tbuckley/cabot-search huggingface dataset:
Clinical and Pathological Validation of CT-Based Regional Harmonization Methods of Amyloid PET
Authors: Soo-Jong Kim, Hyemin Jang, Heejin Yoo, Duk L. Na, Hongki Ham, Hee Jin Kim, Jun Pyo Kim, Gill Farrar, Seung Hwan Moon, Sang Won Seo
Journal: Clinical Nuclear Medicine (2023)

Purpose The CT-based regional direct comparison Centiloid (dcCL) method was developed to harmonize and quantify regional β-amyloid (Aβ) burden. In the present study, we aimed to investigate correlations between the CT-based regional dcCL scales and Aβ pathological burdens and to validate the clinical utility using thresholds derived from pathological assessment. Patients and Methods We included a pathological cohort of 63 cases and a clinical cohort of 4062 participants, and obtained modified Consortium to Establish a Registry for Alzheimer’s Disease criteria (mCERAD) scores by assessment of neuritic plaque burdens in multiple areas of each cortical region. PET and CT images were processed using the CT-based regional dcCL method to calculate scales in 6 distinct regions. Results The CT-based regional dcCL scales were correlated with neuritic plaque burdens represented by mCERAD scores, globally and regionally ( r = 0.56~0.76). In addition, striatum dcCL scales reflected Aβ involvement in the striatum ( P &lt; 0.001). The regional dcCL scales could predict significant Aβ deposition in specific brain regions with high accuracy: area under the receiver operating characteristic curve of 0.81–0.97 with an mCERAD cutoff of 1.5 and area under the receiver operating characteristic curve of 0.88–0.93 with an mCERAD cutoff of 0.5. When applying the dcCL thresholds of 1.5 mCERAD scores, the G(−)R(+) group showed lower performances in memory and global cognitive functions and had less hippocampal volume compared with the G(−)R(−) group ( P &lt; 0.001). However, when applying the dcCL thresholds of 0.5 mCERAD scores, there were no differences in the global cognitive functions between the 2 groups. Conclusions The thresholds of regional dcCL scales derived from pathological assessments might provide clinicians with a better understanding of biomarker-guided diagnosis and distinguishable clinical phenotypes, which are particularly useful when harmonizing different PET ligands with only PET/CT.
BET inhibitors potentiate melanoma ferroptosis and immunotherapy through AKR1C2 inhibition
Authors: Yu Meng, Hui-Yan Sun, Yi He, Qian Zhou, Yi-Huang Liu, Hui Su, Ming-Zhu Yin, Fu-Rong Zeng, Xiang Chen, Guang-Tong Deng
Journal: Military Medical Research (2023)
Association of Lipoprotein(a) Levels With Myocardial Fibrosis in the Multi-Ethnic Study of Atherosclerosis
Authors: Omar Chehab, Ashkan Abdollahi, Seamus P. Whelton, Colin O. Wu, Bharath Ambale-Venkatesh, Wendy S. Post, David A. Bluemke, Michael Y. Tsai, João A.C. Lima
Journal: Journal of the American College of Cardiology (2023)
Safety and Tolerability of Inclisiran for Treatment of Hypercholesterolemia in 7 Clinical Trials
Authors: R. Scott Wright, Wolfgang Koenig, Ulf Landmesser, Lawrence A. Leiter, Frederick J. Raal, Gregory G. Schwartz, Anastasia Lesogor, Pierre Maheux, Christian Stratz, Xiao Zang, Kausik K. Ray
Journal: Journal of the American College of Cardiology (2023)

Inclisiran is a small interfering RNA agent to lower low-density lipoprotein cholesterol. The purpose of this study was to provide reliable evidence to date on the long-term safety profile of inclisiran. This post hoc analysis comprised patients treated with 300 mg inclisiran sodium or placebo in the completed (ORION-1, -3, -5, -9, -10, and -11) and ongoing (ORION-8) trials. Exposure-adjusted incidence rates and Kaplan-Meier estimates of cumulative incidence of reported treatment-emergent adverse events (TEAE), abnormal laboratory measurements, and incidence of antidrug antibodies were analyzed. This analysis included 3,576 patients treated with inclisiran for up to 6 years and 1,968 patients treated with placebo for up to 1.5 years, with 9,982.1 and 2,647.7 patient-years of exposure, respectively. Baseline characteristics were balanced between groups. Kaplan-Meier analyses showed that TEAEs that were serious or led to discontinuation; hepatic, muscle, and kidney events; incident diabetes; and elevations of creatine kinase or creatinine accrued at a comparable rate between groups for up to 1.5 years, with similar trends continuing for inclisiran beyond this period. Numerically fewer major cardiovascular events reported as TEAEs occurred with inclisiran during this period. Treatment-induced antidrug antibodies were uncommon with inclisiran (4.6%), with few of these persistent (1.4%) and not associated with greater incidence of TEAEs leading to study drug discontinuation or serious TEAEs. Long-term treatment with inclisiran was well tolerated in a diverse population, without new safety signals, supporting the safety of inclisiran in patients with dyslipidemia.
A Story With an Interesting Twist
Authors: Chan-Hee Lee, Melvin M. Scheinman
Journal: Circulation (2023)

An 81-year-old woman with hypertension and heart failure was referred to the emergency department after cardiopulmonary resuscitation with documented polymorphic ventricular tachycardia.She was taking levofloxacin and cimetidine.Her potassium level was low at 3.1 mEq/L (normal range, 3.5-5.5 mEq/L) and her magnesium level was 2.4 mg/dL (normal range, 1.9-2.5 mg/ dL).Echocardiography revealed a normal left ventricular systolic function without ventricular hypertrophy and computed tomography of the brain showed no evidence of intracranial hemorrhage.There was no family history of sudden death.A 12-lead ECG (Figure 1A) and Holter monitoring (Figure 1B) were performed on admission.What are the notable ECG findings?What is the mechanism of the polymorphic ventricular tachycardia?Please turn the page to read the diagnosis.
Response by Nademanee et al to Letter Regarding Article, “Long-Term Outcomes of Brugada Substrate Ablation: A Report From BRAVO (Brugada Ablation of VF Substrate Ongoing Multicenter Registry)”
Authors: Koonlawee Nademanee, Michel Haissaguerre, Arthur A.M. Wilde, Elijah Behr, Akihiko Nogami
Journal: Circulation (2023)
Role of the first WHO mutation catalogue in the diagnosis of antibiotic resistance in Mycobacterium tuberculosis in the Valencia Region, Spain: a retrospective genomic analysis
Authors: Ana María García-Marín, Irving Cancino-Muñoz, Manuela Torres-Puente, Luis M Villamayor, Rafael Borrás, María Borrás-Máñez, Montserrat Bosque, Juan J Camarena, Ester Colomer-Roig, Javier Colomina, Isabel Escribano, Oscar Esparcia-Rodríguez, Ana Gil-Brusola, Concepción Gimeno, Adelina Gimeno-Gascón, Bárbara Gomila-Sard, Damiana González-Granda, Nieves Gonzalo-Jiménez, María Remedio Guna-Serrano, José Luis López-Hontangas, Coral Martín-González, Rosario Moreno-Muñoz, David Navarro, María Navarro, Nieves Orta, Elvira Pérez, Josep Prat, Juan Carlos Rodríguez, María Montserrat Ruiz-García, Hermelinda Vanaclocha, Fernando González-Candelas, Victoria Furió, Iñaki Comas
Journal: The Lancet Microbe (2024)

In June, 2021, WHO published the most complete catalogue to date of resistance-conferring mutations in Mycobacterium tuberculosis. Here, we aimed to assess the performance of genome-based antimicrobial resistance prediction using the catalogue and its potential for improving diagnostics in a real low-burden setting.
Mind the Gap
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2023)

Another critical year has almost passed, and the climate outlook is depressingly familiar. 2023 is almost certain to be the hottest year on record with a truly exceptional September breaking previous temperature records by a record margin. The signs of climate impacts on society, and health in particular are becoming clearer all the time — no longer abstract modelled projections, but the lived realities of people around the world.
Haplotype-resolved assemblies and variant benchmark of a Chinese Quartet
Authors: Peng Jia, Lianhua Dong, Xiaofei Yang, Bo Wang, Stephen J. Bush, Tingjie Wang, Jiadong Lin, Songbo Wang, Xixi Zhao, Tun Xu, Yizhuo Che, Ningxin Dang, Luyao Ren, Yujing Zhang, Xia Wang, Fan Liang, Yang Wang, Jue Ruan, Han Xia, Yuanting Zheng, Leming Shi, Yi Lv, Jing Wang, Kai Ye
Journal: Genome biology (2023)

Abstract Background Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology). Results The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent–child genetic map and for each haplotype. We also use long reads to generate haplotype-resolved whole-genome assemblies with completeness and continuity exceeding that of GRCh38. Using this Quartet, we comprehensively catalogue the human variant landscape, generating a dataset of 3,962,453 SNVs, 886,648 indels (&lt; 50 bp), 9726 large deletions (≥ 50 bp), 15,600 large insertions (≥ 50 bp), 40 inversions, 31 complex structural variants, and 68 de novo mutations which are shared between the monozygotic twin daughters. Variants underrepresented in previous benchmarks owing to their complexity—including those located at long repeat regions, complex structural variants, and de novo mutations—are systematically examined in this study. Conclusions In summary, this study provides high-quality haplotype-resolved assemblies and a comprehensive set of benchmarking resources for two Chinese monozygotic twin samples which, relative to existing benchmarks, offers expanded genomic coverage and insight into complex variant categories.
In symptomatic AF with end-stage HF, adding catheter ablation to medical therapy improved clinical outcomes at 18 mo
Authors: James Brophy
Journal: Annals of Internal Medicine (2023)

ACP Journal Club5 December 2023In symptomatic AF with end-stage HF, adding catheter ablation to medical therapy improved clinical outcomes at 18 moJames Brophy, MD, PhDJames Brophy, MD, PhDMcGill University, Montreal, Quebec, Canada (J.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J23-0096 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSohns C, Fox H, Marrouche NF, et al; CASTLE HTx Investigators. Catheter ablation in end-stage heart failure with atrial fibrillation. N Engl J Med. 2023;389:1380-1389. https://pubmed.ncbi.nlm.nih.gov/37634135Clinical Impact RatingsGIM/FP/GP: Cardiology: References1. Bassler D, Briel M, Montori VM, et al; STOPIT-2 Study Group. Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. JAMA. 2010;303:1180-1187. [PMID: 20332404] Google Scholar2. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995;273:408-412. [PMID: 7823387] Google Scholar3. Jüni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ. 2001;323:42-46. [PMID: 11440947] Google Scholar Author, Article, and Disclosure InformationAuthors: James Brophy, MD, PhDAffiliations: McGill University, Montreal, Quebec, Canada (J.B.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0096.This article was published at Annals.org on 5 December 2023.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics December 2023Volume 176, Issue 12 Page: JC137 Keywords Atrial fibrillation Cardiac ablation Cardiac transplantation Catheters Hazard ratio Heart Heart failure Left ventricular assist devices Mortality ePublished: 5 December 2023 Issue Published: December 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
HIV-1 reservoir size after neonatal antiretroviral therapy and the potential to evaluate antiretroviral-therapy-free remission (IMPAACT P1115): a phase 1/2 proof-of-concept study
Authors: Deborah Persaud, Yvonne Bryson, Bryan S Nelson, Camlin Tierney, Mark F Cotton, Anne Coletti, Jennifer Jao, Stephen A Spector, Mark Mirochnick, Edmund V Capparelli, Diane Costello, Joseph Szewczyk, Nicol Nicodimus, Lynda Stranix-Chibanda, Adeodata R Kekitiinwa, Violet Korutaro, Christina Reding, Mary N Carrington, Sai Majji, Dwight E Yin, Patrick Jean-Philippe, Ellen G Chadwick
Journal: The Lancet HIV (2023)
Association of hearing loss with patient-reported functional outcomes in adult survivors of childhood cancer
Authors: Johnnie K Bass, Fang Wang, Mackenzie E Thaxton, Sarah E Warren, Deo Kumar Srivastava, Melissa M Hudson, Kirsten K Ness, Tara M Brinkman
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Hearing loss is prevalent following ototoxic therapy for childhood cancer. Associations between hearing loss, self-perceived hearing handicap, and functional outcomes have not been examined in survivors. Methods Adult survivors treated with platinum or head and neck radiotherapy with hearing loss were recruited. A total of 237 survivors (median age at survey = 37.0 years [range = 30.0-45.0 years]; median = 29.1 years [range = 22.4-35.0 years] since diagnosis; median = 4.0 years [range = 2.9-7.7 years] from last audiogram to survey) completed the Hearing Handicap Inventory for Adults and questionnaires on social and emotional functioning and hearing aid use. Hearing loss severity was defined according to Chang criteria. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between hearing loss, hearing handicap, functional outcomes, and hearing aid use with adjustment for sex, race, age at hearing loss diagnosis, and age at survey. Results Two-thirds of survivors had severe hearing loss, which was associated with increased likelihood of hearing handicap (mild-moderate handicap: OR = 2.72, 95% CI = 1.35 to 5.47; severe handicap: OR = 5.99, 95% CI = 2.72 to 13.18). Survivors with severe hearing handicap had an increased likelihood of social isolation (OR = 8.76, 95% CI = 3.62 to 21.20), depression (OR = 9.11, 95% CI = 3.46 to 24.02), anxiety (OR = 17.57, 95% CI = 3.77 to 81.84), reduced personal income (OR = 2.82, 95% CI = 1.46 to 5.43), and less than full-time employment (OR = 2.47, 95% CI = 1.30 to 4.70). Survivors who did not use a recommended hearing aid were twice as likely to have less than full-time employment (OR = 2.26, 95% CI = 1.10 to 4.61) and reduced personal income (OR = 2.24, 95% CI = 1.08 to 4.63) compared with survivors who wore a hearing aid. Conclusion Self-perceived hearing handicap beyond measured hearing loss is associated with reduced functional outcomes. Assessment of hearing handicap may facilitate targeted interventions in adult survivors with hearing loss.
Dicarboxylic Acid Dietary Supplementation Protects against AKI
Authors: Anne C. Silva Barbosa, Katherine E. Pfister, Takuto Chiba, Joanna Bons, Jacob P. Rose, Jordan B. Burton, Christina D. King, Amy O'Broin, Victoria Young, Bob Zhang, Bharathi Sivakama, Alexandra V. Schmidt, Rebecca Uhlean, Akira Oda, Birgit Schilling, Eric S. Goetzman, Sunder Sims-Lucas
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement In this study, we demonstrate that a common, low-cost compound known as octanedioic acid (DC 8 ) can protect mice from kidney damage typically caused by ischemia-reperfusion injury or the chemotherapy drug cisplatin. This compound seems to enhance peroxisomal activity, which is responsible for breaking down fats, without adversely affecting mitochondrial function. DC 8 is not only affordable and easy to administer but also effective. These encouraging findings suggest that DC 8 could potentially be used to assist patients who are at risk of experiencing this type of kidney damage. Background Proximal tubules are rich in peroxisomes, which are damaged during AKI. Previous studies demonstrated that increasing peroxisomal fatty acid oxidation (FAO) is renoprotective, but no therapy has emerged to leverage this mechanism. Methods Mice were fed with either a control diet or a diet enriched with dicarboxylic acids, which are peroxisome-specific FAO substrates, then subjected to either ischemia-reperfusion injury-AKI or cisplatin-AKI models. Biochemical, histologic, genetic, and proteomic analyses were performed. Results Both octanedioic acid (DC 8 ) and dodecanedioic acid (DC 12 ) prevented the rise of AKI markers in mice that were exposed to renal injury. Proteomics analysis demonstrated that DC 8 preserved the peroxisomal and mitochondrial proteomes while inducing extensive remodeling of the lysine succinylome. This latter finding indicates that DC 8 is chain shortened to the anaplerotic substrate succinate and that peroxisomal FAO was increased by DC 8 . Conclusions DC 8 supplementation protects kidney mitochondria and peroxisomes and increases peroxisomal FAO, thereby protecting against AKI.
Intense 18F-PSMA-1007 Uptake of Splenic Hemangioma
Authors: Guorong Jia, Aisheng Dong, Chao Cheng, Changjing Zuo
Journal: Clinical Nuclear Medicine (2023)

Abstract A 77-year-old man was referred for 18 F-PSMA-1007 PET/CT scan for initial staging of biopsy-proved prostate adenocarcinoma. 18 F-PSMA-1007 PET/CT showed focal intense 18 F-PSMA-1007 of the prostate adenocarcinoma and a focal intense activity (SUV max , 27) in the spleen. The 18 F-PSMA-1007–avid splenic lesion corresponded to a splenic hemangioma, which was initially detected on contrast-enhanced CT 7 months ago and unchanged in size and enhancement pattern on follow-up contrast-enhanced CT. This case indicates that splenic hemangioma should be included in the differential diagnosis of PSMA-avid splenic lesions.
Indication and management of allogeneic haematopoietic stem-cell transplantation in myelofibrosis: updated recommendations by the EBMT/ELN International Working Group
Authors: Nicolaus Kröger, Andrea Bacigalupo, Tiziano Barbui, Markus Ditschkowski, Nico Gagelmann, Martin Griesshammer, Vikas Gupta, Nada Hamad, Claire Harrison, Juan Carlos Hernandez-Boluda, Steffen Koschmieder, Tania Jain, John Mascarenhas, Ruben Mesa, Uday R Popat, Francesco Passamonti, Nicola Polverelli, Alessandro Rambaldi, Marie Robin, Rachel B Salit, Thomas Schroeder, Bart L Scott, Roni Tamari, Ayalew Tefferi, Alessandro M Vannucchi, Donal P McLornan, Giovanni Barosi
Journal: The Lancet Haematology (2023)
Meningeal interleukin-17-producing T cells mediate cognitive impairment in a mouse model of salt-sensitive hypertension
Authors: Monica M. Santisteban, Samantha Schaeffer, Antoine Anfray, Giuseppe Faraco, David Brea, Gang Wang, Melissa J. Sobanko, Rose Sciortino, Gianfranco Racchumi, Ari Waisman, Laibaik Park, Josef Anrather, Costantino Iadecola
Journal: Nature Neuroscience (2023)
Dynamic encounters with red blood cells trigger splenic marginal zone B cell retention and function
Authors: Dan Liu, Benjamin Y. Winer, Marissa Y. Chou, Hanson Tam, Ying Xu, Jinping An, James M. Gardner, Jason G. Cyster
Journal: Nature Immunology (2023)

Abstract Spleen marginal zone (MZ) B cells are important for antibody responses against blood-borne antigens. The signals they use to detect exposure to blood are not well defined. Here, using intravital two-photon microscopy in mice, we observe transient contacts between MZ B cells and red blood cells that are in flow. We show that MZ B cells use adhesion G-protein-coupled receptor ADGRE5 (CD97) for retention in the spleen. CD97 function in MZ B cells depends on its ability to undergo autoproteolytic cleavage and signaling via Gα 13 and ARHGEF1. Red blood cell expression of the CD97 ligand CD55 is required for MZ B cell homeostasis. Applying a pulling force on CD97-transfected cells using an optical C-trap and CD55 + beads leads to accumulation of active RhoA and membrane retraction. Finally, we show that CD97 deficiency leads to a reduced T cell-independent IgM response. Thus, our studies provide evidence that MZ B cells use mechanosensing to position in a manner that enhances antibody responses against blood-borne antigens.
Dermal features derived from optoacoustic tomograms via machine learning correlate microangiopathy phenotypes with diabetes stage
Authors: Angelos Karlas, Nikoletta Katsouli, Nikolina-Alexia Fasoula, Michail Bariotakis, Nikolaos-Kosmas Chlis, Murad Omar, Hailong He, Dimitrios Iakovakis, Christoph Schäffer, Michael Kallmayer, Martin Füchtenbusch, Annette Ziegler, Hans-Henning Eckstein, Leontios Hadjileontiadis, Vasilis Ntziachristos
Journal: Nature Biomedical Engineering (2023)

Skin microangiopathy has been associated with diabetes. Here we show that skin-microangiopathy phenotypes in humans can be correlated with diabetes stage via morphophysiological cutaneous features extracted from raster-scan optoacoustic mesoscopy (RSOM) images of skin on the leg. We obtained 199 RSOM images from 115 participants (40 healthy and 75 with diabetes), and used machine learning to segment skin layers and microvasculature to identify clinically explainable features pertaining to different depths and scales of detail that provided the highest predictive power. Features in the dermal layer at the scale of detail of 0.1-1 mm (such as the number of junction-to-junction branches) were highly sensitive to diabetes stage. A 'microangiopathy score' compiling the 32 most-relevant features predicted the presence of diabetes with an area under the receiver operating characteristic curve of 0.84. The analysis of morphophysiological cutaneous features via RSOM may allow for the discovery of diabetes biomarkers in the skin and for the monitoring of diabetes status.
Perturbational phenotyping of human blood cells reveals genetically determined latent traits associated with subsets of common diseases
Authors: Max Homilius, Wandi Zhu, Samuel S. Eddy, Patrick C. Thompson, Huahua Zheng, Caleb N. Warren, Chiara G. Evans, David D. Kim, Lucius L. Xuan, Cissy Nsubuga, Zachary Strecker, Christopher J. Pettit, Jungwoo Cho, Mikayla N. Howie, Alexandra S. Thaler, Evan Wilson, Bruce Wollison, Courtney Smith, Julia B. Nascimben, Diana N. Nascimben, Gabriella M. Lunati, Hassan C. Folks, Matthew Cupelo, Suriya Sridaran, Carolyn Rheinstein, Taylor McClennen, Shinichi Goto, James G. Truslow, Sara Vandenwijngaert, Calum A. MacRae, Rahul C. Deo
Journal: Nature Genetics (2023)

Abstract Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology.
Spatial omics: An innovative frontier in aging research
Authors: Ying Chen, Shuhao Yang, Kaixu Yu, Jinjin Zhang, Meng Wu, Yongqiang Zheng, Yun Zhu, Jun Dai, Chunyan Wang, Xiaoran Zhu, Yun Dai, Yunhong Sun, Tong Wu, Shixuan Wang
Journal: Ageing Research Reviews (2023)