbital fibroblasts from patients with Graves' ophthalmopathy (GO). The expression of fibrotic proteins, including α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), fibronectin, and collagen type I, was determined by Western blots. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for the ECM homeostasis were examined. After pretreating the GO orbital fibroblasts with pirfenidone (250, 500, and 750 μg/mL, respectively) for one hour followed by TGF-β1 for another 24 h, the expression of α-SMA, CTGF, fibronectin, and collagen type I decreased in a dose-dependent manner. Pretreating the GO orbital fibroblasts with pirfenidone not only abolished TGF-β1-induced TIMP-1 expression but recovered the MMP-2/-9 activities. Notably, pirfenidone inhibited TGF-β1-induced phosphorylation of p38 and c-Jun N-terminal kinase (JNK), the critical mediators in the TGF-β1 pathways. These findings suggest that pirfenidone modulates TGF-β1-mediated myofibroblast differentiation and ECM homeostasis by attenuating downstream signaling of TGF-β1.

Inhibitor of DNA binding ( Id ) genes comprise a family of four helix-loop-helix (HLH) transcriptional inhibitors. Our earlier studies revealed a role for ID2 within the circadian system, contributing to input, output, and core clock function through its interaction with CLOCK and BMAL1. Here, we explore the contribution of ID4 to the circadian system using a targeted disruption of the Id4 gene. Attributes of the circadian clock were assessed by monitoring the locomotor activity of Id4 -/- mice, and they revealed disturbances in its operation. Id4 -mutant mice expressed a shorter circadian period length, attenuated phase shifts in responses to continuous and discrete photic cues, and an advanced phase angle of entrainment under a 12:12 light:dark cycle and under short and long photoperiods. To understand the basis for these properties, suprachiasmatic nucleus (SCN) and retinal structures were examined. Anatomical analysis reveals a smaller Id4 -/- SCN in the width dimension, which is a finding consistent with its smaller brain. As a result of this feature, anterograde tracing in Id4 -/- mice revealed retinal afferents innovate a disproportionally larger SCN area. The Id4 -/- photic entrainment responses are unlikely to be due to an impaired function of the retinal pathways since Id4 -/- retinal anatomy and function tested by pupillometry were similar to wild-type mice. Furthermore, these circadian characteristics are opposite to those exhibited by the Id2 -/- mouse, suggesting an opposing influence of the ID4 protein within the circadian system; or, the absence of ID4 results in changes in the expression or activity of other members of the Id gene family. Expression analysis of the Id genes within the Id4 -/- SCN revealed a time-of-day specific elevated Id1 . It is plausible that the increased Id1 and/or absence of ID4 result in changes in interactions with bHLH canonical clock components or with targets upstream and/or downstream of the clock, thereby resulting in abnormal properties of the circadian clock and its entrainment.

Complementary papers by Nguyen et al. (2021) and Baek et al. (2021) track the assembly of the pre-initiation complexes at gene promoters using single-molecule microscopy, revealing dynamic spatiotemporal regulation of transcription initiation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To compare Pneumocystis jirovecii pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general population METHODS: We identified patients with ARD recorded in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model., Results: We enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16-86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82-10.35, 2.16-12.13, 2.41-6.95, and 2.06-6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk., Conclusion: Underlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide. Key Points • Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD. • Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP. • Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP. • Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Nonradiographic axial spondyloarthropathies (nr-axSpA) are diagnosed by the absence of radiographic sacroiliitis and the presence of bone marrow edema (BME) on magnetic resonance imaging (MRI). According to the classification criteria of the international Assessment of Spondyloarthritis Society (ASAS), structural changes to sacroiliac joints (SIJs) on MRI cannot be used as criteria in the absence of BME. However, less than half the Asian patients with clinically active axSpA show BME. The incidence of human leukocyte antigen (HLA)-B27 is low in Asian populations, which makes it more difficult to identify nr-axSpA. We used MRI to evaluate the structural damage to SIJs in patients with nr-axSpA with and without BME with the aim of identifying the best methodology for accurate diagnosis, especially in populations with less common BME and HLA-B27., Methods: One hundred three patients with inflammatory back pain were included in this prospective study. No patient's radiograph met the definition of positive modified New York criteria. BME and structural damage to SIJ including sclerosis and erosion were assessed independently on coronal and axial short-tau inversion recovery and T1-weighted spin echo MRI scans by two well-trained musculoskeletal radiologists using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Demographics of patients were collected. Disease characteristics and structural damage were analyzed in patients with and without BME on SIJ MRI. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of structural damage., Results: All individuals in the cohort had at least one abnormal finding on SIJ MRI, including BME or structural damage; 36 of 103 patients had BME. We identified a significant positive correlation between SPARCC scores and severe erosion assessed by focal joint space widening (fJSW) (p = 0.001) in these 36 patients. Fifty-eight of the 103 enrolled patients fulfilled the ASAS criteria for nr-axSpA in the either absence or presence of BME. Of these 58 patients, 57 and 19 had erosions or fJSW, respectively, and the presence of BME was significantly correlated with fJSW (phi score of 0.319 and p = 0.015). We demonstrated a significant positive correlation between fJSW and either the presence or the severity of BME in patients with nr-axSpA who met the ASAS definition. There was a positive correlation between BME and fJSW across the whole study cohort (phi score of 0.389; p < 0.001). The area under the ROC curve (AUC) for fJSW on SIJ MRI was 0.736, p < 0.001. In both HLA-B27-positive and -negative groups, BME was more common in the presence of fJSW (phi scores of 0.370 and 0.377, p = 0.018 and 0.003, respectively) and SPARCC scores were higher in patients with fJSW (p < 0.001 and p = 0.005). We also identified a positive correlation between fJSW and BME in patients with nr-axSpA and normal serum levels of C-reactive protein (phi score of 0.362 and p = 0.001)., Conclusion: Structural damage detected on SIJ MRI, sclerosis, erosions and fJSW may be present in patients without detectable inflammation on SIJ MRI. However, fJSW is significantly correlated with the severity of inflammation seen on SIJ MRI, which contributes to the accurate diagnosis of nr-axSpA, and it could be used as an alternative diagnostic test for nr-axSpA in the general population, especially for those who do not carry the HLA-B27 gene, Asian patients without BME, or patients with normal serum inflammatory biomarkers., (© 2021. The Author(s).)

Immunoglobulin E (IgE) and mast cells play important roles in the pathogenesis of allergic asthma. Catalpol, an iridoid glycoside, exerts many biological functions including anti-inflammatory activities. Herein, we investigated catalpol to determine both its antiallergic effects on IgE/ovalbumin (OVA)-stimulated mouse bone marrow-derived mast cells and its therapeutic actions in murine allergic asthma. We found that catalpol dramatically suppressed IgE/OVA-induced mast cell degranulation. Meanwhile, 5 ~ 100 μM of catalpol neither affected the expression level of the high-affinity receptor of IgE (FcεRI) by mast cells nor induced mast cell apoptosis. In addition, mRNA expression levels of inflammatory enzymes including cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were downregulated. Administration of catalpol also suppressed production of prostaglandin D 2 (PGD 2 ), interleukin (IL)-6, and IL-13, while not affecting tumor necrosis factor (TNF)-α production. Further, catalpol pretreatment significantly attenuated the FcεRI-mediated Akt signaling pathway. In mice with IgE/OVA-induced asthma, oral administration of catalpol remarkably suppressed the production of OVA-specific IgE, the development of airway hyperresponsiveness (AHR), and the infiltration of eosinophils and neutrophils into the lungs. Histological studies demonstrated that catalpol substantially inhibited the recruitment of mast cells and increased mucus production in lung tissues. Catalpol-treated mice had significantly lower levels of helper T cell type 2 (Th2) cytokines (IL-4, IL-5, and IL-13), PGD 2 , eotaxin-1, and C-X-C chemokine ligand-1 (CXCL1) in bronchoalveolar lavage fluid (BALF) than did the allergic group. Collectively, these results indicated that the suppressive effects of catalpol on degranulation and mediator generation by mast cells were beneficial in treating allergic asthma., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves' ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves' orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves' orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves' orbital fibroblasts through the p38 and JNK pathways.

Responses to developmental and environmental cues depend on precise spatiotemporal control of gene transcription. Enhancers, which comprise DNA elements bound by regulatory proteins, can activate target genes in response to these external signals. Recent studies have shown that enhancers are transcribed to produce enhancer RNAs (eRNAs). Do eRNAs play a functional role in activating gene expression or are they non-functional byproducts of nearby transcription machinery? The unstable nature of eRNAs and over-reliance on knockdown approaches have made elucidating the possible functions of eRNAs challenging. We focus here on studies using cloned eRNAs to study their function as transcripts, revealing roles for eRNAs in enhancer-promoter looping, recruiting transcriptional machinery, and facilitating RNA polymerase pause-release to regulate gene expression., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in primary Sjogren syndrome (pSS) has rarely been explored. To explore the association between BRONJ and pSS, we conducted a population-based propensity-score-matched cohort study using Taiwan's National Health Insurance Research Database, including pSS patients receiving antiosteoporotic therapy and patients without pSS receiving antiosteoporotic therapy. A 1:4 matched-pair cohort based on propensity score was created. The stratified Cox proportional hazards model compared the risk of BRONJ in the pSS and non-pSS groups. In the study, 23,280 pSS patients and 28,712,152 controls were enrolled. After matching, 348 patients with pSS receiving antiosteoporotic drugs and 50,145 without pSS receiving antiosteoporotic drugs were included for analysis. The risk of developing BRONJ was 1.96 times higher in pSS patients compared with non-pSS patients after adjustment for age, sex, and comorbidities. No dose-response effect was observed in the bisphosphonate-treated pSS cohorts, documented as the cumulative defined daily doses of either < 224 or ≥ 224 (hazard ratio [HR]: 2.407, 95% confidence interval [CI] 1.412-7.790; HR: 2.143, 95% CI 1.046-4.393, respectively) increased risk of developing osteonecrosis of the jaw. In conclusion, the risk of BRONJ is significantly higher in patients with pSS compared with the general population.

Objective: To evaluate the efficacy of three surgical approaches for the treatment of cervicothoracic tuberculosis., Methods: This is a multicenter retrospective study. We analyzed 74 patients with cervicothoracic tuberculosis who were treated in six institutions between January 2000 and January 2015. There were 37 male and 37 female patients, with an average age of 24 years (range, 5-62 years). The operative method was selected according to the indications. A total of 33 patients underwent one-stage anterior surgery (group A); 16 underwent a combined anterior and posterior surgery (group B) and 25 underwent one-stage posterior surgery (group C). Clinical outcomes, laboratory indexes, and radiological results were analyzed., Results: All cases were followed up for approximately 36-96 months post-surgery (average, 39 months). At the last follow-up, patients in all three groups had achieved bone fusion, with pain relief and neurological recovery. No major vessel and nerve injuries were found during the operation. There were significant differences before and after treatment for visual analogue scale (VAS), neck disability index (NDI), and Japanese Orthopedic Association (JOA) score (P < 0.001). Three surgical strategies significantly improved kyphosis (P < 0.001)., Conclusion: The choice of operation for cervicothoracic tuberculosis should be selected based on the pathological changes, scope, and general physical condition of the patient. The indication for a posterior approach is narrow and it should be used selectively. The combined anterior and posterior approach involved a longer operating time, larger blood loss, and greater trauma, and also required a higher level of surgical skill. Therefore, the indications for this approach should be strictly controlled. Anterior approach surgery for the treatment of cervicothoracic tuberculosis showed excellent efficacy and fewer complications., (© 2019 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

ID2 is a rhythmically expressed helix-loop-helix transcriptional repressor, and its deletion results in abnormal properties of photoentrainment. By examining parametric and nonparametric models of entrainment, we have started to explore the mechanism underlying this circadian phenotype. Id2 -/- mice were exposed to differing photoperiods, and the phase angle of entrainment under short days was delayed 2 h as compared with controls. When exposed to long durations of continuous light, enhanced entrainment responses were observed after a delay of the clock but not with phase advances. However, the magnitude of phase shifts was not different in Id2 -/- mice tested in constant darkness using a discrete pulse of saturating light. No differences were observed in the speed of clock resetting when challenged by a series of discrete pulses interspaced by varying time intervals. A photic phase-response curve was constructed, although no genotypic differences were observed. Although phase shifts produced by discrete saturating light pulses at CT16 were similar, treatment with a subsaturating pulse revealed a ~2-fold increase in the magnitude of the Id2 -/- shift. A corresponding elevation of light-induced per1 expression was observed in the Id2 -/- suprachiasmatic nucleus (SCN). To test whether the phenotype is based on a sensitivity change at the level of the retina, pupil constriction responses were measured. No differences were observed in responses or in retinal histology, suggesting that the phenotype occurs downstream of the retina and retinal hypothalamic tract. To test whether the phenotype is due to a reduced amplitude of state variables of the clock, the expression of clock genes per1 and per2 was assessed in vivo and in SCN tissue explants. Amplitude, phase, and period length were normal in Id2 -/- mice. These findings suggest that ID2 contributes to a photoregulatory mechanism at the level of the SCN central pacemaker through control of the photic induction of negative elements of the clock.

Objective: This study assessed the risk of Parkinson disease (PD) in patients with primary Sjögren's syndrome (pSS) using a nationwide, population-based cohort during a 15-year follow-up period., Method: We identified 17,028 patients with pSS by using the catastrophic illness registry in the Taiwan National Health Insurance Research Database, and 68,094 matched non-pSS controls., Results: The pSS cohort showed a higher incidence of PD development than did the non-pSS cohort (1.60% vs. 1.17%, p = 0.0001). The adjusted hazard ratio (aHR) of developing PD was 1.23 times greater in the pSS group than in the non-pSS group. When stratified by sex, age, and comorbidities, the female patients with pSS and patients aged between 61 and 70 years were associated with a higher PD risk (aHR 1.28 and aHR 1.30, respectively). Patients with pSS with no other comorbidity had a higher risk of PD (aHR: 2.17), compared with the non-pSS patients with no other comorbidity. When comparing non-pSS patients without or with comorbidity with pSS without or with comorbidity, pSS patients with comorbidity had highest risk of PD (aHR: 3.814)., Conclusions: All of the above findings suggested that pSS is an independent risk factor for the development of PD. Key Points •The patients with pSS had 1.23 times risk of Parkinson disease than the non-pSS group. •The female patients with pSS and patients aged between 61 and 70 years were associated with a higher PD risk (aHR 1.28 and aHR 1.30, respectively). •The pSS patients with comorbidity had highest risk of PD (aHR: 3.814).

Ultrafine fluorescent gold nanoclusters (AuNCs) have emerged as biocompatible nanoprobes for biomedical imaging in vivo, and the precision surface chemistry of AuNCs is the key for attaining their clinical application. Comparison of two promising candidates for future nanomedicine, i.e. dihydrolipoic acid- versus glutathione-capped AuNCs (AuNC@DHLA vs. AuNC@GSH), was conducted for the first time to clarify their polyethylene glycol-related bioconjugate chemistry (PEGylation) and protein interactions. Gel electrophoresis was performed to separate the number of AuNCs PEGylation, and the molecular weight of the PEG spacer dominated the resolution of the separation in the gel. We have engineered and isolated the mono-PEGylated AuNCs either from the indirect carbodiimide bioconjugate chemistry or the direct Au-S binding. One-pot synthesis showed great efficiency for isolating mono-PEGylated AuNC@GSH from the tailored controlled aggregation of Au(i)-thiolate complexes on in situ generated Au(0) cores. Post-PEGylation of AuNC@GSH was also feasible using monodendate thiol-terminated PEG, but bidendate ligands of AuNC@DHLA exhibited low PEGylated efficiency by Au-S binding. In addition, mono-PEGylated AuNC@GSH significantly enhanced the ability of anti-nonspecific protein adsorption, but mono-PEGylated AuNC@DHLA cannot avoid the nonspecific binding with serum albumin. In addition, specific nano-assembly involving mono-biotinylated AuNCs with streptavidin were also compared using gel electrophoresis. These results provide key insights into the selection, preparation and design of functional AuNCs as nanoprobes for versatile biomedical applications.

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Hui Pan et al.)

Objective: To evaluate the clinical efficacy of an allogeneic bone cage (Biocage; Beijing Datsing Bio-Tech Co., Ltd., Beijing, China) for treatment of single-segment lumbar degenerative disease in patients with a high risk of non-fusion., Methods: From January 2013 to December 2016, 67 patients who underwent lumbar fusion were divided into the Biocage group (n = 33) and polyether ether ketone (PEEK) group (n = 34). The patients were followed up for 24 to 48 months. The mean intervertebral height of the fusion level, fusion rate, height of the intervertebral foramen, visual analog scale score, and Oswestry disability index were compared., Results: The PEEK group had a lower fusion rate than the Biocage group (88.24% vs. 90.91%), although the difference was not statistically significant. During follow-up, the height of the intervertebral space was similar between the Biocage and PEEK groups (12.88 ± 0.45 and 12.84 ± 1.01 mm, respectively). The height of the intervertebral foramen was larger in the Biocage than PEEK group (20.67 ± 1.34 vs. 20.00 ± 2.05 mm). Good clinical efficacy was achieved in both groups., Conclusion: The Biocage is efficient and safe for treatment of single-segment lumbar degenerative disease in patients with a high risk of non-fusion.