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Yu-Jhou Chen,1,2,* Chen-June Seak,2– 4,* Chien-Cheng Chen,2,5,6 Tsung-Hsing Chen,1,2,5 Shih-Ching Kang,7 Chip-Jin Ng,2,4 Chao-Wei Lee,8 Ming-Yao Su,2,9,10 Hsin-Chih Huang,1,2,9 Chun-Hsiang Ooyang,7 Sen-Yung Hsieh,1,2 Hao-Tsai Cheng1,2,5,9 1Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; 3Department of Emergency Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City 23652, Taiwan; 4Department of Emergency Medicine, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 5College of Medicine, Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan 33302, Taiwan; 6Department of Medical Image and Intervention, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 7Division of Trauma and Emergent Surgery, Department of Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 8Division of General Surgery, Department of Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 9Department of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City 23652, Taiwan; 10Board of Directors and Supervisors, Taiwan Association for the Study of Small Intestinal Disease (TASSID), Taoyuan 33305, Taiwan*These authors contributed equally to this workCorrespondence: Hao-Tsai ChengDepartment of Gastroenterology and Hepatology, New Taipei Municipal TuCheng Hospital, No 6, Sec. 2, Jincheng Road, Tucheng Dist., New Taipei City 236, Taiwan (Republic Of China)Tel +886-2-22630588 ext. 6185Fax +886-2-22732688Email hautai@adm.cgmh.org.twPurpose: High prevalence of psychiatric comorbidities (PCs) has been widely documented in caustic substance ingestion cases. However, their effect on the clinical features and prognostic outcomes remains unclear due to the paucity of discussion. We report on detailed clinical courses with long-term multifaceted outcomes and review the association between caustic ingestion and each specific PC.Patients and Methods: The retrospective chart review included 396 adults (median follow-up, 16.6 months) with and 377 without (control group) PCs treated between 1999 and 2018 at Chang Gung Memorial Hospital. All PCs were diagnosed/confirmed by psychiatrists through face-to-face interviews.Results: The PCs predicted serious esophagogastroduodenoscopy grading, higher rates of admission/surgery/intensive care unit stay, increments of systemic/gastrointestinal complications, and poorer 5-year overall survival rates. The poor survival among patients with PCs was highly consistent with their baseline characteristics. Significantly advanced age, more non-PCs, alcoholism, illicit drug abuse, and baseline unhealthy status resulted in statistically higher risks of severe complications and limited recovery.Conclusion: PCs changed clinical patterns and had critical roles in the survival outcomes of caustic injury victims. Clinical awareness achieves benefit by limiting injuries in mild cases or allowing emergent interventions in severe cases. Future studies based on worldwide populations are essential for realizing geographic differences.Keywords: caustic, corrosive, psychiatric, endoscopy, complications, long-term survival

Puo-Hsien Le,1,2 Chia-Jung Kuo,1–3 Ren-Chin Wu,3,4 Jun-Te Hsu,3,5 Ming-Yao Su,1–3 Chun-Jung Lin,1,3 Cheng-Tang Chiu1–3 1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan; 3College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Department of Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Background: Cytomegalovirus (CMV) colitis typically presents in immunocompromised and inflammatory bowel disease (IBD) patients. Several studies have been conducted on the endoscopic characteristics of CMV colitis in IBD patients. Objectives: The endoscopic findings of CMV colitis in non-IBD patients and their relationship with inhospital mortality are unclear. We aimed to describe the endoscopic presentation in these patients and to determine the endoscopic predictors of inhospital mortality. Patients and methods: Patients with CMV colitis diagnosed using histology between April 2002 and December 2016 at the Linkou Chang Gung Memorial Hospital, Taiwan, were retrospectively enrolled. Patients diagnosed with IBD during follow-up were excluded. Patient data, including underlying diseases, endoscopic presentation, laboratory data, clinical course, complications, and clinical outcomes, were collected. The independent risk factors for inhospital mortality were analyzed with logistic regression. The difference of overall survival was compared using Kaplan–Meier survival curve and log rank test. All statistical calculations were performed using SPSS software, version 21. Results: Sixty-nine patients were enrolled, and 8 IBD patients were excluded. Within the 61 non-IBD patients, 31 were diagnosed by colonoscopy and others by sigmoidoscopy. Ulceration (77%) was the most common endoscopic finding, followed by a cobblestone appearance (19.7%), colitis with/without erosions (9.8%), pseudomembrane (9.8%), and tumor/polyp-like lesions (8.2%). Among the patients who underwent full-length colonoscopy, 35.3% presented with right-sided colitis, 23.5% with left-sided colitis, and 32.4% with pancolitis. Pancolitis was identified as a negative predictor of inhospital mortality (odds ratio, 6.8; 95% confidence interval, 1.233–37.497; p=0.028) and overall survival (log rank p=0.018). Conclusion: Colonoscopy is recommended for precise CMV colitis diagnosis and outcome prediction in non-IBD patients. Keywords: cytomegalovirus colitis, CMV, inflammatory bowel disease, endoscopy, colonoscopy, mortality

Shiue-Chin Liou,1 Chen-Ming Hsu,2 Chit Chen,1 Ming-Yao Su,2 Cheng-Tang Chiu2 1Department of Anesthesiology, Chang Gung Memorial Hospital at Taoyuan, Taoyuan, Taiwan; 2Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan Background: Subjects with obstructive sleep apnea (OSA) are vulnerable to sedation-related complications during endoscopic procedures. A significant portion of subjects undergoing routine endoscopy is at high risk of OSA, but most are undiagnosed. The purpose of this study was to estimate the prevalence of high risk for OSA among Chinese subjects undergoing deep sedation for screening gastrointestinal endoscopy and to evaluate the hypoxemia risk of these examinees stratified by Berlin Questionnaire (BQ). Patients and methods: We performed a prospective cohort study in subjects undergoing deep sedation with monitored anesthesia care for combined esophagogastroduodenoscopy plus colonoscopy. Subjects who were Chinese were stratified into high- and low-risk groups for OSA by administration of BQ. Deep sedation was achieved via a propofol target-controlled infusion system. Hypoxemia was defined as pulse oximetry reading of less than 90%. The frequency of hypoxemia was compared between high- and low-risk groups for OSA. Results: A total of 615 Chinese subjects were recruited during the study period, and 614 subjects were included for analysis. Two hundred eighteen (35.5%) subjected were classified to be at high risk of OSA, and 396 (64.5%) were stratified to be at low risk of OSA by BQ. Hypoxemia occurred in 83 (13.5%) subjects during endoscopy procedures. The risk of developing hypoxemia in the high-risk group was significantly higher when compared to that of the low-risk group subjects (24.8% vs 7.3%; relative risk, 3.37; 95% CI, 2.22–5.13). Conclusion: About one-third Chinese subjects undergoing deep sedation for screening endoscopy were at high risk of OSA. Subjects at high risk of OSA are associated with an increased risk of hypoxemia in comparison to the low-risk group when undergoing deep sedation for screening gastrointestinal endoscopy. Keywords: endoscopy, deep sedation, hypoxemia, obstructive sleep apnea, monitored anesthesia care, Berlin Questionnaire

Puo-Hsien Le,1,2 Wey-Ran Lin,1,3 Chia-Jung Kuo,1–3 Ren-Chin Wu,3,4 Jun-Te Hsu,3,5 Ming-Yao Su,1–3 Chun-Jung Lin,1 Cheng-Tang Chiu1–3 1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, 2Taiwan Association for the Study of Small Intestinal Diseases, 3College of Medicine, Chang Gung University, 4Department of Pathology, 5Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Background: Cytomegalovirus (CMV) colitis is considered rare in immunocompetent patients.Objective: The predictors of mortality and the differences between immunocompetent and immunocompromised patients with this disease remain unknown. Thus, the aim of this retrospective cohort study was to clarify these issues.Patients and methods: We enrolled all patients who were histologically diagnosed with CMV colitis between April 2002 and December 2016 in the Linkou Chang Gung Memorial Hospital. Patients were divided into two groups: immunocompetent and immunocompromised, and the differences between them were analyzed to develop in-hospital mortality predictors.Results: A total of 69 patients (42, immunocompetent; 27, immunocompromised) were enrolled. The most common symptoms were melena in the immunocompetent group and diarrhea in the immunocompromised group. The in-hospital mortality rate showed no statistically significant difference between the two groups (26.2% vs 25.9%, P=0.981). Early diagnosis was the only significant independent predictor of in-hospital mortality (odds ratio [OR] 1.075, 95% CI 1.005–1.149, P=0.035). The cutoff of diagnostic timing was 9 days from admission, derived from the receiver operating characteristic curve using the Youden index.Conclusion: CMV colitis in immunocompetent patients is markedly more common and fatal than has generally been acknowledged. Being alert to different ways in which this disease can present itself will enable early diagnosis and significantly reduce mortality. Keywords: cytomegalovirus colitis, immunocompetent, immunocompromised

Chi-Huan Wu,1,2 Tsung-Hsing Chen,1–3 Chen-Ming Hsu,1,2 Ming-Yao Su,1,2 Cheng-Tang Chiu,1,2 Ren-Chin Wu,4 Cheng-Chou Lai5 1Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 2Chang Gung University, College of Medicine, Taoyuan, 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, 4Department of Pathology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 5Department of Colon and Rectal Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan Introduction: Linked-color imaging (LCI) is a recently developed system used in endoscopy. It creates clear and bright endoscopic images using short-wavelength, narrow-band laser light combined with white laser light. The illuminating light and signal processing emphasize slight color differences in abnormal regions that approximate the normal color of the mucosa. As a result, regions initially appearing red become a deeper shade of red, while regions originally appearing white become brighter, yet with natural tones. This process facilitates recognition of slight differences in the color of the mucosa and clarifies the boundaries of the mucosal pit. Aim: To determine whether LCI of the colon can improve the correlation between endoscopic findings and pathological diagnosis. Methods: Consecutive patients who underwent colonoscopy requiring polypectomy or removal by biopsy forceps if possible were recruited. Probable polyp histology was assessed by two endoscopists using the Narrow-band imaging International Colorectal Endoscopic (NICE) classification and LCI data. All detected polyps were sent to the pathology department for pathological diagnosis by two pathologists. Results: In total, 94 polyps were found in 43 patients. The sensitivity, specificity, positive predictive value, and negative predictive value for neoplastic lesion prediction (NICE type2/3) were 96.5%, 83.8%, 90.2%, and 93.9%, respectively. Conclusion: LCI combined with the NICE classification system is a powerful tool for predicting probable histology of colon polyps. Keywords: linked-color imaging, NICE classification, colon polyps, histology, sensitivity, specificity

Mi-Yong Su,1 Yong-Hong Tan,2 Zi-Min Wang,3 Cai-Jun Gan,3 Shou-Hong Chen3 1School of Electronic Engineering, Xidian University, Xi'an, Shaanxi, People's Republic of China; 2College of Information, Mechanical and Electronic Engineering, Shanghai Normal University, Shanghai, People's Republic of China; 3School of Electronic Engineering and Automation, Guilin University of Electronic Technology, Guilin, Guangxi, People's Republic of China Abstract: Devices which can obtain comparable bilaterally symmetrical acupoints (BSA) multifrequency impedances (MFI) are often needed in the detection of the energy balance states of acupoints in traditional Chinese medicine. To satisfy these needs, a two-channel impedance measurement system has been introduced which is capable of accurately and simultaneously measuring BSA MFI. The system includes a set of five electrodes, two of which are injected with exciting current signal to synchronously and equally excite BSA; the other three electrodes are used as sensors to simultaneously sense the response signal from both sides. The system also includes a PC-based time-domain signal testing platform with arbitrary current waveform generation and three channels (one exciting current and two response voltages) simultaneously sampling, and a set of MFI simultaneously unbiased computing algorithms based on special odd multisine current signal input. Preliminary validating experiments suggest that the system allows accurate and synchronous measurement of BSA MFI at least in the frequency range of 10 Hz to 60 kHz, and the obtained BSA MFI are well comparable. Keywords: acupuncture, meridians, Qi, balance, two-channel

This study applied a simulation method to map the temperature distribution based on magnetic resonance imaging (MRI) of individual patients, and investigated the influence of different pelvic tissue types as well as the choice of thermal property parameters on the efficiency of endorectal cooling balloon (ECB). MR images of four subjects with different prostate sizes and pelvic tissue compositions, including fatty tissue and venous plexus, were analyzed. The MR images acquired using endorectal coil provided a realistic geometry of deformed prostate that resembled the anatomy in the presence of ECB. A single slice with the largest two-dimensional (2D) cross-sectional area of the prostate gland was selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue, peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder were manually segmented. Pennes' bioheat thermal model was used to simulate the temperature distribution dynamics, by using an in-house finite element mesh based solver written in MATLAB. The results showed that prostate size and periprostatic venous plexus were two major factors affecting ECB cooling efficiency. For cases with negligible amount of venous plexus and small prostate, the average temperature in the prostate and neurovascular bundles could be cooled down to 25. °C within 30. min. For cases with abundant venous plexus and large prostate, the temperature could not reach 25. °C at the end of 3. h cooling. Large prostate made the cooling difficult to propagate through. The impact of fatty tissue on cooling effect was small. The filling of bladder with warm urine during the ECB cooling procedure did not affect the temperature in the prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model was constructed for volumetric simulation. It was found that the 2D slice with the largest cross-sectional area of prostate had the most abundant venous plexus, and was the most difficult slice to cool, thus it may provide a conservative prediction of the cooling effect. This feasibility study demonstrated that the simulation tool could potentially be used for adjusting the setting of ECB for individual patients during hypothermic radical prostatectomy. Further studies using MR thermometry are required to validate the in silico results obtained using simulation.

© 2015 Springer-Verlag Berlin Heidelberg Purpose: To investigate the differences between imaging features of spinal tuberculosis (TB) and metastatic cancer measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The presentation of TB on convention MRI may not show the typical TB signs, and they may be mis-diagnosed as malignant diseases. DCE-MRI may provide additional information to help making differential diagnosis. Materials and methods: DCE-MRI was performed in 24 TB and 22 metastatic cancer patients. The DCE kinetic pattern was determined as “wash-out”, “plateau” or “persistent enhancement”. The characteristic DCE parameters were calculated from the signal intensity time course. The two-compartmental pharmacokinetic model was used to obtain Ktrans, which is the parameter associated with the delivery of MR contrast agents into the lesion, and kep, which is the parameter associated with the distribution and clearance of contrast agents from the lesion. Results: Of the 24 TB, one case showed the wash-out kinetic pattern, 12 cases showed the plateau pattern, and 11 cases showed the persistent enhancement pattern. Of the 22 metastatic cancers, 12 cases showed wash-out, 7 cases showed plateau, and 3 cases showed persistent enhancement patterns. Compared to the metastatic cancer group, the TB group had a lower kep (0.27 ± 0.15 vs. 0.49 ± 0.23 min−1, P < 0.001). The ROC analysis showed that the area under the curve was 0.780 for kep. Conclusions: DCE-MRI may provide additional information for differentiation between spinal TB and metastasis, when their manifestations on conventional imaging were similar.

BackgroundWe measured breast density (BD) on MRI and correlated with endogenous hormonal levels.Patients and methodsTwenty-four premenopausal women received four weekly breast MRI. A blood sample was collected on the same day of MRI. BD was measured using a computer-based algorithm. The generalized estimation equation method was applied to model mean fibroglandular tissue volume (FV) and mean percent density (PD) from predictor variables including estradiol, progesterone, and week during a cycle.ResultsIn week 3, a borderline significant correlation between estradiol and PD (r = 0.43, P = 0.04), estradiol and FV (r = 0.40, P = 0.05) and between progesterone and FV (r = 0.42, P = 0.04) was noted. The FV and PD measured in weeks 4 and 1 were higher than in weeks 2 and 3, adjusted for variation in endogenous estradiol and progesterone, indicating that the hormone change could not account for the changes in density. No lag effect of endogenous hormone on the change of FV or PD was noted (all P-values > 0.05).ConclusionsOur results showed that BD is not strongly associated with the endogenous hormone. Their association with breast cancer risk was likely coming from different mechanisms, and they should be considered as independent risk factors.

Purpose: To investigate methods developed for the characterisation of the morphology and enhancement kinetic features of both mass and non-mass lesions, and to determine their diagnostic performance to differentiate between malignant and benign lesions that present as mass versus non-mass types. Methods: Quantitative analysis of morphological features and enhancement kinetic parameters of breast lesions were used to differentiate among four groups of lesions: 88 malignant (43 mass, 45 non-mass) and 28 benign (19 mass, 9 non-mass). The enhancement kinetics was measured and analysed to obtain transfer constant (Ktrans) and rate constant (kep). For each mass eight shape/margin parameters and 10 enhancement texture features were obtained. For the lesions presenting as nonmass-like enhancement, only the texture parameters were obtained. An artificial neural network (ANN) was used to build the diagnostic model. Results: For lesions presenting as mass, the four selected morphological features could reach an area under the ROC curve (AUC) of 0.87 in differentiating between malignant and benign lesions. The kinetic parameter (kep) analysed from the hot spot of the tumour reached a comparable AUC of 0.88. The combined morphological and kinetic features improved the AUC to 0.93, with a sensitivity of 0.97 and a specificity of 0.80. For lesions presenting as non-mass-like enhancement, four texture features were selected by the ANN and achieved an AUC of 0.76. The kinetic parameter kepfrom the hot spot only achieved an AUC of 0.59, with a low added diagnostic value. Conclusion: The results suggest that the quantitative diagnostic features can be used for developing automated breast CAD (computer-aided diagnosis) for mass lesions to achieve a high diagnostic performance, but more advanced algorithms are needed for diagnosis of lesions presenting as non-mass-like enhancement. © The Author(s) 2009.

Abstract Background The COVID-19 pandemic, caused by SARS-CoV-2, was one of the greatest modern public health crises that the world has faced. Countries undertook sweeping public health and social measures (PHSM); including environmental actions such as disinfection and ventilation; surveillance and response, such as contact tracing and quarantine; physical, such as crowd control; and restrictions on travel. This study focuses on the public perceptions of PHSM in two countries, Japan and the United Kingdom (UK) as examples of high-income countries that adopted different measures over the course of the pandemic. Methods This study was conducted between November 2021 and February 2022, a period in which the Omicron variant of SARS-CoV-2 was predominant. Fourteen online focus group discussions were conducted in each country. Overall, 106 total participants (50 from the UK and 56 from Japan) participated in 23 focus groups (11 in the UK and 12 in Japan) with an average of three to six participants per group. Both countries were compared using a thematic analysis method. Results Both countries’ participants agreed that vaccination was an effective measure. However, they did not favor mandatory vaccination policies. Working from home was well accepted by both sides, but they reported that schools should have continued to be opened as before COVID-19. Both sides of participants expressed that temperature testing alone in indoor facilities was ineffective as a COVID-19 control measure. There were contrasting views on face covering rules in public spaces, international and domestic movement restrictions. High acceptance of mask-wearing was reflective of Japanese customs, while it was accepted as a strong recommendation for participants in the UK. Japanese participants favored quarantine for international travel, while the UK participants supported banning non-essential travel. Conclusion Similar and contrasting views on PHSM against COVID-19 between Japan and the UK demonstrated how policies in controlling an epidemic should be tailored by country with respect to its norms, cultures, economic and disease burden. Our findings may guide how policy makers can engage with the public through effective health communication and consider regulations that are aligned with the public’s views and capacities in changing their behavior for future pandemic preparedness.

Abstract Background Stroke is a leading cause of death in the world, and the burden of stroke is higher in low- and middle-income countries. Understanding the risk factors, complications, and outcomes of stroke are useful for healthcare planning and resource allocation. Little information on stroke is available for many low- and middle-income Asian countries; including Myanmar, which is the focus of this study. Methods A review was conducted of medical records for stroke admissions during 2017 in a tertiary hospital in Myanmar. The final diagnoses, risk factors, clinical features, complications, and outcomes were systematically collected from computer- and paper-based medical records. Results Of 908 cases analysed, haemorrhagic stroke was the most common type (49%), followed by ischaemic stroke (43%). Unimproved cases were 32%. Identified risk factors of unimproved cases were ‘haemorrhagic stroke’ [adjusted odds ratio (aOR): 1.73], ‘having fever during hospitalization’ [aOR: 2.49], ‘Glasgow Coma Scale (GCS) at the admission between 9 and 14’ [aOR: 4.33], and GCS less than 9 [aOR: 42.86]. Conclusion This study is based on hospital medical records to assess stroke types, risk factors, clinical features, and outcomes in a tertiary hospital, in Nay Pyi Daw, Myanmar. The findings indicated that early case admission, improved hospital care management, and increased awareness of the modifiable risk factors within populations are crucial for preventing stroke incidents.

Survivin, an important inhibitor of apoptosis protein, contributes to cancer cells’ resistance to apoptosis, proliferation, and survival. It is a promising biomarker and therapeutic target due to being highly expressed in cancer cells relative to normal cells and universally expressed in almost all cancer types. Cancer cells release survivin to the tumour microenvironment (TME) not only as a free protein but also encapsulated in extracellular vesicles (EVs), especially small EVs (sEVs). The release of encapsulated survivin from cancer cells can be taken up by neighbouring cells, eliciting pathological responses such as tumorigenesis and metastasis. Consequently, EV survivin holds potential as a diagnostic, prognostic, and therapeutic biomarker for several types of cancer, including breast cancer, prostate cancer, pancreatic cancer, and glioblastoma. EV survivin expression is significantly elevated in cancer patients and correlates with unfavourable clinicopathologic parameters. Although no clinical studies have explored EV survivin as a therapeutic target, future research should explore survivin-based therapies in combination with EV-targeting therapies to effectively disrupt its roles in tumorigenesis and metastasis.

Skin cancer, particularly melanoma, is a severe health threat that necessitates early detection for effective treatment. This research introduces a skin lesion classification system that harnesses the capabilities of three advanced deep learning models: VGG16, Inception-V3, and ResNet-50. By integrating these models into an ensemble, the system leverages their individual strengths to improve classification accuracy and robustness. Every model in the ensemble brings its distinctive contribution, having undergone pre-training on ImageNet and subsequent fine-tuning using dermoscopic images. We evaluated our ensemble approach using the ISIC 2018 dataset, a standard benchmark for skin lesion classification. By employing a weighted averaging method to merge predictions from the three models, our ensemble model demonstrated superior performance. The results show an improvement in classification accuracy, achieving an accuracy of 91% on the original dataset and 97% on the dataset balanced by oversampling compared to the individual models. This system was then evaluated using the HAM10000 dataset. The results using the HAM10000 dataset show an improvement in classification accuracy, achieving an accuracy of 90% on the original dataset and 96% on the dataset balanced by oversampling compared to the individual models. This enhanced performance highlights the effectiveness of our ensemble method in capturing diverse features of skin lesions, leading to more accurate diagnoses. Our findings suggest that this approach can significantly assist dermatologists in early and precise skin cancer detection, potentially improving patient outcomes.

Abstract The signaling pathways governing acetaminophen (APAP)-induced liver injury have been extensively studied. However, little is known about the ubiquitin-modifying enzymes needed for the regulation of APAP-induced liver injury. Here, we examined whether the Pellino3 protein, which has E3 ligase activity, is needed for APAP-induced liver injury and subsequently explored its molecular mechanism. Whole-body Peli3 −/− knockout (KO) and adenovirus-mediated Peli3 knockdown (KD) mice showed reduced levels of centrilobular cell death, infiltration of immune cells, and biomarkers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), upon APAP treatment compared to wild-type (WT) mice. Peli3 deficiency in primary hepatocytes decreased mitochondrial and lysosomal damage and reduced the mitochondrial reactive oxygen species (ROS) levels. In addition, the levels of phosphorylation at serine 9 in the cytoplasm and mitochondrial translocation of GSK3β were decreased in primary hepatocytes obtained from Peli3 −/− KO mice, and these reductions were accompanied by decreases in JNK phosphorylation and mitochondrial translocation. Pellino3 bound more strongly to GSK3β compared with JNK1 and JNK2 and induced the lysine 63 (K63)-mediated polyubiquitination of GSK3β. In rescue experiments, the ectopic expression of wild-type Pellino3 in Peli3 −/− KO hepatocytes restored the mitochondrial translocation of GSK3β, but this restoration was not obtained with expression of a catalytically inactive mutant of Pellino3. These findings are the first to suggest a mechanistic link between Pellino3 and APAP-induced liver injury through the modulation of GSK3β polyubiquitination.

Summary: We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1β and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation.

Abstract Seasonal influenza outbreaks remain an important public health concern, causing large numbers of hospitalizations and deaths among high-risk groups. Understanding the dynamics of individual transmission is crucial to design effective control measures and ultimately reduce the burden caused by influenza outbreaks. In this study, we analyzed surveillance data from Kamigoto Island, Japan, a semi-isolated island population, to identify the drivers of influenza transmission during outbreaks. We used rapid influenza diagnostic test (RDT)-confirmed surveillance data from Kamigoto island, Japan and estimated age-specific influenza relative illness ratios (RIRs) over eight epidemic seasons (2010/11 to 2017/18). We reconstructed the probabilistic transmission trees (i.e., a network of who-infected-whom) using Bayesian inference with Markov-chain Monte Carlo method and then performed a negative binomial regression on the inferred transmission trees to identify the factors associated with onwards transmission risk. Pre-school and school-aged children were most at risk of getting infected with influenza, with RIRs values consistently above one. The maximal RIR values were 5.99 (95% CI 5.23, 6.78) in the 7–12 aged-group and 5.68 (95%CI 4.59, 6.99) in the 4–6 aged-group in 2011/12. The transmission tree reconstruction suggested that the number of imported cases were consistently higher in the most populated and busy districts (Tainoura-go and Arikawa-go) ranged from 10–20 to 30–36 imported cases per season. The number of secondary cases generated by each case were also higher in these districts, which had the highest individual reproduction number (Reff: 1.2–1.7) across the seasons. Across all inferred transmission trees, the regression analysis showed that cases reported in districts with lower local vaccination coverage (incidence rate ratio IRR = 1.45 (95% CI 1.02, 2.05)) or higher number of inhabitants (IRR = 2.00 (95% CI 1.89, 2.12)) caused more secondary transmissions. Being younger than 18 years old (IRR = 1.38 (95%CI 1.21, 1.57) among 4–6 years old and 1.45 (95% CI 1.33, 1.59) 7–12 years old) and infection with influenza type A (type B IRR = 0.83 (95% CI 0.77, 0.90)) were also associated with higher numbers of onwards transmissions. However, conditional on being infected, we did not find any association between individual vaccination status and onwards transmissibility. Our study showed the importance of focusing public health efforts on achieving high vaccine coverage throughout the island, especially in more populated districts. The strong association between local vaccine coverage (including neighboring regions), and the risk of transmission indicate the importance of achieving homogeneously high vaccine coverage. The individual vaccine status may not prevent onwards transmission, though it may reduce the severity of infection.

Construction sludge, generated from tunneling and piling, is typically in a liquid state. It can be improved via physical treatments, such as dehydration, and/or chemical treatments, using stabilizers, in order to to be recycled as construction material. To adjust the strength of sludge, chemical treatments are often preferred. However, chemical treatments frequently result in alkali leaching. Methods to reduce alkalinity by curing the alkaline sludge under CO2 gas at a certain concentration have been proposed in Japan. In recent years, technologies that utilize CO2 to improve the quality of cementitious material have received considerable attention in terms of carbon capture. Therefore, the effects of stabilizers on the CO2 fixation capacity of alkaline sludge during pH neutralization were investigated in this study. Accelerated carbonation and carbonate content measurement tests were conducted to detect the CO2 content fixed in alkaline sludge specimens treated with various stabilizers. The test results showed that the fixed maximum CO2 content per gram of dry mass of sludge, (mCO2)max, increased with the calcium oxide (CaO) content of the stabilizer(s) per gram of dry sludge, CCaO. However, the rate of increase in (mCO2)max with CCaO was significantly affected by the type of stabilizer used. In the case of quicklime (QL), the ratio of (mCO2)max to CCaO was approximately 0.5, whereas, in the cases of fly ash (FA) and steel slag (SS), the ratio was approximately 0.25. The ratios for biomass ash and paper sludge ash were between that for QL and that for FA and SS. Detailed analyses of the test results suggest that the CaO content per gram of stabilizer(s) in the sludge, C*CaO, can provide an estimate of the fixed maximum amount of CO2 per gram of stabilizer(s) in the sludge, (m*CO2)max. However, other factors, including the amount of water-soluble Ca, should be considered for a precise evaluation. Additionally, the experimental results showed that the decrease in pH owing to neutralization increases with the increasing CCaO. However, the type of stabilizer did not significantly affect the relationship between the degree of CO2 fixation and the degree of neutralization.

Globally, breast cancer (BC) is considered a major cause of death among women. Therefore, researchers have used various machine and deep learning-based methods for its early and accurate detection using X-ray, MRI, and mammography image modalities. However, the machine learning model requires domain experts to select an optimal feature, obtains a limited accuracy, and has a high false positive rate due to handcrafting features extraction. The deep learning model overcomes these limitations, but these models require large amounts of training data and computation resources, and further improvement in the model performance is needed. To do this, we employ a novel framework called the Ensemble-based Channel and Spatial Attention Network (ECS-A-Net) to automatically classify infected regions within BC images. The proposed framework consists of two phases: in the first phase, we apply different augmentation techniques to enhance the size of the input data, while the second phase includes an ensemble technique that parallelly leverages modified SE-ResNet50 and InceptionV3 as a backbone for feature extraction, followed by Channel Attention (CA) and Spatial Attention (SA) modules in a series manner for more dominant feature selection. To further validate the ECS-A-Net, we conducted extensive experiments between several competitive state-of-the-art (SOTA) techniques over two benchmarks, including DDSM and MIAS, where the proposed model achieved 96.50% accuracy for the DDSM and 95.33% accuracy for the MIAS datasets. Additionally, the experimental results demonstrated that our network achieved a better performance using various evaluation indicators, including accuracy, sensitivity, and specificity among other methods.

The Industrial Internet of Things (IIoT) ecosystem faces increased risks and vulnerabilities due to adopting Industry 4.0 standards. Integrating data from various places and converging several systems have heightened the need for robust security measures beyond fundamental connection encryption. However, it is difficult to provide adequate security due to the IIoT ecosystem’s distributed hardware and software. The most effective countermeasures must be suggested together with the crucial vulnerabilities, linked threats, and hazards in order to protect industrial equipment and ensure the secure functioning of IIoT systems. This paper presents a thorough analysis of events that target IIoT systems to alleviate such concerns. It also offers a comprehensive analysis of the responses that have been advanced in the most recent research. This article examines several kinds of attacks and the possible consequences to understand the security landscape in the IIoT area. Additionally, we aim to encourage the development of effective defenses that will lessen the hazards detected and secure the privacy, accessibility, and reliability of IIoT systems. It is important to note that we examine the issues and solutions related to IIoT security using the most recent findings from research and the literature on this subject. This study organizes and evaluates recent research to provide significant insight into the present security situation in IIoT systems. Ultimately, we provide outlines for future research and projects in this field.

Abstract Providing elderly mental healthcare in Myanmar is challenging due to the growing elderly population and limited health resources. To understand common mental health problems among Myanmar elderly, this study explored the prevalence and risk factors of anxiety and depression among the elderly in the Nay Pyi Taw Union Territory, Myanmar. A cross-sectional study was conducted among 655 elderly by face-to-face interviews with a pretested questionnaire. Descriptive analysis and multiple logistic regression analyses were performed. The prevalence of anxiety and depression were 39.4% (33.5% for males and 42.4% for females) and 35.6% (33.0% for males and 36.9% for females), respectively. The adjusted odds ratio of having anxiety was significant for having low education level, having comorbidity, having BMI

Abstract Background Diagnosis by computed tomography (CT) and magnetic resonance imaging (MRI) is important for patient care. However, the geographic distribution and utilisation of these machines in countries with limited resources, such as Myanmar, have not been sufficiently studied. Therefore, this study aims to identify the geographic distribution and utilisation of CT and MRI services at public hospitals in Myanmar. Methods This nationwide, cross-sectional study was conducted at 43 public hospitals in Myanmar. Data were collected retrospectively using a prepared form from 1st January 2015 to 31st December 2017 at public hospitals in Myanmar. A descriptive analysis was performed to calculate the number of CT and MRI units per million population in each state and region of Myanmar. The distribution of CT and MRI units was assessed using the Lorenz curve and Gini coefficient, which are indicators of inequality in distribution. Results In total, 45 CT and 14 MRI units had been installed in public hospitals in Myanmar by 2017. In total, 205,570 CT examinations and 18,981 MRI examinations have been performed within the study period. CT units per million population in 2017 varied from 0.30 in Rakhine State to 3.22 in Kayah State. However, MRI units were available only in public hospitals in five states/regions. The Gini coefficient for CT and MRI was 0.35 and 0.69, respectively. An upward trend in the utilisation rate of CT and MRI was also observed during the study period, especially among patients aged between 36 and 65 years. Conclusions Throughout Myanmar, CT units were more equally distributed than MRI units. CT and MRI units were mostly concentrated in the Yangon and Mandalay Regions, where the population density is higher. The geographic distribution and utilisation rate of CT and MRI units varied among states, regions, and patients’ age group. However, the utilisation rates of CT and MRI increased annually in all states and regions during the review period. The Ministry of Health and Sports in Myanmar should consider the utilisation and population coverage of CT and MRI as an important factor when there will be procurement of those medical equipment in the future.

Abstract Background Coronavirus disease 2019 (COVID-19) has spread to almost every region and country in the world, leading to widespread travel restrictions and national lockdowns. Currently, there are limited epidemiological and clinical data on COVID-19 patients from low and middle-income countries. We conducted a retrospective single-center study of the first 100 individuals with suspected COVID-19 (between Jan. 25 and Mar. 29, 2020) admitted to San Lazaro Hospital (SLH), the national infectious diseases referral hospital in Manila, Philippines. Results Demographic data, travel history, clinical features, and outcomes were summarized and compared between COVID-19 confirmed and non-confirmed cases. The first two confirmed cases were Chinese nationals, admitted on Jan. 25. The third confirmed case was a Filipino, admitted on Mar. 8. Trends toward confirmed COVID-19 cases not reporting international travel and being admitted to SLH from the densely populated area of Manila city were observed during Mar. 8-29. All 42 of the 100 confirmed COVID-19 cases were adults, 40% were aged 60 years and above and 55% were male. Three were health workers. Among individuals with suspected COVID-19, confirmed cases were more likely to be older, Filipino, not report international travel history and have at least one underlying disease, particularly diabetes, report difficulty in breathing, and a longer duration of symptoms. In over 90% of non-COVID-19 cases, the alternative diagnosis was respiratory. Nine (21%) confirmed cases died. The median duration from symptoms onset to death was 11.5 (range: 8–18) days. Conclusions Imported COVID-19 cases have reduced but local transmission persists and there is a trend toward cases being admitted to SLH from densely populated areas. This study highlights the difficulty in diagnosing COVID-19 on clinical grounds and the importance of diagnostic capacity in all settings. Difficulty of breathing was the only symptom associated with COVID-19 infection and should alert clinicians to the possibility of COVID-19. Clinical characteristics of confirmed COVID-19 cases and a hospital case fatality rate of 21% are comparable with other settings.

Abstract Background Ready-to-eat (RTE) food consumption has become popular in the working community with the increase in full-time jobs and the limited time to prepare food. Although RTE food is essential for this community, its consumption causes obesity. In Myanmar, obesity is a modifiable risk factor for non-communicable diseases, causing increases in morbidity and mortality. This study aimed to identify the association between body mass index (BMI) and RTE food consumption among sedentary staff in Nay Pyi Taw Union Territory, Myanmar. Methods A cross-sectional study was conducted in 2018, in which 400 respondents participated in face-to-face interviews. The study area was selected using simple random sampling and drawing method. Measuring tape and digital weighing scale were used to measure the height and weight of the respondents. BMI was calculated by dividing the weight by height squared (kg/m2). Overweight and obesity were categorized by World Health Organization cut-off points. The collected data were analyzed using multiple logistic regression to estimate the adjusted odds ratio (AOR), and the 95% confidence interval (CI). Results This study revealed that sedentary staff who consumed RTE food once or more per month were nearly five times more likely to be overweight and obese (AOR = 4.78, 95% CI 1.44–15.85) than those who consumed RTE food less frequently. In addition, five factors namely being older than 32 years (AOR = 3.97, 95% CI 1.82–8.69), preference for RTE food (AOR = 8.93, 95% CI 2.54–31.37), light-intensity of physical exercise (AOR = 3.55, 95% CI 1.63–7.73), sedentary leisure activities (AOR = 3.32, 95% CI 1.22–9.03), and smoking (AOR = 5.62, 95% CI 1.06–29.90) were positively associated with overweight and obesity. Conclusion Frequent consumers of RTE food and less physically active sedentary staff were more likely to be overweight and obese. This study highlights the urgent need to raise awareness regarding healthy lifestyle behaviors among the working community to reduce the burden of obesity-related chronic diseases. Moreover, sedentary workers should be aware of the food-based dietary guidelines of the country. Policy makers should strictly enforce nutritional labeling of RTE food, and strictly prohibit over-branding of RTE food.

Abstract Background T cells exhibit heterogeneous functional states in the tumor microenvironment. Immune checkpoint inhibitors (ICIs) can reinvigorate only the stem cell-like progenitor exhausted T cells, which suggests that inhibiting the exhaustion progress will improve the efficacy of immunotherapy. Thus, regulatory factors promoting T cell exhaustion could serve as potential targets for delaying the process and improving ICI efficacy. Methods We analyzed the single-cell transcriptome data derived from human melanoma and non-small cell lung cancer (NSCLC) samples and classified the tumor-infiltrating (TI) CD8+ T cell population based on PDCD1 (PD-1) levels, i.e., PDCD1-high and PDCD1-low cells. Additionally, we identified differentially expressed genes as candidate factors regulating intra-tumoral T cell exhaustion. The co-expression of candidate genes with immune checkpoint (IC) molecules in the TI CD8+ T cells was confirmed by single-cell trajectory and flow cytometry analyses. The loss-of-function effect of the candidate regulator was examined by a cell-based knockdown assay. The clinical effect of the candidate regulator was evaluated based on the overall survival and anti-PD-1 responses. Results We retrieved many known factors for regulating T cell exhaustion among the differentially expressed genes between PDCD1-high and PDCD1-low subsets of the TI CD8+ T cells in human melanoma and NSCLC. TOX was the only transcription factor (TF) predicted in both tumor types. TOX levels tend to increase as CD8+ T cells become more exhausted. Flow cytometry analysis revealed a correlation between TOX expression and severity of intra-tumoral T cell exhaustion. TOX knockdown in the human TI CD8+ T cells resulted in downregulation of PD-1, TIM-3, TIGIT, and CTLA-4, which suggests that TOX promotes intra-tumoral T cell exhaustion by upregulating IC proteins in cancer. Finally, the TOX level in the TI T cells was found to be highly predictive of overall survival and anti-PD-1 efficacy in melanoma and NSCLC. Conclusions We predicted the regulatory factors involved in T cell exhaustion using single-cell transcriptome profiles of human TI lymphocytes. TOX promoted intra-tumoral CD8+ T cell exhaustion via upregulation of IC molecules. This suggested that TOX inhibition can potentially impede T cell exhaustion and improve ICI efficacy. Additionally, TOX expression in the TI T cells can be used for patient stratification during anti-tumor treatments, including anti-PD-1 immunotherapy.

Summary: Background: Measles outbreaks increased worldwide during 2017-19. The largest outbreak in the World Health Organisation Western Pacific region occurred in the Philippines where first-dose measles-containing vaccine (MCV1) coverage had reduced to 75% in 2018. The aim of this study was to summarise paediatric measles admissions to the national infectious diseases referral hospital in Manila during 2016 to 2019. Methods: A retrospective single-centre observational study including 5,562 children aged under five years admitted with measles from January 2016 to December 2019. We summarised sociodemographic and clinical characteristics, vaccine status, reported exposures, and outcomes. Univariable and multivariable logistic regression analyses were undertaken to assess associations between different characteristics of hospitalised children and death. Findings: The median age of children hospitalised with measles was 11 months (interquartile range: 7-28). 84·5% of cases were reported not to have received any MCV. The risk of mortality was 3·2%, with 41% of deaths occurring among children aged less than 9 months. No children died who had received two MCV. The following characteristics were significantly associated with mortality in the multivariable analysis: age group, residence outside of the national capital region, not having received any MCV, duration between onset of fever and hospital admission of 7-14 days compared with 0-3 days, not receiving vitamin A supplementation, having pneumonia, and gastroenteritis. Interpretation: The Philippines remains at risk of future measles epidemics. Routine immunization needs to be strengthened and earlier timing of MCV1 requires further evaluation to reduce measles incidence and mortality. Funding: This work is in part funded by Nagasaki University (salary support for CS, KAA, RN, SS, KA, KT).

Effective livestock management is critical for cattle farms in today’s competitive era of smart modern farming. To ensure farm management solutions are efficient, affordable, and scalable, the manual identification and detection of cattle are not feasible in today’s farming systems. Fortunately, automatic tracking and identification systems have greatly improved in recent years. Moreover, correctly identifying individual cows is an integral part of predicting behavior during estrus. By doing so, we can monitor a cow’s behavior, and pinpoint the right time for artificial insemination. However, most previous techniques have relied on direct observation, increasing the human workload. To overcome this problem, this paper proposes the use of state-of-the-art deep learning-based Multi-Object Tracking (MOT) algorithms for a complete system that can automatically and continuously detect and track cattle using an RGB camera. This study compares state-of-the-art MOTs, such as Deep-SORT, Strong-SORT, and customized light-weight tracking algorithms. To improve the tracking accuracy of these deep learning methods, this paper presents an enhanced re-identification approach for a black cattle dataset in Strong-SORT. For evaluating MOT by detection, the system used the YOLO v5 and v7, as a comparison with the instance segmentation model Detectron-2, to detect and classify the cattle. The high cattle-tracking accuracy with a Multi-Object Tracking Accuracy (MOTA) was 96.88%. Using these methods, the findings demonstrate a highly accurate and robust cattle tracking system, which can be applied to innovative monitoring systems for agricultural applications. The effectiveness and efficiency of the proposed system were demonstrated by analyzing a sample of video footage. The proposed method was developed to balance the trade-off between costs and management, thereby improving the productivity and profitability of dairy farms; however, this method can be adapted to other domestic species.

Summary: Active brown adipose tissue (BAT) consumes copious amounts of glucose, yet how glucose metabolism supports thermogenesis is unclear. By combining transcriptomics, metabolomics, and stable isotope tracing in vivo, we systematically analyze BAT glucose utilization in mice during acute and chronic cold exposure. Metabolite profiling reveals extensive temperature-dependent changes in the BAT metabolome and transcriptome upon cold adaptation, discovering unexpected metabolite markers of thermogenesis, including increased N-acetyl-amino acid production. Time-course stable isotope tracing further reveals rapid incorporation of glucose carbons into glycolysis and TCA cycle, as well as several auxiliary pathways, including NADPH, nucleotide, and phospholipid synthesis pathways. Gene expression differences inconsistently predict glucose fluxes, indicating that posttranscriptional mechanisms also govern glucose utilization. Surprisingly, BAT swiftly generates fatty acids and acyl-carnitines from glucose, suggesting that lipids are rapidly synthesized and immediately oxidized. These data reveal versatility in BAT glucose utilization, highlighting the value of an integrative-omics approach to understanding organ metabolism.

Background: Although bone morphogenetic protein 6 (BMP6) signaling pathway has been implicated in many types of cancer, its role of tumorigenesis seems to be controversial and its ubiquitin-modifying mechanisms have not been fully addressed. Our study was designed to investigate how BMP6 signaling pathway is regulated by ubiquitin-modifying systems and to address molecular and clinical significance in colorectal cancers. Methods: Human deubiquitnase (DUB) siRNA library was used to screen the specific DUB, named PSMD14, involved in BMP6 signaling pathway. Immunoblot, immunoprecipitation and ubiquitination assays were used to analyze targets of the PSMD14. A role of PSMD14-mediated BMP6 signaling pathway for malignant cancer progression was investigated using in vitro and in vivo model of colorectal cancers as well as clinical samples of colorectal cancer patients. Findings: The deubiquitinase PSMD14 acts as a positive regulator for the initiation of the BMP6 signaling pathway through deubiquitinating K48-linked ALK2 type I receptor ubiquitination mediated by Smurf1 E3 ligase, resulting in increased stability of the ALK2. This role of PSMD14 is independent of its intrinsic role in the 26S proteasome system. Furthermore, either PSMD14 or ALK2 depletion significantly decreases tumorigenesis of HCT116 colorectal cancer cells in a xenograft model as well as cancer stemness/chemoresistance, and expression of the PSMD14 and ALK2 gene are correlated with malignant progression and the survival of colorectal cancer patients. Interpretation: These findings suggest that the PSMD14-ALK2 axis plays an essential role in initiation of the BMP6 signaling pathway and contributes to tumorigenesis and chemoresistance of colorectal cancers. Key words: PSMD14, Deubiqutinase, ALK2 receptor, Smurf1, BMP6, Colorectal cancers

Objective: Understanding the signaling mechanisms that control brown adipose tissue (BAT) development is relevant to understanding energy homeostasis and obesity. The AKT kinases are insulin effectors with critical in vivo functions in adipocytes; however, their role in adipocyte development remains poorly understood. The goal of this study was to investigate AKT function in BAT development. Methods: We conditionally deleted Akt1 and Akt2 either individually or together with Myf5-Cre, which targets early mesenchymal precursors that give rise to brown adipocytes. Because Myf5-Cre also targets skeletal muscle and some white adipocyte lineages, comparisons were made between AKT function in BAT versus white adipose tissue (WAT) and muscle development. We also deleted both Akt1 and Akt2 in mature brown adipocytes with Ucp1-Cre or Ucp1-CreER to investigate AKT1/2 signaling in BAT maintenance. Results: AKT1 and AKT2 are individually dispensable in Myf5-Cre lineages in vivo for establishing brown and white adipocyte precursor cell pools and for their ability to differentiate (i.e. induce PPARγ). AKT1 and AKT2 are also dispensable for skeletal muscle development, and AKT3 does not compensate in either the adipocyte or muscle lineages. In contrast, AKT2 is required for adipocyte lipid filling and efficient downstream AKT substrate phosphorylation. Mice in which both Akt1 and Akt2 are deleted with Myf5-Cre lack BAT but have normal muscle mass, and doubly deleting Akt1 and Akt2 in mature brown adipocytes, either congenitally (with Ucp1-Cre), or inducibly in older mice (with Ucp1-CreER), also ablates BAT. Mechanistically, AKT signaling promotes adipogenesis in part by stimulating ChREBP activity. Conclusions: AKT signaling is required in vivo for BAT development but dispensable for skeletal muscle development. AKT1 and AKT2 have both overlapping and distinct functions in BAT development with AKT2 being the most critical individual isoform. AKT1 and AKT2 also have distinct and complementary functions in BAT maintenance. Keywords: Brown adipose tissue, White adipose tissue, Development, Adipogenesis, Insulin signaling, AKT, mTORC2, Obesity, Lipodystrophy

Background: Myanmar is listed as one of the countries with the highest burden of tuberculosis and HIV infections (TB–HIV) in the world. However, the survival rate and risk factors for mortality among TB–HIV co-infected patients in the country remain unstudied. Therefore, the purpose of this study was to examine these factors. Methods: A 12-year retrospective follow-up study was conducted among 3598 TB–HIV co-infected patients (2452 male and 1146 female) aged 15 years and above, enrolled on antiretroviral therapy (ART) from July 1, 2005 to December 31, 2016. Hazard ratios (HR) were estimated using the Cox proportional hazards model. Survival rates at the beginning of ART were calculated using the Kaplan–Meier method. Results: A total of 494 (13.7%) patients died during this period. The survival rate of TB–HIV co-infected patients was 82.0% at 5 years and 58.1% at 10 years. The risk factors for mortality were being bedridden (adjusted hazard ratio (aHR) 2.70, 95% confidence interval (CI) 2.13–3.42), having a low baseline CD4 count (aHR 1.53, 95% CI 1.25–1.87), and being on a second-line ART regimen (aHR 8.12, 95% CI 3.56–18.54). Conclusions: Two out of five TB–HIV patients died within 10 years after ART initiation. Current HIV prevention and treatment programs should focus more on bedridden patients, those on second-line ART, and those with low baseline CD4 counts. Keywords: Survival, TB–HIV, Antiretroviral therapy, Mortality, Myanmar

Summary: Overweight and obesity are associated with type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and cancer, but all fat is not equal, as storing excess lipid in subcutaneous white adipose tissue (SWAT) is more metabolically favorable than in visceral fat. Here, we uncover a critical role for mTORC2 in setting SWAT lipid handling capacity. We find that subcutaneous white preadipocytes differentiating without the essential mTORC2 subunit Rictor upregulate mature adipocyte markers but develop a striking lipid storage defect resulting in smaller adipocytes, reduced tissue size, lipid re-distribution to visceral and brown fat, and sex-distinct effects on systemic metabolic fitness. Mechanistically, mTORC2 promotes transcriptional upregulation of select lipid metabolism genes controlled by PPARγ and ChREBP, including genes that control lipid uptake, synthesis, and degradation pathways as well as Akt2, which encodes a major mTORC2 substrate and insulin effector. Further exploring this pathway may uncover new strategies to improve insulin sensitivity.

ObjectivesTo examine the associations of current tobacco use with tobacco advertising, promotion and sponsorship (TAPS), and illicit tobacco sales exposures among Myanmar high school students.DesignA quantitative, cross-sectional study.SettingSeven high schools from both urban and rural areas of four states and regions in Myanmar.ParticipantsIn total, 1174 high school students (482 males and 692 females) were interviewed using a self-administered questionnaire.Main outcome measureCurrent tobacco use of participants, defined as using any kind of smoked or smokeless tobacco product at least one occasion within the past 30 days.ResultsThe prevalence of TAPS exposure was 90.9% among high school students in Myanmar. Current tobacco use was positively associated with being over 14 years old (adjusted OR (AOR) 9.81; 95% CI 4.54 to 21.19), being male (AOR 28.06; 95% CI 13.29 to 59.25), exposure to any kind of TAPS (AOR 6.59; 95% CI 2.33 to 18.64), having seen any smoked tobacco product for sale inside or within 100 feet of the school premises (AOR 4.17; 95% CI 1.65 to 10.58), having seen the sale or gifting of any smoked tobacco product to minors (AOR 6.46; 95% CI 2.18 to 19.12) and having seen the sale or distribution of any smoked tobacco product by minors (AOR 2.42; 95% CI 1.42 to 4.10). Having ever received health education about tobacco use (AOR 0.45; 95% CI 0.27 to 0.78), or having a higher perception score of tobacco use (AOR 0.17; 95% CI 0.10 to 0.30) were negatively associated with current tobacco use.ConclusionsThere was an alarming prevalence of TAPS exposure among Myanmar high school students. TAPS exposure and violations of tobacco sale regulations were strong risk factors for current tobacco use among Myanmar high school students, while health education about tobacco products was reported as an effective protective factor. Specific smokeless tobacco sale regulations for minors are needed immediately in Myanmar.

BACKGROUND:Cyberbullying is a global public health concern with tremendous negative impacts, not only on the physical and mental health of students but also on their well-being and academic performance. However, there are very few studies on cyberbullying among university students, especially in Myanmar. This study aims to determine the percentage of university students who suffered cyberbullying victimization in the last 12 months, and the association between students' socio-demographic characteristics, adverse events following cyberbullying and cyberbullying victimization. METHODS:A cross-sectional study was conducted among university students aged 18 years and older at one medical university in Magway, Myanmar. A total of 412 students (277 males and 135 females) participated in the study. Data were collected from August to September, 2018 using a self-administered questionnaire. Multiple logistic regression analyses (models I and II) were performed to estimate the unadjusted (UOR) and adjusted odds ratios (AOR), and 95% confidence intervals (CI). RESULTS:In total, 40.8% of males and 51.1% of females in the study had suffered cyberbullying victimization in the past 12 months. In model I, students who had been studying at the university for 3 years or less (AOR = 1.81; 95% CI 1.14-2.85), and who had witnessed psychological, physical or sexual violence, or cyberbullying in their neighborhoods, (AOR = 2.95; 95% CI 1.48-5.91) were more likely to have suffered cyberbullying victimization in the past 12 months. In model II, being a victim of cyberbullying was associated with difficulties in concentrating and understanding lectures (AOR = 3.96; 95% CI 1.72-9.11), and substance abuse (AOR = 2.37; 95% CI 1.02-5.49). Non-resident students were at a higher risk of being cyberbullying victims than their resident peers (AOR = 1.86; 95% CI 1.04-3.34). CONCLUSION:Two out of five students had suffered cyberbullying victimization in the past 12 months, and only half of the victims discussed their experience(s) with someone else. Students who suffered cyberbullying victimization faced academic difficulties and started or increased smoking, betel chewing or alcohol drinking. Counter measures to prevent and mitigate the adverse events related to cyberbullying victimization are urgently needed among university students in Myanmar. Periodic screening for cyberbullying, counseling services, cyber-safety educational programs, and awareness raising campaigns should be implemented.

BACKGROUND:Globally, alcohol consumption is a significant public health concern and it is one of the most important risk behaviours among university students. Alcohol consumption can lead to poor academic performance, injuries, fights, use of other substances, and risky sexual behaviours among students. However, the study explored the prevalence of alcohol consumption and the associated risk factors among university students since these have not been fully examined in previous research. Therefore, the aim of this study was to explore the prevalence of alcohol consumption and the associated risk factors among university students in Myanmar. METHODS:The present cross-sectional study was conducted using a sample of 15-24-year-old university students who were selected from six universities in Mandalay, Myanmar, in August 2018. In total, 3,456 students (males: 1,301 and females: 2,155) were recruited and asked to respond to a self-administered questionnaire. Multiple logistic regression analysis was used to estimate the adjusted odds ratio (AOR) and 95% confidence interval (CI) for alcohol consumption among university students. RESULTS:The prevalence of alcohol consumption in the previous 30 days was 20.3% (males: 36.0%, females: 10.8%). The alcohol consumption was significantly higher among males (AOR = 2.3, 95% CI; 1.9-2.9), truant students (AOR = 2.1, 95% CI; 1.3-3.3), smokers (AOR = 7.0, 95% CI; 5.1-9.7), students who reported feeling of hopelessness or sadness (AOR = 1.4, 95% CI; 1.2-1.8), peers' alcohol consumption (AOR = 7.5, 95% CI; 4.8-11.7). CONCLUSION:The present study revealed that males, smokers, peer alcohol consumption, and truant students had higher odds of alcohol consumption among the students. Therefore, effective campus-based counselling, peer education, and national surveillance systems that can monitor risky drinking behaviours among university students should be implemented. Further, government regulations that control the production, sale, promotion, advertising, and restriction of alcohol should be well developed and strengthened, as in the case of other Southeast Asian countries.

BackgroundGlobally, elderly population with impaired cognitive function, such as dementia, has been accelerating, and Myanmar is no exception. However, cognitive function among elderly in Myanmar has rarely been assessed. This study aimed to identify the rate of cognitive impairment and its risk factors among the elderly in Myanmar.MethodsThis cross-sectional study was conducted at rural health centers in Nay Pyi Taw Union Territory, Myanmar, from December 2018 to January 2019. In total, 757 elderly individuals aged 60 years or over (males: 246 [32.5%], females: 511 [67.5%]) were interviewed using a face-to-face method with a pre-tested questionnaire. Descriptive statistics and multivariable logistic regression analyses were performed.ResultsThe rate of impaired cognitive function among participants was 29.9% (males: 23.6%; females: 32.9%). The following participants were more likely to present cognitive impairment: those aged 70-79 years (adjusted odds ratio [AOR] = 1.8; 95% confidence interval [CI]: 1.19-2.70) and 80 years or older (AOR = 3.9; 95% CI: 2.25-6.76); those who were illiterate (AOR = 9.1; 95% CI: 3.82-21.51); and those dependent on family members (AOR = 1.6; 95% CI: 1.04-2.44). The elderly livening with their families and those who reported having good health (AOR = 0.7; 95% CI: 0.44-0.99) were less likely to have cognitive impairment.ConclusionUsing the HDS-R Myanmar version, this study reported that there out of five elderly participants had cognitive impairment, and its risk factors, altering policy makers that Myanmar needs to prepare for adequate healthcare services and social support for elderly with cognitive impairment. Future research should be performed not only to detect general cognitive impairment but also to differentiate specific cognitive domains impairments among Myanmar elderly. Longitudinal studies are needed to observe the causal and protective factors associated with cognitive impairments in Myanmar.

BackgroundIn the context of an aging population, quality of life (QOL) is an important consideration for the well-being of the elderly. However, there is limited information on the QOL of the elderly in Myanmar. This study aimed to explore the risk factors for low QOL among the elderly in urban and peri-urban areas of the Yangon Region, Myanmar.MethodsA community-based, cross-sectional study was conducted among the elderly aged 60 years or older in two urban and two peri-urban townships in the Yangon Region from July to September 2019. A multi-stage sampling method was used to recruit study participants using a pre-tested questionnaire. A total of 616 (305 males and 311 females) elderly people were interviewed using a face-to-face interview technique. Multiple linear regression analysis was performed on the four domains (physical health, psychological health, social relationship, and environment) of QOL measured with the WHOQOL-BREF.ResultsIncome level and having intimate friends influenced the QOL scores of the elderly in all domains, while education level and marital status influenced psychological health, social relationship, and environment domains. Social interaction with neighbors increased the QOL scores for physical health, social relationship, and environment domains. Living in peri-urban areas was associated with lower QOL scores for physical health, psychological health, and environment, while participation in group activities increased QOL scores in these domains. Having comorbidities affected the QOL for psychological health and environment domains, while the frequency of going out affected physical health, and the frequency of religious performance affected social relationship.ConclusionResidential location, education level, marital status, income, comorbidities, social interactions with neighbors and friends, participation in group activities, and frequencies of going out and religious activities should be considered in planning and implementing programs for the elderly in Myanmar. Peri-urban development, strengthening healthcare and social security systems, and encouraging social interaction and participation in group activities play critical roles in improving the QOL for elderly residing in Myanmar.

Abstract Background Methamphetamine (MA) use is a significant public health concern due to its negative effects on health. However, to date, no epidemiological research has examined high-risk sexual behaviors (inconsistent condom use, having multiple sexual partners and having a history of sexually transmitted infections) among MA users. This topic is particularly important in Myanmar, which is recognized as one of the key MA production countries in the Southeast Asia region. Therefore, this study examined factors associated with high-risk sexual behaviors among MA users in Muse city, Myanmar. Methods A community-based cross-sectional study was conducted from January to March 2013 in Muse city, Northern Shan State, Myanmar. In total, 1183 MA users (772 male; 411 female) were recruited using respondent-driven sampling and a computer assisted self-interviewing method. Generalized estimating equation models were used to examine factors associated with high-risk sexual behaviors. Results A large proportion of MA users engaged in high-risk sexual behaviors (inconsistent condom use: males, 90.7%, females, 85.2%; multiple sexual partners: males, 94.2%, females, 47.2%; and history of STIs: males, 55.7%, females, 56.0%). Among males, being a multiple stimulants drug user (adjusted odds ratio [AOR] =1.77; 95% confidence interval [CI] =1.30–2.41) and being a client of sex workers (AOR = 1.41; 95% CI = 1.08–1.83) were risk factors for engaging in high-risk sexual behaviors. Among females, being a migrant worker (AOR = 2.70; 95% CI = 1.86–3.93) and being employed (AOR = 1.57; 95% CI = 1.13–2.18) were risk factors for engaging in high-risk sexual behaviors as well. Conclusions High-risk sexual behaviors were particularly pronounced among both male and female MA users. MA prevention programs that reflect gender considerations should be developed to pay more attention to vulnerable populations such as migrants, clients of sex workers, and less educated female MA users.

Background: Topical pharyngeal anesthesia as an adjunct to intravenous sedation to facilitate gastroscopy has been widely acknowledged; however, its efficacy has not been established when it is used in patients under deep sedation with propofol.Aims: To demonstrate the limited value of topical pharyngeal anesthesia in patients under moderate to deep sedation with propofol.Methods: One hundred and twenty-nine patients undergoing gastroscopy were prospectively randomized to receive 10 % lidocaine or distilled water topical spray as an adjunct to intravenous propofol via target-controlled infusion. Verbal and somatic responsiveness, presence of gag reflex and hiccup to esophageal intubation, and the overall ease of the procedure were evaluated by the anaesthetists and gastroenterologists. Hemodynamic parameters including peripheral oxygen saturation, systolic/diastolic blood pressure (SBP/DBP), heart rate (HR), bispectral index, and SBP × HR were compared at 5 time points: on arrival, after 5 spontaneous breaths, when estimated brain concentration of propofol, Ce, reached 3.5 μg/ml, on esophageal intubation, and on awakening.Results: No statistical difference was observed between the lidocaine and distilled water group in verbal or somatic responses, gag reflex or hiccups on esophageal intubation. Similarly, BIS, SBP, DBP, and HR showed no significant difference between the groups.Conclusions: The use of topical pharyngeal anesthesia in combination with target-controlled infusion with propofol in the performance of diagnostic gastroscopy might be eliminated without adversely affecting patient care or outcomes. [ABSTRACT FROM AUTHOR]