Search

Background: Simulations by transport codes are indispensable for extracting valuable physical information from heavy-ion collisions. Pion observables such as the π-/π+ yield ratio are expected to be sensitive to the symmetry energy at high densities. Purpose: To evaluate, understand, and reduce the uncertainties in transport-code results originating from different approximations in handling the production of Δ resonances and pions. Methods: We compare ten transport codes under controlled conditions for a system confined in a box, with periodic boundary conditions, and initialized with nucleons at saturation density and at a temperature of 60 MeV. The reactions NN↔NΔ and Δ↔Nπ are implemented, but the Pauli blocking and the mean-field potential are deactivated in the present comparison. Thus, these are cascade calculations including pions and Δ resonances. Results are compared to those from the two reference cases of a chemically equilibrated ideal gas mixture and of the rate equation. Results: For the numbers of Δ and π, deviations from the reference values are observed in many codes, and they depend significantly on the size of the time step. These deviations are tied to different ways in ordering the sequence of reactions, such as collisions and decays, that take place in the same time step. Better agreements with the reference values are seen in the reaction rates and the number ratios among the isospin species of Δ and π. Both the reaction rates and the number ratios are, however, affected by the correlations between particle positions, which are absent in the Boltzmann equation, but are induced by the way particle scatterings are treated in many of the transport calculations. The uncertainty in the transport-code predictions of the π-/π+ ratio, after letting the existing Δ resonances decay, is found to be within a few percent for the system initialized at n/p=1.5. Conclusions: The uncertainty in the final π-/π+ ratio in this simplified case of particles in a box is sufficiently small so that it does not strongly impact constraining the high-density symmetry energy from heavy-ion collisions. Most of the sources of uncertainties have been understood, and individual codes may be further improved in future applications. This investigation will be extended in the future to heavy-ion collisions to ensure the problems identified here remain under control.

We report the first measurements with sub-kiloparsec spatial resolution of strongly inverted gas-phase metallicity gradients in two dwarf galaxies at z ∼ 2. The galaxies have stellar masses ∼109 , specific star formation rate ∼20 Gyr-1, and global metallicity (1/4 solar), assuming the strong-line calibrations of [O iii]/Hβ and [O ii]/Hβ from Maiolino et al. Their radial metallicity gradients are measured to be highly inverted, i.e., 0.122 ± 0.008 and 0.111 ± 0.017 dex kpc-1, which is hitherto unseen at such small masses in similar redshift ranges. From the Hubble Space Telescope observations of the source nebular emission and stellar continuum, we present two-dimensional spatial maps of star formation rate surface density, stellar population age, and gas fraction, which show that our galaxies are currently undergoing rapid mass assembly via disk inside-out growth. More importantly, using a simple chemical evolution model, we find that the gas fractions for different metallicity regions cannot be explained by pure gas accretion. Our spatially resolved analysis based on a more advanced gas regulator model results in a spatial map of net gaseous outflows, triggered by active central starbursts, that potentially play a significant role in shaping the spatial distribution of metallicity by effectively transporting stellar nucleosynthesis yields outwards. The relation between wind mass loading factors and stellar surface densities measured in different regions of our galaxies shows that a single type of wind mechanism, driven by either energy or momentum conservation, cannot explain the entire galaxy. These sources present a unique constraint on the effects of gas flows on the early phase of disk growth from the perspective of spatially resolved chemical evolution within individual systems.

While a large variety of organic and molecular materials have been found to exhibit charge memory effects, the underlying mechanism is not well-understood, which hinders rational device design. Here, we study the charge retention mechanism of a nanoscale memory system, an organic monolayer on a silicon substrate, with Au nanoparticles on top serving as the electrical contact. Combining scanning probe imaging/manipulation and density functional simulations, we observe stable charge retention effects in the system and attributed it to polaron effects at the amine functional groups. Our findings can pave the way for applications in nonvolatile memory, neuromorphic computing, and high dielectric breakdown devices.

Cosmic ray (CR) interactions can be a challenging source of background for neutrino oscillation and cross-section measurements in surface detectors. We present methods for CR rejection in measurements of charged-current quasielastic-like (CCQE-like) neutrino interactions, with a muon and a proton in the final state, measured using liquid argon time projection chambers (LArTPCs). Using a sample of cosmic data collected with the MicroBooNE detector, mixed with simulated neutrino scattering events, a set of event selection criteria is developed that produces an event sample with minimal contribution from CR background. Depending on the selection criteria used a purity between 50 and 80% can be achieved with a signal selection efficiency between 50 and 25%, with higher purity coming at the expense of lower efficiency. While using a specific dataset and selection criteria values optimized for the MicroBooNE detector, the concepts presented here are generic and can be adapted for various studies of exclusive νμ CCQE interactions in LArTPCs.

Using high-resolution angle-resolved photoemission spectroscopy and ab initio calculation, we have studied the bulk and surface electronic structure of metallic rutile 5d transition metal oxide IrO2 that harbors both edge and corner sharing Ir-O octahedrons. We observe strong modulation of the band structure by spin-orbit coupling (SOC). The measured band structure is well reproduced by our ab initio calculation without band renormalization, suggesting the absence of the SOC-enhanced correlation effect in IrO2. In accordance with the calculation, we visualize two types of Dirac nodal lines (DNLs) protected by mirror symmetry and nonsymmorphic crystal symmetry, respectively. SOC gaps the first type of DNLs, which may contribute largely to the strong spin Hall effect. The second type of DNLs at the edges of Brillouin zone, however, remain intact against SOC. Our results not only provide important insights into the exotic transport properties of IrO2, but also shed light on the understanding of the role of SOC in the iridate family.

We have developed a convolutional neural network that can make a pixel-level prediction of objects in image data recorded by a liquid argon time projection chamber (LArTPC) for the first time. We describe the network design, training techniques, and software tools developed to train this network. The goal of this work is to develop a complete deep neural network based data reconstruction chain for the MicroBooNE detector. We show the first demonstration of a network's validity on real LArTPC data using MicroBooNE collection plane images. The demonstration is performed for stopping muon and a νμ charged-current neutral pion data samples.

We report the first measurement of the flux-integrated cross section of νμ charged-current single π0 production on argon. This measurement is performed with the MicroBooNE detector, an 85 ton active mass liquid argon time projection chamber exposed to the Booster Neutrino Beam at Fermilab. This result on argon is compared to past measurements on lighter nuclei to investigate the scaling assumptions used in models of the production and transport of pions in neutrino-nucleus scattering. The techniques used are an important demonstration of the successful reconstruction and analysis of neutrino interactions producing electromagnetic final states using a liquid argon time projection chamber operating at the Earth's surface.

Current worldwide fixed nitrogen utilization efficiency (NUE) is low, leading to significant environmental problems. An important aspect of this problem involves NH3 released from bacterially degraded, N-containing organic waste such as animal manure. Acidifying organic waste with nitric acid traps NH3 as NH4NO3, thus increasing the nitrogen content of the resulting organic fertilizer and reducing the environmental effects of NH3 emission. Air plasmas have been proposed for this purpose through production of NOx from air which can be readily converted to nitric acid. However, a major challenge remains in reducing the energy cost of NOx production in air plasmas to make the technology economically competitive. Different types of discharges such as arcs, sparks, dielectric barrier discharges have been investigated for NOx production but they are challenging to compare due to differences in their structure, geometry and excitation modes etc. Different discharges also utilize potentially different chemical reaction pathways to produce NOx. As of yet, there are no general evaluation criteria to determine the qualities of an appropriate discharge configuration for energy-efficient NOx production. In this study, we report on four types of discharges; dielectric barrier, glow, spark and extending arc discharge to examine NOx production efficiency under different conditions. Based on our results and previously published results from the literature, we propose a dimensionless parameter to guide the design of appropriate plasma sources for reduced energy cost NOx production.

The MicroBooNE detector utilizes a liquid argon time projection chamber (LArTPC) with an 85 t active mass to study neutrino interactions along the Booster Neutrino Beam (BNB) at Fermilab. With a deployment location near ground level, the detector records many cosmic muon tracks in each beam-related detector trigger that can be misidentified as signals of interest. To reduce these cosmogenic backgrounds, we have designed and constructed a TPC-external Cosmic Ray Tagger (CRT) . This sub-system was developed by the Laboratory for High Energy Physics (LHEP), Albert Einstein center for fundamental physics, University of Bern. The system utilizes plastic scintillation modules to provide precise time and position information for TPC-traversing particles. Successful matching of TPC tracks and CRT data will allow us to reduce cosmogenic background and better characterize the light collection system and LArTPC data using cosmic muons. In this paper we describe the design and installation of the MicroBooNE CRT system and provide an overview of a series of tests done to verify the proper operation of the system and its components during installation, commissioning, and physics data-taking.

Despite efforts to develop increasingly targeted and personalized cancer therapeutics, dosing of drugs in cancer chemotherapy is limited by systemic toxic side effects. We have designed, built, and deployed porous absorbers for capturing chemotherapy drugs from the bloodstream after these drugs have had their effect on a tumor, but before they are released into the body where they can cause hazardous side effects. The support structure of the absorbers was built using 3D printing technology. This structure was coated with a nanostructured block copolymer with outer blocks that anchor the polymer chains to the 3D printed support structure and a middle block that has an affinity for the drug. The middle block is polystyrenesulfonate which binds to doxorubicin, a widely used and effective chemotherapy drug with significant toxic side effects. The absorbers are designed for deployment during chemotherapy using minimally invasive image-guided endovascular surgical procedures. We show that the introduction of the absorbers into the blood of swine models enables the capture of 64 ± 6% of the administered drug (doxorubicin) without any immediate adverse effects. Problems related to blood clots, vein wall dissection, and other biocompatibility issues were not observed. This development represents a significant step forward in minimizing toxic side effects of chemotherapy.

We measure a large set of observables in inclusive charged current muon neutrino scattering on argon with the MicroBooNE liquid argon time projection chamber operating at Fermilab. We evaluate three neutrino interaction models based on the widely used GENIE event generator using these observables. The measurement uses a data set consisting of neutrino interactions with a final state muon candidate fully contained within the MicroBooNE detector. These data were collected in 2016 with the Fermilab Booster Neutrino Beam, which has an average neutrino energy of 800MeV, using an exposure corresponding to 5.0 × 10 19 protons-on-target. The analysis employs fully automatic event selection and charged particle track reconstruction and uses a data-driven technique to separate neutrino interactions from cosmic ray background events. We find that GENIE models consistently describe the shapes of a large number of kinematic distributions for fixed observed multiplicity.

A momentum resolved resonant inelastic X-ray scattering (qRIXS) experimental station with continuously rotatable spectrometers and parallel detection is designed to operate at different beamlines at synchrotron and free electron laser (FEL) facilities. This endstation, currently located at the Advanced Light Source (ALS), has five emission ports on the experimental chamber for mounting the high-throughput modular soft X-ray spectrometers (MXS) [24]. Coupled to the rotation from the supporting hexapod, the scattered X-rays from 27.5° (forward scattering) to 152.5° (backward scattering) relative to the incident photon beam can be recorded, enabling the momentum-resolved RIXS spectroscopy. The components of this endstation are described in details, and the preliminary RIXS measurements on highly oriented pyrolytic graphite (HOPG) reveal the low energy vibronic excitations from the strong electron-phonon coupling at C K edge around σ* band. The grating upgrade option to enhance the performance at low photon energies is presented and the potential of this spectroscopy is discussed in summary.

Shan Qiao,1,2,* Quan-Ye Sun,3,* Shan-Chao Zhang,1 Ran-Ran Zhang,4 Yu-Jiao Wu,4 Zhi-Hao Wang,4 Xue-Wu Liu4,5 1Department of Neurology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 2Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Research Center of Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Department of Neurology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 5Institute of Epilepsy, Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Wu Liu, Email snlxw1966@163.comPurpose: Syncytin-1 may play a role in several neuropsychiatric disorders, but its function in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is unknown. The purpose of this study was to examine the possible mechanism of action of syncytin-1 in patients with anti-NMDAR encephalitis.Patients and Methods: Twenty patients with anti-NMDAR encephalitis and eight controls were recruited. The protein levels of syncytin-1 in serum were determined using an enzyme-linked immunosorbent assay, and the transcript levels of syncytin-1 were determined using real-time quantitative PCR. Flow cytometry was used for peripheral blood lymphocyte subset detection. Further, the relationship between syncytin-1 levels and clinical features of anti-NMDAR encephalitis and peripheral blood lymphocyte subsets was analyzed.Results: Compared with those in controls, higher syncytin-1 levels and percentage of B cells (CD3-CD19+) were observed in patients with anti-NMDAR encephalitis. Among anti-NMDAR encephalitis patients, the level of syncytin-1 positively correlated with the proportion of B cells and modified Rankin scale score at onset and after immunotherapy and negatively correlated with the proportion of CD3+ T cells.Conclusion: An increased expression of Syncytin-1 is associated with the pathogenesis of anti-NMDAR encephalitis, providing evidence for elucidating the pathogenesis of the disease and suggesting novel therapeutic targets. Further, this study clarifies the role of syncytin-1 in neuroimmune disorders.Keywords: autoimmune encephalitis, neuroinflammation, syncytin-1, B cells, pathogenesis

Qu-Zhen Tashi,1 Sang-Bu Tsering,1 Na-Ni Zhou,2 Yi Zhang,2 Yu-Juan Huang,3 Jia Jia,2 Ting-Jun Li3 1Department of Pediatrics, Shigatse Peopel’s Hospital, Shigatse, Tibet, 857000, People’s Republic of China; 2Fujungenetics Technologies Inc. Shanghai, Shanghai, 200333, People’s Republic of China; 3Department of Emergency, Children’s Hospital of Shanghai, Shanghai, 200062, People’s Republic of ChinaCorrespondence: Ting-Jun Li, Department of Emergency, Children’s Hospital of Shanghai, No. 355 of Huding Road, Putuo District, Shanghai, 200062, People’s Republic of China, Tel +86 18930590701, Email lijuntingta@126.com Jia Jia, Fulgent Technologies Inc, No. 70 of Tongchuan Road, Putuo District, Shanghai, 200333, People’s Republic of China, Tel +86 18658176000, Email jiajiajjyat@126.comObjective: High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common inducement is respiratory tract infection. The clinical differential diagnosis is difficult because the symptoms of HAHD are similar to those of congenital heart disease; Due to the limitation of medical conditions, many patients are in the state of losing follow-up or not seeking medical treatment, resulting in poor prognosis of HAHD and becoming a high-altitude disease with high mortality. Clarifying the molecular mechanism of HAHD, developing early molecular screening technology and accurate treatment methods of HAHD are the key to improve the ability of prevention and treatment of HAHD.Methods: First, the literature in the PubMed and CNKI databases were screened based on keywords and abstracts. Then, the literature for the study was identified based on the fitness between the content of the literature, the research objectives, and the timeliness of the literature. Finally, a systematic molecular mechanism of HAHD was established by investigating the literature and sorting out the genetic adaptations of Tibetan populations compared with low-altitude populations that migrated to the plateau.Results: With the investigation of the 48 papers screened, it was found that genes capable of enhancing the hypoxic ventilatory response and resistance to pulmonary hypertension were all correlated with the hypoxia-inducible factor (HIF) pathway, consisting mainly of three pathways, HIF-1α, HIF-2α, and NO.Conclusion: The low prevalence of HAHD in Tibetan aboriginal children was mainly due to the genetic adaptation of the Tibetan population to the high altitude environment, which coordinated the cellular response to hypoxia by regulating the downstream hypoxia control genes in the HIF pathway.Keywords: altitude sickness, pediatric, high altitude heart disease, HAHD, molecular mechanism

Yu-Jun Shi,1,* Li-Feng Wang,1,* Jun Ma,1 Yi Chen,1 Wei-Jun Wang,2 Cui-Ying Xie1 1Department of Emergency, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cui-Ying Xie, Department of Emergency, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel +86 13817204797, Email xiecuiying25@126.comObjective: The clinical manifestations and treatment of three patients with hemodynamically unstable lupus myocarditis (LM) were analyzed.Methods: The clinical data of three patients with LM with hemodynamic instability, who were admitted to the emergency ICU of the south hospital of the Renji Hospital, School of Medicine, Shanghai Jiao Tong University of Medicine from January 2018 to December 2021, were collected and analyzed, and relevant literatures were reviewed.Results: Two of the three patients had the first onset of systemic lupus erythematosus. The other patient had mixed connective tissue disease in the past, and lupus was the main manifestation of this disease. At the onset of the disease, all patients had chest tightness and shortness of breath; two patients had a fever, and the markers of myocardial injury increased. Cardiac color Doppler ultrasound indicated that left ventricular ejection fraction decreased significantly. Cardiac insufficiency with cardiogenic shock rapidly appeared as the main manifestation. Two patients immediately started veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and ECMO was also started in one patient after a pacemaker placement was ineffective. For all three patients, high-dose hormones were given to control the primary disease, and then the ECMO machines were removed successfully.Conclusion: VA-ECMO treatment should be implemented in patients with hemodynamically unstable LM as soon as possible to maintain the patient’s hemodynamics and help them overcome the crisis of cardiac dysfunction, allowing more time for primary disease treatment.Keywords: VA-ECMO, lupus myocarditis, hemodynamic instability

Xiao-Lan Li,1 Chun-Yan Luan,1 Ying-Jun Fan,2 Xiao-Ying Lin,1 Dong Jiang,1 Mei-Xian Su,3 Gang Wang,4 Xu Yang5 1Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 2Department of Rheumatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 3Department of Emergency Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 4Department of Intensive Care Unit, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of China; 5Laboratory Bacteria Room, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, People’s Republic of ChinaCorrespondence: Xiao-Lan Li, Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, No. 374 of Dian-Mian Avenue, Wu-Hua District, Kunming, 650101, People’s Republic of China, Tel +86 871 63402212, Fax +86 871 65334416, Email lixiaolan880923@163.comBackground: Purpura fulminans (PF), a rare, life-threatening disorder, is a hematological emergency in which there is skin necrosis, disseminated intravascular coagulation (DIC), and protein C deficiency. In PF, the skin necrosis and DIC are secondary to protein C deficiency. This may progress rapidly to multiorgan failure caused by the thrombotic occlusion of small- and medium-sized blood vessels.Case Report: This article presents the case of a 22-year-old male with fever as well as necrotic and purpuric skin lesions. The ultrasound and computed tomography scans revealed infections in the skin wounds as well as venous microthrombosis and thrombosis in multiple intracranial and pulmonary vessels. The laboratory tests showed signs of sepsis, thrombocytopenia, an abnormal decrease in protein C and antithrombin III, DIC, multiple organ and system failures, gastric varices, and gastrointestinal hemorrhage. The blood, sputum, and secretions under the skin lesions were cultured and were positive for Klebsiella pneumoniae. The results of the high-throughput genetic testing of the pathogenic microorganism DNA were consistent. In addition, human herpesvirus type 5 was detected. The histopathological examination of the skin lesions revealed pathological features consistent with PF. After successful treatment by the departments of Dermatology, Emergency Critical Care Medicine, and the Intensive Care Unit, the patient was discharged after 67 days of hospitalization.Conclusion: Adults with acquired protein C and/or S deficiency states, including certain bacterial and viral infections, who drink alcohol and take varieties of non-steroidal anti-inflammatory analgesics at the same time, may develop acute infectious PF. Clinicians should be aware of this for early diagnosis and treatment.Keywords: acute infectious purpura fulminans, Klebsiella pneumoniae, human herpesvirus type 5, disseminated intravascular coagulation, multiple organ and system failures

Seohyun Lee,1 Young-Ji Lee,2 SeYeon Kim,2 Wonil Choi,2 Yoojin Jeong,2 Nina Jinjoo Rhim,3 Ilwon Seo,4 Sun-Young Kim2,5 1Department of Global Public Administration, Yonsei University Mirae Campus, Wonju, Republic of Korea; 2Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea; 3Good Neighbors International, Seoul, Republic of Korea; 4Good Neighbors Ghana, Accra, Ghana; 5Institute of Health and Environment, Seoul National University, Seoul, Republic of KoreaCorrespondence: Sun-Young Kim, Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea, Tel +82-2-880-2768, Fax +82-2-762-2888, Email sykim22@snu.ac.krPurpose: An electronic health record (EHR) system known as the e-Tracker was introduced in community health facilities in Ghana and numerous advantages were expected for clinical staff, as evidenced by previous literature. However, little is known about public health officials’ views, specifically in low-resource settings. This study aimed to investigate the perceptions of district health officers on data quality, use, and management following the adoption of tablet-based electronic health records in Ghana.Methods: A pre- and post-survey was conducted in two regions of Ghana that adopted the e-Tracker for the entire districts during the early stages of the national rollout. Sociodemographic information, internet connection environment, and perceptions on data quality, use, and management were measured. McNemar’s test and Wilcoxon Signed-Rank test were performed to identify changes in perceptions. Chi-square test and Mann–Whitney U-test were used to find any statistical differences in demographic characteristics between the two regions.Results: Twenty-four out of 25 districts in Volta and 24 out of 26 districts in Eastern regions participated in both pre- and post-surveys, with a total of 73 participants. In terms of efficiency in data management, the district health officers reported reduced time commitment in data validation and aggregation. Within less than a year, however, no statistically significant improvement was found in data quality and the use of electronic data for relevant tasks.Conclusion: A new EHR system in low-resource settings can rapidly improve efficiency in data management from the public health officials’ perspectives. Further impact evaluation is warranted to assess the long-term effect of the EHR system.Keywords: mHealth, maternal and child health, Sub-Saharan Africa, LMIC

Ming-Chuan Lee,1 Yu-Tsang Wang,2 Yu-Ju Li,1 Ching-Yi Tsai,1 Su-Te Chen,1 Wun-Jyun Jhuang,1,3 Meng-Chi Chang,1 Mei-Yu Chien,1 Hsiang-Chun Lee1,3– 5 1Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 2Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 3Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 4Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 5Institute/Center of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 804, TaiwanCorrespondence: Hsiang-Chun Lee, Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan, Tel +886-7-3121101#2293, Fax +886-7-3234845, Email hclee@kmu.edu.twPurpose: Manifestations of metabolic syndrome (MetS) carry risks for atrial fibrillation (AF). The study determined whether any electrocardiographic parameter can reflect increased AF risk in individuals with MetS.Patients and Methods: From our University Hospital database, we examined the presence of AF and its correlation with MetS manifestations, renal function, lipid profiles, and electrocardiographic parameters (P wave duration, PR interval, QRS width, and QTc intervals). Between January 2008 and December 2015, data from 4479 adults (women 41.6% vs men 58.4%) were identified.Results: The overall prevalence of AF was 12.4%, without sex differences (women, 12.8% vs men, 12.1%). Patients with AF were older (age 73.9 ± 11.8 vs non-AF 67 ± 13.5 years), with lower lipid levels (TG, total cholesterol, and LDL-cholesterol, all p < 0.0001), and at lower eGFR level (64.1 ± 30.9 vs non-AF 68.8 ± 41.4 mL/min/1.73m2, p < 0.0001). Besides, sex differences were present in all electrocardiographic parameters (all p < 0.05). Hypertension had the highest odds ratio (1.33; p = 0.026) for AF. Comparing AF to non-AF, the QTc of quartiles was significantly different (p < 0.0089). The shortest and longest QTc quartiles had an increased incidence of AF.Conclusion: AF risk in patients with MetS phenotypes can be reflected by QTc quartiles.Keywords: atrial fibrillation, electrocardiography, metabolic syndrome, lipid, QTc interval

Yi-Jun Du, Ni-Na Liu, Xing Zhong, Tian-Rong Pan Department of Endocrinology, The Second Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Tian-Rong Pan, Department of Endocrinology, The Second Hospital of Anhui Medical University, No. 678 of Furong Road, Jingkai District, Hefei, 230601, People’s Republic of China, Tel +86 15305609568, Email pantianrongptr@126.comObjective: To explore the risk factors for nonalcoholic fatty liver disease (NAFLD) in postmenopausal women with type 2 diabetes mellitus (T2DM) and the correlation with bone mineral density (BMD) in different areas of the body.Methods: A total of 434 postmenopausal women with T2DM were enrolled and categorized as 198 patients in the NAFLD group and 236 patients in the non-NAFLD group based on color Doppler ultrasound of the liver. The BMD of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry.Results: In postmenopausal women with T2DM, the prevalence of NAFLD was 45.6%. The body mass index (BMI), systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), triacylglycerol (TG), uric acid (UA), and homeostatic model assessment for insulin resistance (HOMA-IR) C-peptide (CP) were significantly higher in the NAFLD group than in the non-NFALD group, and the duration of diabetes, and high-density lipoprotein cholesterol (HDL-C) were lower than in the non-NAFLD group (P < 0.05). Logistic regression analysis revealed that BMI (odds ratio [OR] = 1.303, 95% confidence interval [CI]: 1.152– 1.346), HbA1c (OR = 1.263, 95% CI: 1.095– 1.392), TG (OR = 1.263, 95% CI: 1.031– 1.601), and SUA (OR = 1.005, 95% CI: 1.001– 1.007) were correlated with NAFLD (P < 0.05). The BMD of the total hip and femoral neck in the NAFLD group was higher than in the non-NAFLD group (P < 0.05).Conclusion: Complicated NAFLD in postmenopausal women with T2DM is associated with weight gain, poor blood glucose control, abnormal lipid metabolism, and elevated UA levels. In addition, the NAFLD group had higher femoral neck and total hip BMD than the non-NAFLD group, suggesting NAFLD in postmenopausal women with T2DM may reduce the risk of osteoporosis.Keywords: postmenopausal period, type 2 diabetes mellitus, nonalcoholic fatty liver disease, bone mineral density

Da-Hye Son,1,2,&ast; Seung-Ah Song,1,&ast; Yong-Jae Lee1 1Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea; 2Department of Integrative Medicine, Yonsei University Graduate School, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Yong-Jae Lee, Department of Family Medicine, Yonsei University College of Medicine Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul, 06273, Korea, Tel +82 2 2019 2630; +82 10 7292 9169, Fax +82 3462 8209, Email ukyjhome@yuhs.acBackground: Chronic inflammation plays a key role in the pathophysiology of frailty and loss of physical performance, which are closely associated with sarcopenia. In women, the decline in muscle mass and strength is accelerated after menopause. Thus, we examined the association between high sensitivity C-reactive protein (hs-CRP) and relative handgrip strength (HGS) in postmenopausal women.Methods: This cross-sectional study included 2171 postmenopausal women aged ≥ 45 years who participated in the Korean National Health and Nutrition Survey (KNHNES) between 2015 and 2018. Relative HGS was categorized into quartiles as follows: Q1, < 0.810 (kg/BMI); Q2, 0.810– 0.968 (kg/BMI); Q3, 0.969– 1.119 (kg/BMI); Q4, > 1.119 (kg/BMI). The odds ratios (ORs) and 95% confidence intervals (95% CIs) for high hs-CRP (> 1.0 mg/L, 75 percentile of the current samples) were calculated across relative HGS quartiles using multiple logistic regression analysis.Results: The prevalence of high hs-CRP decreased with relative HGS quartiles. Compared to the highest quartile, the OR (95% CI) of the lowest relative HGS quartile for high hs-CRP was 3.266 (2.227– 4.789) after adjusting for age, hypertension, diabetes mellitus, dyslipidemia, education, household income, physical activity, strength exercise, smoking, and alcohol ingestion.Conclusion: Serum hs-CRP level was inversely and independently associated with relative HGS. Our findings indicate that low-grade inflammation is inversely associated with muscle strength in postmenopausal women.Keywords: C-reactive protein, hand strength, menopause, inflammation, sarcopenia

Zhi-Ying Lv,1,&ast; Yang-Lin Shi,1,&ast; Gabriel Shimizu Bassi,1 Yan-Jiao Chen,1 Lei-Miao Yin,1 Yu Wang,1 Luis Ulloa,2 Yong-Qing Yang,1 Yu-Dong Xu1 1Shanghai Research Institute of Acupuncture and Meridian, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Duke University, Durham, NC, USA&ast;These authors contributed equally to this workCorrespondence: Yu-Dong Xu; Yong-Qing Yang, Email xuyudong@shutcm.edu.cn; yyq@shutcm.edu.cnPurpose: Sepsis is the main cause of death in intensive care unit. Maladaptive cytokine storm and T-cell lymphopenia are critical prognosis predictors of sepsis. Electroacupuncture (EA) is expected to be an effective intervention to prevent sepsis. This study aims to determine the potential of EA at ST36 (Zusanli) to prevent experimental septic mice.Methods: Mice were randomly assigned into PBS, LPS, or EA+LPS group. EA (0.1 mA, continuous wave, 10 Hz) was performed stimulating the ST36 for 30 min, once a day for 3 days. After the third day, all mice were challenged with PBS or LPS (4 mg/kg) simultaneously. Mice were evaluated for survival, ear temperature, and other clinical symptoms. Lung and small intestine tissue injuries were analyzed by hematoxylin and eosin staining. Bio-Plex cytokine assay was used to analyze the concentration of cytokines. T lymphocytes were analyzed by flow cytometry and Western blot assays. The role of T cells in preventing sepsis by EA was analyzed by using nude mice lacking T lymphocytes.Results: EA at ST36 improved survival, symptom scores, and ear temperature of endotoxemic mice. EA also improved dramatically pulmonary and intestinal injury by over 50% as compared to untreated mice. EA blunted the inflammatory cytokine storm by inducing a lasting inhibition of the production of major inflammatory factors (TNF-α, IL-1β, IL-5, IL-6, IL-10, IL-17A, eotaxin, IFN-γ, MIP-1β and KC). Flow cytometry and Western blot analyses showed EA significantly reduced T-lymphocyte apoptosis and pyroptosis. Furthermore, T lymphocytes were critical for the effects of EA at ST36 stimulation blunted serum TNF-α levels in wild-type but not in nude mice.Conclusion: EA halted systemic inflammation and improved survival in endotoxemic mice. These effects are associated with the protective effect of EA on T lymphocytes, and T cells are required in the anti-inflammatory effects of EA in sepsis.Keywords: electroacupuncture, sepsis, inflammation, cytokine storm, lymphopenia

Han-Ni Chuang,1,&ast; Chien-Hung Shih,1,&ast; Hung-Wen Tsai,2 Rong-San Jiang,1 Tzu-Hung Hsiao,2– 4 Po-Yu Liu,5 Yee-Jee Jan,6 Jiunn-Min Wang6 1Department of Medical Research, Taichung Veterans General Hospital, Taichung, 407204, Taiwan; 2Medical Administration Department, Taichung Veterans General Hospital, Taichung, 47204, Taiwan; 3Department of Public Health, Fu Jen Catholic University, New Taipei City, 24205, Taiwan; 4Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, 40227, Taiwan; 5Division of Infection, Taichung Veterans General Hospital, Taichung, 47204, Taiwan; 6Department of Pathology & Laboratory Medicine, Taichung Veterans General Hospital, Taichung, 407, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yee-Jee Jan; Jiunn-Min Wang, Department of Pathology & Laboratory Medicine, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, 40705, Taiwan, Tel +886-4-23592525, Fax +886-4-2359-5046, Email yejan@vghtc.gov.tw; jmwang@vghtc.gov.twAbstract: The COVID-19 pandemic has reaffirmed the critical significance of effective diagnostics in outbreak response. In Taiwan, the COVID-19 wave in May 2021 led to a rapidly growing demand for SARS-CoV-2 diagnostic tests. To meet the challenge, an extensive system-wide emergency preparedness plan, hospital emergency incident command system (HEICS), was developed to deal with emergencies involving healthcare systems. During the wave of the COVID-19 outbreak, a 19.4-fold increase in SARS-CoV-2 PCR (polymerase chain reaction) diagnostic tests occurred in the hospital. The incident commander of TCVGH reviewed COVID-19 related events daily and purchased a high-throughput PCR machine for SARS-CoV-2 PCR diagnostic tests. In addition, the Department of Operations was responsible for staff scheduling and educational training. The turn-around times of SARS-CoV-2 diagnostic tests were shortened from 21.2 hours to 5.8 hours in the second week of the COVID-19 wave. Implementation of HEICS integrated resources could be helpful for expanding surge capacity during future outbreaks.Keywords: COVID-19, hospital emergency incident command system, pandemics

Jin Namgoong,1 Yun-Ha Lee,1 Ah Ra Ju,1 Jiwon Chai,1 DongJoo Choi,1 Hyo Jung Choi,1 Ji-Yeon Seo,1 Kyoung Sun Park,2 Yoon Jae Lee,1,3 Jinho Lee,2 In-Hyuk Ha1,3 1Bucheon Jaseng Hospital of Korean Medicine, 414 KR in Sangdong, Bucheon-si, Gyeonggi-do, Republic of Korea; 2Jaseng Hospital of Korean Medicine, Seoul, Republic of Korea; 3Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of KoreaCorrespondence: In-Hyuk Ha, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 3F JS Tower, 538 Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea, Tel +82 2 2222 2740, Fax +82 2 3218 2244, Email hanihata@gmail.comPurpose: Integrative Korean medicine treatment (KMT) is a conservative treatment approach for the ossification of the posterior longitudinal ligament (OPLL) in Korea; nonetheless, relevant studies focusing on KMT for OPLL are lacking. A multicenter retrospective analysis of patient medical records and a questionnaire survey were conducted to investigate the effectiveness of integrative KMT in patients with OPLL treated for neck pain.Patients and Methods: A total of 78 inpatients radiologically diagnosed with OPLL and treated for neck pain at four Korean medicine hospitals from April 1, 2016, to December 31, 2019, were enrolled. The primary index was an improvement in the numeric rating scale (NRS) score for neck pain, whereas the secondary outcome indices were improvements in the NRS score for arm pain, neck disability index (NDI) score, and EuroQol 5-dimension 5-level (EQ-5D-5L) score.Results: At discharge, the NRS score for neck pain, NRS score for arm pain, and NDI score decreased by 2.47 (95% confidence interval [CI], − 2.81 to − 2.14), 1.32 (95% CI, − 1.73 to − 0.91), and 16.02 (95% CI, − 18.89 to − 13.15), respectively, as compared with the scores at admission (p < 0.001). The EQ-5D-5L score increased by 0.12 (95% CI, 0.09 to 0.16) as compared with the score at admission (p < 0.001). This trend was also evident during follow-up. With respect to Patient Global Impression of Change evaluation, 33 (61.1%) patients claimed to have very much improved, whereas 17 (31.5%) patients reported to have much improved.Conclusion: Inpatients with OPLL who received integrative KMT showed improvements in neck pain, arm pain, the NDI, and quality of life, which were retained throughout the follow-up period.Keywords: integrative medicine, Korean medicine, OPLL, neck pain

Qian Zhang,1,2,&ast; Yuan-Jie Liu,1,2,&ast; Jie-Pin Li,1– 3 Shu-Hong Zeng,1,2 Hui Shen,3 Mei Han,1 Shun Guo,1,2 Shen-Lin Liu,1,2 Xi Zou1,2,4 1Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 2No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 3Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 4Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Zou; Shun Guo, Email zxvery@126.com; retinoid@163.comBackground: As one of the most immunogenic malignancies, skin cutaneous melanoma (SKCM) is mainly characterized by a high prevalence in immune-compromised patients and a brisk lymphocyte infiltration in the tumor microenvironment (TME). However, to date, studies on deubiquitination in SKCM are still very limited.Methods: Public data with regard to this study in SKCM patients were acquired from The Cancer Genome Atlas (TCGA) and the Gene-Expression Omnibus (GEO) databases. We stratified TCGA-SKCM cases using consensus clustering and identified independent prognostic factors in deubiquitinating enzymes encoding genes (DECGs) by LASSO-Cox analysis. USP35 transcriptome level was examined using public data and validated by Immunohistochemical (IHC) staining at the protein level. Enrichment analysis was used to explore the potential functions of USP35, and the TISCH database, providing further evidence at the single-cell level. The CIBERSORT algorithm was used to assess the relationship between USP35 and the immune microenvironment, and IHC was used to further evaluate the relationship between USP35 and immunotherapy response. Finally, we used the cBioPortal and the Methsurv database to analyze the significance of genomic alterations of USP35 in melanoma.Results: Our results showed that DECGs can be effectively used to stratify SKCM patients, suggesting their potential significance in the development of SKCM. Furthermore, USP35 overexpression was significantly associated with an unfavorable prognosis. We further revealed that USP35 may be involved in the activation of TORC1 signaling. Most importantly, USP35 was found to be significantly associated with an immunosuppressive TME, both in terms of negative correlation with the abundance of infiltrating CD8+ T cells and in terms of the fact that patients with high USP35 expression may benefit less from immunotherapy than those with low USP35 expression.Conclusion: Deubiquitinating enzymes are of great importance in the diagnosis and treatment of SKCM, and USP35 is an extremely promising target for immunotherapy.Keywords: skin cutaneous melanoma, deubiquitinating enzymes, USP35, immunotherapy

Jing Yang,1 Min Zhao,1 Xiao-Rui Zhang,1 Xiao-Rui Wang,1 Zhi-Hao Wang,1 Xiao-Yue Feng,2 Ya-Juan Lei,1 Jian-Wen Zhang1,3 1Department of Anesthesiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China; 2Department of Pain Management, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China; 3Department of Day Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of ChinaCorrespondence: Jian-Wen Zhang, Department of Anesthesiology and Department of Day Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical University, Tongji Shanxi Hospital, No. 99 of Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86 13994299284, Email zhangjianwen88_dr@163.comObjective: This study aimed to investigate the effect of ropivacaine with dexmedetomidine or dexamethasone in a thoracic paravertebral nerve block (TPVB) combined with an erector spinae plane block (ESPB) for thoracoscopic lobectomy analgesia.Methods: A total of 97 patients undergoing thoracoscopic lobectomy under general anesthesia were enrolled in this study and randomly divided into three groups, ie, a ropivacaine group (Group R), a ropivacaine + dexmedetomidine group (Group R1), and a ropivacaine + dexamethasone group (Group R2). Ultrasound-guided TPVB combined with an erector spinae plane block was given after anesthesia induction. The following were applied to each group: Group R received 30 mL of 0.5% ropivacaine + 5 mL of a normal saline mixture; Group R1 received 30 mL of 0.5% ropivacaine + 5 mL of a 1 μg/kg dexmedetomidine mixture; Group R2 received 30 mL of 0.5% ropivacaine + 5 mL of an 8 mg dexamethasone mixture. The primary observation index was the time to the first postoperative remedial analgesia. The secondary observation indexes were the intraoperative consumption of propofol and sufentanil, time to waking from anesthesia, time to extubation, postoperative numerical rating scaltpe (NRS) score, postoperative sufentanil consumption, remedial analgesic dosage, and adverse reactions.Results: When compared with Group R, the time to first postoperative remedial analgesia was longer, the intraoperative and postoperative sufentanil consumption and flurbiprofen axetil remedial analgesic dose were lower, and the time to waking from anesthesia and time to extubation were shorter in groups R1 and R2 (P < 0.05). The NRS scores at 1, 6, 12, and 24 h postoperatively in groups R1 and R2 were lower than in Group R at the same time points (P < 0.05).Conclusion: Ropivacaine with dexmedetomidine or dexamethasone in TPVB combined with ESPB could prolong the time to first postoperative remedial analgesia, reduce perioperative sufentanil and postoperative remedial analgesic drug consumption, and decrease the postoperative NRS score in patients undergoing thoracoscopic lobectomy.Keywords: ropivacaine, local anesthetic adjuvant, dexmedetomidine, dexamethasone, thoracic paravertebral nerve block, erector spinae plane block, thoracoscopic surgery, perioperative analgesia

THz Time-Resolved Photoconductivity is used to probe carrier dynamics in the dilute III-V nitride GaP0.49As0.47N0.036. In these measurements a femtosecond optical pump-pulse excites electron-hole pairs, and a delayed THz pulse measures the change in conductivity. We find the photoconductivity is dominated by localized carriers. The decay of photoconductivity after excitation is consistent with bimolecular electron-hole recombination with recombination constant r = 3.2 0.8 10-8 cm3 s-1. We discuss the implications for applications in solar energy.

The primary goals of the STRong lensing Insights into the Dark Energy Survey (STRIDES) collaboration are to measure the dark energy equation of state parameter and the free streaming length of dark matter. To this aim, STRIDES is discovering strongly lensed quasars in the imaging data of the Dark Energy Survey and following them up to measure time delays, high resolution imaging, and spectroscopy sufficient to construct accurate lens models. In this paper, we first present forecasts for STRIDES. Then, we describe the STRIDES classification scheme, and give an overview of the Fall 2016 follow-up campaign. We continue by detailing the results of two selection methods, the outlier selection technique and a morphological algorithm, and presenting lens models of a system that could possibly be a lensed quasar in an unusual configuration. We conclude with the summary statistics of the Fall 2016 campaign. Including searches presented in companion papers (Anguita et al.; Ostrovski et al.), STRIDES followed up 117 targets identifying 7 new strongly lensed systems, and 7 nearly identical quasars, which could be confirmed as lenses by the detection of the lens galaxy. 76 candidates were rejected and 27 remain otherwise inconclusive, for a success rate in the range of 6-35 per cent. This rate is comparable to that of previous searches like SDSS Quasar Lens Search even though the parent data set of STRIDES is purely photometric and our selection of candidates cannot rely on spectroscopic information.

BackgroundThe Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry.Methods and resultsA total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Epithelial cells aggregate into spheroids when deprived of matrix, and the proclivity for spheroid formation and survival is a hallmark of normal and tumorigenic mammary stem cells. We show here that Nuclear Respiratory Factor 1 (NRF1) is a spheroid promoter by in silico identification of this transcription factor as highly connected to top shRNA-hits deduced from re-iterative selections for shRNAs enriched in MCF10A spheroids. NRF1-promoted spheroid survival is linked to its stimulation of mitochondrial OXPHOS, cell migration, invasion, and mesenchymal transition. Conversely, NRF1 knockdown in breast cancer MDA-MB-231 cells reduced spheroids, migration, invasion, and mesenchymal marker expression. NRF1 knockdown also reduced tumor burden in mammary fat pads and lungs of orthotopic- or tail vein-transplanted mice. With the Luminal A subtype of breast cancer, higher NRF1 expression is associated with lower survival. These results show that NRF1, an activator of mitochondrial metabolism, supports mammary spheroid survival and tumor development.

We report on broadly based systematic investigations of the modeling components for open heavy-flavor diffusion and energy loss in strongly interacting matter in their application to heavy-flavor observables in high-energy heavy–ion collisions, conducted within an EMMI Rapid Reaction Task Force framework. Initial spectra including cold-nuclear-matter effects, a wide variety of space-time evolution models, heavy-flavor transport coefficients, and hadronization mechanisms are scrutinized in an effort to quantify pertinent uncertainties in the calculations of nuclear modification factors and elliptic flow of open heavy-flavor particles in nuclear collisions. We develop procedures for error assessments and criteria for common model components to improve quantitative estimates for the (low-momentum) heavy-flavor diffusion coefficient as a long-wavelength characteristic of QCD matter as a function of temperature, and for energy loss coefficients of high-momentum heavy-flavor particles.

Transcriptome analysis reveals a strong positive correlation between human Schlafen family member 11 (SLFN11) expression and the sensitivity of tumor cells to DNA-damaging agents (DDAs). Here, we show that SLFN11 preferentially inhibits translation of the serine/threonine kinases ATR and ATM upon DDA treatment based on distinct codon usage without disrupting early DNA damage response signaling. Type II transfer RNAs (tRNAs), which include all serine and leucine tRNAs, are cleaved in a SLFN11-dependent manner in response to DDAs. Messenger RNAs encoded by genes with high TTA (Leu) codon usage, such as ATR, display utmost susceptibility to translational suppression by SLFN11. Specific attenuation of tRNA-Leu-TAA sufficed to ablate ATR protein expression and restore the DDA sensitivity of SLFN11-deficient cells. Our study uncovered a novel mechanism of codon-specific translational inhibition via SLFN11-dependent tRNA cleavage in the DNA damage response and supports the notion that SLFN11-deficient tumor cells can be resensitized to DDAs by targeting ATR or tRNA-Leu-TAA.

Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

In 2018, Refacto AF R , a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AF R ; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 > 0.6 BU, 1 high titre) after they switched to Refacto AF R ; all were children 100 exposure days, none related to surgery or intensive treatment; all received Kovaltry R before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AF R is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding Kovaltry R might have contributed to inhibitor development.

Yuan-jie Liu,1,2,&ast; Mei Han,1,&ast; Jie-pin Li,1– 3 Shu-hong Zeng,1,2 Qian-wen Ye,1,2 Zhong-hua Yin,1,2 Shen-lin Liu,1,2 Xi Zou1,2,4 1Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People’s Republic of China; 2No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, People’s Republic of China; 4Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Zou; Shen-lin Liu, Email zxvery@126.com; lsljsszyy@126.comBackground: Gap junctions, as one of the major ways to maintain social connections between cells, are now considered as one of the potential regulators of tumor metastasis. However, to date, studies on the relationship between gap junctions and colorectal cancer (CRC) are limited.Methods: We synthesized connexins-coding gene expression data from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as MEXPRESS database, Gene Set Cancer Analysis (GSCA) database, Human Protein Atlas (HPA) database, Tumor Immune Single Cell Hub (TISCH) database, Search Tool for Retrieval of Gene Interaction Relationships (STRING), and Cytoscape software, etc., to investigate the biological mechanisms that may be involved in connexins. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of GJA4.Results: We found that CRC patients can be divided into two connexin clusters and that patients in cluster C1 had shorter survival than in cluster C2. The infiltration of M1 macrophages and NK cells was lower in cluster C1, while the levels of M2 macrophages and immune checkpoints were higher, indicating an immunosuppressed state in cluster C1. In addition, the epithelial–mesenchymal transition (EMT) phenotype was significantly activated in cluster C1. We observed that GJA4 was up-regulated in colorectal cancer tissues, which was related to poor prognosis. It was mainly expressed in fibroblasts, but the expression levels in normal intestinal epithelial cells were low. Finally, we found that GJA4 was associated with M2 macrophages and may be a potential immunosuppressive factor.Conclusion: We found that there is a significant correlation between abnormal connexins expression and patients’ prognosis, and connexins play an important role in stromal-tumor interactions. Connexins, especially GJA4, can help enhance our understanding of tumor microenvironment (TME) and may guide more effective immunotherapeutic strategies.Keywords: colorectal cancer, gap junction protein alpha 4, cancer-associated fibroblasts, M2 macrophage, bioinformatics

James Cheng-Chung Wei,1– 3 Yi-Jung Chang,4 Yu-Hsun Wang,5 Chih-Jung Yeh6 1Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; 2Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 4Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; 5Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; 6Department of Public Health, Chung Shan Medical University, Taichung, TaiwanCorrespondence: Chih-Jung Yeh, Department of Public Health, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, South District, Taichung, 40201, Taiwan, Tel +886 4 24739595 #11794, Fax +886 4 24637389, Email alexyeh@csmu.edu.twBackground: Previous research has pointed to the relationship between psoriasis and the development of gout. However, most previous studies had either small sample sizes or short study durations. Therefore, in this nationwide cohort study, we investigated the effect of psoriasis on the risk of gout development.Methods: The study group included one million patients from Taiwan, whom we followed for 14 years. The participants were divided into two cohorts designated as psoriasis and non-psoriasis. A 1:4 propensity score matching test was used to compare age, sex, and index year between the two cohorts. Cox proportional hazard regression was used to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of gout. Sensitivity analyses were conducted to evaluate the HR for gout after the occurrence of psoriasis.Results: The incidence densities of gout in the psoriasis and non-psoriasis cohorts were 6.96 and 5.09 per 1000 person-years, respectively. After adjusting for age, sex, urbanization, comorbidities, and nonsteroidal anti-inflammatory drug (NSAID) use, the adjusted hazard ratio (aHR) with 95% CI for incidental gout in the psoriasis group was 1.38 (1.2– 1.6). Moreover, the aHR (95% CI) values for gout risk in patients with psoriasis using NSAIDs and those who did not were 1.21 (1.0– 1.47) and 1.65 (1.33– 2.05), respectively.Conclusion: This study demonstrated an association between psoriasis and risk of developing gout. Clinically, patients with psoriasis should be evaluated for incidental gout.Keywords: psoriasis, gout, epidemiology, corticosteroids, NHIRD, cohort

Yao Jie Xie,1 Meijuan Lin,1 Yuen Ting Wong,2 Linjia Yan,3 Dexing Zhang,4 Yang Gao5 1School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region; 2Faculty of Social Science, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region; 3Yibin Health School of Sichuan, Yibin City, Sichuan Province, People’s Republic of China; 4JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Shantin, N.T., Hong Kong Special Administrative Region; 5Department of Sport, Physical Education and Health, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong Special Administrative RegionCorrespondence: Yao Jie Xie, School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Special Administrative Region, Tel +852 3400-3798, Fax +852 2364-9663, Email grace.yj.xie@polyu.edu.hkObjective: This study aimed to examine the prevalence and features of migraine and explore the possible migraine triggers in a sample of university nursing students in Hong Kong.Methods: A cross-sectional study using self-administered questionnaires was conducted in the Hong Kong Polytechnic University in 2016. The questionnaire included ID Migraine™ for migraine screening and items measuring the frequency, duration, severity, associated symptoms, and trigger factors of migraine. Years 2– 5 undergraduate nursing students from the university completed the questionnaires. Binary logistic regression was conducted to examine the migraine-associated factors.Results: A total of 702 nursing students, including 168 males and 534 females, were successfully screened. Their mean age was 20.8 ± 1.4 years. The overall prevalence of migraine reached 11.8%. Over half (67.5%) of the students with migraine experienced attacks at least once per month. Each attack had a median duration of 3 h (interquartile range: 1– 4 h) and the mean pain intensity score of 6.4 ± 1.6. Students with a family history of migraine (adjusted odds ratio [OR]: 1.89; 95% confidence interval [CI]: 1.10, 3.25; p < 0.05) and poor general health status (Adjusted OR: 3.41, 95% CI: 1.05, 11.09; p < 0.05) were more likely to suffer from migraine than those without. The three most common migraine triggers were the lack of sleep (94.0%), change in sleep schedule (83.1%), and noise (81.9%). Female students were more likely to experience fatigue-triggered migraine than male students (85.9% vs 63.2%, p < 0.05).Conclusion: Migraine prevalence was relatively high among undergraduate nursing students in Hong Kong. Sleep problem was the most frequent trigger factor. The students’ awareness of migraine attacks should be increased, and migraine management must be improved by avoiding common trigger factors in this population.Keywords: migraine, prevalence, trigger factor, nursing student, Hong Kong

Quan Lu,1,2,&ast; Mei-feng Yang,3,&ast; Yu-jie Liang,4,&ast; Jing Xu,5 Hao-ming Xu,5 Yu-qiang Nie,5 Li-sheng Wang,1,2 Jun Yao,1,2 De-feng Li1,2 1Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 2Department of Gastroenterology, Shenzhen People’s Hospital (The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 3Department of Hematology, Yantian District People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 4Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China; 5Department of Gastroenterology and Hepatology, Guangzhou First People’s Hospital (School of Medicine of South China University of Technology), Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Yao; De-feng Li, Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University), No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 755 25533018, Email yao.jun@szhospital.com; ldf830712@163.comAbstract: As a main digestive organ and an important immune organ, the intestine plays a vital role in resisting the invasion of potential pathogens into the body. Intestinal immune dysfunction remains important pathogenesis of inflammatory bowel disease (IBD). In this review, we explained the interactions among symbiotic flora, intestinal epithelial cells, and the immune system, clarified the operating mechanism of the intestinal immune system, and highlighted the immunological pathogenesis of IBD, with a focus on the development of immunotherapy for IBD. In addition, intestinal fibrosis is a significant complication in patients with long-term IBD, and we reviewed the immunological pathogenesis involved in the development of intestinal fibrogenesis and provided novel antifibrotic immunotherapies for IBD.Keywords: inflammatory bowel disease, immune system, immunological pathogenesis, immunotherapy

Muhammad Zada,1 Shagufta Zada,1,2 Jawad Khan,3 Imran Saeed,4 Yong Jun Zhang,1 Alejandro Vega-Muñoz,5 Guido Salazar-Sepúlveda6 1Business School Henan University, Kaifeng, 475000, People’s Republic of China; 2Department of Business Administration, Faculty of Management Sciences, Ilma University, Karachi, Pakistan; 3Department of Business Administration, Iqra National University, Peshawar, Pakistan; 4IBMS, The University of Agriculture, Peshawar, Pakistan; 5Public Policy Observatory, Universidad Autónoma de Chile, Santiago, 7500912, Chile; 6Departamento de Ingeniería Industrial, Facultad de Ingeniería, Universidad Católica de la Santísima Concepción, Concepción, 4090541, ChileCorrespondence: Yong Jun Zhang, Business School Henan University, Kaifeng, Henan, 475000, People’s Republic of China, Email 10090055@vip.henu.edu.cnPurpose: This study aims to investigate the impact of servant leadership on the psychological distress of healthcare staff during the Covid-19 crisis. The authors propose that work engagement mediates and mindfulness moderates the direct relationship between servant leadership and psychological distress.Methods: Time-lagged data were collected from 277 healthcare staff working at different hospitals in Pakistan. Process Macro version 3.1 on SPSS 23 was used for statistical analysis. For model fitness, we used AMOS V 22.Results: The results show that servant leadership is negatively related to psychological distress. Furthermore, work engagement mediates the relationship between servant leadership and psychological distress. Moreover, mindfulness is anticipated to moderate the direct relationship between servant leadership and psychological distress, drawing on the social exchange and conservation of resources theory.Discussion: This study finds that servant leadership is vital for the mental health of healthcare staff. Thus, it extends the utility of the concept of servant leadership to the psychology and crisis management literature.Keywords: servant leadership, mindfulness, Covid-19 crisis, work engagement, psychological distress, healthcare staff

Yap-Hang Chan,1 Michael Cheong Ngai,2 Yan Chen,1,3 Mei-Zhen Wu,1 Yu-Juan Yu,1 Zhe Zhen,1 Kevin Lai,1 Ho-Yin Chung,4 Chak-Sing Lau,4 Hung-Fat Tse,1,3 Kai-Hang Yiu1,3 1Cardiology Division, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 2Division of Hematology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of China; 3Cardiology Division, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Division of Rheumatology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, Special Administrative Regions, People’s Republic of ChinaCorrespondence: Kai-Hang Yiu, Cardiology Division, Department of Medicine, The University of Hong Kong-Shenzhen Hospital, 1 Haiyuan 1st Road, Futian District, Shenzhen, 518053, Guangdong, People’s Republic of China, Tel +852 22553633, Fax +852 28186304, Email khkyiu@hku.hkBackground and Aim: Rheumatoid arthritis is associated with both abnormal bone metabolism and accelerated vascular aging but a mechanistic link was lacking. This study aims to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPCs) in vascular aging, as determined by arterial calcifications in rheumatoid arthritis.Methods: We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+ versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography.Results: Osteogenic EPCs OCN+CD34+KDR+ (P = 0.002) and OCN+CD34+ (P = 0.001), together with clinical parameters of age, history of hypertension, systolic blood pressure, serum levels of triglycerides, HbA1c and creatinine, use of leflunomide and brachial-ankle pulse-wave velocity (all P < 0.05), were associated with the clustered presence of aortic and carotid calcification. Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B = 14.4 [95% CI 4.0 to 24.8], P = 0.007) and OCN+CD34+ (B = 9.6 [95% CI 4.9 to 14.3], P < 0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B = 0.8 [95% CI 0.1 to 1.5], P = 0.023), but not OCN+CD34+KDR+ EPC (B = 1.2 [95% CI − 0.2 to 2.6], P = 0.09), was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P = 0.46 and 0.88, respectively).Conclusion: Circulating level of osteogenic EPC is associated with increased vascular aging in terms of calcification of the large arteries in patients with rheumatoid arthritis. The findings may suggest a role of the bone-vascular axis underlying vascular aging in rheumatic diseases. Further research is needed to characterize the mechanistic links and basis of these observations.Keywords: osteocalcin, endothelial progenitor cells, vascular aging, rheumatoid arthritis

Hyun Jung Lee,1 Ji Seon Chae,2 Sang-Mee An,2 Hye-Won Oh,1 Youn Jin Kim,1 Jae Hee Woo1 1Department of Anesthesiology and Pain Medicine, College of Medicine, Ewha Womans University, Seoul, South Korea; 2Department of Anesthesiology and Pain Medicine, Ewha Womans University Seoul Hospital, Seoul, South KoreaCorrespondence: Jae Hee Woo, Department of Anesthesiology and Pain Medicine, College of Medicine, Ewha Womans University, 260 Gonghangdaero, Gangseo-gu, Seoul, 07804, South Korea, Tel +82-2-6986-4300, Fax +82-2-6986-4960, Email jheewoo@ewha.ac.krPurpose: Monitoring end-tidal carbon dioxide partial pressure (PETCO2) is a noninvasive, continuous method, but its accuracy is reduced by prolonged capnoperitoneum and the steep Trendelenburg position in robot-assisted radical prostatectomy (RARP). Transcutaneous carbon dioxide partial pressure (PTCCO2) monitoring, which is not affected by ventilator–perfusion mismatch, has been suggested as a suitable alternative. We compared the agreement of noninvasive measurements with the arterial carbon dioxide partial pressure (PaCO2) over a long period of capnoperitoneum, and investigated its sensitivity and predictive power for detecting hypercapnia.Patients and Methods: The patients who underwent RARP were enrolled in this study prospectively. Intraoperative measurements of PETCO2, PTCCO2, and PaCO2 were analyzed. The primary outcome was the agreement of noninvasive monitoring with PaCO2 during prolonged capnoperitoneum. Bias and precision between noninvasive measurements and PaCO2 were assessed using Bland–Altman analysis. The bias and mean absolute difference were compared using a two-tailed Wilcoxon signed-rank test for pairs. The secondary outcome was the sensitivity and predictive power for detecting hypercapnia. To assess this, the Yates corrected chi-square test and the area under the receiver operating characteristic curve were used.Results: The study analyzed 219 datasets from 46 patients. Compared with PETCO2, PTCCO2 had lower bias, greater precision, and better agreement with PaCO2 throughout the RARP. The mean absolute difference in PETCO2 and PaCO2 was larger than that of PTCCO2 and PaCO2, and continued to exceed the clinically acceptable range of 5 mmHg after 1 hour of capnoperitoneum. The sensitivity during capnoperitoneum and overall predictive power of PTCCO2 for detecting hypercapnia were significantly higher than those of PETCO2, suggesting a greater contribution to ventilator adjustment, to treat hypercapnia.Conclusion: PTCCO2 monitoring measured PaCO2 more accurately than PETCO2 monitoring during RARP requiring prolonged capnoperitoneum and a steep Trendelenburg position. PTCCO2 monitoring also provides more sensitive measurements for ventilator adjustment and detects hypercapnia more effectively than PETCO2 monitoring.Keywords: intraoperative carbon dioxide monitoring, capnoperitoneum, robotic surgery, end-tidal carbon dioxide monitoring, general anesthesia

Yuan-Jie Liu,1,2,&ast; Shu-hong Zeng,2,3,&ast; Wei-hua Qian,1 Min-xian Tao,1 Ying-ying Zhu,4 Jie-pin Li1– 3 1Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 2Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People’s Republic of China; 3No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 4Department of Oncology, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Jiangsu, 215600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie-pin Li, Email zjgzy027@njucm.edu.cnPurpose: Low-grade gliomas (LGG) are primary brain tumors that often affect predominantly young adults, which usually have a painless course, and have a longer survival period compared to patients with high-grade gliomas. Relatively established treatment options include surgery, radiotherapy, chemotherapy or combination therapy, as well as individualized management based on tumor location, histology, molecular features and patient characteristics. Due to the rapid development of targeted therapies, the development of new molecular targets is now a very promising research direction.Methods: We explored the diagnostic value, clinical relevance, and molecular function of deoxynucleotidyl transferase terminal-interacting proteins 2 (DNTTIP2) in LGG using MethSurv, MEXPRESS, STRING, cBioPortal, Tumor Immunity Estimation Resource (TIMER) database, Gene Expression Profiling Interactive Analysis (GEPIA) databases. Besides, the “CIBERSORT” algorithm was conducted to estimate immune cells infiltration abundance, with “ggplot2” package visualizing the results. In vivo and vitro experiments were used to verify the speculations of bioinformatics analysis.Results: In LGG patients, DNTTIP1/2 were over-expressed at mRNA levels and high DNTTIP1/2 levels correlated with poor survival in LGG patients. We confirmed that DNTTIP2 significantly promotes M2 macrophage activation and angiogenesis, which may be related to the IL6/JAK/STAT3 signaling pathway. In addition, we found that DNTTIP2 amplification was associated with an unfavorable prognosis in LGG patients. We demonstrated, finally, a correlation between DNTTIP2 gene hypermethylation and a poor prognosis in LGG.Conclusion: This study demonstrated that DNTTIP1/2 had diagnostic and prognostic value in LGG patients. The biological mechanisms of DNTTIP2 regarding angiogenesis and macrophage activation may provide new insights into the treatment of glioma.Keywords: low-grade glioma, DNTTIP2, angiogenesis, M2 macrophages infiltration, bioinformatics

Chien-Feng Lee,1,* Yunn-Jy Chen,2,* Wen-Chi Huang,3 Jen-Wen Hou,4 Yu-Ting Liu,5 Tiffany Ting-Fang Shih,6 Pei-Lin Lee,7– 10 Chong-Jen Yu1,8,9 1Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; 2Department of Dentistry, School of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan; 4Graduate Institute of Electronics Engineering, National Taiwan University, Taipei, Taiwan; 5MediaTek Inc., Hsinchu, Taiwan; 6Department of Radiology and Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; 7Center of Sleep Disorder, National Taiwan University Hospital, Taipei, Taiwan; 8Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 9School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 10Center for Electronics Technology Integration, National Taiwan University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Pei-Lin Lee, Tel +886-2-2356-2755, Fax +886-2-2358-2867, Email leepeilin@ntu.edu.twObjective: Both continuous positive airway pressure (CPAP) pressure and polysomnographic phenotypes have been associated with mandibular advancement device (MAD) treatment response, but the precise relationship has not been fully elucidated. We hypothesized that utilizing CPAP pressure would predict the MAD response in treatment-naïve patients with moderate-severe obstructive sleep apnea (OSA), and the MAD response would be associated with two polysomnographic phenotypes, including sleep stage dependency and positional dependency.Methods: OSA treatment-naïve patients with an apnea-hypopnea index (AHI) ≥ 15/h who declined CPAP treatment and received MAD treatment for 3– 6 months were enrolled. The MAD treatment response was defined as 1) residual AHI under MAD (AHIMAD) < 5/h and 2) AHIMAD < 10/h. Logistic regression was applied to identify the association between CPAP pressure and MAD treatment responders. The predictability of the MAD responder status utilizing CPAP pressure was assessed with the area under the receiver operating characteristic (AUROC).Results: A total of 128 enrolled patients (AHI ≥ 30/h in 74.2%) were recruited, of whom 119 patients and 80 patients were included for analysis of sleep stage and positional dependency, respectively. REM-predominant OSA had lower AHI than stage-independent OSA, while the supine-predominant phenotype had lower anthropometrics than the nonpositional-dependent phenotype. The response rates for AHIMAD < 5/h and AHIMAD < 10/h were 25.8% and 48.4%, respectively. Lower anthropometrics, baseline AHI, and supine predominance were associated with the responder status, while CPAP pressure was an independent predictor. The AUROCs for the prediction of AHIMAD < 5/h and AHIMAD < 10/h responders were 0.635 and 0.664, respectively. Utilizing a CPAP level > 14 cmH2O as the cutoff to predict criterion 1 and 2 nonresponders, the sensitivity was 93.9% and 95.2%, respectively.Conclusion: In treatment-naïve patients with moderate-severe OSA, the supine-predominant phenotype and lower CPAP pressure were associated with the MAD response, while the sleep stage dependency phenotype was not. Utilization of a CPAP level > 14 cmH2O could be a sensitive measure to identify nonresponders.Keywords: continuous positive airway pressure, mandibular advancement device, polysomnography, phenotype, sleep apnea, obstructive

Hyun Woo Cho,1 Ju Hun Park,1 Dong Hwi Yoo,1 Dong Wook Hwang,1 Sang Don Kim,1 Eun-San Kim,2 Kyoung Sun Park,3 Yoon Jae Lee,2 Jinho Lee,3 Changsop Yang,4 Chang Hyun Han,4,5 In-Hyuk Ha2 1Haeundae Jaseng Hospital of Korean Medicine, Busan, 48102, Republic of Korea; 2Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, 06110, Republic of Korea; 3Jaseng Hospital of Korean Medicine, Seoul, 06110, Republic of Korea; 4KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea; 5Korean Convergence Medical Science, Korea Institute of Oriental Medicine School, University of Science & Technology, Daejeon, 34054, Republic of KoreaCorrespondence: Chang Hyun Han, Clinical Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea, Tel +82 42-868-9498, Email chhan@kiom.re.kr In-Hyuk Ha, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, 3F 538 Gangnam-daero, Gangnam-gu, Seoul, 06110, Republic of Korea, Tel +82 2-2222-2740, Email hanihata@gmail.comPurpose: Cervical myelopathy (CM) is generally considered an indication for surgery in Western medicine. Case reports have indicated that Korean medicine (KM) treatments are effective in improving CM-associated symptoms. We investigated the effectiveness of non-surgical KM treatment of CM patients through a retrospective chart review and follow-up survey.Patients and Methods: We retrospectively analyzed the medical records and surveyed follow-up data of CM patients with neurological symptoms admitted to KM hospitals between January 2011 and January 2018. The admission and discharge assessments included the numeric rating scale (NRS) for neck and arm pain, neck disability index (NDI), and 5-level EuroQol 5-dimension (EQ-5D-5L). A follow-up survey was conducted about whether surgery was subsequently performed or recommended, symptom recurrence, discomfort in daily living, current treatment, as well as NRS, NDI, EQ-5D-5L, and patient global impression of change (PGIC) scores.Results: The NRS for neck pain decreased from 4.88 ± 2.03 (95% CI: 4.23‒5.52) at admission to 3.23 ± 1.64 (95% CI: 2.70‒3.75) at discharge and 2.24 ± 1.84 (95% CI: 1.43‒3.05) at follow-up. The NRS for radiating arm pain decreased from 5.42 ± 1.55 (95% CI: 4.93‒5.92) to 3.77 ± 1.54 (95% CI: 3.28‒4.27) at discharge and 2.43 ± 1.60 (95% CI: 1.72‒3.13) at follow-up. The NDI decreased significantly from 36.24 ± 18.79 (95% CI: 30.24‒42.24) at admission to 30.89 ± 15.54 (95% CI: 25.93‒35.86) at discharge and 13.35 ± 11.95 (95% CI: 8.08‒18.63) at follow-up. The EQ-5D score improved significantly from 0.70 ± 0.21 (95% CI: 0.63‒0.77) to 0.78 ± 0.17 (95% CI: 0.73‒0.84) at discharge and 0.84 ± 0.08 (95% CI: 0.80‒0.88) at follow-up. At the follow-up, four patients experienced persistent pain and were undergoing treatment (19.1%), while 20 patients (95.8%) reported symptom improvement.Conclusion: From a long-term perspective, integrative KM treatment may help to reduce pain and improve function, and improve quality of life of CM patients.Keywords: cervical myelopathy, Korean medicine, acupuncture, musculoskeletal manipulations, pharmacopuncture, Shinbaro