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This present study documents the incidence of plastic digestion by shortfin mako shark (Isurus oxyrinchus), caught by the Taiwanese small-scale tuna longline fishery in the Northwest Pacific Ocean (between the northeast coast of Taiwan and Japan). In 20 stomachs of shortfin mako, nearly 10% of samples contained at least one piece of plastic debris. The ingested plastic debris was found in the forms of films (5.0 cm) and fragments (3.0 mm) and was identified as polypropylene (PP) based on its polymer characteristics. The results from the analysis provide evidence for the anthropogenic origin and potential intake pathway of direct engulfment of ingested plastics. Our results also confirmed the low incidence of plastic ingestion in shortfin mako, suggesting that pelagic marine species may be relatively less affected by plastic pollution. Future research efforts are thus needed to assess the long-term impact of plastic pollution on marine species., (Copyright © 2021. Published by Elsevier Ltd.)

Content-Centric Networking (CCN) has emerged as a potential Internet architecture that supports name-based content retrieval mechanism in contrast to the current host location-oriented IP architecture. The in-network caching capability of CCN ensures higher content availability, lesser network delay, and leads to server load reduction. It was observed that caching the contents on each intermediate node does not use the network resources efficiently. Hence, efficient content caching decisions are crucial to improve the Quality-of-Service (QoS) for the end-user devices and improved network performance. Towards this, a novel content caching scheme is proposed in this paper. The proposed scheme first clusters the network nodes based on the hop count and bandwidth parameters to reduce content redundancy and caching operations. Then, the scheme takes content placement decisions using the cluster information, content popularity, and the hop count parameters, where the caching probability improves as the content traversed toward the requester. Hence, using the proposed heuristics, the popular contents are placed near the edges of the network to achieve a high cache hit ratio. Once the cache becomes full, the scheme implements Least-Frequently-Used (LFU) replacement scheme to substitute the least accessed content in the network routers. Extensive simulations are conducted and the performance of the proposed scheme is investigated under different network parameters that demonstrate the superiority of the proposed strategy w.r.t the peer competing strategies.

Aim: This study aimed to develop an AI model for detecting a caller's emotional state during out-of-hospital cardiac arrest calls by processing audio recordings of dispatch communications., Methods: Audio recordings of 337 out-of-hospital cardiac arrest calls from March-April 2011 were retrieved. The callers' emotional state was classified based on the emotional content and cooperative scores. Mel-frequency cepstral coefficients extracted essential information from the voice signals. A support vector machine was utilised for the automatic judgement, and repeated random sub-sampling cross validation (RRS-CV) was applied to evaluate robustness. The results from the artificial intelligence classifier were compared with the consensus of expert reviewers., Results: The audio recordings were classified into five emotional content and cooperative score levels. The proposed model had an average positive predictive value of 72.97%, a negative predictive value of 93.47%, sensitivity of 38.76%, and specificity of 98.29%. If only the first 10 seconds of the recordings were considered, it had an average positive predictive value of 84.62%, a negative predictive value of 93.57%, sensitivity of 52.38%, and specificity of 98.64%. The artificial intelligence model's performance maintained preferable results for emotionally stable cases., Conclusion: Artificial intelligence models can possibly facilitate the judgement of callers' emotional states during dispatch conversations. This model has the potential to be utilised in practice, by pre-screening emotionally stable callers, thus allowing dispatchers to focus on cases that are judged to be emotionally unstable. Further research and validation are required to improve the model's performance and make it suitable for the general population., 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 © 2021. Published by Elsevier B.V.)

Bananas are among the world's most important cash and staple crops but are threatened by various devastating pathogens. The phytohormone salicylic acid (SA) plays a key role in the regulation of plant immune response. Tracking the expression of SA-responsive marker genes under pathogen infection is important in pathogenesis elucidation. However, the common SA-responsive marker genes are not consistently induced in different banana cultivars or different organs. Here, we conducted transcriptome analysis for SA response of a banana cultivar, 'Pei-Chiao' (Cavendish, AAA genome), and identified three genes, MaWRKY40 , MaWRKY70 , and Downy Mildew Resistant 6 (DMR6)-Like Oxygenase 1 ( MaDLO1 ) that are robustly induced upon SA treatment in both the leaves and roots. Consistent induction of these three genes by SA treatment was also detected in both the leaves and roots of bananas belonging to different genome types such as 'Tai-Chiao No. 7' (Cavendish, AAA genome), 'Pisang Awak' (ABB genome), and 'Lady Finger' (AA genome). Furthermore, the biotrophic pathogen cucumber mosaic virus elicited the expression of MaWRKY40 and MaDLO1 in infected leaves of susceptible cultivars. The hemibiotrophic fungal pathogen Fusarium oxysporum f. sp. cubense tropical race 4 (TR4) also consistently induced the expression of MaWRKY40 and MaDLO1 in the infected roots of the F. oxysporum f. sp. cubense TR4-resistant cultivar. These results indicate that MaWRKY40 and MaDLO1 can be used as reliable SA-responsive marker genes for the study of plant immunity in banana. Revealing SA-responsive marker genes provides a stepping stone for further studies in banana resistance to pathogens.

Background: Coronavirus disease 2019 (COVID-19) spread all over the world in 2020. In the face of the sudden pandemic, workforce mobilization has been of critical concern to medical institutions. During the pandemic, the public's behaviors of seeking medical assistance have also changed. Using the real-world data of a large medical center in Taiwan, this study aimed to analyze the fluctuations of outpatient visits among various departments and divisions in the early phase of the COVID-19 pandemic and to provide suggestions for staff allocation in similar future events., Methods: Data of outpatient visits at Taipei Veterans General Hospital were obtained for analysis. The weekly fluctuations of outpatient visits among 36 departments or divisions were computed for 8 weeks from February 3 to March 29, 2020, the early phase of the pandemic. The monthly data of outpatient visits by department and division in March 2020 were also extracted for comparison with those in March 2019. A simple regression equation was used to calculate the weekly trends., Results: Average outpatient visits decreased by 26% in 2 months following the outbreak. Among the 36 departments or divisions, ophthalmology, orthopedics, and cardiology underwent marked declines after the outbreak; the slopes of the simple regression equation were -110.8, -100.7, and -99.2, respectively. By contrast, transfusion medicine, toxicology, transplantation surgery, pediatric surgery, chest surgery, technical aid, and oncology were divisions less influenced. In the year-over-year comparison, infection was the only department or division with positive growth (20.5%), whereas all others exhibited negative growth., Conclusion: In the future, we can fulfil the additional personnel needs during a pandemic by redeploying physicians from departments experiencing a reduced workload. Hospitals should also establish preparatory employee training programs to ensure that the reassigned personnel are adequately equipped to serve in their new positions., Competing Interests: Conflicts of interest: Dr. Tzeng-Ji Chen and Dr. Shinn-Jang Hwang, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Background: Out-of-hospital cardiac arrest (OHCA) is a critical condition with poor outcomes. Although the survival rate increases in those who undergo defibrillation, the utility of on-time defibrillation among bystanders remained low. An evaluation of the deployment strategy for public access defibrillators (PADs) is necessary to increase their use and accessibility. This study was to conduct a systematic review for deployment strategies of PADs., Methods: Two authors independently searched for articles published before October 2019 from PubMed, Embase, Web of Science, and Cochrane Library. An independent librarian provided the search strategy and assisted the literature research. We included articles that were focused on the main topic, but excluded those which were missing results or that used an unclear definition. The qualitative outcomes were the utility and OHCA coverage of PADs. We performed a qualitative analysis across the studies, but a quantitative analysis was not available due to the studies' heterogeneity in design and variety of outcomes., Results: We eventually included 15 studies. Three strategies were presented: guidelines-based, grid-based, and landmark-based. The guidelines-based deployment was common fit for OHCA events. The grid-based method increased the use of bystander defibrillation 3-fold, and 30-day survival doubled. The top 3 landmarks in the landmark-based strategy were offices (18.6%), schools (13.3%), and sports facilities (12.9%). Utility of PADs might increase if we optimize PAD location by mathematical modeling and evaluation feedback., Conclusion: Three deployment strategies were presented. Although the optimal method could not be fully identified, a more efficient PAD deployment could benefit the population in terms of OHCA coverage and survival among patients with OHCA., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The benefit and the risk profile of Gamma Knife radiosurgery (GKRS) for intracerebral cavernoma remains incompletely defined in part due to the natural history of low incidence of bleeding and spontaneous regression of this vascular malformation. In this study, we retrieved cases from a prospectively collected database to assess the outcome of intracerebral cavernoma treated with GKRS using a double blinded review process for treatment., Methods: From 2003 to 2018, there were 94 cases of cavernoma treated by GKRS in the doubly blinded assessments by two experienced neurological and approved for GKRS treatment. All the patients received GKRS with margin dose of 11-12 (Gray) Gy and afterwards were assessed for neurological outcome, radiologic response, and quality of life., Results: The median age of the patients was 48 (15-85) years with median follow up of 77 (26-180) months post SRS. The mean target volume was 1.93 ± 3.45 cc. In those who has pre-SRS epilepsy, 7 of 16 (43.7%) achieved seizure freedom (Engel I/II) and 9 of 16 (56.3%) achieved decreased seizures (Engel III) after SRS. Rebleeding occurred in 2 cases (2.1%) at 13 and 52 months post SRS. The radiologic assessment demonstrated 20 (21.3%) cases of decreased cavernoma volume, 69 (73.4%) were stable, and 5 (7.3%) increased size. Eighty-seven of 94 (92.5%) cases at the last follow up achieve improvement in their quality of life, but 7 cases (7.4%) showed a deterioration. In statistical analysis, the effective seizure control class (Engel I/II) was highly correlated with patient harboring a single lesion (p < 0.05) and deep seated location of the cavernoma (p < 0.01). New neurological deficits were highly correlated with decreased mental (p < 0.001) and physical (p < 0.05) components of quality of life testing, KPS (p < 0.001), deep seated location (p < 0.01), and increased nidus volume (p < 0.05). Quality of life deterioration either in physical component (p < 0.01), mental component (p < 0.01), and KPS (p < 0.05) was highly correlated with increased cavernoma volume., Conclusion: Low margin dose GKRS for intracerebral cavernoma offers reasonable seizure control and improved quality of life while conferring a low risk of treatment complications including adverse radiation effect., (© 2021. The Author(s).)

Background: During pandemics, acquiring outpatients' travel, occupation, contact, and cluster histories is one of the most important measures in assessing the disease risk among incoming patients. Previous means of acquiring this information in the examination room have been insufficient in preventing disease spread., Objective: This study aimed to demonstrate the deployment of an automatic system to triage outpatients over the internet., Methods: An automatic system was incorporated in the existing web-based appointment system of the hospital and deployed along with its on-site counterpart. Automatic queries to the virtual private network travel and contact history database with each patient's national ID number were made for each attempt to acquire the patient's travel and contact histories. Patients with relevant histories were denied registration or entry. Text messages were sent to patients without a relevant history for an expedited route of entry if applicable., Results: A total of 127,857 visits were recorded. Among all visits, 91,195 were registered on the internet. In total, 71,816 of them generated text messages for an expedited route of entry. Furthermore, 65 patients had relevant histories, as revealed by the virtual private network database, and were denied registration or entry., Conclusions: An automatic triage system to acquire outpatients' relevant travel and contact histories was deployed rapidly in one of the largest academic medical centers in Taiwan. The updated system successfully denied patients with relevant travel or contact histories entry to the hospital, thus preventing long lines outside the hospital. Further efforts could be made to integrate the system with the electronic medical record system., (©Ding-Heng Lu, Chia-An Hsu, Eunice J Yuan, Jun-Jeng Fen, Chung-Yuan Lee, Jin-Lain Ming, Tzeng-Ji Chen, Wui-Chiang Lee, Shih-Ann Chen. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 27.07.2021.)

Geochemical chronologies were constructed from otoliths of adult Pacific bluefin tuna (PBT) to investigate the timing of age-specific egress of juveniles from coastal nurseries in the East China Sea or Sea of Japan to offshore waters of the Pacific Ocean. Element:Ca chronologies were developed for otolith Li, Mg, Mn, Zn, Sr, and Ba, and our assessment focused on the section of the otolith corresponding to the age-0 to age-1 + interval. Next, we applied a common time-series approach to geochemical profiles to identify divergences presumably linked to inshore-offshore migrations. Conspicuous geochemical shifts were detected during the juvenile interval for Mg:Ca, Mn:Ca, and Sr:Ca that were indicative of coastal-offshore transitions or egress generally occurring for individuals approximately 4-6 mo. old, with later departures (6 mo. or older) linked to overwintering being more limited. Changepoints in otolith Ba:Ca profiles were most common in the early age-1 period (ca. 12-16 mo.) and appear associated with entry into upwelling areas such as the California Current Large Marine Ecosystem following trans-Pacific migrations. Natal origin of PBT was also predicted using the early life portion of geochemical profile in relation to a baseline sample comprised of age-0 PBT from the two primary spawning areas in the East China Sea and Sea of Japan. Mixed-stock analysis indicated that the majority (66%) of adult PBT in our sample originated from the East China Sea, but individuals of Sea of Japan origin were also detected in the Ryukyu Archipelago., (© 2021. The Author(s).)

Background: The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD., Results: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome., Conclusions: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development., Trial Registration: The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.

Background: Galactose-deficient IgA 1 (Gd-IgA 1 ) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA 1 level remains unclear., Methods: Ninety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA 1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients., Results: At baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA 1 than control subjects. Gd-IgA 1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA 1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA 1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression., Conclusions: Our results indicate a close relationship between alternative complement pathway activation, Gd-IgA 1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients., 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 Chiu, Lin, Shu, Fang, Chang, Chou, Wu, Chiang, Lin, Chen and Wu.)

Prolyl hydroxylase domain enzyme (PHD) inhibitors are effective in the treatment of chronic kidney disease (CKD)-associated anemia by stabilizing hypoxia inducible factor (HIF), thereby increasing erythropoietin and consequently erythropoiesis. However, concern for CKD progression needs to be addressed in clinical trials. Although pre-clinical studies showed an anti-inflammatory effect in kidney disease models, the effect of PHD inhibitors on kidney fibrosis was inconsistent probably because the effects of HIF are cell type and context dependent. The major kidney erythropoietin-producing cells are pericytes that produce erythropoietin through HIF-2α-dependent gene transcription. The concern for the impact of HIF in pericytes on kidney fibrosis arises from the fact that pericytes are the major precursor cells of myofibroblasts in CKD. Since cells expressing Gli1 fulfill the morphologic and anatomic criteria for pericytes, we induced Gli1 + cell-specific HIF stabilization or knockout to study the impact of HIF in pericytes on kidney pathology of mice with or without fibrotic injury induced by unilateral ureteral obstruction. Compared with the littermate controls, mice with pericyte-specific HIF stabilization due to von Hippel-Lindau protein or PHD2 knockout showed increased serum erythropoietin and polycythemia rather than a discernible difference in kidney fibrosis. Compared with Gli1 + pericytes sorted from littermate controls, Gli1 + pericytes sorted from PHD2 knockout mice showed increased erythropoietin gene expression rather than discernible changes in Col1a1 or Acta2 expression. Furthermore, pericyte-specific knockout of HIF-1α or HIF-2α did not affect kidney fibrosis. Thus, our study supports the absence of negative effects of PHD inhibitors on kidney fibrosis of mice despite HIF stabilization in pericytes., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background/purpose: The study aim was to develop a model for predicting patients with emergency medical service (EMS) witnessed out-of-hospital cardiac arrest (OHCA)., Methods: We used fire-based EMS data from Taipei city to develop the prediction model. Patients included in this study were those who were initially alive, non-traumatic, and age ≧20 years. Data were extracted from electronic records of ambulance run sheets and an Utstein-style OHCA registry. The primary outcome (EMS-witnessed OHCA) was defined as cardiac arrest occurring during the service of emergency medical technicians before arrival at a receiving hospital. Area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration. The point value system with Youden's J Index was used to find the optimal cut-off value., Results: From 2011 to 2015, a total of 252,771 patients were included. Of them, 660 (0.26%) were EMS-witnessed OHCA. The model, including the predictors of male gender, respiratory rate≦10 cycles/min, heart rate <60 or ≧120 beats/min, systolic blood pressure <100 mmHg, level of consciousness, and oxygen saturation <94%, reached excellent discrimination with an AUROC of 0.94 [95% confidence interval (CI), 0.93-0.95] and excellent calibration (p = 0.42 for HL test) in a randomly selected derivation cohort. The results were comparable to those found in a validation cohort. The optimal cut-off value (≧13) of the tool demonstrated high sensitivity (87.84%) and specificity (86.20%)., Conclusion: This newly developed prediction model will help identify high-risk patients with EMS-witnessed OHCA., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Endometrial cancer is the most common malignant tumors of gynecologic neoplasms in Western society. In recent years, the incidence of endometrial cancer has increased, and it has become the third most common female gynecological cancer (after ovarian and cervical cancer) in Taiwan. Adlay ( Coix lachryma-jobi L. var. Ma-yuen Stapf.) has been demonstrated to have bioactive polyphenols, flavonoids, phytosterols, and essential nutrients for health benefits, including anticancer effects in humans. However, little is known about the effect of adlay seeds on endometrial cancer. Our study aimed to investigate the potential growth inhibitory effects of several adlay seed fractions, including ethyl acetate (ATE-EA) and its bioactive constituents, separately on endometrial cancer cells-HEC-1A (phosphatase and tensin homolog-positive) and RL95-2 (phosphatase and tensin homolog-negative)-and identify related active ingredients. In addition, the potential active fractions and the phytochemical compounds were elucidated. The results demonstrate superior activity of ATE-EA with significant in vitro cell proliferation inhibitory capacity, particularly its C.D.E.F-subfraction. Moreover, HPLC- and GC/FID-based quantification of ATE-EA subfractions showed that phenolic compounds (caffeic acid, protocatechuic acid, and p-hydroxybenzaldehyde), flavonoids, steroids, and fatty acid compounds exert anti-proliferative effects in the cell model. Finally, it was shown that cell growth and cell cycle arrest most significantly occurred in the in G1 or G2/M phase under ATE-EA treatment. Collectively, our results demonstrate an antiproliferative effect of ATE-EA on endometrial cancer cells that suggest a positive health outcome for women from consumption of these compounds.

Background: Phalaenopsis is one of the important ornamental plants worldwide. It plays the most significant role in flower exportation in Taiwan. However, the yellow leaf disease caused by Fusarium spp. has reduced the orchid flower yield 10-50 % yearly. Varieties resistant to yellow leaf disease associated with Fusarium is urgently needed for orchid growers and breeders, and is the ultimate solution for the long-term goal. To achieve this, phenotyping is the first step and the most necessary information for further studies, such as resistance gene identification, quantitative trait loci identification, and genome-wide association study., Results: The inoculation of Fusarium was performed in either abbreviated stem or detached leaf, and the pros and cons were compared. The former is the general method of phenotyping for estimating the tolerance to yellow leaf disease of Phalaenopsis, but it is time-consuming and spacy, and thus not suitable for the assessment of large numbers of samples. In contrast, the latter not only showed a similar trend of disease severity with time reduced to only one fourth of the former one but also less space needed., Conclusions: This solution allows a better phenotyping approach for the fast detection of yellow leaf disease associated with Fusarium in a large number of Phalaenopsis samples.

We report spin-dependent transport properties and I-V hysteresis characteristics in an [Formula: see text]-based magnetic tunnel junction (MTJ). The bipolar resistive switching and the magnetoresistances measured at high resistance state (HRS) and low resistance state (LRS) yield four distinctive resistive states in a single device. The temperature dependence of resistance at LRS suggests that the resistive switching is not triggered by the metal filaments within the [Formula: see text] layer. The role played by oxygen vacancies in [Formula: see text] is the key to determine the resistive state. Our study reveals the possibility of controlling the multiple resistive states in a single [Formula: see text]-based MTJ by the interplay of both electric and magnetic fields, thus providing potential applications for future multi-bit memory devices.

Competing Interests: Competing interests: We have read and understood The BMJ policy on declaration of interests and have no relevant interests to declare.

The escalated growth of the Internet of Things (IoT) has started to reform and reshape our lives. The deployment of a large number of objects adhered to the internet has unlocked the vision of the smart world around us, thereby paving a road towards automation and humongous data generation and collection. This automation and continuous explosion of personal and professional information to the digital world provides a potent ground to the adversaries to perform numerous cyber-attacks, thus making security in IoT a sizeable concern. Hence, timely detection and prevention of such threats are pre-requisites to prevent serious consequences. The survey conducted provides a brief insight into the technology with prime attention towards the various attacks and anomalies and their detection based on the intelligent intrusion detection system (IDS). The comprehensive look-over presented in this paper provides an in-depth analysis and assessment of diverse machine learning and deep learning-based network intrusion detection system (NIDS). Additionally, a case study of healthcare in IoT is presented. The study depicts the architecture, security, and privacy issues and application of learning paradigms in this sector. The research assessment is finally concluded by listing the results derived from the literature. Additionally, the paper discusses numerous research challenges to allow further rectifications in the approaches to deal with unusual complications.

Renal fibrosis, a common pathological manifestation of virtually all types of chronic kidney disease (CKD), often results in diffuse kidney scarring and predisposes to end-stage renal disease. Currently, there is no effective therapy against renal fibrosis. Recently, our laboratory identified an ER-resident protein, thioredoxin domain containing 5 (TXNDC5), as a critical mediator of cardiac fibrosis. Transcriptome analyses of renal biopsy specimens from patients with CKD revealed marked TXNDC5 upregulation in fibrotic kidneys, suggesting a potential role of TXNDC5 in renal fibrosis. Employing multiple fluorescence reporter mouse lines, we showed that TXNDC5 was specifically upregulated in collagen-secreting fibroblasts in fibrotic mouse kidneys. In addition, we showed that TXNDC5 was required for TGF-β1-induced fibrogenic responses in human kidney fibroblasts (HKFs), whereas TXNDC5 overexpression was sufficient to promote HKF activation, proliferation, and collagen production. Mechanistically, we showed that TXNDC5, transcriptionally controlled by the ATF6-dependent ER stress pathway, mediated its profibrogenic effects by enforcing TGF-β signaling activity through posttranslational stabilization and upregulation of type I TGF-β receptor in kidney fibroblasts. Using a tamoxifen-inducible, fibroblast-specific Txndc5 knockout mouse line, we demonstrated that deletion of Txndc5 in kidney fibroblasts mitigated the progression of established kidney fibrosis, suggesting the therapeutic potential of TXNDC5 targeting for renal fibrosis and CKD.

Background: After years of setting up public automated external defibrillators (AEDs), the rate of bystander AED use remains low all over the world. This study aimed to assess the public awareness and willingness of bystanders to use AEDs and to investigate the awareness on the Good Samaritan Law (GSL) and the factors associated with the low rate of bystander AED use., Methods: Using stratified random sampling, national telephone interviews were conducted using an author-designed structured questionnaire. The results were weighted to match the census data in Taiwan. The factors associated with public awareness and willingness of bystanders to use AEDs were analysed by logistic regression., Results: Of the 1073 respondents, only 15.2% had the confidence to recognise public AEDs, and 5.3% of them had the confidence to use the AED. Concerns on immature technique and legal issues remain the most common barriers to AED use by bystanders. Moreover, only 30.8% thought that the public should use AEDs at the scene. Few respondents (9.6%) ever heard of the GSL in Taiwan, and less than 3% understood the meaning of GSL. Positive awareness on AEDs was associated with high willingness of bystanders to use AEDs. Respondents who were less likely to use AEDs as bystanders were healthcare personnel and women., Conclusion: The importance of active awareness and the barriers to the use of AEDs among bystanders seemed to have been underestimated in the past years. The relatively low willingness to use AEDs among bystander healthcare providers and women needs further investigation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Injury is a leading cause of death among young adults. An accurately implemented fi led triage scheme (FTS) by emergency medical technicians (EMTs) is the first step for delivering right patients to the right hospital. However, the training effect of FTS on EMTs with different levels and backgrounds has scarcely been reported. We evaluated training effects of FTS among EMTs in Taipei. Standard FTS contains physiologic status, anatomical sites of injury, and mechanism of injury criteria. The intervention was a 30-minute lecture and pre-and-post tests, each containing five questions about trauma severity judgment (i.e., mechanism of injury [2 questions], anatomic sites of injury [2 questions], and physiological status [1 question]). The change in EMT accuracy was measured before and after training. Subgroup analyses were performed across EMTs with different levels and seniorities. From September 1, 2015 to March 31, 2016, 821 EMTs were enrolled, including 740 EMT-intermediates and 81 paramedics. Overall, EMT accuracy improved after the intervention in the intermediate (73.2% vs. 85.5%, p < 0.05) and paramedic (76.0% vs. 85.7%, p <0.01) groups. All trainees showed improvements in physiology and mechanism criteria, but paramedics showed decreased accuracy in anatomic criteria. The subgroup analysis showed that accuracy positively associated with prehospital care experience for major trauma cases 1 year before the training course, and the anatomical criterion accuracy was adversely associated with paramedic seniority. Field triage training can improve EMT accuracy for FTS. The anatomical aspect is more diffi cult to improve and should be emphasized in FTS training courses., Competing Interests: None., (Copyright © 2021 by Taiwan Society of Emergency Medicine & Ainosco Press. All Rights Reserved.)

Background: It is suggested that a prehospital scale should be utilized to identify patients with emergent large vessel occlusion (ELVO). We aimed to perform external validation of nine ELVO scales., Methods: This single center retrospective observational study included patients with ischemic stroke visiting the emergency department (ED) within 6 h of symptom onset. Participants were excluded if individual items of the National Institute of Health Stroke Scale scores were not recorded or they did not receive brain computed tomography angiography or magnetic resonance imaging before intravenous thrombolysis or endovascular thrombectomy, and within 24 h of ED admission. The first definition of ELVO was emergent occlusion of the internal carotid artery (ICA) and middle cerebral artery segment 1 (M1). The second definition was emergent occlusion of ICA, M1, basilar artery, middle cerebral artery segment 2, anterior cerebral artery segment 1, and posterior cerebral artery segment 1. Area under the receiver operating characteristic curve (AUROC) was constructed to examine discrimination. The sensitivity, specificity, positive predictive value, and negative predictive value of the nine scales under the two ELVO definitions were calculated., Results: A total of 1231 patients were included in the study. No significant differences were observed in the AUROC under the two ELVO definitions. However, sensitivity values of these scales were largely different, ranging from 44.56% to 93.68% under the first ELVO definition. The sensitivity values among scales were also different under the second ELVO definition., Conclusion: Stakeholders in the community should choose suitable scales according to their own system conditions., Competing Interests: Declaration of Competing Interest All authors disclose that there were no potential interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Orthognathic surgery (OGS) is frequently used to correct facial deformities associated with skeletal malocclusion and facial asymmetry. An accurate evaluation of facial symmetry is a critical for precise surgical planning and the execution of OGS. However, no facial symmetry scoring standard is available. Typically, orthodontists or physicians simply judge facial symmetry. Therefore, maintaining accuracy is difficult. We propose a convolutional neural network with a transfer learning approach for facial symmetry assessment based on 3-dimensional (3D) features to assist physicians in enhancing medical treatments. We trained a new model to score facial symmetry using transfer learning. Cone-beam computed tomography scans in 3D were transformed into contour maps that preserved 3D characteristics. We used various data preprocessing and amplification methods to determine the optimal results. The original data were enlarged by 100 times. We compared the quality of the four models in our experiment, and the neural network architecture was used in the analysis to import the pretraining model. We also increased the number of layers, and the classification layer was fully connected. We input random deformation data during training and dropout to prevent the model from overfitting. In our experimental results, the Xception model and the constant data amplification approach achieved an accuracy rate of 90%., 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 © 2021 Elsevier B.V. All rights reserved.)

Cell morphology encodes essential information on many underlying biological processes. It is commonly used by clinicians and researchers in the study, diagnosis, prognosis, and treatment of human diseases. Quantification of cell morphology has seen tremendous advances in recent years. However, effectively defining morphological shapes and evaluating the extent of morphological heterogeneity within cell populations remain challenging. Here we present a protocol and software for the analysis of cell and nuclear morphology from fluorescence or bright-field images using the VAMPIRE algorithm ( https://github.com/kukionfr/VAMPIRE&#95;open ). This algorithm enables the profiling and classification of cells into shape modes based on equidistant points along cell and nuclear contours. Examining the distributions of cell morphologies across automatically identified shape modes provides an effective visualization scheme that relates cell shapes to cellular subtypes based on endogenous and exogenous cellular conditions. In addition, these shape mode distributions offer a direct and quantitative way to measure the extent of morphological heterogeneity within cell populations. This protocol is highly automated and fast, with the ability to quantify the morphologies from 2D projections of cells seeded both on 2D substrates or embedded within 3D microenvironments, such as hydrogels and tissues. The complete analysis pipeline can be completed within 60 minutes for a dataset of ~20,000 cells/2,400 images.

Although the direct health impact of Coronavirus disease (COVID-19) pandemic on child health is low, there are indirect impacts across many aspects. We compare childhood vaccine uptake in three types of healthcare facilities in Singapore - public primary care clinics, a hospital paediatric unit, and private paediatrician clinics - from January to April 2020, to baseline, and calculate the impact on herd immunity for measles. We find a 25.6% to 73.6% drop in Measles-Mumps-Rubella (MMR) uptake rates, 0.4 - 10.3% drop for Diphtheria-Tetanus-Pertussis-inactivated Polio-Haemophilus influenza (5-in-1), and 8.0-67.8% drop for Pneumococcal conjugate vaccine (PCV) across all 3 sites. Consequent herd immunity reduces to 74-84% among 12-month- to 2-year-olds, well below the 95% coverage that is protective for measles. This puts the whole community at risk for a measles epidemic. Public health efforts are urgently needed to maintain efficacious coverage for routine childhood vaccines during the COVID-19 pandemic., 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 © 2021 Elsevier Ltd. All rights reserved.)

Background: Suspicion of beta-lactam (BL) hypersensitivity is often based on parental report. Evaluation is important as incorrect labelling has clinical consequence., Objective: To describe the outcomes of drug provocation test (DPT) in children with suspected hypersensitivity., Methods: A retrospective study of patients who completed BL DPT from 1 August 2016 to 31 December 2017 at a paediatric allergy centre in Singapore. Suspected hypersensitivity reactions were classified as immediate (onset ≤1 hour) or delayed (onset > 1 hour). Patients with immediate reactions underwent skin prick test (SPT) followed by DPT if SPT was negative. Patients with delayed reactions underwent DPT directly., Results: We identified 120 children who reported 121 suspected hypersensitivity reactions. The median age at reaction was 2.0 years (interquartile range [IQR], 1.0-5.0 years) and the median age at DPT was 7.4 years (IQR, 4.2-11.1 years). The timing of suspected hypersensitivity reaction was immediate in 21% (25 of 121), delayed in 66% (80 of 121), and uncertain in 13% (16 of 121). Commonly implicated drugs were amoxicillin in 45% (54 of 121), amoxicillin-clavulanate in 37% (45 of 121), and cephalexin in 8% (10 of 121). Commonly reported symptoms were maculopapular rash 44% (53 of 121), urticaria 34% (41 of 121), and angioedema 22% (27 of 121). All SPTs (n = 26) were negative. There were 118 diagnostic DPTs to index drug and 3 DPTs to alternative drug. A negative challenge result was obtained in 93% (110 of 118) of diagnostic DPTs: 92% (96 of 104) and 100% (14 of 14) of DPTs to penicillin group and cephalosporins respectively. All challenge reactions were mild., Conclusion: Our study supports the opinion that prior skin tests may not be necessary for children who report nonsevere reactions and directly performing diagnostic DPT is a safe approach in the evaluation of suspected childhood BL hypersensitivity., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2021. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Our study aimed to compare the effect of self-instruction with manikin feedback to that of instructor-led method on cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) skill performance. In our randomized non-inferiority trial, 64 non-healthcare providers were randomly allocated into self-instruction and instructor-led groups. Both groups watched a 27-min standardized teaching video. Participants in the self-instruction group then performed hands-on practice on the Resusci Anne QCPR with a device-driven feedback, while those in the instructor-led group practiced manikins; feedback was provided and student's questions were answered by instructors. Outcomes were measured by blinded evaluators and SkillReporter software. The primary outcome was the pass rate. Secondary outcomes were scores of the knowledge test and items of individual skill performance. The baseline characteristics of the two groups were similar. The pass rates were 93.8% in both group (absolute difference 0%, p = 0.049 for noninferiority). The knowledge test scores were not significantly different. However, the self-instruction group performed better in some chest compression and ventilation skills, but performed worse in confirming environmental safety and checking normal breathing. There was no difference in AED skills between the two groups. Our results showed the self-instruction method is not inferior to the instructor-led method.

Objectives: To set up a prediction model for the 7-day in-hospital mortality of patients admitted from the emergency department (ED) because it is high but no appropriate initial alarm score is available., Design: This is a prospective cohort study for prediction model development., Setting: In a tertiary referred hospital in northern Taiwan., Participants: ED-admitted medical patients in hospitalist care wards were enrolled during May 2010 to October 2016. Two-thirds of them were randomly assigned to a derivation cohort for development of the model and cross-validation was performed in the validation cohort., Primary Outcome Measured: 7-day in-hospital mortality., Results: During the study period, 8649 patients were enrolled for analysis. The mean age was 71.05 years, and 51.91% were male. The most common admission diagnoses were pneumonia (36%) and urinary tract infection (20.05%). In the derivation cohort, multivariable Cox proportional hazard regression revealed that a low Barthel Index Score, triage level 1 at the ED, presence of cancer, metastasis and admission diagnoses of pneumonia and sepsis were independently associated with 7 days in-hospital mortality. Based on the probability developed from the multivariable model, the area under the receiver operating characteristic curve in the derivation group was 0.81 (0.79-0.85). The result in the validation cohort was comparable. The prediction score modified by the six independent factors had high sensitivity of 88.03% and a negative predictive value of 99.51% for a cut-off value of 4, whereas the specificity and positive predictive value were 89.61% and 10.55%, respectively, when the cut-off value was a score of 6., Conclusion: The 7-day in-hospital mortality in the hospitalist care ward is 2.8%. The initial alarm score could help clinicians to prioritise or exclude patients who need urgent and intensive care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The 2019 Nobel Prize in Physiology or Medicine was awarded to William G. Kaelin Jr, Sir Peter J. Ratcliffe, and Gregg L. Semenza "for their discoveries of how cells sense and adapt to oxygen availability." The three pioneers discovered the hypoxia-inducible factor (HIF), elucidated the oxygen sensing mechanism of cells, and confirmed the critical role of HIF in hypoxic cellular responses. The broad and profound biological effects of HIF open up the possibilities for clinical translation. HIF stabilizers have been proven effective on anemia of chronic kidney disease in phase III clinical trials. HIF antagonists for cancer treatment are under phase II clinical trials. It is imperative to gain insight into the biology of HIF. In this article, the discovery of HIF and its oxygen-dependent enzymatic regulation will be introduced, based largely on the groundbreaking work of the three Nobel laureates. Next, the biology of HIF in the kidney will be reviewed. Studies on the HIF stabilizers in the context of kidney disease, as well as the manipulation of HIF in different renal cell types will be covered. Lastly, the clinical application of HIF stabilizers and HIF antagonists for the treatment of anemia and cancer, respectively, will be discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Large pelagic fishes often dive and surface repeatedly as if they were airbreathers, raising a question about the functions of these movements. Some species (e.g., bigeye tuna, ocean sunfish) apparently alternate foraging in deep cold waters and rewarming in shallow warm waters. However, it is unclear how prevalent this pattern is among species. Blue sharks are the widest-ranging pelagic shark with expanded vertical niches, providing a model for studying foraging-thermoregulation associations. We used electronic tags, including video cameras, to record the diving behaviour, muscle temperature, and foraging events of two blue sharks. During repeated deep dives (max. 422 m), muscle temperature changed more slowly than ambient water temperature. Sharks shifted between descents and ascents before muscle temperature reached ambient temperature, leading to a narrower range (8 °C) of muscle temperature than ambient temperature (20 °C). 2.5-h video footage showed a shark catching a squid, during which a burst swimming event was recorded. Similar swimming events, detected from the entire tag data (20 - 22 h), occurred over a wide depth range (5 - 293 m). We conclude that, instead of alternating foraging and rewarming, blue sharks at our study site forage and thermoregulate continuously in the water column. Furthermore, our comparative analyses showed that the heat exchange rates of blue sharks during the warming and cooling process were not exceptional among fishes for their body size. Thus, behavioural thermoregulation linked to foraging, rather than enhanced abilities to control heat exchange rates, is likely key to the expanded thermal niches of this ectothermic species., Supplementary Information: The online version contains supplementary material available at 10.1007/s00227-021-03971-3., Competing Interests: Conflicts of interestThe authors have no conflicts of interest to declare., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

Background: Bystander-initiated cardiopulmonary resuscitation (CPR) and the use of automated external defibrillation (AED) is pivotal in the community chain of survival, but little is known regarding the bystander experience of performing CPR and AED, and their psychological infl uence from the incidents in the Asian community. This qualitative study was conducted to explore the experiences of lay rescuers who had performed CPR and AED in public locations in Taiwan., Methods: Lay rescuers who had provided initial CPR and defi brillation with AED in public locations across Taiwan in 2015 were selectively recruited from Taiwan Public AED Registry for a semi-structured interview., Results: Nine participants were included in the study, and event-to-interview duration was within 1 year (n = 4) and 1-2 years (n = 5). The major fi ndings from the study were: (1) the lay rescuers possessed helping traits and high motivation; (2) the lay rescuers reported certain aspects of rescue reality that differed much from prior training and expectations, including diffi culty in the depth of chest compression, and uncertainties in real emergency situations; (3) the lay rescuers gained positive personal fulfi llment in sharing their experience and receiving positive feedback from others, and were willing to help next time, although they experienced a short-term negative psychological impact from the event., Conclusions: This study provides valuable information on strategies to increase layperson CPR rates and effectiveness in CPR training. Measures should be taken to increase layperson's confi dence and situation awareness, reduce training-reality discrepancy, build up a support system to avoid negative psychological effects, and prepare lay rescuers for the next resuscitation., Competing Interests: None., (Copyright © 2020 by Taiwan Society of Emergency Medicine & Ainosco Press. All Rights Reserved.)

Background: Whether rapid transportation can benefit patients with trauma remains controversial. We determined the association between prehospital time and outcome to explore the concept of the "golden hour" for injured patients., Methods and Findings: We conducted a retrospective cohort study of trauma patients transported from the scene to hospitals by emergency medical service (EMS) from January 1, 2016, to November 30, 2018, using data from the Pan-Asia Trauma Outcomes Study (PATOS) database. Prehospital time intervals were categorized into response time (RT), scene to hospital time (SH), and total prehospital time (TPT). The outcomes were 30-day mortality and functional status at hospital discharge. Multivariable logistic regression was used to investigate the association of prehospital time and outcomes to adjust for factors including age, sex, mechanism and type of injury, Injury Severity Score (ISS), Revised Trauma Score (RTS), and prehospital interventions. Overall, 24,365 patients from 4 countries (645 patients from Japan, 16,476 patients from Korea, 5,358 patients from Malaysia, and 1,886 patients from Taiwan) were included in the analysis. Among included patients, the median age was 45 years (lower quartile [Q1]-upper quartile [Q3]: 25-62), and 15,498 (63.6%) patients were male. Median (Q1-Q3) RT, SH, and TPT were 20 (Q1-Q3: 12-39), 21 (Q1-Q3: 16-29), and 47 (Q1-Q3: 32-60) minutes, respectively. In all, 280 patients (1.1%) died within 30 days after injury. Prehospital time intervals were not associated with 30-day mortality. The adjusted odds ratios (aORs) per 10 minutes of RT, SH, and TPT were 0.99 (95% CI 0.92-1.06, p = 0.740), 1.08 (95% CI 1.00-1.17, p = 0.065), and 1.03 (95% CI 0.98-1.09, p = 0.236), respectively. However, long prehospital time was detrimental to functional survival. The aORs of RT, SH, and TPT per 10-minute delay were 1.06 (95% CI 1.04-1.08, p < 0.001), 1.05 (95% CI 1.01-1.08, p = 0.007), and 1.06 (95% CI 1.04-1.08, p < 0.001), respectively. The key limitation of our study is the missing data inherent to the retrospective design. Another major limitation is the aggregate nature of the data from different countries and unaccounted confounders such as in-hospital management., Conclusions: Longer prehospital time was not associated with an increased risk of 30-day mortality, but it may be associated with increased risk of poor functional outcomes in injured patients. This finding supports the concept of the "golden hour" for trauma patients during prehospital care in the countries studied., Competing Interests: The authors have declared that no competing interests exist.

The efficacy and safety of statin and ezetimibe combination therapy in patients with chronic kidney disease (CKD) remains unclear. To assess the effect of statin and ezetimibe combination therapy on controlling lipid profiles and reducing cardiovascular events in patients with CKD, we conducted a systematic review and meta-analysis. We selected randomized controlled trials comparing this combination therapy with statin monotherapy or placebo in patients with CKD from the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases published before September 1, 2018 on the Internet. Eight articles on seven studies, with a total of 14,016 patients with CKD, were selected from 412 full-text articles. Statin and ezetimibe combination therapy had beneficial effects on serum total cholesterol (weighted mean difference (WMD) -20.31 mg/dL, 95% confidence interval (CI), -26.87 to -13.75 mg/dL, P < 0.001), low-density lipoprotein cholesterol (WMD -17.22 mg/dL, 95% CI, -18.93 to -15.51 mg/dL, P < 0.001), and triglycerides (WMD -15.08 mg/dL, 95% CI, -23.41 to -6.75 mg/dL, P < 0.001) compared with statin monotherapy. Statin and ezetimibe combination therapy significantly reduced all-cause mortality and major adverse cardiovascular events (risk ratio 0.86, 95% CI, 0.77 to 0.97, P = 0.01). The incidence of adverse events was low, with no significant difference between statin and ezetimibe combination therapy and statin monotherapy. In conclusion, the statin and ezetimibe combination therapy significantly improved serum lipid profiles and reduced risks of all-cause deaths and major adverse cardiovascular events compared with the control group in patients with CKD., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Objective: The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined., Methods: We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC)., Results: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive., Conclusion: Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.

The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injury-induced AKI (IRI-AKI). Myofibroblasts underwent apoptosis during renal recovery but one-fifth of them survived in the recovered kidneys on day 28 after IRI-AKI and their cell numbers increased again after day 56. Microarray data showed the distinctive gene expression patterns of qPericytes, activated pericytes (aPericytes, myofibroblasts), and inactivated pericytes (iPericytes) isolated from kidneys before, on day 7, and on day 28 after IRI-AKI. Hypermethylation of the Acta2 repressor Ybx2 during IRI-AKI resulted in epigenetic modification of iPericytes to promote the transition to chronic kidney disease (CKD) and aggravated fibrogenesis induced by a second AKI induced by adenine. Mechanistically, transforming growth factor-β1 decreased the binding of YBX2 to the promoter of Acta2 and induced Ybx2 hypermethylation, thereby increasing α-smooth muscle actin expression in aPericytes. Demethylation by 5-azacytidine recovered the microvascular stabilizing function of aPericytes, reversed the profibrotic property of iPericytes, prevented AKI-CKD transition, and attenuated fibrogenesis induced by a second adenine-AKI. In conclusion, intervention to erase hypermethylation of pericytes after AKI provides a strategy to stop the transition to CKD.

Objective: To evaluate the morphologic characteristics and clinical significance of epidural gas based on computed tomography (CT) and magnetic resonance imaging (MRI) findings and to determine their relationship with radiculopathy., Materials and Methods: Between March 2009 and November 2018, 110 epidural gas lesions were identified in 103 patients who underwent both CT and MRI for suspected herniated disc in the authors' institution. Patterns of epidural gas were classified as air pseudocyst, air cyst, air-contained disc herniation, and honeycomb-like air cyst. These gas patterns were compared, and possible correlations between these gas patterns and radiculopathy were evaluated., Results: Overall agreement between CT and MRI findings for evaluation of all lesions and for differentiation of epidural gases was good (kappa [κ] = 0.775). Air pseudocysts demonstrated a moderate correlation (κ = 0.496) and air cysts showed a good correlation (κ = 0.661) with radiculopathy on MRI, whereas air-contained disc herniation and honeycomb-like cysts demonstrated a strong correlation (κ = 0.810 and 0.927, respectively) with radiculopathy on MRI., Conclusions: This study's results help delineate new classifications of epidural gases. In addition, lumbar epidural gas with disc material (e.g., air-contained disc herniation and honeycomb-like cysts) on MRI was associated with radiculopathy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hidradenitis suppurativa (HS) is known to have association with systemic diseases with chronic inflammation such as psoriasis. We aim to describe the concomitant systemic inflammation in patients with HS using 18F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) scan. This was a case-control study conducted in three tertiary hospitals in Northern Malaysia from January to December 2017, involving HS patients aged 18 years and above. Thirty-two HS patients with age- and sex-matched controls were recruited with a mean age of 31.4 years (range: 18-56). Numerous cutaneous inflammatory foci were detected on FDG-PET/CT scan in clinically unapparent sites (27/32, 84.4%). Approximately 90.6%, 93.8%, and 50.0% of the patients had significantly higher cutaneous uptake over nasal, mandibular, and scalp regions, respectively ( P < 0.0001). PET/CT scan did not detect any systemic inflammation unlike those found in psoriasis. Three (9.4%) patients had thyroid nodules with high uptake (maximum standard uptake values ranging from 2.9 to 11.3). Two of them were confirmed to have papillary thyroid carcinoma, while the third patient has inconclusive finding. 18 F-FDG PET/CT scan may be useful to map disease burden of HS. Nonlesional inflammatory foci on the skin of the nose, mandibular, and scalp are probably significant. The association of thyroid carcinoma in HS warrants further evaluation., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 World Journal of Nuclear Medicine.)

Most biological functions involve protein-protein interactions. Our understanding of these interactions is based mainly on those of structured proteins, because encounters between intrinsically disordered proteins (IDPs) or proteins with intrinsically disordered regions (IDRs) are much less studied, regardless of the fact that more than half eukaryotic proteins contain IDRs. RNA-binding proteins (RBPs) are a large family whose members almost all have IDRs in addition to RNA binding domains. These IDRs, having low sequence similarity, interact, but structural details on these interactions are still lacking. Here, using the IDRs of two RBPs (hnRNA-A2 and TDP-43) as a model, we demonstrate that the rate at which TDP-43's IDR undergoes the neurodegenerative disease related α-helix-to-β-sheet transition increases in relation to the amount of hnRNP-A2's IDR that is present. There are more than 1500 RBPs in human cells and most of them have IDRs. RBPs often join the same complexes to regulate genes. In addition to the structured RNA-recognition motifs, our study demonstrates a general mechanism through which RBPs may regulate each other's functions through their IDRs.

Background: The timing of transcranial direct current stimulation (tDCS) with neurorehabilitation interventions may affect its modulatory effects. Motor function has been reported to be modulated by the timing of tDCS; however, whether the timing of tDCS would also affect restoration of daily function and upper extremity motor control with neurorehabilitation in stroke patients remains largely unexplored. Mirror therapy (MT) is a potentially effective neurorehabilitation approach for improving paretic arm function in stroke patients. This study aimed to determine whether the timing of tDCS with MT would influence treatment effects on daily function, motor function and motor control in individuals with chronic stroke., Methods: This study was a double-blinded randomized controlled trial. Twenty-eight individuals with chronic stroke received one of the following three interventions: (1) sequentially combined tDCS with MT (SEQ), (2) concurrently combined tDCS with MT (CON), and (3) sham tDCS with MT (SHAM). Participants received interventions for 90 min/day, 5 days/week for 4 weeks. Daily function was assessed using the Nottingham Extended Activities of Daily Living Scale. Upper extremity motor function was assessed using the Fugl-Meyer Assessment Scale. Upper extremity motor control was evaluated using movement kinematic assessments., Results: There were significant differences in daily function between the three groups. The SEQ group had greater improvement in daily function than the CON and SHAM groups. Kinematic analyses showed that movement time of the paretic hand significantly reduced in the SEQ group after interventions. All three groups had significant improvement in motor function from pre-intervention to post-intervention., Conclusion: The timing of tDCS with MT may influence restoration of daily function and movement efficiency of the paretic hand in chronic stroke patients. Sequentially applying tDCS prior to MT seems to be advantageous for enhancing daily function and hand movement control, and may be considered as a potentially useful strategy in future clinical application., Trial Registration: ClinicalTrials.gov Identifier: NCT02827864 . Registered on 29th June, 2016.