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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.

Context. The determination of accurate photometric redshifts (photo-zs) in large imaging galaxy surveys is key for cosmological studies. One of the most common approaches is machine learning techniques. These methods require a spectroscopic or reference sample to train the algorithms. Attention has to be paid to the quality and properties of these samples since they are key factors in the estimation of reliable photo-zs. Aims. The goal of this work is to calculate the photo-zs for the Year 3 (Y3) Dark Energy Survey (DES) Deep Fields catalogue using the Directional Neighborhood Fitting (DNF) machine learning algorithm. Moreover, we want to develop techniques to assess the incompleteness of the training sample and metrics to study how incompleteness affects the quality of photometric redshifts. Finally, we are interested in comparing the performance obtained by DNF on the Y3 DES Deep Fields catalogue with that of the EAzY template fitting approach. Methods. We emulated – at a brighter magnitude – the training incompleteness with a spectroscopic sample whose redshifts are known to have a measurable view of the problem. We used a principal component analysis to graphically assess the incompleteness and relate it with the performance parameters provided by DNF. Finally, we applied the results on the incompleteness to the photo-z computation on the Y3 DES Deep Fields with DNF and estimated its performance. Results. The photo-zs of the galaxies in the DES deep fields were computed with the DNF algorithm and added to the Y3 DES Deep Fields catalogue. We have developed some techniques to evaluate the performance in the absence of “true” redshift and to assess the completeness. We have studied the tradeoff in the training sample between the highest spectroscopic redshift quality versus completeness. We found some advantages in relaxing the highest-quality spectroscopic redshift requirements at fainter magnitudes in favour of completeness. The results achieved by DNF on the Y3 Deep Fields are competitive with the ones provided by EAzY, showing notable stability at high redshifts. It should be noted that the good results obtained by DNF in the estimation of photo-zs in deep field catalogues make DNF suitable for the future Legacy Survey of Space and Time (LSST) and Euclid data, which will have similar depths to the Y3 DES Deep Fields.

Nguyen Van An,1 Hai Thi Nguyen,2 Van Nguyen Le,1 Ha Thi Thu Van,1 Nguyen Minh Hai,1 Vu Huy Luong,3,4 Vinh Thi Ha Nguyen,4,5 Hoa Quynh Pham,6 Hung Van Le,4,6 Dinh Viet Hung,7 Hoang Trung Kien,8 Minh Nhat Le,9,10 Nguyen Hoang Viet,11 Luong Cong Thuc,12 Ta Ba Thang,13 Tran Viet Tien,14 Le Huy Hoang,15 Nguyen Thuy Tram,15 Tuan Dinh Le,16 Nguyen Tien Son,16 Hai Ha Long Le17,18 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Central Laboratory, Bac Ninh Provincial General Hospital, Bac Ninh, Vietnam; 3Department of Laser and Skincare, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 4Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 5Department of General Planning, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 6Department of Microbiology, Mycology and Parasitology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 7Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 8Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 9Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 10Antimicrobial Resistance Research Center, National Institute of Infectious Disease, Tokyo, Japan; 11Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 12Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 13Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 14Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 15Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam; 16Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 17Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 18Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, VietnamCorrespondence: Hai Ha Long Le, Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, 100000, Vietnam, Tel +84978520055, Email lehalonghai@gmail.comPurpose: Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA) strain, can become resistant to all classes of clinically available antibiotics and causes skin infections and severe infections in the lungs, heart, and bloodstream. The study aimed to evaluate antimicrobial susceptibility patterns and MRSA exhibiting multidrug resistance obtained through a microbiological culture of clinical specimens at Bac Ninh Provincial General Hospital in Bac Ninh Province, Vietnam.Methods: We employed a cross-sectional analysis at Bac Ninh Provincial General Hospital in Vietnam. 15,232 clinical samples from inpatients were examined. S. aureus isolates were identified using established protocols and tested for MRSA and antibiotic susceptibility. Data was analyzed using R software, with statistical calculations to assess associations between variables.Results: Staphylococcus aureus was isolated from 417 samples (2.7%), with 77.2% being MRSA and 22.8% methicillin-susceptible Staphylococcus aureus (MSSA). Significant sources of MRSA were wounds (64.6%) and the surgical unit (50%) according to sample types and hospital wards, respectively. S. aureus showed high resistance rates, the highest being azithromycin (83.2%), and was fully susceptible to vancomycin. Among 294 multidrug-resistant (MDR) strains, the prevalence was 82.0% in MRSA and 18.0% in MSSA.Conclusion: The study highlights widespread antimicrobial resistance among MRSA isolates from a provincial hospital in Vietnam, emphasizing the urgent need for antibiotic surveillance, formulation of antibiotic policies, and preventive measures to tackle the increasing prevalence of multidrug-resistant MRSA.Keywords: Staphylococcus aureus, antibiotic resistance, MRSA, MDR, Vietnam

BackgroundVaccine hesitancy, delaying or refusing to vaccinate despite the availability of vaccines, impedes the progress of achieving optimal HPV vaccine coverage. Little is known about the sources of human papillomavirus (HPV) vaccine hesitancy among racially/ethnically and geographically diverse communities. The purpose of this paper is to explore HPV vaccine hesitancy among rural, Slavic, and Latino communities that reside in counties with low HPV vaccine uptake rates.MethodsKey informant interviews and focus groups were conducted with rural, Slavic, and Latino communities that reside within counties in California that have low HPV vaccine up to date rates (16-25%). Qualitative data were transcribed verbatim and analyzed using inductive and deductive thematic analysis.ResultsA total of seven focus groups and 14 key informant interviews were conducted with 39 individuals from seven California counties. Salient themes that contributed to HPV vaccine hesitancy included the following: social media and the anti-vaccination movement; a strong belief in acquiring immunity naturally; prior vaccine experiences; and vaccine timing concerns. Participants suggested the provision of culturally appropriate, in-language, in-person easy to understand HPV vaccine education to mitigate HPV vaccine hesitancy.ConclusionsOur findings can inform future interventions to increase HPV vaccine uptake among hesitant communities.

Oscar Rosenkrantz,1,2 Jannik Wheler,1 Mats Christian Westphal Thrane,3 Lars Pedersen,1 Henrik Toft Sørensen1 1Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; 2Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, Copenhagen, Denmark; 3Danish Health Data Authority, Copenhagen, DenmarkCorrespondence: Oscar Rosenkrantz, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43, 45, DK, Aarhus N, 8200, Denmark, Tel +45 87 16 72 12, Email oscar.oelrich.rosenkrantz@clin.au.dkBackground: The Danish National Hospital Medication Register (DHMR), one of the first nationwide in-hospital medication registries in the world, contains detailed information on medication administration and dispensing.Objective: To provide an overview of the information recorded in the DHMR and to highlight its strengths and limitations as a pharmacoepidemiological research tool.Methods: We reviewed the registry´s geographic and clinical specialty coverage and medications recorded according to the main groups of the Anatomical Therapeutic Chemical classification system.Results: From May 2018 through December 2023, the DHMR recorded data on more than 1.9 million unique patients from all approximately 50 public hospitals and associated hospital outpatient clinics, totaling 105.3 million recordings of hospital medication use. The registry records detailed data on the indication for medication, medication type, pharmaceutical form, dosage, and administration time, collected through electronic medical record systems. Although the data quality has not yet been evaluated in a scientific context, some potential limitations are known. These include regional differences in the data collection and a lack of data from certain clinical specialties. Due to its recent establishment in 2018, the registered number of patients treated may still be limited for some rarely used medications.Conclusion: The DHMR is an important new resource for research in Denmark. Combined with the Danish National Prescription Registry, which covers all community pharmacies, it offers access to accurate data on medication exposure in the Danish population. Users should be aware of potential issues with lack of information before 2018.Keywords: pharmacoepidemiology, hospital medication system, pharmacotherapy, data source, drug databases, registry data, Denmark

Jakob Kjølby Eika,1,2,* Kasper Bonnesen,1,2,* Lars Pedersen,1,2 Vera Ehrenstein,1,2 Henrik Toft Sørensen,1,2 Morten Schmidt1– 3 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Department of Cardiology, Gødstrup Regional Hospital, Herning, Denmark*These authors contributed equally to this workCorrespondence: Morten Schmidt, Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark and Department of Clinical Medicine, Aarhus University, Olof Palmes Allé 43– 45, Aarhus, 8200, Denmark, Tel +45 87 16 72 12, Email morten.schmidt@clin.au.dkPurpose: Ibuprofen is used to treat acute pericarditis, but high-dose ibuprofen has also been associated with increased cardiovascular risks. We examined the cardiovascular safety of using ibuprofen for acute pericarditis.Patients and Methods: A Danish nationwide, population-based cohort study including patients ≥ 18 years with first-time acute pericarditis (n=12,381) during 1996– 2020 was conducted. Ibuprofen use was modelled in two ways: First, we considered patients exposed based on the tablet strength of their first ibuprofen filling (a proxy for an intention-to-treat analysis). Second, we considered patients exposed in a time-varying manner (a proxy for an as-treated analysis). The primary outcome of major adverse cardiovascular events (MACE) was a composite of myocardial infarction, ischemic stroke, congestive heart failure, and cardiovascular death.Results: In the intention-to-treat analysis, the 1-year risk of MACE was 1.37% (95% confidence interval [CI]: 1.03– 1.79) for ibuprofen initiators and 4.32% (95% CI: 3.89– 4.78) for non-initiators. Compared with non-initiators within 1-year follow-up, the adjusted hazard ratio for MACE was 0.75 (95% CI: 0.67– 0.85) for initiators overall, 0.38 (95% CI: 0.28– 0.52) for initiators of > 400 mg tablets, and 0.87 (95% CI: 0.76– 0.99) for initiators of ≤ 400 mg tablets. In the as-treated analysis, compared with no use, the hazard ratio associated with ibuprofen use was 0.69 (95% CI: 0.54– 0.89) for MACE, 0.82 (95% CI: 0.54– 1.26) for myocardial infarction, 0.74 (95% CI: 0.45– 1.22) for ischemic stroke, 0.67 (95% CI: 0.47– 0.96) for congestive heart failure, and 0.60 (95% CI: 0.31– 1.17) for cardiovascular death.Conclusion: Ibuprofen use for acute pericarditis was not associated with increased cardiovascular risks, supporting its safety in current practice.Keywords: Pericarditis, Anti-Inflammatory Agents, non-steroidal, Cohort Study, Epidemiology

Tian-Yu Yao, Jia-Song Wang, Hua-Tao Xie, Ming-Chang Zhang Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Hua-Tao Xie; Ming-Chang Zhang, Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +86-27-85726662, Email huataoxie@hust.edu.cn; mingc_zhang@hust.edu.cnObjective: To compare differences in postoperative pain, foreign body sensation, photophobia, and lacrimation between balafilcon A and samfilcon A bandage contact lenses (BCLs) in the early stage following pterygium surgery.Methods: A total of 66 eyes with pterygium conjunctival grafts fixed with sutures were included in this study, comprising 32 eyes fixed with samfilcon A and 34 eyes fixed with balafilcon A. Demographic data, postoperative corneal epithelialization time, and subjective discomfort, such as pain (using the visual analog scale [VAS]), were recorded and compared.Results: Significant differences were noted in VAS scores between the first day (P< 0.01) and the second day post-surgery (P=0.03), suggesting that patients experienced less pain after wearing samfilcon A. However, no significant differences were observed in corneal epithelialization time, VAS score before lens removal, foreign body sensation, photophobia, lacrimation, insomnia, and demographic data between the two groups. Finally, only two balafilcon A patients required nonsteroidal analgesics.Conclusion: After pterygium surgery, samfilcon A BCL was associated with lower pain levels compared with balafilcon A BCL and could assist in reducing postoperative discomfort in patients and concurrently improving patient satisfaction.Keywords: bandage contact lenses, pterygium, pain, visual analog scale, samfilcon A, balafilcon A

Bright Etumuse,1 Majesty Greer,2 Jane Onyemachi,1 Youshaa El-Abed,3 Sai Kamma,1 Jay D Shah,4 Henry Tuan Tran,1 Nasir Hussain,5 Thomas P Pittelkow,6 Ryan S D’Souza6 1University of Texas Medical Branch School of Medicine, Galveston, TX, USA; 2Howard University College of Medicine, Washington, DC, USA; 3Kansas City University, Kansas City, MO, USA; 4Department of Anesthesiology, Baylor College of Medicine, Houston, TX, USA; 5Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 6Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USACorrespondence: Ryan S D’Souza, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic 200 First St. SW, Rochester, MN, 55905, USA, Email Dsouza.ryan@mayo.eduBackground: As cannabis legalization expands nationally and globally, its use for chronic pain increases, prompting people to seek information on social media platforms like YouTube. This study evaluates the accuracy and quality of information of popular YouTube videos on cannabis for chronic pain.Methods: Using search terms related to cannabis for pain, the top 66 videos by view count were selected. Each video was classified as useful, misleading, or neither. The quality and reliability of each video were assessed using the modified DISCERN, mDISCERN, score and the Global Quality Scale, GQS. The video characteristics, usefulness classification, mDISCERN scores, and GQS scores were summarized. Continuous and categorical outcomes were compared using t-test and chi-square, respectively.Results: Of the 66 videos, 22.73% (n=15) were classified as useful, and 77.27% (n=51) were classified as neither. Of useful videos, 40.00% (n=6) were uploaded by physicians, 40.00% (n=6) were uploaded by corporations, and 6.67% (n=1) were uploaded by an independent user. Of videos classified as neither useful nor misleading, news sources uploaded 27.45% (n=14) of these videos (P=0.02). Physicians uploaded 37.50% (n = 18) of videos with a GQS score ≥ 3 (P=0.04), while independent users uploaded significantly more videos with a mDISCERN score < 3 (22.20%, P=0.02). Useful videos had a mean GQS of 4.00 ± 0.65 compared to a mean GQS of 2.76 ± 0.86 for videos deemed neither (P< 0.0001).Conclusion: This study suggests a moderate quality of YouTube content on cannabis use for chronic pain. Given cannabis’s growing popularity and potential for misinformation on popular social media platforms, healthcare professionals and organizations should consider uploading educational videos on this topic on YouTube.Keywords: social media, cannabis, medical cannabis, analgesics, YouTube

Shruti Handa,1 Megan R Heffernan,2 Summer Tan,3 David A Keith,1 Annika Rosén,4– 6 Hsinlin Thomas Cheng7 1Division of Oral and Maxillofacial Surgery, Department of Surgery, Massachusetts General Hospital and Harvard School of Dental Medicine, Boston, MA, USA; 2Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; 3Department of Dentistry, Harvard School of Dental Medicine, Boston, MA, USA; 4Department of Oral and Maxillofacial Surgery, Eastman Institute, Stockholm, Sweden; 5Department of Clinical Dentistry, University of Bergen, Bergen, Norway; 6Department of Oral and Maxillofacial Surgery, Haukeland University Hospital, Bergen, Norway; 7Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USACorrespondence: Shruti Handa, Department of Surgery, Massachusetts General Hospital, 165 Cambridge Street, Suite &num;401, Boston, Massachusetts, 02114, USA, Email shanda1@mgh.harvard.eduPurpose: Orofacial Pain (OFP) affects 15% of the general population. OFP conditions can be myofascial, also known as temporomandibular disorders (TMDs) or neuropathic. The underlying pathophysiology in several chronic OFP conditions, is unknown. Small fiber neuropathy (SFN) is a disorder of thinly myelinated A-delta and non-myelinated C-fibers and can manifest as sensory and autonomic neuropathies. SFN has been demonstrated in some OFP conditions. Our study aims to assess the presence of OFP in patients with sensory and autonomic neuropathies and assess the correlation between OFP, skin biopsy and autonomic dysfunction.Patients and Methods: This is a retrospective study (2018– 2020) of patients from the SFN registry, Massachusetts General Hospital, Boston, USA, for the presence of OFP. All patients were included. Primary outcome: Prevalence of OFP in patients with chronic neuropathies. Secondary outcomes: Correlation between OFP and skin biopsy, dysautonomia, headaches, chronic nociceptive pain, psychological conditions, and patient factors, such as mean age and BMI.Results: Charts of 450 patients with sensory and autonomic neuropathies were reviewed. 22.67% (n=102) had OFP. The mean (range) age at biopsy in patients with OFP was 48.36 (20– 81) years, female: male ratio 3.25:1. More OFP patients had negative skin biopsy results (p value< 0.05) than those with sensory neuropathies. Patients with OFP had significantly higher prevalence of psychological conditions (p value 0.000), and higher BMI > 30 (p value 0.025). Dysautonomia was significantly higher in patients with TMDs when compared to the ones without TMDs (p value 0.030). There was no significant difference in mean age, gender predilection, presence of headaches, peripheral neuropathies, and nociceptive pain between patients with and without OFP.Conclusion: OFP and sensory neuropathies can be overlapping conditions. Patients presenting with concomitant TMD and dysautonomia can be further tested for SFN. This can further help us understand a correlation if any, between idiopathic TMD/OFP conditions and SFN and further our understanding of the pathophysiology of these conditions.Keywords: idiopathic facial pain, orofacial pain, temporomandibular disorders, skin biopsy, autonomic dysfunction, sensory neuropathic pain, dysautonomia, small fiber neuropathy

Addyson E Sand,1 Tyler E Powell,1 Helen T Marry,1 Heather R Rathbun,1 Jenna R Steege,1 Allison LeMahieu,2 Adam K Jacob,1 Ryan S D’Souza,1 Oludare O Olatoye1 1Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; 2Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USACorrespondence: Oludare O Olatoye, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA, Email Olatoye.Oludare@mayo.eduBackground: Patients receiving methadone, buprenorphine, and naltrexone for either chronic pain or substance use disorder (SUD) pose perioperative challenges. Due to their complex pharmacology, perioperative recommendations continue to evolve. Deviations from these recommendations may result in worse perioperative outcomes. A formal preoperative evaluation (POE) and optimization of patients on these medications are recommended to address these concerns.Methods: A single-center retrospective electronic health record review was performed with adult patients on methadone, buprenorphine, and naltrexone undergoing elective surgery between January 1, 2010 and December 31, 2020. The primary outcome of interest was the percentage of patients referred to the POE clinic for evaluation prior to the scheduled elective surgery. In addition, we assessed differences in variables (perioperative opioid, hospital length of stay, perioperative multimodal analgesics, perioperative complications, inpatient pain service consult, readmission within 30 days, cancellation of surgery, addiction medicine consult) based on POE clinic evaluation. This analysis was performed separately for patients prescribed these medications for SUD versus chronic pain. Continuous outcomes were analyzed using linear regression with generalized estimating equations (GEE) and robust variance estimates.Results: A total of 714 patients were included in the final analysis, of which 572 (80%) took buprenorphine, methadone, or naltrexone for chronic pain and 142 (20%) took these medications for SUD. Within the chronic pain and SUD subpopulations, 193 (34%) and 35 (25%) patients had formal POE clinic assessments, respectively. Among those taking these medications for chronic pain, POE clinic evaluation was associated with a higher likelihood for receiving non-opioid multimodal analgesics perioperatively (p = 0.016).Conclusion: Formal preoperative evaluations are currently underutilized in patients who take buprenorphine, methadone, or naltrexone for chronic pain or SUD. These patients may benefit from POE clinic assessment to optimize perioperative outcomes.Keywords: preoperative evaluation, chronic opioid therapy, substance use disorder, naltrexone, buprenorphine, methadone, perioperative pain management

Dong-Mei Guan,1,&ast; Yuan-Zhuang Shan,1,&ast; Hao-Tian Zhao,2 Ying Meng,2 Zhong-Rui Yan,2 Hai-Lin Zhang2 1Shandong University of Tradition Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Jining No.1 People’s Hospital, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this studyCorrespondence: Hai-Lin Zhang, Department of Neurology, Jining No.1 People’s Hospital, No. 6 of Healthy Road, Rencheng District, Jining, Shandong, 272000, People’s Republic of China, Tel +86 176 6130 0365, Email zhanghailin_zhl@126.comBackground: Hemiplegic migraine, a less common variant of migraine, is the focus of this paper. Within the scope of this study, we present a case of hemiplegic migraine that bears the potential for misdiagnosis, particularly as encephalitis.Brief introduction to the Disease: The patient developed a right-sided headache a day prior to admission, accompanied by fever, nausea, vomiting, and left-sided limb weakness. On the fourth day, the patient experienced a grand mal epilepsy, marked by unconsciousness, leftward deviation of both eyes, limb convulsions, and foaming at the mouth. Cerebrospinal fluid analysis revealed no apparent abnormalities, Electroencephalography showed abnormal slow waves, imaging studies indicated swelling and meningeal thickening in the right cortex, and genetic testing identified a heterozygous mutation in the ATPIA2 gene. The diagnosis was hemiplegic migraine, and the patient received symptomatic supportive treatment, leading to improvement and subsequent discharge. Flunarizine and sodium valproate were prescribed post-discharge, and the patient achieved complete recovery after a one-month follow-up.Conclusion: Apart from experiencing headaches, patients with hemiplegic migraine may exhibit additional symptoms like fever, epilepsy, and hemiplegia. These manifestations warrant clinical attention, and if deemed necessary, genetic testing should be conducted, and this is an autosomal dominant pattern.Keywords: ATP1A2 gene mutation, encephalitis, migraine, hemiplegic migraine, swelling of the cortex

Frederik PB Kristensen,1 Sia K Nicolaisen,1 Jens S Nielsen,2,3 Diana H Christensen,1,4 Kurt Højlund,2,3 Henning Beck-Nielsen,2 Jørgen Rungby,5 Søren G Friborg,6 Ivan Brandslund,7,8 Jens S Christiansen4 ,† Peter Vestergaard,9,10 Niels Jessen,11– 13 Michael H Olsen,14,15 Mette K Andersen,16 Torben Hansen,16 Charlotte Brøns,5 Allan Vaag,5,17 Reimar W Thomsen,1 Henrik T Sørensen1 1Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark; 2Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark; 3Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Steno Diabetes Center Copenhagen, Herlev, Denmark; 6Department of Endocrinology, Odense University Hospital, Odense, Denmark; 7Department of Biochemistry, Lillebaelt Hospital, Vejle, Denmark; 8Regional Health Research, University of Southern Denmark, Odense, Denmark; 9Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 10Steno Diabetes Center North Denmark, Aalborg, Denmark; 11Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; 12Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark; 13Department of Biomedicine, Aarhus University, Aarhus, Denmark; 14Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 15Department of Internal Medicine and Steno Diabetes Center Zealand, Holbæk Hospital, Holbæk, Denmark; 16Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark; 17Lund University Diabetes Centre, Lund University, Malmö, Sweden†Dr Jens S Christiansen passed away on 16 December 2015Correspondence: Frederik PB Kristensen, Department of Clinical Epidemiology, Aarhus University, Olof Palmes Alle 43-45, Aarhus N, 8200, Denmark, Tel +45 87 16 82 37, Email fpk@clin.au.dkPurpose: This paper provides an overview of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort and biobank, including baseline characteristics of participants enrolled up to 2023, and post-enrollment rates of cardiovascular disease outcomes and mortality.Methods: Since 2010, the DD2 project has enrolled individuals with type 2 diabetes mellitus (T2DM) recently diagnosed by general practitioners and by hospital-based clinicians across Denmark. Data from questionnaires, clinical examinations, and biological samples are collected at enrollment. Additional baseline and longitudinal follow-up data are accessed via linkage to health registries.Results: Between 2010 and 2023, the DD2 project enrolled 11,369 participants (41.3% women, median age 61.4 years). Median T2DM duration at enrollment was 1.3 years, and median BMI was 31.6 kg/m2 for women and 30.5 kg/m2 for men. 18.3% were smokers, 5.7% consumed more than 14/21 units of alcohol weekly (women/men), and 17.9% reported leisure-time physical inactivity. Original midwife records dating back > 80 years revealed that 20.2% of cohort participants had birth weights < 3000 g. Based on complete hospital contact history 10 years before enrollment, 20.7% of cohort participants had macrovascular complications, 17.0% had microvascular complications, and 21.7% had kidney disease based on eGFR or urine albumin-creatinine measurements. At enrollment, statins were used by 68.2%, antihypertensive drugs by 69.9%, and glucose-lowering drugs by 86.5% of individuals. Median HbA1c was 48 mmol/mol and median LDL cholesterol 2.2 mmol/L. Genome-wide genotyping and biomarker data have been analyzed for over 9000 individuals. During the current follow-up time from the enrollment date (median 7.9 years), incident cardiovascular disease rate has been 13.8 per 1000 person-years and the mortality rate has been 17.6 per 1000 person-years.Conclusion: The DD2 cohort, with its detailed information and long-term follow up, can improve our understanding of the progression and prevention of complications among individuals with newly diagnosed T2DM.Keywords: cohort profile, type 2 diabetes mellitus, patient characteristics, Denmark

Wei-Li Xia,1,&ast; Xiao-Hui Zhao,2,&ast; Yuan Guo,1 Hong-Tao Hu,1 Hai-Liang Li1 1Department of Interventional Radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2Department of Interventional Radiology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hai-Liang Li, Department of interventional radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, 127 Dongming Road, Zhengzhou, Henan Province, 450008, People’s Republic of China, Tel +86 13903861969, Fax +0371 65587181, Email lihailianggy@163.comBackground and Objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS.Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed.Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients’ 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02).Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.Keywords: hepatocellular carcinoma, transarterial chemoembolization, portal vein tumor thrombus, 125I seed, arterioportal shunts

Background and objectiveKnowledge about exposure to cannabidiol (CBD) in breastfed infants can provide an improved understanding of potential risk. The aim was to predict CBD exposure in breastfed infants from mothers taking CBD and CBD-containing products.MethodsCannabidiol concentrations in milk previously attained from data collected through an existing human milk research biorepository were used to simulate infant doses and identify subgroups. A developed pediatric physiologically based pharmacokinetic model produced virtual breastfed infants administered the simulated CBD doses. Predicted breastfed infant exposures and upper area under the curve ratios were compared to the lowest therapeutic dose for approved indications in children.ResultsThe existing human milk research biorepository contained 200 samples from 181 unique breastfeeding mothers for whom self-reported administration data and CBD concentrations had previously been measured. Samples that were above the lower limit of quantification with only one maternal administration type revealed that administration type, i.e., joint/blunt or edible versus oil or pipe, resulted in significantly different subgroups in terms of milk concentrations. Resulting simulated infant doses (ng/kg) were described by lognormal distributions with geometric means and geometric standard deviations: 0.61 ± 2.41 all concentrations, 0.10 ± 0.37 joint/blunt or edible, and 2.23 ± 8.15 oil or pipe. Doses administered to breastfed infants had exposures magnitudes lower than exposures in children aged 4-11 years administered the lowest therapeutic dose for approved indications, and low upper area under the curve ratios.ConclusionsBased on real-world use, breastfeeding infants are predicted to receive very small exposures of CBD through milk. Studies examining adverse reactions will provide further insight into potential risk.

BackgroundAtrial fibrillation (AF)-the most common sustained cardiac arrhythmia-increases thromboembolic stroke risk 5-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C (protein phosphatase 1 regulatory subunit 12C)-the PP1 (protein phosphatase 1) regulatory subunit targeting MLC2a (atrial myosin light chain 2)-causes hypophosphorylation of MLC2a and results in atrial hypocontractility.MethodsRight atrial appendage tissues were isolated from human patients with AF versus sinus rhythm controls. Western blots, coimmunoprecipitation, and phosphorylation studies were performed to examine how the PP1c (PP1 catalytic subunit)-PPP1R12C interaction causes MLC2a dephosphorylation. In vitro studies of pharmacological MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with electrophysiology studies.ResultsIn human patients with AF, PPP1R12C expression was increased 2-fold versus sinus rhythm controls (P=2.0×10-2; n=12 and 12 in each group) with >40% reduction in MLC2a phosphorylation (P=1.4×10-6; n=12 and 12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF (P=2.9×10-2 and 6.7×10-3, respectively; n=8 and 8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a and dephosphorylation of MLC2a. Mice treated with lentiviral PPP1R12C vector demonstrated a 150% increase in left atrial size versus controls (P=5.0×10-6; n=12, 8, and 12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in mice treated with lentiviral PPP1R12C vector was significantly higher than in controls (P=1.8×10-2 and 4.1×10-2, respectively; n=6, 6, and 5).ConclusionsPatients with AF exhibit increased levels of PPP1R12C protein compared with controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key determinant of atrial contractility in AF.

Clusters of galaxies trace the most non-linear peaks in the cosmic density field. The weak gravitational lensing of background galaxies by clusters can allow us to infer their masses. However, galaxies associated with the local environment of the cluster can also be intrinsically aligned due to the local tidal gradient, contaminating any cosmology derived from the lensing signal. We measure this intrinsic alignment in Dark Energy Survey (DES) Year 1 REDMAPPER clusters. We find evidence of a non-zero mean radial alignment of galaxies within clusters between redshifts 0.1–0.7. We find a significant systematic in the measured ellipticities of cluster satellite galaxies that we attribute to the central galaxy flux and other intracluster light. We attempt to correct this signal, and fit a simple model for intrinsic alignment amplitude (AIA) to the measurement, finding AIA = 0.15 ± 0.04, when excluding data near the edge of the cluster. We find a significantly stronger alignment of the central galaxy with the cluster dark matter halo at low redshift and with higher richness and central galaxy absolute magnitude (proxies for cluster mass). This is an important demonstration of the ability of large photometric data sets like DES to provide direct constraints on the intrinsic alignment of galaxies within clusters. These measurements can inform improvements to small-scale modelling and simulation of the intrinsic alignment of galaxies to help improve the separation of the intrinsic alignment signal in weak lensing studies.

The fiducial cosmological analyses of imaging surveys like DES typically probe the Universe at redshifts z < 1. We present the selection and characterization of high-redshift galaxy samples using DES Year 3 data, and the analysis of their galaxy clustering measurements. In particular, we use galaxies that are fainter than those used in the previous DES Year 3 analyses and a Bayesian redshift scheme to define three tomographic bins with mean redshifts around z ∼0.9, 1.2, and 1.5, which extend the redshift coverage of the fiducial DES Year 3 analysis. These samples contain a total of about 9 million galaxies, and their galaxy density is more than 2 times higher than those in the DES Year 3 fiducial case. We characterize the redshift uncertainties of the samples, including the usage of various spectroscopic and high-quality redshift samples, and we develop a machine-learning method to correct for correlations between galaxy density and survey observing conditions. The analysis of galaxy clustering measurements, with a total signal to noise S/N ∼70 after scale cuts, yields robust cosmological constraints on a combination of the fraction of matter in the Universe

The radiation pattern within high energy quark- and gluon-initiated jets (jet substructure) is used extensively as a precision probe of the strong force as well as an environment for optimizing event generators with numerous applications in high energy particle and nuclear physics. Looking at electron-proton collisions is of particular interest as many of the complications present at hadron colliders are absent. A detailed study of modern jet substructure observables, jet angularities, in electron-proton collisions is presented using data recorded using the H1 detector at HERA. The measurement is unbinned and multi-dimensional, using machine learning to correct for detector effects. All of the available reconstructed object information of the respective jets is interpreted by a graph neural network, achieving superior precision on a selected set of jet angularities. Training these networks was enabled by the use of a large number of GPUs in the Perlmutter supercomputer at Berkeley Lab. The particle jets are reconstructed in the laboratory frame, using the kT jet clustering algorithm. Results are reported at high transverse momentum transfer Q2>150GeV2, and inelasticity 0.2

Recently, a blaNDM-9 and mcr-1 co-harboring E. coli ST 617 isolate was identified from an asymptomatic carrier in Korea. An 81-year-old female was admitted to a university hospital for aortic cardiac valve repair surgery. Following surgery, she was admitted to the intensive care unit (ICU) for three days, and carbapenem-resistant E. coli YMC/2017/02/MS631 was isolated from a surveillance culture (rectal swab). Antimicrobial susceptibility testing (AST) for colistin was not performed at that time. Upon retrospective study, further AST revealed resistance to all tested antibiotics, including meropenem, imipenem, ceftazidime-avibactam, amikacin, gentamicin, ciprofloxacin, trimethoprim-sulfamethoxazole, and colistin, with the exception of tigecycline. Whole genome sequencing analyses showed that this strain belonged to the ST617 serotype O89/162: H10 and harbored three β-lactamase genes (blaTEM-1B, blaCTX-M-55, blaNDM-9), mcr-1, and 14 other resistance genes. Seven plasmid replicon types (IncB, IncFII, IncI2, IncN, IncY, IncR, IncX1) were identified. Horizontal transfer of blaNDM-9 and mcr-1 from donor cells to the recipient E. coli J53 has been observed. blaNDM-9 and mcr-1 were carried by IncB and IncI2 plasmids, respectively. To speculate on the incidence of this strain, routine rectal swab screening to identify asymptomatic carriers might be warranted, in addition to the screening of ICU patients.

Dexter Tadiwanashe Chiveto,1,2 Cuthbert Musarurwa,3 Herbert T Mapira,3 Farayi Kaseke,4 Tawanda Nyengerai,5 Timothy Kaseke,6 Elizabeth Gori7 1Department of Laboratory Diagnostic and Investigative Sciences - Chemical Pathology Unit, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe; 2Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa; 3Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda; 4Department of Physiotherapy, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali, Rwanda; 5The Best Health Solutions, Johannesburg, Gauteng, South Africa; 6Zimbabwe Aids Prevention Project, ZAPP, Harare, Zimbabwe; 7Department of Medical Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, RwandaCorrespondence: Elizabeth Gori, Department of Medical Biochemistry, Molecular Biology & Genetics, College of Medicine and Health Sciences-School of Medicine and Pharmacy, University of Rwanda, P.O. Box 117-Butare, Huye, Rwanda, Tel +250 7920 47482, Email e.gori@ur.ac.rwPurpose: Type 2 diabetes mellitus (T2DM) frequently presents with modified cardiometabolic risk profiles, indicative of an elevated susceptibility to cardiovascular disease (CVD). Cardiometabolic risk factors such as obesity, hyperglycemia, hypertension, insulin resistance and dyslipidemia are known contributors to increased CVD hazard in individuals with T2DM. This study evaluated the glycemic control-based cardiometabolic risk profiles of black Zimbabweans with T2DM.Patients and Methods: A cross-sectional study of 116 T2DM patients recruited from diabetic clinics at Parirenyatwa and Sally Mugabe Hospitals, Harare, Zimbabwe, was conducted. Blood samples were collected for glycated hemoglobin (HbA1c) and lipid profile assessment. The Framingham risk scores (FRS) based on body mass index (BMI) and lipid profile were used to determine CVD risk. Parametric variables were analyzed using one-way analysis of variance (ANOVA) with post hoc Bonferroni correction, while non-parametric variables were compared using the Kruskal–Wallis test with post hoc Dunn test for multiple comparisons.Results: The overall frequency of dyslipidemia was 83.6% (n=97) and hypoalphalipoproteinemia was the most prevalent dyslipidemia (79.3%). Median HDLC levels were significantly lower in participants with poor glycemic control (1.12 mmol/L) compared to those with good glycemic control group (1.37 mmol/L) (p=0.011). Despite lack of significant variations in Framingham Risk Scores, there was a trend towards lower FRS-BMI in the good control group (29.8%) compared to the inadequate control (35.4%) and poor control (32.7%) groups (p=0.078).Conclusion: Duration since DM diagnosis was observed to be an important risk factor for poor glycemic control being significantly shorter in those with good glycemic control compared to those with inadequate and poor control. Overall, there was no significant difference in HbA1c status by age but individuals with poor glycemic control were significantly older than those with good control. The most prevalent dyslipidemia among the study participants was hypoalphalipoproteinemia which is reportedly associated with genetic predisposition, warranting further investigations.Keywords: glycated hemoglobin, dyslipidemia, hypoalphalipoproteinemia, Framingham risk score

Nguyen Van An,1,&ast; Hoang Trung Kien,2,&ast; Le Huy Hoang,3 Nguyen Hung Cuong,1 Hoang Xuan Quang,1 Tuan Dinh Le,4 Ta Ba Thang,5 Tien Tran Viet,6 Luong Cong Thuc,7 Dinh Viet Hung,8 Nguyen Hoang Viet,9 Le Nhat Minh,10,11 Vu Huy Luong,12,13 Vinh Thi Ha Nguyen,13,14 Pham Quynh Hoa,15 Hai Ha Long Le16,17 1Department of Microbiology, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 2Department of Immunology, Vietnam Military Medical University, Hanoi, Vietnam; 3Department of Bacteriology, National of Hygiene and Epidemiology, Hanoi, Vietnam; 4Department of Rheumatology and Endocrinology, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 5Respiratory Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 6Department of Infectious Diseases, Military Hospital 103, Vietnam Medical Military University, Hanoi, Vietnam; 7Cardiovascular Center, Military Hospital 103, Vietnam Military Medical University, Hanoi, Vietnam; 8Department of Psychiatry, Military Medical 103, Vietnam Military Medical University, Hanoi, Vietnam; 9Molecular Pathology Department, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 10Antimicrobial Resistance Research Center, National Institute of Infectious Disease, NIID, Tokyo, Japan; 11Tay Nguyen Institute of Science Research, Vietnam Academy of Science and Technology, VAST, Hanoi, Vietnam; 12Department of Laser and Skincare, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 13Department of Dermatology and Venereology, Hanoi Medical University, Hanoi, Vietnam; 14Department of General Planning, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 15Department of Microbiology, Mycology and Parasitology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 16Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam; 17Department of Biochemistry, Hematology and Immunology, National Hospital of Dermatology and Venereology, Hanoi, Vietnam&ast;These authors contributed equally to this workCorrespondence: Hai Ha Long Le, Department of Clinical Microbiology and Parasitology, Faculty of Medical Technology, Hanoi Medical University, Hanoi, 100000, Vietnam, Tel +84 978520055, Email lehalonghai@hmu.edu.vnPurpose: At a teaching Hospital in Vietnam, the persistently high incidence of diagnosed wound infection poses ongoing challenges to treatment. This study seeks to explore the causative agents of wound infection and their antimicrobial and multidrug resistance patterns.Methods: A cross-sectional study was conducted at the Department of Microbiology, Military Hospital 103, Vietnam. Data on microorganisms that caused wound infection and their antimicrobial resistance patterns was recorded from hospitalized patients from 2014 to 2021. Using the chi-square test, we analyzed the initial isolation from wound infection specimens collected from individual patients.Results: Over a third (34.9%) of wound infection samples yielded bacterial cultures. Staphylococcus aureus was the most prevalent bacteria, followed by Pseudomonas aeruginosa. Worryingly high resistance rates were observed for several antibiotics, particularly among Gram-negative bacteria. Ampicillin displayed the highest resistance (91.9%), while colistin and ertapenem remained the most effective. In Gram-positive bacteria, glycopeptides like teicoplanin and vancomycin (0% and 3.3% resistance, respectively) were most effective, but their use was limited. Clindamycin and tetracycline showed decreasing effectiveness. Resistance rates differed between surgical and non-surgical wards, highlighting the complex dynamics of antimicrobial resistance within hospitals. Multidrug resistance (MDR) was substantial, with Gram-negative bacteria exhibiting a 63.6% MDR rate. Acinetobacter baumannii showed the highest MDR rate (88.0%).Conclusion: This study investigated wound infection characteristics, antibiotic resistance patterns of common bacteria, and variations by hospital ward. S. aureus was the most prevalent bacteria, and concerning resistance rates were observed, particularly among Gram-negative bacteria. These findings highlight the prevalence of multidrug resistance in wound infections, emphasizing the importance of infection control measures and judicious antibiotic use.Keywords: wound infection, multidrug resistance, antimicrobial resistance, AMR in Vietnam

Jin-yu Shi,1,* Ting-ting Li,1,2,* Hui-ting Yang,1 Shi Zhang,2 Ran An,2 Liang Mao,2 Yang Li,2 Qian Li,2 Guang-yi Luan,2 Yan Shen,2 En-long Wang,2 Guang-hui Liu1,2 1First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guang-hui Liu, First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110847, People’s Republic of China; Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, No. 33, Beiling Street, Huanggu District, Shenyang, Liaoning, 110032, People’s Republic of China, Email guanghui04-09@163.comObjective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome.Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis.Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters.Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.Keywords: headache, blood stasis syndrome, acupuncture, treatment rule, data mining

Niels Obel,1,2 Matthew P Fox,3 Malte M Tetens,2 Lars Pedersen,4 Tyra Grove Krause,5 Henrik Ullum,5 Henrik Toft Sørensen4 1Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, 2300, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital – Rigshospitalet, Copenhagen, 2100, Denmark; 3Departments of Epidemiology and Global Health, School of Public Health, Boston University, Boston, MA, USA; 4Department of Clinical Epidemiology, Aarhus University, Aarhus N, 8200, Denmark; 5Statens Serum Institut, Copenhagen, 2300, DenmarkCorrespondence: Niels Obel, Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Artillerivej 5, Copenhagen, 2300, Denmark, Tel +4532683252, Email niob@ssi.dkBackground: Observational studies of SARS-CoV-2 vaccine effectiveness are prone to confounding, which can be illustrated using negative control methods.Methods: Nationwide population-based cohort study including two cohorts of Danish residents 60– 90 years of age matched 1:1 on age and sex: A vaccinated and a non-vaccinated cohort, including 61052 SARS-CoV-2 vaccinated individuals between 1 March and 1 July 2021 and 61052 individuals not vaccinated preceding 1 July 2021. From these two cohorts, we constructed negative control cohorts of individuals diagnosed with SARS-CoV-2 infection or acute myocardial infarction, stroke, cancer, low energy fracture, or head-trauma. Outcomes were SARS-CoV-2 infection, negative control outcomes (eg, mammography, prostate biopsy, operation for cataract, malignant melanoma, examination of eye and ear), and death. We used Cox regression to calculate adjusted incidence and mortality rate ratios (aIRR and aMRR).Results: Risks of SARS-CoV2 infection and all negative control outcomes were elevated in the vaccinated population, ranging from an aIRR of 1.15 (95% CI: 1.09– 1.21) for eye examinations to 3.05 (95% CI: 2.24– 4.14) for malignant melanoma. Conversely, the risk of death in the SARS-CoV-2 infected cohort and in all negative control cohorts was lower in vaccinated individuals, ranging from an aMRR of 0.23 (95% CI: 0.19– 0.26) after SARS-CoV-2 infection to 0.50 (95% CI: 0.37– 0.67) after stroke.Conclusion: Our findings indicate that observational studies of SARS-CoV-2 vaccine effectiveness may be subject to substantial confounding. Therefore, randomized trials are essential to establish vaccine efficacy after the emergence of new SARS-CoV-2 variants and the rollout of multiple booster vaccines.Plain Language Summary: Why was this study done: After the emergence of new SARS-CoV-2 variants and the rollout of multiple booster SARS-CoV-2 vaccines, the impact of vaccination on risk of SARS-CoV-2 infection and death after the infection has mainly been explored in observational studies. We used negative control methods to investigate whether confounding affects the results of observational SARS-CoV-2 vaccine effectiveness studies.Findings: We used Danish registry data obtained during the SARS-CoV-2 vaccine roll-out to conduct a nationwide, matched population-based cohort study of Danish residents 60– 90 years in which we compared vaccinated individuals with non-vaccinated individuals. Compared with unvaccinated individuals, vaccinated individuals had increased risks of SARS-CoV2 infection but also had increased risks of all negative control outcomes (mammography, prostate biopsy, operation for cataract, malignant melanoma, examination of eye and ear). The risk of death after SARS-CoV2 infection was lower in the vaccinated cohort, as was the risk of death after acute myocardial infarction, stroke, cancer, low energy fracture, and head-trauma.Meaning: The negative control methods indicate that observational studies of SARS-CoV-2 vaccine effectiveness may be prone to substantial confounding which may impact the observed associations. This bias may both lead to underestimation of vaccine effectiveness (increased risk of SARS-CoV2 infection among vaccinated individuals) and overestimation of the vaccine effectiveness (decreased risk of death after of SARS-CoV2 infection among vaccinated individuals). Our results highlight the need for randomized vaccine efficacy studies after the emergence of new SARS-CoV-2 variants and the rollout of multiple booster vaccines.Keywords: COVID-19, vaccines, cohort studies, bias, confounding factors, epidemiologic

Huong Tu Lam,1 Thang Dinh Nguyen,2 Hoang Huu Bui,1 Thong Duy Vo1,3 1Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Department of Gastroenterology, Cho Ray Hospital, Ho Chi Minh City, Vietnam; 3Department of Gastroenterology, University Medical Center Ho Chi Minh City, Ho Chi Minh City, VietnamCorrespondence: Thong Duy Vo, Department of Gastroenterology, University Medical Center Ho Chi Minh City, 215 Hong Bang, Ward 11, Dis. 5, Ho Chi Minh City, 72714, Vietnam, Tel +84 932039888, Email thong.vd@umc.edu.vnIntroduction: The Charlson Comorbidity Index ≥ 2, in-Hospital onset, Albumin < 2.5 g/dL, altered Mental status, Eastern Cooperative Oncology Group Performance status ≥ 2, Steroid use (CHAMPS) score is a novel and promising prognostic tool. We present an initial external validation of the CHAMPS score for predicting mortality in acute nonvariceal upper gastrointestinal bleeding (NVUGIB) across multiple clinical outcomes.Methods: A prospective cohort study was conducted on adult patients with NVUGIB admitted to the Department of Gastroenterology between November 2022 and June 2023. The CHAMPS score performance in predicting in-hospital outcomes was evaluated by employing area under the receiver operating characteristic (AUROC) curves, followed by a comparative analysis with five pre-existing scores.Results: A total of 140 patients were included in the study. The CHAMPS score showed its highest performance in predicting mortality rates (AUROC = 0.89), significantly outperforming the Glasgow-Blatchford Bleeding Score (GBS) as well as the Albumin level < 3.0 mg/dL, International normalized ratio > 1.5, altered Mental status, Systolic blood pressure ≤ 90 mmHg, and age > 65 years (AIMS65) score (AUROC = 0.72 and 0.71, respectively; all p < 0.05). Subgroup analysis for bleeding-related and non-bleeding-related mortality further confirmed the robust predictive capability of the CHAMPS score (AUROC = 0.88 and 0.87, respectively). The CHAMPS score failed to predict rebleeding and intervention reliably, exhibiting AUROC values of 0.43 and 0.55, respectively. The optimal CHAMPS score cutoff value for predicting mortality was 3 points, achieving 100% sensitivity and 71.2% specificity. In the low-risk category defined by both CHAMPS and GBS scores, mortality and rebleeding rates were 0%. However, within the CHAMPS score-based low-risk group, 58.8% required intervention, contrasting with a 0% intervention rate for the GBS score-based low-risk group (GBS score ≤ 1).Conclusion: The CHAMPS score consistently demonstrated a robust predictive performance for mortality (AUROC > 0.8), facilitating the identification of high-risk patients requiring aggressive treatment and low-risk patients in need of localized treatment or safe discharge after successful bleeding control.Keywords: non-variceal upper gastrointestinal bleeding, CHAMPS, mortality prediction, risk scores, GBS

Runjie Li,1,2,&ast; Rongna Lian,1,3,&ast; Hiruni T Siriwardena,4 Jiaojiao Jiang,5 Ming Yang1,3 1National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Geriatrics, Ya ‘an People’s Hospital, Ya ‘an, People’s Republic of China; 3Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 5Rehabilitation Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Yang, Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, People’s Republic of China, Tel\Fax +86 28 8542 2321, Email yangmier@gmail.com; yangmier@scu.edu.cn Jiaojiao Jiang, Rehabilitation Center, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, People’s Republic of China, Tel\Fax +86 28 8542 2313, Email jiangjiaojiao1997@163.comAbstract: Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our bibliometric study examined research status, hotspots, and future trends. We utilized bibliometric techniques to search the Science Citation Index Extended Database on February 27, 2023, using the Bibliometrix package in R to create a map displaying scientific production and subject categories. Collaborative network maps between countries/regions were visualized using Scimago Graphica, while VOSviewer explored collaboration modes among individuals and institutions. We analyzed the top 25 emerging keywords, top co-occurring keyword networks, and co-occurring keyword clusters using CiteSpace. A total of 997 articles were retrieved for sarcopenia and microbiome, of which 633 papers were analyzed. Both the number of publications and total citation frequency had been continuously increasing. The United States had the highest total citation frequency, while China had the highest number of publications. Research on the impact of the microbiome on sarcopenia was in its nascent stage and spans multiple disciplines, including nutrition, microbiology, geriatrics, immunology, endocrinology and metabolism, molecular biology, and sports medicine. The University of Copenhagen contributed the most to the number of publications (n=16), with Tibbett M (n=7) and Hulver MW (n=7) among the top authors. The most published journal was “Nutrients” (n=24). Analysis of keywords and clusters revealed new research hotspots in microbes and sarcopenia, such as malnutrition, dietary fiber, signaling pathways, frailty, and intestinal permeability. Research on the impact of the microbiome on sarcopenia is in its infancy and spans multiple disciplines. Malnutrition, dietary fiber, signaling pathways, frailty, and intestinal microbes are currently research hotspots. Furthermore, the visual atlas analysis of research on microbes and sarcopenia helps to track the knowledge structure in research fields related to sarcopenia and microbes, providing direction for future research. Keywords: bibliometric analysis, microbes, skeletal muscle, scientometrics, muscle wasting

Yu Chen Xu,1,&ast; Qiu Qin Wang,1,&ast; Meng Yuan Chen,1 Yu Jie Gao,1 Jia Yi Wang,1 Hao Tian Ge,1 Heng Weng,1 Ju Ping Chen,2 Gui Hua Xu1 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Department of Neurology, Changshu Hospital of Traditional Chinese Medicine, Suzhou, 215500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui Hua Xu, School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email 7115@njucm.edu.cn Ju Ping Chen, Department of Neurology, Changshu Hospital of Traditional Chinese Medicine, Suzhou, 215500, People’s Republic of China, Email 1523515573@qq.comPurpose: Pain is a common yet undertreated symptom of Parkinson’s disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD.Patients and Methods: A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I–III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10).Results: The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred.Conclusion: The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.Keywords: Parkinson’s disease, pain, Gua Sha therapy, randomized controlled trial

ABSTRACT Aims/Introduction To determine the population health burden attributable to the development of diabetes among women with a history of gestational diabetes mellitus (GDM). Materials and Methods We conducted a retrospective analysis of women with a history of GDM attending the Hong Kong Hospital Authority between 2000 and 2019. The time‐varying population attributable fraction was calculated. Results A total of 76,181 women with a history of gestational diabetes mellitus were included, 6,606 of them developed diabetes during a median follow‐up of 8.6 years. The respective hazard ratios (95% confidence interval) among women with GDM who developed diabetes vs those with GDM only were 2.8 (2.2, 3.7) for cardiovascular disease (CVD), 4.8 (3.0, 7.7) for end‐stage kidney disease (ESKD), 2.2 (1.9, 2.6) for infection‐related hospitalization, and 1.8 (1.3, 2.4) for all‐cause mortality. The development of diabetes was associated with 1.3 (0.8, 1.7), 0.6 (0.3, 0.8), 3.2 (2.4, 4.0), and 0.5 (0.2, 0.9) additional incident cases per 1,000 person‐years, accounting for 24.0% (13.2%, 35.9%), 42.0% (22.5%, 58.8%), 10.8% (7.1%, 14.9%), and 6.0% (−3.1%, 16.1%) of absolute number of CVD, ESKD, infection‐related hospitalization, and all‐cause mortality over 20 years after GDM, respectively. Conclusions Diabetes is a significant contributor to the population health burden of some clinical outcomes in women with a history of gestational diabetes mellitus, but other risk factors need to be considered.

Huan Thanh Nguyen,1,2 Huong Thanh Do,2 Hai Van Be Nguyen,2 Tan Van Nguyen1,3 1Department of Geriatrics and Gerontology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam; 2Department of Cardiology, Thong Nhat Hospital, Ho Chi Minh City, Vietnam; 3Department of Interventional Cardiology, Thong Nhat Hospital, Ho Chi Minh City, VietnamCorrespondence: Huan Thanh Nguyen, Department of Geriatrics and Gerontology University of Medicine and Pharmacy at Ho Chi Minh City, 17 Hong Bang Street, Ward 11, District 5, Ho Chi Minh City, Vietnam, Tel +84-909097849, Email huannguyen@ump.edu.vnPurpose: To investigate the prevalence and factors associated with frailty and impact of frailty on hospitalization due to any cause in elderly patients with chronic coronary syndrome (CCS).Patients and Methods: We conducted a study wherein we assessed frailty using Fried frailty phenotype for outpatients aged ≥ 60 years with CCS. Logistic regression analysis was performed to assess the factors associated with frailty. Frailty was adjusted for demographic and geriatric variables and comorbidities to assess its impact on hospitalization.Results: Overall, 420 patients (median age 70 years [interquartile range, 65– 77]; men, 74.5%) who completed the 3-month follow-up period were analyzed. Coronary revascularization for > 1 year was the most common clinical scenario for CCS (59.8%; n = 251). The prevalence of non-frail, pre-frail, and frail patients were 22.4% (n = 94), 49.7% (n = 209), and 27.9% (n = 117), respectively. In the adjusted model, three factors associated with frailty were age ≥ 75 years (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.39– 3.75, P = 0.001), limitations in instrumental activity of daily living (OR 3.89, 95% CI 2.33– 6.48, P < 0.001), and heart failure (OR 2.30, 95% CI 1.32– 4.02, P = 0.003). The overall 3-month hospitalization rate was higher in frail patients than in non-frail patients (23.9% vs 13.5%, P = 0.012). Frailty was associated with hospitalization (OR 1.85, 95% CI 1.04– 3.30, P = 0.037) but in a weak strength of association (r = 0.126).Conclusion: The prevalence of frailty was 27.9% in the elderly patients with CCS. Age ≥ 75 years, limitations in functional status, and heart failure were associated with increased odds of frailty. Frailty was a predictor of 3-month all-cause hospitalization in these patients.Keywords: frailty, chronic coronary syndrome, elderly

ABSTRACT: We present the first systematic follow-up of Planck Sunyaev–Zeldovich effect (SZE) selected candidates down to signal-to-noise (S/N) of 3 over the 5000 deg2 covered by the Dark Energy Survey. Using the MCMF cluster confirmation algorithm, we identify optical counterparts, determine photometric redshifts, and richnesses and assign a parameter, fcont, that reflects the probability that each SZE-optical pairing represents a random superposition of physically unassociated systems rather than a real cluster. The new PSZ-MCMF cluster catalogue consists of 853 MCMF confirmed clusters and has a purity of 90 per cent. We present the properties of subsamples of the PSZ-MCMF catalogue that have purities ranging from 90 per cent to 97.5 per cent, depending on the adopted fcont threshold. Halo mass estimates M500, redshifts, richnesses, and optical centres are presented for all PSZ-MCMF clusters. The PSZ-MCMF catalogue adds 589 previously unknown Planck identified clusters over the DES footprint and provides redshifts for an additional 50 previously published Planck-selected clusters with S/N>4.5. Using the subsample with spectroscopic redshifts, we demonstrate excellent cluster photo-z performance with an RMS scatter in Δz/(1 + z) of 0.47 per cent. Our MCMF based analysis allows us to infer the contamination fraction of the initial S/N>3 Planck-selected candidate list, which is ∼50 per cent. We present a method of estimating the completeness of the PSZ-MCMF cluster sample. In comparison to the previously published Planck cluster catalogues, this new S/N>3 MCMF confirmed cluster catalogue populates the lower mass regime at all redshifts and includes clusters up to z∼1.3.

Using the Planck Low Frequency Instrument (LFI) and WMAP data within the global Bayesian BEYONDPLANCK framework, we constrained the polarized foreground emission between 30 and 70 GHz. We combined, for the first time, full-resolution Planck LFI time-ordered data with low-resolution WMAP sky maps at 33, 40, and 61 GHz. The spectral parameters were fit with a likelihood defined at the native resolution of each frequency channel. This analysis represents the first implementation of true multi-resolution component separation applied to CMB observations for both amplitude and spectral energy distribution (SED) parameters. For the synchrotron emission, we approximated the SED as a power-law in frequency and we find that the low signal-to-noise ratio of the current data strongly limits the number of free parameters that can be robustly constrained. We partitioned the sky into four large disjoint regions (High Latitude; Galactic Spur; Galactic Plane; and Galactic Center), each associated with its own power-law index. We find that the High Latitude region is prior-dominated, while the Galactic Center region is contaminated by residual instrumental systematics. The two remaining regions appear to be signal-dominated, and for these we derive spectral indices of βsSpur=3.17±0.06 and βsPlane=3.03±0.07, which is in good agreement with previous results. For the thermal dust emission, we assumed a modified blackbody model and we fit a single power-law index across the full sky. We find βda =â 1.64±0.03, which is slightly steeper than the value reported in Planck HFI data, but still statistically consistent at the 2Ï confidence level.

We describe the computational infrastructure for end-to-end Bayesian cosmic microwave background (CMB) analysis implemented by the BeyondPlanck Collaboration. The code is called Commander3. It provides a statistically consistent framework for global analysis of CMB and microwave observations and may be useful for a wide range of legacy, current, and future experiments. The paper has three main goals. Firstly, we provide a high-level overview of the existing code base, aiming to guide readers who wish to extend and adapt the code according to their own needs or re-implement it from scratch in a different programming language. Secondly, we discuss some critical computational challenges that arise within any global CMB analysis framework, for instance in-memory compression of time-ordered data, fast Fourier transform optimization, and parallelization and load-balancing. Thirdly, we quantify the CPU and RAM requirements for the current BEYONDPLANCK analysis, finding that a total of 1.5 TB of RAM is required for efficient analysis and that the total cost of a full Gibbs sample for LFI is 170 CPU-hrs, including both low-level processing and high-level component separation, which is well within the capabilities of current low-cost computing facilities. The existing code base is made publicly available under a GNU General Public Library (GPL) license.

We constrained the level of polarized anomalous microwave emission (AME) on large angular scales using Planck Low-Frequency Instrument (LFI) and WMAP polarization data within a Bayesian cosmic microwave background (CMB) analysis framework. We modeled synchrotron emission with a power-law spectral energy distribution, as well as the sum of AME and thermal dust emission through linear regression with the Planck High-Frequency Instrument (HFI) 353 GHz data. This template-based dust emission model allowed us to constrain the level of polarized AME while making minimal assumptions on its frequency dependence. We neglected CMB fluctuations, but show through simulations that these fluctuations have a minor impact on the results. We find that the resulting AME polarization fraction confidence limit is sensitive to the polarized synchrotron spectral index prior. In addition, for prior means βsâ

We present a Bayesian calibration algorithm for cosmic microwave background (CMB) observations as implemented within the global end-to-end BEYONDPLANCK framework and applied to the Planck Low Frequency Instrument (LFI) data. Following the most recent Planck analysis, we decomposed the full time-dependent gain into a sum of three nearly orthogonal components: one absolute calibration term, common to all detectors, one time-independent term that can vary between detectors, and one time-dependent component that was allowed to vary between one-hour pointing periods. Each term was then sampled conditionally on all other parameters in the global signal model through Gibbs sampling. The absolute calibration is sampled using only the orbital dipole as a reference source, while the two relative gain components were sampled using the full sky signal, including the orbital and Solar CMB dipoles, CMB fluctuations, and foreground contributions. We discuss various aspects of the data that influence gain estimation, including the dipole-polarization quadrupole degeneracy and processing masks. Comparing our solution to previous pipelines, we find good agreement in general, with relative deviations of 0.67% (0.84%) for 30 GHz, 0.12% (0.04%) for 44 GHz and 0.03% (0.64%) for 70 GHz, compared to Planck PR4 and Planck 2018, respectively. We note that the BEYONDPLANCK calibration was performed globally, which results in better inter-frequency consistency than previous estimates. Additionally, WMAP observations were used actively in the BEYONDPLANCK analysis, which both breaks internal degeneracies in the Planck data set and results in an overall better agreement with WMAP. Finally, we used a Wiener filtering approach to smoothing the gain estimates. We show that this method avoids artifacts in the correlated noise maps as a result of oversmoothing the gain solution, which is difficult to avoid with methods like boxcar smoothing, as Wiener filtering by construction maintains a balance between data fidelity and prior knowledge. Although our presentation and algorithm are currently oriented toward LFI processing, the general procedure is fully generalizable to other experiments, as long as the Solar dipole signal is available to be used for calibration.

We present a Gibbs sampling solution to the mapmaking problem for cosmic microwave background (CMB) measurements that builds on existing destriping methodology. Gibbs sampling breaks the computationally heavy destriping problem into two separate steps: noise filtering and map binning. Considered as two separate steps, both are computationally much cheaper than solving the combined problem. This provides a huge performance benefit as compared to traditional methods and it allows us, for the first time, to bring the destriping baseline length to a single sample. Here, we applied the Gibbs procedure to simulated Planck 30 GHz data. We find that gaps in the time-ordered data are handled efficiently by filling them in with simulated noise as part of the Gibbs process. The Gibbs procedure yields a chain of map samples, from which we are able to compute the posterior mean as a best-estimate map. The variation in the chain provides information on the correlated residual noise, without the need to construct a full noise covariance matrix. However, if only a single maximum-likelihood frequency map estimate is required, we find that traditional conjugate gradient solvers converge much faster than a Gibbs sampler in terms of the total number of iterations. The conceptual advantages of the Gibbs sampling approach lies in statistically well-defined error propagation and systematic error correction. This methodology thus forms the conceptual basis for the mapmaking algorithm employed in the BEYONDPLANCK framework, which implements the first end-to-end Bayesian analysis pipeline for CMB observations.

We present Planck Low Frequency Instrument (LFI) frequency sky maps derived within the BEYONDPLANCK framework. This framework draws samples from a global posterior distribution that includes instrumental, astrophysical, and cosmological parameters, and the main product is an entire ensemble of frequency sky map samples, each of which corresponds to one possible realization of the various modeled instrumental systematic corrections, including correlated noise, time-variable gain, as well as far sidelobe and bandpass corrections. This ensemble allows for computationally convenient end-to-end propagation of low-level instrumental uncertainties into higher-level science products, including astrophysical component maps, angular power spectra, and cosmological parameters. We show that the two dominant sources of LFI instrumental systematic uncertainties are correlated noise and gain fluctuations, and the products presented here support -for the first time -full Bayesian error propagation for these effects at full angular resolution. We compared our posterior mean maps with traditional frequency maps delivered by the Planck Collaboration, and find generally good agreement. The most important quality improvement is due to significantly lower calibration uncertainties in the new processing, as we find a fractional absolute calibration uncertainty at 70 GHz of δg0/g0â =â 5Ã - 105, which is nominally 40 times smaller than that reported by Planck 2018. However, we also note that the original Planck 2018 estimate has a nontrivial statistical interpretation, and this further illustrates the advantage of the new framework in terms of producing self-consistent and well-defined error estimates of all involved quantities without the need of ad hoc uncertainty contributions. We describe how low-resolution data products, including dense pixel-pixel covariance matrices, may be produced from the posterior samples directly, without the need for computationally expensive analytic calculations or simulations. We conclude that posterior-based frequency map sampling provides unique capabilities in terms of low-level systematics modeling and error propagation, and may play an important role for future Cosmic Microwave Background (CMB) B-mode experiments aiming at nanokelvin precision.

We describe the BEYONDPLANCK project in terms of our motivation, methodology, and main products, and provide a guide to a set of companion papers that describe each result in more detail. Building directly on experience from ESA's Planck mission, we implemented a complete end-to-end Bayesian analysis framework for the Planck Low Frequency Instrument (LFI) observations. The primary product is a full joint posterior distribution P(Ï â £d), where Ï represents the set of all free instrumental (gain, correlated noise, bandpass, etc.), astrophysical (synchrotron, free-free, thermal dust emission, etc.), and cosmological (cosmic microwave background -CMB -map, power spectrum, etc.) parameters. Some notable advantages of this approach compared to a traditional pipeline procedure are seamless end-to-end propagation of uncertainties; accurate modeling of both astrophysical and instrumental effects in the most natural basis for each uncertain quantity; optimized computational costs with little or no need for intermediate human interaction between various analysis steps; and a complete overview of the entire analysis process within one single framework. As a practical demonstration of this framework, we focus in particular on low-â CMB polarization reconstruction with Planck LFI. In this process, we identify several important new effects that have not been accounted for in previous pipelines, including gain over-smoothing and time-variable and non-1/f correlated noise in the 30 and 44 GHz channels. Modeling and mitigating both previously known and newly discovered systematic effects, we find that all results are consistent with the Î CDM model, and we constrained the reionization optical depth to Ï â =â 0.066±0.013, with a low-resolution CMB-based Ï 2 probability to exceed of 32%. This uncertainty is about 30% larger than the official pipelines, arising from taking a more complete instrumental model into account. The marginal CMB solar dipole amplitude is 3362.7±1.4â μK, where the error bar was derived directly from the posterior distribution without the need of any ad hoc instrumental corrections. We are currently not aware of any significant unmodeled systematic effects remaining in the Planck LFI data, and, for the first time, the 44 GHz channel is fully exploited in the current analysis. We argue that this framework can play a central role in the analysis of many current and future high-sensitivity CMB experiments, including LiteBIRD, and it will serve as the computational foundation of the emerging community-wide COSMOGLOBE effort, which aims to combine state-of-the-art radio, microwave, and submillimeter data sets into one global astrophysical model.

We present the first application of the COSMOGLOBE analysis framework by analyzing nine-year WMAP time-ordered observations that uses similar machinery to that of BEYONDPLANCK for the Planck Low Frequency Instrument (LFI). We analyzed only the Q-band (41 GHz) data and report on the low-level analysis process based on uncalibrated time-ordered data to calibrated maps. Most of the existing BEYONDPLANCK pipeline may be reused for WMAP analysis with minimal changes to the existing codebase. The main modification is the implementation of the same preconditioned biconjugate gradient mapmaker used by the WMAP team. Producing a single WMAP Q1-band sample requires 22 CPU-hrs, which is slightly more than the cost of a Planck 44 GHz sample of 17 CPU-hrs; this demonstrates that a full end-to-end Bayesian processing of the WMAP data is computationally feasible. In general, our recovered maps are very similar to the maps released by the WMAP team, although with two notable differences. In terms of temperature, we find a ∼2â μK quadrupole difference that most likely is caused by different gain modeling, while in polarization we find a distinct 2.5â μK signal that has been previously referred to as poorly measured modes by the WMAP team. In the COSMOGLOBE processing, this pattern arises from temperature-to-polarization leakage from the coupling between the CMB Solar dipole, transmission imbalance, and sidelobes. No traces of this pattern are found in either the frequency map or TOD residual map, suggesting that the current processing has succeeded in modeling these poorly measured modes within the assumed parametric model by using Planck information to break the sky-synchronous degeneracies inherent in the WMAP scanning strategy.

We present posterior sample-based cosmic microwave background (CMB) constraints from Planck LFI and WMAP observations as derived through global end-to-end Bayesian processing within the BeyondPlanck framework. We first used these samples to study correlations between CMB, foreground, and instrumental parameters. We identified a particularly strong degeneracy between CMB temperature fluctuations and free-free emission on intermediate angular scales (400 ≤ ∫ ≤ 600), mitigated through model reduction, masking, and resampling. We compared our posterior-based CMB results with previous Planck products and found a generally good agreement, however, with notably higher noise due to our exclusion of Planck HFI data.We found a best-fit CMB dipole amplitude of 3362:7 ± 1:4 μK, which is in excellent agreement with previous Planck results. The quoted dipole uncertainty is derived directly from the sampled posterior distribution and does not involve any ad hoc contributions for Planck instrumental systematic effects. Similarly, we find a temperature quadrupole amplitude of φTT 2 = 229 ± 97 μK2, which is in good agreement with previous results in terms of the amplitude, but the uncertainty is one order of magnitude greater than the naive diagonal Fisher uncertainty. Concurrently, we find less evidence of a possible alignment between the quadrupole and octopole than previously reported, due to a much larger scatter in the individual quadrupole coeffcients that is caused both by marginalizing over a more complete set of systematic effects – as well as by requiring a more conservative analysis mask to mitigate the free-free degeneracy. For higher multipoles, we find that the angular temperature power spectrum is generally in good agreement with both Planck and WMAP. At the same time, we note that this is the first time that the sample-based, asymptotically exact Blackwell-Rao estimator has been successfully established for multipoles up to ∫ ≤ 600. It now accounts for the majority of the cosmologically important information. Overall, this analysis demonstrates the unique capabilities of the Bayesian approach with respect to end-to-end systematic uncertainty propagation and we believe it can and should play an important role in the analysis of future CMB experiments. Cosmological parameter constraints are presented in a companion paper.

End-to-end simulations play a key role in the analysis of any high-sensitivity cosmic microwave background (CMB) experiment, providing high-fidelity systematic error propagation capabilities that are unmatched by any other means. In this paper, we address an important issue regarding such simulations, namely, how to define the inputs in terms of sky model and instrument parameters. These may either be taken as a constrained realization derived from the data or as a random realization independent from the data. We refer to these as posterior and prior simulations, respectively. We show that the two options lead to significantly different correlation structures, as prior simulations (contrary to posterior simulations) effectively include cosmic variance, but they exclude realization-specific correlations from non-linear degeneracies. Consequently, they quantify fundamentally different types of uncertainties. We argue that as a result, they also have different and complementary scientific uses, even if this dichotomy is not absolute. In particular, posterior simulations are in general more convenient for parameter estimation studies, while prior simulations are generally more convenient for model testing. Before BEYONDPLANCK, most pipelines used a mix of constrained and random inputs and applied the same hybrid simulations for all applications, even though the statistical justification for this is not always evident. BEYONDPLANCK represents the first end-to-end CMB simulation framework that is able to generate both types of simulations and these new capabilities have brought this topic to the forefront. The BEYONDPLANCK posterior simulations and their uses are described extensively in a suite of companion papers. In this work, we consider one important applications of the corresponding prior simulations, namely, code validation. Specifically, we generated a set of one-year LFI 30 GHz prior simulations with known inputs and we used these to validate the core low-level BEYONDPLANCK algorithms dealing with gain estimation, correlated noise estimation, and mapmaking.

We present cosmological parameter constraints estimated using the Bayesian BeyondPlanck analysis framework. This method supports seamless end-to-end error propagation from raw time-ordered data onto final cosmological parameters. As a first demonstration of the method, we analyzed time-ordered Planck LFI observations, combined with selected external data (WMAP 33–61 GHz, Planck HFI DR4 353 and 857 GHz, and Haslam 408 MHz) in the form of pixelized maps that are used to break critical astrophysical degeneracies. Overall, all the results are generally in good agreement with previously reported values from Planck 2018 and WMAP, with the largest relative difference for any parameter amounting about 1φ when considering only temperature multipoles between 30 ≤ ∫ ≤ 600. In cases where there are differences, we note that the BeyondPlanck results are generally slightly closer to the high- ∫ HFI-dominated Planck 2018 results than previous analyses, suggesting slightly less tension between low and high multipoles. Using low- ∫ polarization information from LFI and WMAP, we find a best-fit value of φ = 0:066±0:013, which is higher than the low value of φ = 0:052 ± 0:008 derived from Planck 2018 and slightly lower than the value of 0:069 ± 0:011 derived from the joint analysis of offcial LFI and WMAP products. Most importantly, however, we find that the uncertainty derived in the BeyondPlanck processing is about 30% greater than when analyzing the offcial products, after taking into account the different sky coverage. We argue that this uncertainty is due to a marginalization over a more complete model of instrumental and astrophysical parameters, which results in more reliable and more rigorously defined uncertainties. We find that about 2000 Monte Carlo samples are required to achieve a robust convergence for a low-resolution cosmic microwave background (CMB) covariance matrix with 225 independent modes, and producing these samples takes about eight weeks on a modest computing cluster with 256 cores.

We present a Bayesian method for estimating instrumental noise parameters and propagating noise uncertainties within the global BEYONDPLANCK Gibbs sampling framework, which we applied to Planck Low Frequency Instrument (LFI) time-ordered data. Following previous works in the literature, we initially adopted a 1/f model for the noise power spectral density (PSD), but we found the need for an additional lognormal component in the noise model in the 30 and 44 GHz bands. We implemented an optimal Wiener-filter (or constrained realization) gap-filling procedure to account for masked data. We then used this procedure to both estimate the gapless correlated noise in the time-domain, ncorr, and to sample the noise PSD parameters, ξnâ =â {Ï0,â fknee,â α,â Ap}. In contrast to previous Planck analyses, we assumed piecewise stationary noise only within each pointing period (PID), and not throughout the full mission, but we adopted the LFI Data Processing Center results as priors on α and fknee. We generally found best-fit correlated noise parameters that are mostly consistent with previous results, with a few notable exceptions. However, a detailed inspection of the time-dependent results has revealed many important findings. First and foremost, we find strong evidence for statistically significant temporal variations in all noise PSD parameters, many of which are directly correlated with satellite housekeeping data. Second, while the simple 1/f model appears to be an excellent fit for the LFI 70 GHz channel, there is evidence for additional correlated noise that is not described by a 1/f model in the 30 and 44 GHz channels, including within the primary science frequency range of 0.1-1 Hz. In general, most 30 and 44 GHz channels exhibit deviations from 1/f at the 2-3Ï level in each one-hour pointing period, motivating the addition of the lognormal noise component for these bands. For certain periods of time, we also find evidence of strong common mode noise fluctuations across the entire focal plane. Overall, we conclude that a simple 1/f profile is not adequate for obtaining a full characterization of the Planck LFI noise, even when fitted hour-by-hour, and a more general model is required. These findings have important implications for large-scale CMB polarization reconstruction with the Planck LFI data and the current work is a first attempt at understanding and mitigating these issues.

We study the effect of magnification in the Dark Energy Survey Year 3 analysis of galaxy clustering and galaxy-galaxy lensing, using two different lens samples: a sample of luminous red galaxies, redMaGiC, and a sample with a redshift-dependent magnitude limit, MagLim. We account for the effect of magnification on both the flux and size selection of galaxies, accounting for systematic effects using the Balrog image simulations. We estimate the impact of magnification on the galaxy clustering and galaxy-galaxy lensing cosmology analysis, finding it to be a significant systematic for the MagLim sample. We show cosmological constraints from the galaxy clustering autocorrelation and galaxy-galaxy lensing signal with different magnifications priors, finding broad consistency in cosmological parameters in ΛCDM and wCDM. However, when magnification bias amplitude is allowed to be free, we find the two-point correlation functions prefer a different amplitude to the fiducial input derived from the image simulations. We validate the magnification analysis by comparing the cross-clustering between lens bins with the prediction from the baseline analysis, which uses only the autocorrelation of the lens bins, indicating that systematics other than magnification may be the cause of the discrepancy. We show that adding the cross-clustering between lens redshift bins to the fit significantly improves the constraints on lens magnification parameters and allows uninformative priors to be used on magnification coefficients, without any loss of constraining power or prior volume concerns.