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Mindy Hong,1 Jeffrey Krauss,1 Grace Wang,2 Ken Cohen,3 Christine E Chaisson,4 Amitabh Gulati5 1Hinge Health, San Francisco, CA, USA; 2Weitzman Institute, Middletown, CT, USA; 3Optum Care Center for Research and Innovation, Eden Prairie, MN, USA; 4Yale University Center for Clinical Investigation, New Haven, CT, USA; 5Memorial Sloan Kettering Cancer Center, New York, NY, USACorrespondence: Mindy Hong, Email mindy.hong@hingehealth.comPurpose: Physical therapy (PT) and conservative care are recommended first-line treatments for musculoskeletal (MSK) pain. While essential to high-quality care, these solutions often do not provide immediate or sufficient pain relief. Traditional transcutaneous electronic nerve stimulation (TENS) devices are often recommended; however, there is mixed evidence behind their effectiveness. A novel approach called hybrid form impulse therapy (HFIT) incorporates a priming pulse with a traditional TENS pulse width and frequency. This randomized controlled trial (RCT) aimed to compare the effectiveness of HFIT versus traditional TENS versus usual care among members of a digital MSK program.Patients and Methods: A three-arm RCT comparing HFIT versus TENS versus usual care was conducted. A total of 325 people with chronic back or knee pain who were members of a digital MSK program consisting of PT-guided exercise therapy, education, and coaching were randomized. Outcomes including pain, function, anxiety, and depression were examined at 1, 2, and 4 weeks (primary endpoint). Engagement was measured through exercise therapy (ET) sessions completed. Unadjusted and adjusted logistic generalized estimating equations were conducted.Results: Adjusted per-protocol results at 4 weeks showed significantly lower odds of achieving pain improvement for both TENS (OR: 0.42, 95% CI: [0.19, 0.92]) and usual care (OR: 0.35, 95% CI: [0.17, 0.72]) groups, compared to HFIT group. Both HFIT and usual care users had significantly higher engagement than the TENS users (p=0.026 and p=0.002, respectively). No adverse events were reported throughout the study.Conclusion: More participants of a digital MSK program who were randomized to the HFIT group experienced meaningful pain improvement at 4 weeks than participants who used TENS and usual care. HFIT can be an effective, non-pharmaceutical solution for relief as a complement to first-line treatments for patients with chronic back and knee pain.Keywords: HFIT, pain, chronic pain, neuromodulation, noninvasive treatment

Achieving high material perfection in aluminum (Al) films and their associated Al/AlOx heterostructures is essential for enhancing the coherence time in superconducting quantum circuits. We grew Al films with thicknesses ranging from 3 to 30 nanometers (nm) epitaxially on sapphire substrates using molecular beam epitaxy (MBE). An integral aspect of our work involved electron-beam (e-beam) evaporation to directly deposit aluminum oxide (Al2O3) films on the freshly grown ultrathin epitaxial Al films in an ultra-high-vacuum (UHV) environment. This in situ oxide deposition is critical for preventing the oxidation of parts of the Al films, avoiding the formation of undesired native oxides, and thereby preserving the nm-thick Al films in their pristine conditions. The thicknesses of our Al films in the study were accurately determined; for example, coherence lengths of 3.0 and 20.2 nm were measured in the nominal 3.0 and 20 nm thick Al films, respectively. These Al films were epitaxially grown on sapphire substrates, showing an orientational relationship, denoted as Al (111) ⟨ 2 1 ¯ 1 ¯ ⟩ ∥ sapphire (0001) [ 2 1 ¯ 1 ¯ 0 ]. The Al/sapphire interface was atomically ordered without any interfacial layers, as confirmed by in situ reflection high-energy electron diffraction (RHEED) and cross-sectional scanning transmission electron microscopy (STEM). All sample surfaces exhibited smoothness with a roughness in the range of 0.1–0.2 nm. The Al films are superconducting with critical temperatures ranging from 1.23 to around 2 K, depending on the film thickness. [ABSTRACT FROM AUTHOR]

The fate of influenza A virus (IAV) infection in the host cell depends on the balance between cellular defence mechanisms and viral evasion strategies. To illuminate the landscape of IAV cellular restriction, we generated and integrated global genetic loss-of-function screens with transcriptomics and proteomics data. Our multi-omics analysis revealed a subset of both IFN-dependent and independent cellular defence mechanisms that inhibit IAV replication. Amongst these, the autophagy regulator TBC1 domain family member 5 (TBC1D5), which binds Rab7 to enable fusion of autophagosomes and lysosomes, was found to control IAV replication in vitro and in vivo and to promote lysosomal targeting of IAV M2 protein. Notably, IAV M2 was observed to abrogate TBC1D5-Rab7 binding through a physical interaction with TBC1D5 via its cytoplasmic tail. Our results provide evidence for the molecular mechanism utilised by IAV M2 protein to escape lysosomal degradation and traffic to the cell membrane, where it supports IAV budding and growth.

We have attained low leakage current, low interfacial traps, and low border traps by effectively passivating both p- and n-In0.53Ga0.47As (InGaAs) surfaces using the same gate dielectrics of ultra-high-vacuum deposited Al2O3/Y2O3. Gate leakage currents below 2 × 10−7 A/cm2 at gate fields of ±4 MV/cm were obtained after 800 °C rapid thermal annealing, demonstrating the intactness of the interface and heterostructure. Negligibly small frequency dispersions in the capacitance–voltage (C–V) characteristics of p- and n-type metal-oxide-semiconductor capacitors (MOSCAPs) were obtained from accumulation, flatband, to depletion as measured from 300 K to 77 K, indicative of low border and interfacial trap density; the C–V frequency dispersions in the accumulation region are 1.5%/dec (300 K) and 0.19%/dec (77 K) for p-InGaAs, and 2.2%/dec (300 K) and 0.97%/dec (77 K) for n-InGaAs. Very low interfacial trap densities (Dit's) of (1.7–3.2) × 1011 eV−1cm−2 and (6.7–8.5) × 1010 eV−1cm−2, as extracted from the conductance method, were achieved on p- and n-InGaAs MOSCAPs, respectively. [ABSTRACT FROM AUTHOR]

Chenjing Qian,1,* Qiuling Wu,1,* Zhixuan Ruan,2 Fang Liu,1 Weiming Li,1 Wei Shi,1 Ling Ma,3 Danyue Peng,1 Hua Yin,1 Lan Yao,1 Zixuan Li,1 Mei Hong,1,4 Linghui Xia1 1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of China; 2Faculty of Natural, Mathematical and Engineering Sciences, King’s College, London, UK; 3Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Collaborative Innovation Center of Hematology, Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Hong; Linghui Xia, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road No. 1277, Wuhan, Hubei Province, People’s Republic of China, Tel +8613037137937 ; +8618627733999, Email hmxh@hust.edu.cn; linghuixia@hust.edu.cnBackground: Bloodstream infection (BSI) due to carbapenem-resistant organisms (CROs) has emerged as a worldwide problem associated with high mortality. This study aimed to evaluate the risk factors associated with mortality in HM patients with CROs BSI and to establish a scoring model for early mortality prediction.Methods: We conducted a retrospective cohort study at our hematological department from January 2018 to December 2021, including all HM patients with CROs BSI. The outcome measured was death within 30-day of BSI onset. Survivor and non-survivor subgroups were compared to identify predictors of mortality. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors and develop a nomogram.Results: In total, 150 HM patients were included in the study showing an overall 30-day mortality rate of 56%. Klebsiella pneumonia was the dominant episode. Cox regression analysis showed that pre-infection length of stay was > 14 days (score 41), Pitt score > 4 (score 100), mucositis (score 41), CAR (The ratio of C-reactive protein to albumin) > 8.8 (score 57), early definitive therapy (score 44), and long-duration (score 78) were positive independent risk predictors associated with 30-day mortality, all of which were selected into the nomogram. Furthermore, all patients were divided into the high-risk group (≥ 160 points) or the low-risk group based on the prediction score model. The mortality of the high-risk group was 8 times more than the low-risk group. Kaplan-Meier analysis showed that empirical polymyxin B therapy was associated with a lower 30-day mortality rate, which was identified as a good prognostic factor in the high-risk group. In comparison, empirical carbapenems and tigecycline were poor prognostic factors in a low-risk group.Conclusion: Our score model can accurately predict 30-day mortality in HM patients with CROs BSI. Early administration of CROs-targeted therapy in the high-risk group is strongly recommended to decrease mortality.Keywords: carbapenem-resistant organisms, predictive model, nomogram, hematological malignancies, bloodstream infection

Mindy Hong,1 Melanie Topete,1 Manshu Yang,2 Jeannie F Bailey3 1Hinge Health, Inc, San Francisco, CA, USA; 2Department of Psychology, University of Rhode Island, Kingston, RI, USA; 3Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USACorrespondence: Mindy Hong, Hinge Health, Inc, 455 Market Street, Suite 700, San Francisco, CA, 94105, USA, Email mindy.hong@hingehealth.comBackground: There is limited research on whether digital interventions can prevent acute or subacute pain from developing into chronic pain. This observational study’s primary objective examined whether chronic pain was more likely to be prevented in digital acute MSK program participants than nonparticipants. An exploratory objective was time to pain relief for program participants versus nonparticipants.Patients and Methods: The intervention group participants conducted video visits with physical therapists and were recommended exercise therapies and educational articles delivered through an app dedicated to addressing musculoskeletal (MSK) needs. This study used a multidimensional approach incorporating pain, function, depression, and anxiety scores to determine whether chronic pain prevention was achieved at 12 weeks. Descriptive analyses, unadjusted, and adjusted logistic regression were conducted. Time-to-event analysis was performed to compare the time to pain relief between groups.Results: A total of 171 participants (intervention: 75, nonparticipants: 96) with baseline and 3, 6, and 12 week follow-up data were included in the sample. Baseline mean (SD) age was 44.2 (11.8) years and mean VAS pain was 43.3 (22.9), out of 100. Results showed significantly higher odds of achieving chronic pain prevention at 12 weeks in the intervention participants versus nonparticipants. After adjusting for age, pain region, registration month, number of weeks of pain experienced, and healthcare service use at 12 weeks, 20.5% of the intervention group and 5.5% of the nonparticipant group achieved chronic pain prevention. At 91 days, the probability of developing chronic pain was 77.7% for nonparticipants and 46.5% for intervention participants (p< 0.001; Log rank test).Conclusion: A digital acute MSK program may help to prevent chronic pain from developing among those with acute and subacute MSK needs. Study results also suggest that program participants achieve chronic pain relief sooner compared to nonparticipants.Keywords: acute, chronic, musculoskeletal, pain, prevention, telemedicine

Antisense oligonucleotide–mediated (AO-mediated) therapy is a promising strategy to treat several neurological diseases, including spinal muscular atrophy (SMA). However, limited delivery to the CNS with AOs administered intravenously or subcutaneously is a major challenge. Here, we demonstrate a single subcutaneous administration of cell-penetrating peptide DG9 conjugated to an AO called phosphorodiamidate morpholino oligomer (PMO) reached the CNS and significantly prolonged the median survival compared with unconjugated PMO and R6G-PMO in a severe SMA mouse model. Treated mice exhibited substantially higher expression of full-length survival of motor neuron 2 in both the CNS and systemic tissues compared with nontreated and unmodified AO–treated mice. The treatment ameliorated the atrophic musculature and improved breathing function accompanied by improved muscle strength and innervation at the neuromuscular junction with no signs of apparent toxicity. We also demonstrated DG9-conjugated PMO localized in nuclei in the spinal cord and brain after subcutaneous injections. Our data identify DG9 peptide conjugation as a powerful way to improve the efficacy of AO-mediated splice modulation. Finally, DG9-PMO is a promising therapeutic option to treat SMA and other neurological diseases, overcoming the necessity for intrathecal injections and treating body-wide tissues without apparent toxicity.

Background: Mirror syndrome is a rare disease characterized by "triple edema", while Hemolytic Uremic Syndrome (PHUS) is a serious disease that occurs within a short period of time after the end of pregnancy, with a low prevalence and poor prognosis, and it is even rarer for both to occur in the same patient. Methods: We report a case of mirror syndrome combined with PHUS and analyze the clinical data to improve the understanding of the disease. Results: The patient presented clinically with "triple edema" and was diagnosed with mirror image syndrome. After cesarean section, the patient developed cardiac insufficiency, renal insufficiency, hemolysis, and other symptoms and was diagnosed as PHUS. After active treatment, the maternal prognosis was good. Conclusions: Mirror syndrome and PHUS are both clinically rare diseases with poor long-term prognosis if not diagnosed and treated in a timely manner; therefore, awareness of the diseases, early and accurate diagnosis and timely and correct treatment should be improved. [ABSTRACT FROM AUTHOR]

Sang-Min Lee,1 Hyeon-Kyoung Cheong,2 In-Hwan Oh,3 Minha Hong4 1Department of Psychiatry, Kyung Hee University School of Medicine, Seoul, Korea; 2Department of Internal Medicine, Korea University School of Medicine, Ansan, Korea; 3Department of Preventive Medicine, Kyung Hee University School of Medicine, Seoul, Korea; 4Department of Psychiatry, Myongji Hospital, Hanyang University College of Medicine, Goyang, KoreaCorrespondence: Minha HongDepartment of Psychiatry, Myongji Hospital, Hanyang University College of Medicine, 55 Hwasu-ro 14 beon-gil, Deogyang-gu, Goyang, 10475, KoreaTel +82-10-8433-0124Fax +82-31-969-0500Email hmh0124@hanmail.net; minhahong@hanyang.ac.krPurpose: Long-term treatment of attention deficit/hyperactivity disorder (ADHD) is important, but adherence and persistence in practice are still suboptimal. To better understand medication compliance for ADHD, we divided adults with ADHD into groups based on their history of childhood and adolescent ADHD, and compared their characteristics, medication adherence and persistence, and associated factors.Patients and Methods: This study included participants aged 18– 23 years with claims related to ADHD (International Classifications of Diseases 10th edition, F90.0x) and anti-ADHD medication from July 1, 2017 to December 31, 2018, and with a history of any F90.0x claim(s) from January 1, 2007 to June 30, 2017 in the Korean National Health Insurance System Claims database. Participants were divided into those diagnosed with ADHD in childhood and adulthood. Persistence with or without a 30-day gap and adherence according to a medication possession ratio (MPR) > 80% were calculated.Results: There were 10,604 patients included in the study. Adults with a childhood diagnosis of ADHD showed significant male predominance, more use of National Health Insurance, and were more often treated by psychiatrists and in hospitals than those with an adulthood diagnosis. Combination therapy was the most common initial treatment in those with an adulthood diagnosis, while monotherapy with Concerta was most common in those with a childhood diagnosis. Both groups had over 60% of participants with an MPR > 80% and over 50% with persistence without a 30-day gap. Treatment in a private clinic and initial monotherapy with bupropion were found to be significantly associated with adherence in both groups.Conclusion: The significant differences found between these groups add evidence to suggest that adult with ADHD diagnosed in adulthood may be a separate entity from those in childhood. A thorough evaluation at diagnosis and treatment in private clinics may improve medication compliance in this population.Keywords: adult ADHD, persistence, adherence, compliance

Kasra Amirdelfan,1 Mindy Hong,2 Bobby Tay,3 Surekha Reddy,4 Vinay Reddy,4 Michael Yang,5 Krishn Khanna,3 Prasad Shirvalkar,6 Christopher Abrecht,7 Amitabh Gulati8 1IPM Medical Group, Walnut Creek, CA, USA; 2Hinge Health, San Francisco, CA, USA; 3Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA, USA; 4Spine and Nerve Diagnostic Center, Roseville, CA, USA; 5Summit Pain Alliance, Santa Rosa, CA, USA; 6UCSF Weill Institute of Neurosciences University of California San Francisco, San Francisco, CA, USA; 7Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA; 8Memorial Sloan Kettering Cancer Center, New York, NY, USACorrespondence: Amitabh GulatiMemorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USATel +1 212 639-2000Email amitabhgulati@gmail.comPurpose: This study aims to examine high-frequency impulse therapy (HFIT) impact on pain and function among patients undergoing care for chronic low back pain (CLBP).Methods: A pilot randomized-controlled trial of HFIT system versus sham was conducted across 5 orthopedic and pain center sites in California, USA. Thirty-six patients seeking clinical care for CLBP were randomized. Primary outcome was function measured by the Six Minute Walk Test (6MWT). Secondary outcomes were function (Timed Up and Go [TUG] and Oswestry Disability Index [ODI]), pain (Numerical Rating Scale [NRS]), quality of life (Patient Global Impression of Change [PGIC]), and device use. Patients were assessed at baseline and every week for 4 weeks of follow-up. Mann–Whitney U-test was used to analyze changes in each outcome. Repeated measures ANOVA was used to assess the effect of treatment over time.Results: The average age of subjects was 53.9 ± 15.7 (mean ± SD) years, with 12.1 ± 8.8 years of chronic low back pain. Patients who received an HFIT device had a significantly higher 6MWT score at weeks 2 [Cohen’s d (95% CI): 0.33 (0.02, 0.61)], 3 [0.32 (0.01, 0.59)] and 4 [0.31 (0.01, 0.60)], respectively, as compared to their baseline scores (p < 0.05). Patients in the treatment group had significantly lower TUG scores at week 3 [0.30 (0.04, 0.57)] and significantly lower NRS scores at weeks 2 [0.34 (0.02, 0.58)] and 4 [0.41 (0.10, 0.67)] (p < 0.05).Conclusion: A larger-scale RCT can build on the findings of this study to test whether HFIT is effective in reducing pain and improving function in CLBP patients. This study shows encouraging evidence of functional improvement and reduction in pain in subjects who used HFIT. The efficacy and minimally invasive nature of HFIT is anticipated to substantially improve the management of CLBP patients.Keywords: HFIT, pain, chronic pain, neuromodulation, noninvasive treatment

Heidi Joyce,1 Michael R Taylor,1 Andrew Moffat,1 Mia Hong,1 Debra Isaac,2 Nowell Fine,2 Steven C Greenway1– 3 1Department of Pediatrics and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 2Department of Cardiac Sciences and Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 3Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaCorrespondence: Steven C GreenwaySection of Cardiology, Alberta Children’s Hospital, 28 Oki Drive NW, Calgary, AB, T3B 6A8, CanadaTel +1-403-955-5049Fax +1-403-955-7621Email scgreenw@ucalgary.caIntroduction: Interactions between our commensal microbes and immune system are well recognized but the impact of immunosuppression on this relationship is less well characterized, particularly outside of the gastrointestinal tract. In this pilot case-control study, we examined microbial composition and inferred function in the saliva of patients after heart transplantation.Methods: Saliva samples were collected from 26 healthy adolescent and adult heart transplant patients and 27 healthy non-transplant controls. Bacterial DNA was isolated and the V3 and V4 regions of the 16S rRNA gene were sequenced. Measures of bacterial diversity and inferred function were calculated using the software packages DADA2, Phyloseq, QIIME, PICRUSt and STAMP.Results: Transplant patients were on average 51.6 ± 18.2 years of age and 8.6 ± 5.3 years post-transplant. Both alpha (p = 0.0009) and beta (p = 0.001) diversity differed significantly between the groups, and there were statistically significant changes (p < 0.01) in 101 individual functional pathways.Discussion: We conclude that the effects of chronic immunosuppression on bacterial composition and function in the oropharynx appear relatively subtle with no obvious ill effects on patient health. Full interpretation is limited by our lack of knowledge for many of the bacterial functional pathways.Keywords: microbiome, saliva, transplant, heart, immune suppression

Abstract Background The association between allogeneic blood transfusion and healthcare-associated infection (HAI) is considered dose-dependent. However, this association may be confounded by transfusion duration, as prolonged hospitalization stay increases the risk of HAI. Also, it is not clear whether specific blood products have different dose–response risks. Methods In this retrospective cohort study, a logistic regression was used to identify confounding factors, and the association between specific blood products and HAI were analyzed. Then Cox regression and restricted cubic spline regression was used to visualize the hazard of HAI per transfusion product. Results Of 215,338 inpatients observed, 4.16% were transfused with a single component blood product. With regard to these transfused patients, 480 patients (5.36%) developed a HAI during their hospitalization stay. Logistic regression showed that red blood cells (RBCs) transfusion, platelets transfusion and fresh-frozen plasmas (FFPs) transfusion were risk factors for HAI [odds ratio (OR) 1.893, 95% confidence interval (CI) 1.656–2.163; OR 8.903, 95% CI 6.646–11.926 and OR 1.494, 95% CI 1.146–1.949, respectively]. However, restricted cubic spline regression analysis showed that there was no statistically dose–response relationship between different transfusion products and the onset of HAI. Conclusions RBCs transfusion, platelets transfusion and FFPs transfusion were associated with HAI, but there was no dose–response relationship between them.

Nonlinear features extracted from Lamb wave signals (e.g., second harmonic generation) are demonstrably sensitive to microscopic damage, such as fatigue and material thermal degradation. While a majority of the existing studies in this context is focused on detecting undersized damage in metallic materials, the present study is aimed at expanding such a detection philosophy to the domain of composites, by linking the relative acoustic nonlinearity parameter (RANP) – a prominent nonlinear signal feature of Lamb waves – to barely visible impact damage (BVID) in composites. Nevertheless, considering immense uncertainties inevitably embedded in acquired signals (due to instrumentation, environment, operation, computation/estimation, etc.) which can adversely obfuscate nonlinear features, it is necessary to quantify the uncertainty of the RANP (i.e., its statistics) in order to enhance decision-making associated with its use as a detection feature. A probabilistic model is established to numerically evaluate the statistical distribution of the RANP. Using piezoelectric wafers, Lamb waves are acquired and processed to produce histograms of RANP estimates in both the healthy and damaged conditions of a CF/EP laminate, to which the model is compared, with good agreement observed between the model-predicted and experimentally-obtained statistic distributions of the RANP. With the model, BVID in the laminate is predicted. The model is further made use of to quantify the level of confidence in damage prediction results based on the concept of a receiver operating characteristic, enabling the practitioners to better understand the obtained results in the presence of uncertainties.

Summary: Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses. However, few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue. We identified the RNA helicase DHX16 as a potential pattern recognition receptor (PRR). Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. These effects extended to members of other virus families, including Zika and SARS-CoV-2. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6. DHX16 recognizes a signal in influenza RNA segments that undergo splicing and requires its RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a PRR that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored poly-Ub.

Minha Hong,1 JJ Sandra Kooij,2,3 Bongseog Kim,4 Yoo-Sook Joung,5 Hanik K Yoo,6 Eui-Jung Kim,7 Soyoung Irene Lee,8 Soo-Young Bhang,9 Seung Yup Lee,10 Doug Hyun Han,11 Young Sik Lee,11 Geon Ho Bahn10 1Department of Psychiatry, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea; 2PsyQ, Psycho-Medical Programs, Expertise Center Adult ADHD, The Hague, The Netherlands; 3Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands; 4Department of Psychiatry, Inje University College of Medicine, Seoul, Korea; 5Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 6Department of Clinical Psychiatry, Seoul Brain Research Institute, Seoul, Korea; 7Department of Psychiatry, College of Medicine, Ewha Womans University, Seoul, Korea; 8Department of Psychiatry, Soonchunhyang University College of Medicine, Bucheon, Korea; 9Department of Psychiatry, Nowon Eulji University Hospital, Eulji University School of Medicine, Seoul, Korea; 10Department of Psychiatry, Kyung Hee University School of Medicine, Seoul, Korea; 11Department of Psychiatry, Chung-Ang University College of Medicine, Seoul, KoreaCorrespondence: Geon Ho Bahn Department of PsychiatryKyung Hee University School of Medicine, 23 Kyungheedae-Ro, Dongdaemungu, Seoul 02447, KoreaTel +82-2-958-8556Fax +82-2-957-1997Email mompeian@khu.ac.krBackground: This study was to assess the validity of the Korean version of the semi-structured Diagnostic Interview for Adult ADHD, third edition (DIVA-5). The secondary aim was to compare sociodemographic and psychiatric comorbidities in adult patients with and without a diagnosis of ADHD.Methods: A total of 279 participants were recruited from nine psychiatric outpatient clinics in Korea. All participants were administered the Mini-International Neuropsychiatric Interview (MINI) Plus v.5.0.0, the Adult ADHD Self-Report Scale v1.1 (ASRS-v1.1) Symptom Checklist, and DIVA-5. Diagnosis concordance between two board-certified psychiatrists and DIVA-5 were analysed.Results: The DIVA-5 showed a diagnostic accuracy of 92%, a sensitivity of 91.30%, and a specificity of 93.62%. Significant clinical and demographic differences between ADHD and control groups were found.Conclusion: The Korean version of DIVA-5 is a reliable tool for assessing and diagnosing ADHD in adult Korean populations.Keywords: adult ADHD, validity, DIVA-5, Korean

Lei Song,1,2 Yi Luo,1 Shaoling Li,2 Ming Hong,1 Qi Wang,1 Xiaoling Chi,2 Cong Yang1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of China; 2The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, People’s Republic of ChinaCorrespondence: Cong Yang; Xiaoling ChiScience and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, People’s Republic of ChinaTel +86 15625016580Email yangcong303@163.com; chixiaolingqh@163.comAims: Isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, has previously been reported to have anti-tumor effects in vivo and in vitro. However, the mechanisms whereby ISL exerts its anticancer effects remain poorly understood in hepatocellular carcinoma (HCC).Purpose: In the present study, we investigated the anticancer efficacy and associated mechanisms of ISL in HCC MHCC97-H and SMMC7721 cells.Results: We found that ISL inhibited cell viability and proliferation and induced apoptosis in a dose- and time-dependent manner in liver cancer lines. Furthermore, ISL could activate autophagy in HCC cells, and the autophagy inhibitor HCQ enhances ISL-induced apoptosis in HCC cells. Additionally, ISL induced apoptosis and autophagy through inhibition of the PI3K/Akt/mTOR pathway. Most importantly, in a xenograft tumor model in nude mice, data showed that the administration of ISL decreased tumor growth and concurrently promoted the expression of LC3-II and cleaved-caspase-3. Interestingly, we found that ISL inhibits mTOR by docking onto the ATP-binding pocket of mTOR (ie, it competes with ATP). We thus suggest that mTOR is a potential target for ISL inhibition of hepatocellular carcinoma development, which could be of interest for future investigations.Conclusion: Taken together, the results reveal that ISL effectively inhibited proliferation and induced apoptosis in HCC through autophagy induction in vivo and in vitro, probably via the PI3K/Akt/mTOR pathway. ISL may be a potential therapeutic agent for hepatocellular carcinoma.Keywords: isoliquiritigenin, hepatocellular carcinoma, apoptosis, autophagy, mTOR

Minyoung Hong,* In-Seon Lee,* Dha-Hyun Choi, Younbyoung Chae Acupuncture & Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Younbyoung Chae Email ybchae@khu.ac.krObjective: Despite the many medical benefits, cupping therapy can be difficult for some patients due to unpleasant marks on the skin. As patients are afraid of the potential painful sensation from cupping therapy, the skin reactions might produce vigilance for treatment as pain-related information. We investigated whether individuals show negative emotions and attentional bias toward pain-related residual marks from cupping therapy on the body using an eye-tracking method.Methods: Fifty pain-free volunteers were presented with four different kinds of visual stimulation, such as the back or face region and with or without cupping marks on the skin. A cupping and a control image were presented on one screen with one image on the left side of the screen and the other on the right (locations of the images were counterbalanced across participants). The eye movements of the participants were measured while they viewed the pictures. They completed the Empathy Quotient questionnaire before the experiment and evaluated the unpleasantness level to each image during the task.Results: Images of the back and face with cupping marks were rated significantly more unpleasant and showed a significant attentional bias (significantly longer percentage fixation time) than the control images (attentional bias score: Back + cupping: 48.1 ± 2.8%; Back: − 0.7 ± 3.4%; Face + cupping: 34.5 ± 2.5%; Face: − 2.2 ± 2.9%). Individuals with greater empathy exhibited significantly higher unpleasantness (r = 0.323, p < 0.05) and less attentional bias (r = − 0.279, p < 0.05) to the images with cupping marks.Conclusion: The skin reactions caused by cupping therapy evoked negative emotional responses as well as attentional bias to the reaction sites. Our findings suggest that the emotional and attentional responses to cupping therapy might reflect potential reluctance to this therapy.Keywords: attentional bias, cupping, emotion, empathy, eye-tracking

Abstract Background On January 7, 2019, we observed an outbreak of healthcare-associated infection (HAI) caused by Carbapenem-resistant Acinetobacter baumannii (CRAB) in the neurosurgical intensive care unit (NSICU). A follow-up epidemiological investigation was conducted, and an emergency response was initiated. We aimed to study the clonal transmission of CRAB and its possible source. Methods A matched case-control (1:2) study was performed to identify the possible predisposing factors. A multifaceted intervention was implemented to control the outbreak. We collected environmental samples from patients’ rooms and living area of the staff. CRAB isolates were tested for genetic relatedness by Pulsed-Field Gel Electrophoresis (PFGE). Results Environmental sampling showed that a faucet aerator was contaminated with A. baumannii. Molecular typing revealed the only outbreak strain, which was isolated from tracheal aspirate cultures of the first case of community-acquired infection and 3 cases of HAI. In environmental samples, the outbreak strain was found only in the faucet aerator of the dining room. This CRAB outbreak was discovered in time, and further progress of this outbreak was prevented through a pre-set emergency response procedure. Conclusions The faucet aerator acted as a reservoir for bacteria in the outbreak, and contamination of the faucet aerator might have occurred from splashes originating from handwashing by the healthcare workers (HCWs). In high-risk areas, such as NSICU, the faucet aerators should not be used during an outbreak or they should be regularly cleaned and disinfected. The start-up criteria for the emergency response played a key role in controlling the CRAB outbreak, and its settings should be discussed more widely.