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Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

The Data Acquisition System (DAQ) for the LUX-ZEPLIN (LZ) dark matter detector is described. The signals from 745 PMTs, distributed across three subsystems, are sampled with 100-MHz 32-channel digitizers (DDC-32s). A basic waveform analysis is carried out on the on-board Field Programmable Gate Arrays (FPGAs) to extract information about the observed scintillation and electroluminescence signals. This information is used to determine if the digitized waveforms should be preserved for offline analysis. The system is designed around the Kintex-7 FPGA. In addition to digitizing the PMT signals and providing basic event selection in real time, the flexibility provided by the use of FPGAs allows us to monitor the performance of the detector and the DAQ in parallel to normal data acquisition. The hardware and software/firmware of this FPGA-based Architecture for Data acquisition and Realtime monitoring (FADR) are discussed and performance measurements are described.

Preceding a core-collapse supernova (CCSN), various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande (SK) via inverse beta decay interactions. Once these pre-supernova (pre-SN) neutrinos are observed, an early warning of the upcoming CCSN can be provided. In light of this, KamLAND and SK, both located in the Kamioka mine in Japan, have been monitoring pre-SN neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and SK on pre-SN neutrino detection. A pre-SN alert system combining the KamLAND detector and the SK detector was developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-SN neutrino signal from a 15 M ⊙ star within 510 pc of the Earth at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hr in advance.

LUX-ZEPLIN (LZ) is a tonne-scale experiment searching for direct dark matter interactions and other rare events. It is located at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. The core of the LZ detector is a dual-phase xenon time projection chamber (TPC), designed with the primary goal of detecting Weakly Interacting Massive Particles (WIMPs) via their induced low energy nuclear recoils. Surrounding the TPC, two veto detectors immersed in an ultra-pure water tank enable reducing background events to enhance the discovery potential. Intricate calibration systems are purposely designed to precisely understand the responses of these three detector volumes to various types of particle interactions and to demonstrate LZ’s ability to discriminate between signals and backgrounds. In this paper, we present a comprehensive discussion of the key features, requirements, and performance of the LZ calibration systems, which play a crucial role in enabling LZ’s WIMP-search and its broad science program. The thorough description of these calibration systems, with an emphasis on their novel aspects, is valuable for future calibration efforts in direct dark matter and other rare-event search experiments.

Particle dark matter could belong to a multiplet that includes an electrically charged state. WIMP dark matter (χ0) accompanied by a negatively charged excited state (χ−) with a small mass difference (e.g. < 20 MeV) can form a bound-state with a nucleus such as xenon. This bound-state formation is rare and the released energy is O(1−10) MeV depending on the nucleus, making large liquid scintillator detectors suitable for detection. We searched for bound-state formation events with xenon in two experimental phases of the KamLAND-Zen experiment, a xenon-doped liquid scintillator detector. No statistically significant events were observed. For a benchmark parameter set of WIMP mass mχ0=1 TeV and mass difference Δm=17 MeV, we set the most stringent upper limits on the recombination cross section times velocity 〈σv〉 and the decay-width of χ− to 9.2×10−30 cm3/s and 8.7×10−14 GeV, respectively at 90% confidence level.

This White Paper presents an overview of the current status and future perspective of QCD research, based on the community inputs and scientific conclusions from the 2022 Hot and Cold QCD Town Meeting. We present the progress made in the last decade toward a deep understanding of both the fundamental structure of the sub-atomic matter of nucleon and nucleus in cold QCD, and the hot QCD matter in heavy ion collisions. We identify key questions of QCD research and plausible paths to obtaining answers to those questions in the near future, hence defining priorities of our research over the coming decades.

Searches for dark matter with liquid xenon time projection chamber experiments have traditionally focused on the region of the parameter space that is characteristic of weakly interacting massive particles, ranging from a few GeV/c2 to a few TeV/c2. Models of dark matter with a mass much heavier than this are well motivated by early production mechanisms different from the standard thermal freeze-out, but they have generally been less explored experimentally. In this work, we present a reanalysis of the first science run of the LZ experiment, with an exposure of 0.9 tonne×yr, to search for ultraheavy particle dark matter. The signal topology consists of multiple energy deposits in the active region of the detector forming a straight line, from which the velocity of the incoming particle can be reconstructed on an event-by-event basis. Zero events with this topology were observed after applying the data selection calibrated on a simulated sample of signal-like events. New experimental constraints are derived, which rule out previously unexplored regions of the dark matter parameter space of spin-independent interactions beyond a mass of 1017 GeV/c2.

Global biodiversity gradients are generally expected to reflect greater species replacement closer to the equator. However, empirical validation of global biodiversity gradients largely relies on vertebrates, plants, and other less diverse taxa. Here we assess the temporal and spatial dynamics of global arthropod biodiversity dynamics using a beta-diversity framework. Sampling includes 129 sampling sites whereby malaise traps are deployed to monitor temporal changes in arthropod communities. Overall, we encountered more than 150,000 unique barcode index numbers (BINs) (i.e. species proxies). We assess between site differences in community diversity using beta-diversity and the partitioned components of species replacement and richness difference. Global total beta-diversity (dissimilarity) increases with decreasing latitude, greater spatial distance and greater temporal distance. Species replacement and richness difference patterns vary across biogeographic regions. Our findings support long-standing, general expectations of global biodiversity patterns. However, we also show that the underlying processes driving patterns may be regionally linked.

Following the first science results of the LUX-ZEPLIN (LZ) experiment, a dual-phase xenon time projection chamber operating from the Sanford Underground Research Facility in Lead, South Dakota, USA, we report the initial limits on a model-independent nonrelativistic effective field theory describing the complete set of possible interactions of a weakly interacting massive particle (WIMP) with a nucleon. These results utilize the same 5.5 t fiducial mass and 60 live days of exposure collected for the LZ spin-independent and spin-dependent analyses while extending the upper limit of the energy region of interest by a factor of 7.5 to 270 keV. No significant excess in this high energy region is observed. Using a profile-likelihood ratio analysis, we report 90% confidence level exclusion limits on the coupling of each individual nonrelativistic WIMP-nucleon operator for both elastic and inelastic interactions in the isoscalar and isovector bases.

We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at midrapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.

Background: Breast cancer is the most common cancer among females, worldwide. Cancer screening in developing countries is mainly opportunistic type, characterized by low coverage and over-screening of women with increased access to health care services. This study was thus designed to understand the various factors preventing the participation and utilization of breast cancer screening, thereby study the different approaches for encouraging their participation and also the effectiveness of different ways of communication to Anganwadi Workers (AWW) and Anganwadi Helpers (AWH) in increasing breast cancer screening uptake at cancer screening camps. Settings and Design: It was a mixed-method study design among Anganwadi workers and helpers. Methods and Material: The study included 376 Anganwadi workers working in Kolar and Bangarpete Talukas. The trained Anganwadi supervisor followed by the respective PHC medical officer (in the intervention group) invited the AWW and AWH for breast cancer screening and only through Anganwadi supervisor (in control group). Those women (AWW and AWH) who did not attend the breast cancer screening camp were listed and contacted through mobile phone to find out the reasons for the same. Statistical Analysis Used: The data were analysed using SPSS statistics version 22; Chi-square and logistic regression were used to test significance. Results: There were 186 subjects in the intervention and 190 subjects in the control group. The mean (SD) age in intervention and control groups was 43.7 (8.5) and 44.2 (8.7) years, respectively. Amongst the 376 women (AWW and AWH) invited for the breast cancer screening service from both the groups, a total of 238 (63.2%) of them attended screening camp. The screening uptake was more in the intervention group (73.4%) compared with the control group (53.6%). This difference across the two groups (20%) was found to be statistically significant. The sub-category ‘anxiety’ (31.9%) was reported to be the highest barrier and least was in the sub-category ‘no replacement’ (4.3%). The sub-categories are also supported by verbatim quotes. Conclusions: The uptake of screening was more in the intervention group (73.4%) compared with the control group (53.6%). This difference of 20% was found to be statistically significant on univariate analysis (P < 0.001). After adjusting for confounders, it was found that both the approaches were equally effective.

Efforts for empowering women have been a priority agenda in development because women make crucial contributions to society. One of the significant issues that women are well positioned to address is the stunting or impaired development of children due to poor nutrition. As this issue is a threat for national development in Indonesia, the central government has initiatives to tackle stunting, and one of these is the Sustainable Food Garden, or Pekarangan Pangan Lestari (P2L). The innovative program is designed to prevent stunting by empowering women, which also contributes to the attainment of Sustainable Development Goals (SDGs). This research is focused on the implementation of the P2L initiative in Jombang Regency in East Java, Indonesia. More specifically, it explores how the program capacity, especially at the organizational level, plays a significant role in the implementation of P2L through women's involvement in Kelompok Wanita Tani (KWT) or the Women Farmers' Group. The fieldwork research was performed in four KWTs villages in Kesamben District, one of the focal locations for addressing stunting and food insecurity in Jombang. By using qualitative research methods involving interviews, observation, and analysis of relevant documents, this study finds that within the implementation of the P2L program in Jombang Regency, the program capacity, especially at the organizational level has been fulfilled well. Such program capacity, which includes political capacity, analytical capacity, and operational capacity, has led stakeholders' commitment to fulfill the program's goals and objective, and above all to empower women. In this, Women Farmers' Groups (KWTs) have also contributed to improving nutrition, decreasing the prevalence of stunting in Jombang Regency, and supporting economic growth for women and families, and thus the attainment of Sustainable Development Goals (SDGs). Keywords: Policy capacity, Program capacity, Women's empowerment, Women farmers, Sustainable food garden programs, SDGs, Stunting, Introduction Indonesia is a country where patriarchal culture remains dominant in many parts of its society. This patriarchal culture affects various areas of women's lives, including economics, education, politics, and [...]

Cultivation of students' higher-order thinking ability has become the main agenda of the education curriculum. The transfer of knowledge pertaining to higher-order thinking by teachers to the students can prepare the latter with the necessary attributes for the 21st century. The present study is aimed at exploring Malaysian secondary ESL (English as a Second Language) school teachers' self-assessment of, and perceptions on the higher-order thinking skills practices for teaching writing. Using a mixed-method research design, the validated 30-item five-point Likert scale questionnaire with an open-ended question was administered to a group of respondents consisting of 72 ESL teachers. The findings indicated that the overall mean score of ESL teachers' self-assessment of using higher-order thinking skills practices for teaching writing was at a high level. Meanwhile, their perceptions on the integration of higher-order thinking skills in the teaching of writing include the concern of students' low proficiency, difficulties in implementing HOTS in writing, poor participation by passive students, and teachers' attitude towards using HOTs for teaching writing. This study suggests that fostering and creating awareness of mastering the elements of HOTS can benefit both the teachers and the students. Teachers have to be creative and innovative in their teaching so that the students can be given the opportunity to showcase their knowledge, skills and abilities in the quest to imbue them with the 21st century life skills.

Kuan-Hsien Lu,1 Huey-Juan Lin,1 Chung-Han Ho,2 Kuan-Hung Lin1 1Department of Neurology, Chi Mei Medical Center, Tainan, Taiwan, Republic of China; 2Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan, Republic of ChinaCorrespondence: Kuan-Hung Lin, Department of Neurology, Chi Mei Medical Center, No. 901, Zhonghua Road Yongkang Dist, Tainan City, 71004, Taiwan, Republic of China, Tel +886-6-2812811 ext. 57110 or 53744, Email bbrick0326@gmail.comPurpose: Acute stroke significantly increases the risk of long-term care facility (LTCF) admission, due to sudden functional impairments. This study aims to identify risk factors associated with LTCF admission among stroke patients, specifically targeting those who transitioned from independence to disability after stroke.Patients and Methods: We retrospectively enrolled 2027 stroke patients admitted between 2017 and 2022 from the Chi Mei Medical Center’s stroke registry in Southern Taiwan, focusing on those with pre-stroke modified Rankin Scale (mRS) scores ≤ 2 and post-stroke mRS scores ≥ 3. Patients were categorized into LTCF and non-LTCF groups. Stroke severity, comorbidities, and discharge outcomes were evaluated, using logistic regression analyses to identify LTCF admission risk factors.Results: Of the 2027 patients, 343 (16.9%) were admitted to LTCFs post-discharge. The LTCF group exhibited higher discharge mRS and National Institute of Health Stroke Scale scores, and lower Barthel Index scores. Factors linked to LTCF admission included higher discharge mRS scores, lower Barthel Index scores, nasogastric tube placement at discharge, and longer hospital stays. Barthel Index scores showed no significant change from admission to discharge in the LTCF group.Conclusion: Stroke severity, post-stroke functional status and nasogastric tube placement are significant predictors of LTCF admission in stroke patients. Early recognition of these factors is crucial for effective discharge planning and reducing the need for institutionalization. The study emphasizes the need for personalized interventions targeting these risk factors to improve patient outcomes and optimize medical resource utilization.Keywords: institutionalization, health care facilities, cerebrovascular accident, risk factors, patient discharge

Wonnam Kim,1,&ast; Yeon-Cheol Park,2,3,&ast; Bonhyuk Goo,2 Jung-Hyun Kim,2 Dongwoo Nam,3,4 Eunseok Kim,5,6 Hyun-Jong Lee,7 Dong-Hyun Pyun,8,9 Hae Sun Suh,8– 10 Yoonsung Lee,11 Man S Kim,11 Byung-Kwan Seo,2,3 Yong-Hyeon Baek2,3 1Division of Pharmacology, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 2Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea; 3Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea; 4Department of Acupuncture & Moxibustion, Kyung Hee University College of Korean Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 5Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 6Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 7Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 8Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea; 9Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul, Republic of Korea; 10College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; 11Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Yong-Hyeon Baek, Department of Acupuncture & Moxibustion, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea, Tel +82 2 440 6099, Fax +82 2 440 714, Email byhacu@khu.ac.krPurpose: Knee osteoarthritis (KOA) is one of the most prevalent degenerative joint diseases worldwide. The herbal decoction, Dokhwalgisaeng-tang (DHGST), has been commonly used in East Asia to treat osteoarthritis. However, there is insufficient evidence to draw clear conclusions concerning its effectiveness and safety for patients with KOA. We aim to determine the efficacy, safety, and economic feasibility of DHGST compared with Celecoxib, an oral COX-2 inhibitor, for patients with degenerative KOA.Trial Design and Methods: This multicenter, randomized, noninferiority trial, involving 160 participants who will be randomized using block randomization with 1:1 allocation, will compare DHGST and Celecoxib. The total trial period is 24 weeks after random allocation, comprising 12 weeks of treatment and 12 weeks of follow-up. Participants with KOA will be administered 200 mg of DHGST (treatment group) or Celecoxib capsules (control group) for 12 weeks. Efficacy and safety evaluations will be conducted at weeks 0, 4, 8, and 12, and 24. The primary outcome measurement is the Korean Western Ontario McMaster score at week 12. Changes in pain intensity using a 100 mm visual analog scale, changes in quality of life using a EuroQol 5-dimension 5-level self-report survey, and patient satisfaction will also be measured to evaluate effectiveness between the two groups. A trial-based economic feasibility evaluation will be conducted to analyze treatment cost-effectiveness from societal and healthcare system perspectives. Drug safety will be assessed through adverse reactions and laboratory test findings.Discussion: This trial protocol has the following limitations. Applying a double-dummy design is not possible, as the tablet and granule forms can easily be distinguished visually, and achieving participant blinding is challenging. The trial findings are intended to inform participants, physicians, and other stakeholders in determining whether DHGST could be used as an alternative therapeutic option for KOA.Trial Registration Number: KCT0008424 (Clinical Research Information Service of the Republic of Korea), registered on 12 May 2023.Keywords: degenerative joint disease, Dokhwalgisaeng-tang, noninferiority trial, randomized controlled trial

Dan Wang,1,2,&ast; Jing-Hui Hu,1,2,&ast; Hai-Jing Shi,1,2,&ast; Min-Yuan Zhuang,1,2 Wei Dou,1,2 Fu-Hai Ji,1,2 Ke Peng1,2 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Peng, Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67780055, Email pengke0422@163.comBackground: Emergence agitation (EA) is a state of psychomotor hyperactivity following general anesthesia and is associated with postoperative complications. Patients undergoing ear, nose, and throat (ENT) surgery are at a high risk for EA. We aim to assess whether preoperative dexmedetomidine nasal spray reduces the occurrence of EA for patients undergoing ENT surgery.Methods: This is a protocol for a randomized, double-blind, controlled trial that will include 160 adults scheduled for ENT surgery. Patients will be randomly assigned, in a 1:1 ratio, to receive dexmedetomidine nasal spray (100 μg) or a same volume of normal saline approximately 30 min before general anesthesia induction. The primary endpoint is the incidence of EA, defined as a Riker sedation agitation scale (RSAS) score ≥ 5 from discontinuation of sevoflurane until 5 min after tracheal extubation. Secondary endpoints include (1) the maximal RSAS score during emergence; (2) the incidence of agitation in the postoperative care unit (PACU); (3) pain at rest and while coughing in the PACU and at 24 h postoperatively; (4) postoperative sleep disturbance on the first night after surgery; (5) anxiety within 24 h postoperatively; and (6) postoperative delirium during the first 24 h after surgery. All analyses will be performed on a modified intention-to-treat basis. For the primary endpoint, subgroup analysis will be conducted on sex, age, and type of surgery.Discussion: We expect that preoperative dexmedetomidine nasal spray would reduce the incidence of EA after ENT surgery. Our results offer clinical evidence for improving anesthetic care for patients undergoing ENT surgery.Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR2400086731).Keywords: emergence agitation, dexmedetomidine, intranasal administration, ENT surgery

Guo-Han Zhu,1,2,&ast; Jing-Hui Hu,1,2,&ast; Min-Yuan Zhuang,1,2,&ast; Hai-Jing Shi,1,2 Feng Zhou,3 Hong Liu,4 Fu-Hai Ji,1,2 Ke Peng1,2 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Urology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA&ast;These authors contributed equally to this workCorrespondence: Ke Peng, Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-159-6215-5989, Email pengke0422@163.comBackground: Patients undergoing laparoscopic renal surgery often experience significant postoperative pain. Quadratus lumborum block (QLB) provides effective postoperative pain control after laparoscopic procedures, while lidocaine administered intravenously also exerts analgesic effects for surgical patients. We design this trial to compare the effects of i.v. lidocaine infusion with QLB on postoperative analgesia in patients undergoing laparoscopic renal surgery.Methods: In this randomized noninferiority trial, a total of 120 adult patients undergoing laparoscopic renal surgery will be randomized to receive either i.v. lidocaine or unilateral QLB for postoperative pain management. Lidocaine will be i.v. administered at 1.5 mg/kg (ideal body weight) over 10 min during anesthesia induction, followed by an infusion of 1.5 mg/kg/h intraoperatively and in a post-anesthesia care unit. Ultrasound-guided anterior QLB with 0.375% ropivacaine 30 mL will be conducted before the start of surgery. Patient-controlled i.v. sufentanil will be used for pain relief during the first 48 h after surgery. The primary outcome is the cumulative sufentanil consumption during 0– 24 h postoperatively, with a noninferiority margin of 5 μg. Secondary outcomes include pain intensity at rest and on coughing at 1, 6, 24, and 48 h postoperatively; sufentanil consumption within 24– 48 h after surgery; rescue analgesic use within 0– 48 h after surgery; nausea and vomiting within 0– 48 h postoperatively; and quality of recovery at 24 and 48 h after surgery.Discussion: The results of this trial will add to the clinical evidence for improving postoperative pain management in patients who undergo laparoscopic renal surgery.Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400082974).Keywords: intravenous lidocaine, quadratus lumborum block, postoperative analgesia, quality of recovery, laparoscopic renal surgery

Sangshin Park,1,&ast; Dong-Hwa Lee,2,&ast; Shinyoung Lee,1 Hyun Jeong Jeon2 1Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea; 2Department of Internal Medicine, Chungbuk National University College of Medicine and Chungbuk National University Hospital, Cheongju, Korea&ast;These authors contributed equally to this workCorrespondence: Hyun Jeong Jeon, Department of Internal Medicine, Chungbuk National University College of Medicine 1 Chungbuk Na-Tional University Hospital, 776, 1Sunhwan-ro, Seowon-gu, Cheongju-si, Chungcheongbuk-do, 28644, South Korea, Tel +82-43-269-6352, Email endoann@daum.netPurpose: Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family, and the MCP-1 2518 A/G gene polymorphism is reported to be correlated with chronic inflammatory diseases, including insulin resistance and metabolic syndrome. However, few studies have investigated the association between MCP-1 gene polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM). We conducted a retrospective case-control study and evaluated the association between the MCP-1 2518 A/G polymorphism and obesity in Korean patients with T2DM.Patients and Methods: This single-center, retrospective, case-control study enrolled 526 Korean patients with T2DM. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze MCP-1 2518 A/G polymorphism; the genotypes was presented as GG, AG, or AA. We compared the MCP-1 2518 A/G polymorphism with the prevalence of diabetic complications, as well as clinical and biochemical characteristics.Results: The obese group had a higher number of females and higher C-peptide, insulin, triglycerides, aspartate transaminase (AST), and alanine transaminase (ALT) levels. The obese group also had a higher prevalence of cardiovascular disease than the non-obese group. The obese group had a higher frequency of the MCP-1 2518 AA genotype and the A allele than the non-obese group. The results of multiple logistic regression analysis showed that the non-G allele of MCP-1 was significantly associated with obesity (odds ratio (OR), 1.888; P=0.016).Conclusion: This study demonstrates that the MCP-1 2518 A/G polymorphism is associated with obesity in Korean patients with T2DM. Further studies involving various ethnic groups are required to validate our results.Keywords: obesity, MCP-1 protein, polymorphism, diabetes mellitus

Xin Luo,1,&ast; Hai-Jun Hou,2,&ast; Pei-Shan Chen,1 Xin-Lu Chang,1 Yang Li,1 Li-Xin An,1 Fu-Kun Liu,1 Fu-Shan Xue1,3 1Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pain Medicine, Guanganmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fu-Shan Xue, Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86-13911177655, Fax +86-0591-88217841, Email xuefushan@aliyun.com; fushanxue@outlook.comObjective: Postoperative pain is a common yet often underestimated complication following esophageal endoscopic submucosal dissection (ESD), with limited strategies for effective management. This prospective, double-blind, randomized controlled trial assessed the effects of adding dexmedetomidine (DEX) to the anesthesia regimen on postoperative pain and early recovery in patients undergoing esophageal ESD.Methods: In total, 60 patients scheduled for elective esophageal ESD under general anesthesia were randomly assigned to the DEX or control group. The DEX group received an intravenous loading dose of DEX at 1 μg/kg for 10 min, followed by a continuous intravenous infusion of 0.6 μg/kg/h, which was stopped 30 min before the end of the procedure. The control group received normal saline as a placebo. The study’s primary outcome was the incidence of moderate-to-severe postoperative pain. Secondary outcomes included postoperative pain scores, hemodynamic parameters, the occurrence of postoperative nausea and vomiting (PONV), patient satisfaction, and lengths of stay in the post-anesthesia care unit (PACU) and hospital.Results: The incidence of moderate-to-severe postoperative pain in the DEX group was significantly lower than that in the control group (absolute difference: − 33.4%; OR: 0.250; 95% CI: 0.085– 0.731, P = 0.01). Pain scores at 1 h postoperatively (0.5[2.0] vs 3.0[1.3], P = 0.003) were significantly lower in the DEX group. Additionally, morphine dosage in the PACU (0[0] vs 1.0[2.0] P = 0.004) was significantly reduced in the DEX group compared with the control group. In the DEX group, the incidence and severity of PONV were significantly decreased and the length of PACU stay was shorter than in the control group (P

Hong-Jing Zhu,1,&ast; Sheng-Yu Zhou,1,&ast; Yang Qu,1 Ying-Ying Sun,1 Ke-Jia Zhang,1 Shu-Yan Pang,1 Yi Yang,1 Zhen-Ni Guo1,2 1Stroke Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China; 2Neuroscience Research Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Ni Guo; Yi Yang, Stroke Center, Department of Neurology, The First Hospital of Jilin University, Xinmin Street 1&num;, Changchun, 130021, People’s Republic of China, Tel +86-18186872986 ; +86-13756661217, Fax +86-431-88782378, Email zhen1ni2@163.com; yang_yi@jlu.edu.cnPurpose: Although recombinant tissue plasminogen activator (rt-PA) treatment is efficient in patients with acute ischemic stroke (AIS), a significant percentage of patients who received rt-PA intravenous thrombolysis (IVT) do not achieve a good prognosis. Therefore, the factors that affect the poor prognosis of patients with IVT are needed. The Fibrosis-4 (FIB-4) index has been used as a liver fibrosis biomarker. We aimed to investigate the relationship between the FIB-4 index and functional outcomes in patients with AIS receiving IVT.Patients and Methods: This study prospectively included consecutive patients with AIS receiving IVT between April 2015 and May 2022. We collected clinical and laboratory data and calculated the FIB-4 index. Clinical outcome was poor functional outcome (mRS ≥ 3) at 3 months after IVT. Multivariate logistic regression analysis was used to analyze the association between FIB-4 and outcome. We explored the interactive effect of FIB-4 and dyslipidemia on poor outcomes, and subgroup analysis was performed. Furthermore, an individualized prediction model based on the FIB-4 for functional outcome was established in the dyslipidemia group.Results: A total of 1135 patients were included, and 41.50% had poor 3-month outcomes. After adjusted by other variants that P value < 0.05 in univariable analysis, FIB-4 was independently associated with poor outcomes (OR=1.420; 95% CI: 1.113– 1.812; P=0.004). There was a significant interaction between FIB-4 and dyslipidemia on poor outcome (P=0.036), and the independent association between FIB-4 and poor outcome was maintained in the dyslipidemia subgroup (OR=1.646; 95% CI: 1.228– 2.206; P=0.001). Furthermore, in the dyslipidemia group, the FIB-4-based prediction model had good predictive value (the AUC of the training and validation sets were 0.767 and 0.708, respectively), good calibration (P-values for the Hosmer–Lemeshow test > 0.05), and clinical usefulness.Conclusion: FIB-4 is an independent risk factor for poor outcomes in IVT patients with dyslipidemia, which can be used as a simple predictor of their prognosis.Keywords: Fibrosis-4, acute ischemic stroke, intravenous thrombolysis, prognosis, dyslipidemia

Olulade Ayodele,1 Howard J Cabral,2,3 David D McManus,4 Susan S Jick1,5 1Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; 2Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; 3Biostatistics and Research Design Program, Boston University Clinical and Translational Science Institute, Boston, MA, USA; 4Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA; 5Boston Collaborative Drug Surveillance Program, Lexington, MA, USACorrespondence: Susan S Jick, Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA, Tel +1 (781) 862-6660, Email sjick@bu.eduBackground: A substantial proportion of adults receive statins for treatment of hypercholesterolemia and cardiovascular risk, and statins have been found to improve outcomes in this patient population. However, studies have not consistently demonstrated the potential benefits of statins in preventing venous thromboembolism (VTE). Therefore, we conducted this study to investigate this association.Methods: We conducted a cohort analysis in a study sample comprised of 40– 79-year-old patients with hyperlipidemia who received at least one fibrate or statin prescription between January 1995 and December 2018 in the United Kingdom Clinical Practice Research Datalink (CPRD) GOLD. We evaluated the association between statin use and incident unprovoked VTE, compared to fibrate use, an active comparator, using Kaplan–Meier (KM) analysis, Poisson regression (with and without propensity score matching), and inverse probability of treatment weights (IPTW) marginal structural models (MSM).Results: In this cohort of 166,292 patients with hyperlipidemia, 0.81% (N=1,353) developed incident unprovoked VTE. In analyses using the KM method, patients who received statins had a slightly lower risk of VTE compared to those who received fibrates (Log rank test: p=0.0524). The adjusted incident rate ratio (95% CI) for VTE, calculated using Poisson regression, controlling for serum cholesterol and other baseline covariates, in patients prescribed statins compared to fibrates was 0.77 (0.45– 1.33) in the full cohort, 0.74 (0.38– 1.45) in the propensity score matched analysis, and 0.51 (95% conservative CI: 0.34– 0.76) in the IPTW MSM analysis.Conclusion: While the magnitude of effect varied across the different analytic methods, there is consistent evidence for a protective effect of statin use on the occurrence of unprovoked VTE.Keywords: hyperlipidemia, statin, fibrate, VTE

Yea-Jin Lee,1,2 Namgue Hong,2 Eun Seo Choi,3 Sun-Hyang Choi,2 Eun Young Kim,2 Hyeong Ju Park,4 Jin-Chul Ahn1,2 1Department of Medicine, Dankook University, Cheonan-si, 31116, Republic of Korea; 2Medical Laser Research Center, Graduate School of Medicine, Dankook University, Cheonan-si, 31116, Republic of Korea; 3Department of Physics, Chosun University, Gwangju, 61452, Republic of Korea; 4Bio&Health Photonics Research Center, Korea Photonics Technology Institute, Gwangju, 61007, Republic of KoreaCorrespondence: Hyeong Ju Park; Jin-Chul Ahn, Email phj020603@kopti.re.kr; jcahn@dankook.ac.krPurpose: To evaluate the efficacy and safety of abdominal fat reduction in mini-pigs, utilizing at 1060 nm diode laser with a wavelength of 1060 nm.Patients and Methods: The laser system non-invasively disrupts adipose tissue; its effectiveness and safety were evaluated by ultrasound imaging and histological analysis. Laser irradiation was performed with various powers, and the cooling function was activated to prevent skin surface damage.Results: The dermal tissue temperature increased to at least 43°C during laser exposure, leading to a decrease in abdominal fat thickness after 30 days. Blood tests revealed no significant changes in kidney and liver function but showed increased blood levels of nonessential free acids (NEFAs), likely due to the release of fatty tissue-derived free fatty acids. Histological evaluation demonstrated rapid transformation of adipose tissue into collagen, muscle fibers, and intracellular fibrous tissue.Conclusion: The 1060 nm laser showed promise as a non-invasive and safe tool for reducing abdominal fat.Keywords: diode laser, fat, abdominal, non-invasive, preclinical

Hikmat Abdel-Razeq,1,2 Baha Sharaf,1 Suhaib Khater,1 Huda Jafar Baidoun,2 Hira Bani Hani,1 Ayat Taqash,3 Osama El Khatib,1 Sarah Edaily,1 Mahmoud Abunasser,1 Faris Tamimi,1 Yosra Nabeel Al-Masri,1 Tamer Moh’d Waleed Al-Batsh,1 Anas Zayed,1 Tala Ghatasheh,1 Tala Radaideh1 1Department of Internal Medicine, Section of Hematology and Medical Oncology, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, the University of Jordan, Amman, Jordan; 3Office of Scientific Affairs and Research. King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, Section of Hematology and Medical OncologyKing Hussein Cancer Center, 202 Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman, 11941, Jordan, Tel: +962-6 5300460, Email habdelrazeq@khcc.joBackground: Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2 −) metastatic breast cancer (MBC). Here, we present the real-world clinical outcomes and toxicity data of patients treated at a single cancer center.Methods: A retrospective analysis was conducted on patients with HR+/HER2− MBC treated with ribociclib plus endocrine therapy (ET). Outcomes measured included progression-free survival (PFS), overall survival (OS), and adverse events.Results: A total of 356 patients (median age 52, range 27– 91 years) were enrolled, all with metastatic disease; 204 (57.5%) had de novo metastasis, and 183 (51.4%) had visceral metastasis. Ribociclib was combined with aromatase inhibitors in 321 patients (90.2%) and with fulvestrant in 35 patients (9.8%). Dose reduction was needed in 101 patients (28.4%), primarily due to neutropenia (21.3%) and abnormal liver enzymes (5.9%). After a median follow-up of 36.3 months, median PFS was 27.3 months (95% CI: 21.3– 31.7). PFS was significantly better in patients receiving ribociclib as first-line therapy (32.1 months, 95% CI: 27.7– 42.1, p < 0.0001) and those with non-visceral metastasis (38.6 months, 95% CI: 29.8–NR, p < 0.0001). Similarly, OS was significantly better in first-line treatment (48.6 months, 95% CI: 39.1–NR) and non-visceral metastasis cases (NR, 95% CI: 40.6–NR, p < 0.0001). No significant differences in 3-year PFS and OS were found between patients with and without dose reductions.Conclusion: In real-world settings, and away from the stringency of controlled clinical trials, endocrine therapy in combination with ribociclib in patients with HR-positive/HER2-negative MBC is an effective and well-tolerated therapy with a manageable toxicity profile and a low drug discontinuation rate. Dose reduction due to toxicity did not worsen the outcome.Keywords: metastatic breast cancer, MBC, CDK4/6 inhibitors, ribociclib, aromatase inhibitors, fulvestrant

Jia Wei,1,&ast; Mingfen Song,1,&ast; Hong Jing Mao,1 Ruobing Qi,1 Lili Yang,1 You Xu,1 Pan Yan,1 Linlin Hu2 1Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310013, People’s Republic of China; 2Sleep Medicine Center, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Jing Mao, Email maohongjing@hz7hospital.comBackground: The effectiveness of medication combined with smartphone-delivered cognitive behavioral therapy for insomnia (CBT-I) has been well verified, but there are few studies on the sequence of remission of insomnia symptoms. This study aims to understand the sequence of symptom improvement and the factors influencing the treatment effectiveness in patients with insomnia.Methods: Smartphone-delivered CBT, as a form of Online CBT, allows for training through mobile devices at any time and place. We utilized the Good Sleep 365 app to conduct a survey, involving 2820 patients who met the baseline inclusion criteria. These patients were assessed using a general demographic questionnaire and the Pittsburgh Sleep Quality Index (PSQI) to evaluate general demographic information and insomnia symptoms, and subsequently underwent CBT training using the Good Sleep 365 app. A total of 1179 patients completed follow-ups at 4 weeks, 8 weeks, 16 weeks, and 24 weeks.Results: At 4 weeks and 8 weeks, the descending order of the reduction rates of PSQI components (excluding component 6: use of sleeping medication) was: sleep latency, subjective sleep quality, sleep efficiency, sleep disturbance, sleep maintenance, and daytime dysfunction. At 16 weeks and 24 weeks, the descending order was subjective sleep quality, sleep latency, sleep efficiency, daytime dysfunction, sleep maintenance, and sleep disturbance. There were significant differences in the reduction rates of PSQI components (excluding component 6: use of sleeping medication) both at the same follow-up times and at different follow-up times (all P< 0.05). Multivariable logistic regression analysis showed that patients older than 30 years and those with a college degree or above had better treatment outcomes, whereas those with a disease duration of more than three years had worse outcomes.Conclusion: The sequence of symptom improvement in patients with insomnia changes over time, and age, educational level, and duration of disease are factors influencing treatment outcomes.Keywords: insomnia, CBT-I, PSQI, influencing factors

Chen Qu,1,&ast; Fei Xia,2,&ast; Ling Chen,1 Hong-Jian Li,2 Wei-Min Li1 1Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, People’s Republic of China; 2Department of Ultrasonography, Huai’an Cancer Hospital, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Jian Li, Department of Ultrasonography, Huai’an Cancer Hospital, Huai’an, Jiangsu, 223232, People’s Republic of China, Tel +8613511507565, Email 492938595@qq.com Wei-Min Li, Department of Ultrasonography, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China, Tel +8613912362309, Email 1005342597@qq.comPurpose: : To explore the diagnostic value of artificial intelligence (AI)-based on real-time dynamic ultrasound imaging system for minimal breast lesions.Patients and Methods: Minimal breast lesions with a maximum diameter of ≤ 10mm were selected in this prospective study. The ultrasound equipment and AI system were activated Simultaneously. The ultrasound imaging video is connected to the server of AI system to achieve simultaneous output of AI and ultrasound scanning. Dynamic observation of breast lesions was conducted via ultrasound. And these lesions were evaluated and graded according to the Breast Imaging Reporting and Data System (BI-RADS) classification system through deep learning (DL) algorithms in AI. Surgical pathology was taken as the gold standard, and ROC curves were drawn to determine the area under the curve (AUC) and the optimal threshold values of BI-RADS. The diagnostic efficacy was compared with the use of a BI-RADS category > 3 as the threshold for clinically intervening in diagnosing minimal breast cancers.Results: 291 minimal breast lesions were enrolled in the study, of which 228 were benign (78.35%) and 63 were malignant (21.65%). The AUC of the ROC curve was 0.833, with the best threshold value > 4A. When using >BI-RADS 3 and >BI-RADS 4A as threshold values, the sensitivity and negative predictive value for minimal breast cancers were higher for >BI-RADS 3 than >BI-RADS 4A (100% vs 65.08%, 100% vs 89.91%, P values < 0.001). However, the corresponding specificity, positive predictive value, and accuracy were lower than those for >BI-RADS 4A (42.11% vs 85.96%, 32.31% vs 56.16%, and 54.64% vs 81.44%, P values < 0.001).Conclusion: The AI-based real-time dynamic ultrasound imaging system shows good capacity in diagnosing minimal breast lesions, which is helpful for early diagnosis and treatment of breast cancer, and improves the prognosis of patients. However, it still results in some missed diagnoses and misdiagnoses of minimal breast cancers.Keywords: Breast cancer, ultrasound, artificial intelligence, diagnostic

Marella CE van Ruissen,1,2 Sebastiaan JW van Kraaij,1,2 Pim Gal,1,2 Wouter A Bakker,1,2 Hemme J Hijma,1,2 Geert Jan Groeneveld,1,2 Marieke L de Kam,1 Jacobus Burggraaf,1,2 Matthijs Moerland1,2 1Center for Human Drug Research, Leiden, The Netherlands; 2Leiden University Medical Center, Leiden, The NetherlandsCorrespondence: Matthijs Moerland, Center for Human Drug Research, Zernikedreef 8, Leiden, 2333CL, The Netherlands, Tel +31 71 524 6400, Fax +31 71 5246 499, Email mmoerland@chdr.nlAbstract: Dermal allyl isothiocyanate (AITC) administration and whole-body heat stress (WBHS) are two challenge models that are used to evaluate physiological mechanisms of vasodilation and pharmacological activity in humans. Their exact vasodilatory mechanisms in humans are not fully elucidated but are likely to be nitric oxide (NO)-mediated. This study aimed to evaluate whether there is overlap in the vasodilatory pathways of dermal AITC application and WBHS by combining the challenges. In this open-label interventional study, healthy volunteers underwent dermal administration of AITC twice: under basal conditions and during WBHS. Dermal blood flow (DBF) was non-invasively measured using laser speckle contrast imaging four times, once in each of the following situations: baseline, WBHS only, AITC only, and WBHS combined with AITC. A total of 12 male volunteers, aged 18– 61 years, participated in the study. Compared to baseline, following AITC application, their DBF increased by 63.43 AU (baseline: 32.55, 95% CI [17.78, 47.31] AU, AITC only: 95.97, 95% CI [81.21, 110.7] AU, p < 0.0001). During WBHS, the increase in DBF after AITC was 42.76 AU (WBHS only: 87.25, 95% CI [72.49, 102.0] AU, WBHS+AITC: 130.0, 95% CI [115.2, 144.8] AU, p < 0.0001). The combination of WBHS and AITC resulted in a lower DBF than the sum of the DBF responses to AITC and WBHS when applied separately (ED 20.67, 95% CI [− 3.532, 44.88], p = 0.0916). This might point towards the presence of an interaction in the vasodilatory mechanism of AITC application and WBHS, possibly indicating overlap in their NOS-driven vasodilatory pathways.Keywords: clinical study, vasodilatory pathways, laser speckle contrast imaging, pharmacological challenge models

Na Yang,1,2,&ast; Yong-Bo Hou,2,3,&ast; Tian-Hao Cui,2 Jun-Ma Yu,2 Shu-Fang He,4,5 Hai-Juan Zhu1 1Department of Anesthesiology, Maternal and Child Medical Center of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui, People’s Republic of China; 3Department of Anesthesiology, Wannan Medical College, Wuhu, Anhui, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Fang He; Hai-Juan Zhu, Email sfhe@ahmu.edu.cn; 35880762@qq.comBackground: Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism.Methods: Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI.Results: IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-β (TGF-β) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-β 1in MI rats.Conclusion: IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-β pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair. Keywords: ischemic preconditioning, myocardial infarction, Exosomes, MicroRNAs, cardiac function, myocardial fibrosis

Dong-Xia Wu,1,&ast; Jing-Xian Hu,2,&ast; Jian-Hong Ma,1,&ast; Ke-Yi Chang,1,&ast; Yun Zhang,1 Xiao-Li Quan,1 Jia-Ning Han,1 Hai-Jing Long,1 Chen Chen,1 Wei Zhai,1 Huan-Huan Guo,1 Li-Li Zhang,2 Xiao-Lan Wang2 1Department of Infection and Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Nursing, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li Zhang; Xiao-Lan Wang, Department of Nursing, Beijing Youan Hospital, Capital Medical University, No. 8 of Xitoutiao, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86 010 8399 7143, Email lillizhang3200z@163.comPurpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies.Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA.Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA’s place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05).Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.Keywords: HIV/AIDS, AIDS, self-management

Hong-Mei Shu,1,&ast; Chang-Qing Lin,1 Bei He,1 Wang Wang,1 Ling Wang,1 Ting Wu,1 Hai-Juan He,1 Hui-Juan Wang,1 He-Ping Zhou,2 Guo-Zheng Ding1,&ast; 1Department of Pulmonary and Critical Care Medicine, Anqing Municipal Hospital, Anhui, People’s Republic of China; 2Neurosurgery Department, Anqing Municipal Hospital, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Mei Shu, Email shuxin501@163.comBackground: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes.Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The “ConsensusClusterPlus” package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT – PCR to detect the expression levels of eight genes in COPD patient and normal.Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them.Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.Keywords: chronic obstructive pulmonary disease, pyroptosis, gene, biomarkers, immune Infiltration

The LUX-ZEPLIN (LZ) experiment is a dark matter detector centered on a dual-phase xenon time projection chamber. We report searches for new physics appearing through few-keV-scale electron recoils, using the experiment's first exposure of 60 live days and a fiducial mass of 5.5 t. The data are found to be consistent with a background-only hypothesis, and limits are set on models for new physics including solar axion electron coupling, solar neutrino magnetic moment and millicharge, and electron couplings to galactic axionlike particles and hidden photons. Similar limits are set on weakly interacting massive particle (WIMP) dark matter producing signals through ionized atomic states from the Migdal effect.

We report on new measurements of elliptic flow (v2) of electrons from heavy-flavor hadron decays at mid-rapidity (|y|

Aminath Afaa Mohamed,1,2 Juen Kiem Tan,1,2 Michelle Maryanne Tan,3 Ching Soong Khoo,1,2 Wan Nur Nafisah Wan Yahya,1,2 Muhammad Samir Haziq Abd Rahman,2 Rosnah Sutan,2,4 Hui Jan Tan1,2 1Department of Medicine, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, 56000, Malaysia; 2Department of Medicine, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, 56000, Malaysia; 3Department of Medicine, Hospital Tengku Ampuan Rahimah, Klang, 41200, Malaysia; 4Department of Community Health, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, 56000, MalaysiaCorrespondence: Hui Jan Tan, Department of Medicine, Faculty of Medicine, National University of Malaysia, Kuala Lumpur, Malaysia, Email tanhuijan@gmail.com; tanhuijan@ukm.edu.myPurpose: Stroke is the second leading cause of global deaths. Post-stroke seizures (PSS) can lead to lasting complications, such as prolonged hospitalizations, increased disability rates, and higher mortality. Our study investigates the associated factors that contribute to post-stroke seizures in patients at a local tertiary hospital.Patients and Methods: We designed a case–control study where patients admitted with PSS were recruited with consent. Controls admitted for stroke without seizure were then included. Suitability based on exclusion criteria was ensured before recording their sociodemographic and clinical data. An EEG was performed and read by two certified neurologists before the data was analyzed.Results: We recruited 180 participants, 90 cases and 90 matched controls. Gender (p=0.013), race (p=0.015), dyslipidemia (p< 0.001), prior stroke (p< 0.031), large artery atherosclerosis (p< 0.001), small vessel occlusions (p< 0.001), blood pressure on presentation (p< 0.028) and thrombolysis administration (p< 0.029) were significantly associated with the occurrence of PSS. An increase in odds of PSS was observed in the male gender (1.974), dyslipidemia (3.480), small vessel occlusions (4.578), and in participants with epileptiform changes on EEG (3.630). Conversely, lower odds of PSS were seen in participants with high blood pressure on presentation (0.505), large artery atherosclerosis (0.266), and those who underwent thrombolysis (0.319).Conclusion: This study emphasized that identifying post-stroke seizures may be aided by EEGs and recognizing at-risk groups, which include males of Chinese descent in Asia, dyslipidemia, small vessel occlusions, those with low to normal blood pressure on presentation, and epileptiform changes in EEGs.Plain Language Summary: The research aims to establish the risk factors associated with post-stroke seizures in an Asian population and their similarity to the Western literature. Our findings highlight the critical risk factors to identify in at-risk patients, which may prompt changes in guidelines in future to enhance patient outcomes and improve the quality of care.Keywords: seizures, stroke, post-stroke epilepsy, epilepsy, electroencephalogram

Salma S AlSharhan,1 Wasan F AlMarzouq,1 Hamzah K Alshaikh,2 Hussain J Aljubran,3 Rizam Alghamdi,4 Sarah M AlQahtani,4 Aseel F Almarzouq,5 Naheel A AlAmer6 1Department of Otorhinolaryngology Head & Neck Surgery, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 2Department of Otorhinolaryngology Head & Neck Surgery, King Fahd Military Medical Complex, Dhahran, Saudi Arabia; 3College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 4Department of Otorhinolaryngology Head & Neck Surgery, Dammam Medical Complex, Dammam, Saudi Arabia; 5College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia; 6Department of Family and Community Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi ArabiaCorrespondence: Salma S AlSharhan, Department of Otorhinolaryngology Head & Neck Surgery, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, 34212, Saudi Arabia, Tel +966505951801, Email ssalsharhan@iau.edu.saPurpose: Otolaryngology has experienced notable advancements and growth in the application of artificial intelligence (AI). However, otolaryngologists’ perception of these tools are lacking. This study aims to assess the knowledge and attitudes of otolaryngologists toward AI.Patients and Methods: A cross-sectional study was conducted among 110 otolaryngologists in the Eastern Province of Saudi Arabia. A piloted questionnaire was used to gather information on knowledge, attitude, and opinions regarding AI. Data analysis was conducted using SPSS version 26.Results: Of the sample, 60% indicated average perceived knowledge of AI, while approximately 44.5% perceived their AI knowledge in the field of otolaryngology to be below average. A significant positive correlation was identified between knowledge and attitude scores. It was found that a higher knowledge score was more closely associated with seeing more than 15 patients per day, while a higher attitude score was more closely associated with being older, being a consultant, and having more years of professional experience. Of the sample, 38.2% strongly agreed that the application of AI in scientific research should be included in the residency training program.Conclusion: These findings underscore the importance of incorporating AI tools into certain aspects of the otolaryngology residency training program, highlighting their significance.Keywords: otolaryngology, artificial intelligence, machine learning, knowledge, attitude

Yu-Chieh Ho,1,&ast; Chia-Ti Wang,1,&ast; Tzu-Chieh Weng,2 Chung-Han Ho,3,4 Kang-Ting Tsai,5,6 Chien-Chin Hsu,1,7 Hung-Jung Lin,1,7,8 Hsiu-Chin Chen,5,9 Chien-Cheng Huang1,7,10 1Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan; 2Division of Hospital Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 3Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 4Department of Information Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 5Department of Senior Welfare and Services, Southern Taiwan University of Science and Technology, Tainan, Taiwan; 6Division of Geriatrics and Gerontology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 7School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan; 8Department of Emergency Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan; 10Department of Emergency Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Chien-Cheng Huang, Department of Emergency Medicine, Chi Mei Medical Center, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email jasonhuang0803@gmail.com Hsiu-Chin Chen, Department of Nursing, Chi Mei Medical Center, Tainan, Taiwan, 901 Zhonghua Road, Yongkang District, Tainan City, 710, Taiwan, Tel +886-6-281-2811, Fax +886-6-281-6161, Email 300006@mail.chimei.org.twPurpose: The home-based medical integrated program (HMIP) is a novel model for home healthcare (HHC) in Taiwan, initiated in 2016 to enhance care quality. However, the outcomes of this program on health outcomes and medical resource utilization in HHC patients remain unclear. Thus, we conducted this study to clarify it.Patients and Methods: The authors utilized the Taiwan National Health Insurance Research Database to identify HHC patients who received HMIP and those who did not between January 2015 and December 2017. A retrospective cohort study design was used. Convenience sampling was employed to select patients who met the inclusion criteria: being part of the HHC program and having complete data for analysis.Results: A total of 4982 HHC patients in the HMIP group and 10,447 patients in the non-HMIP group were identified for this study. The mean age in the HMIP group and non-HMIP group was 77.6 years and 76.1 years, respectively. Compared with the non-HMIP group, the HMIP group had lower total medical costs for HHC, fewer outpatient department visits and lower medical costs, lower medical costs for emergency department visits, fewer hospitalizations, and a lower mortality rate (34.6% vs 41.2%, p< 0.001).Conclusion: The HMIP is a promising model for improving care quality and reducing medical resource utilization in HHC patients. While this suggests that the non-HMIP model should be replaced, it’s important to note that both non-HMIP and HMIP models currently coexist. The HMIP may serve as an important reference for other nations seeking to improve care quality and reduce medical resource utilization in their own HHC systems.Keywords: home-based medical integrated plan, health outcomes, medical resource utilization, Taiwan