tbuckley/cabot-search huggingface dataset:
Tissue-resident memory CD8 <sup>+</sup> T cells cooperate with CD4 <sup>+</sup> T cells to drive compartmentalized immunopathology in the CNS
Authors: Ilena Vincenti, Nicolas Page, Karin Steinbach, Alexander Yermanos, Sylvain Lemeille, Nicolas Nunez, Mario Kreutzfeldt, Bogna Klimek, Giovanni Di Liberto, Kristof Egervari, Margot Piccinno, Ghazal Shammas, Alexandre Mariotte, Nicolas Fonta, Nicolas Liaudet, Danielle Shlesinger, Anna Rita Liuzzi, Ingrid Wagner, Cynthia Saadi, Christine Stadelmann, Sai Reddy, Burkhard Becher, Doron Merkler
Journal: Science Translational Medicine (2022)

In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (TRM) represent a potentially important cellular player in this process. Here, we investigated whether resting CD8+ TRM persisting after cleared infection with attenuated lymphocytic choriomeningitis virus (LCMV) can initiate immune responses directed against cognate self-antigen in the CNS. We demonstrated that time-delayed conditional expression of the LCMV glycoprotein as neo-self-antigen by glia cells reactivated CD8+ TRM. Subsequently, CD8+ TRM expanded and initiated CNS inflammation and immunopathology in an organ-autonomous manner independently of circulating CD8+ T cells. However, in the absence of CD4+ T cells, TCF-1+ CD8+ TRM failed to expand and differentiate into terminal effectors. Similarly, in human demyelinating CNS autoimmune lesions, we found CD8+ T cells expressing TCF-1 that predominantly exhibited a TRM-like phenotype. Together, our study provides evidence for CD8+ TRM-driven CNS immunopathology and sheds light on why inflammatory processes may evade current immunomodulatory treatments in chronic autoimmune CNS conditions.
Solitary Periaortic Tuberculous Granuloma Mimicking Neoplastic Disease on 18F-FDG PET/CT
Authors: Na Guo, Anhui Zhu, Meixin Zhao, Hui Li, Weifang Zhang
Journal: Clinical Nuclear Medicine (2022)

Abstract Solitary tuberculoma of periaortic space is extremely rare. We report a case of periaortic tuberculous granuloma revealed by 18 F-FDG PET/CT in a 51-year-old woman without pulmonary or any other organ involvement. Awareness of this rare but possible atypical presentation of tuberculosis is helpful for the differential diagnosis of periaortic mass.
Reticulation Is a Risk Factor of Progressive Subpleural Nonfibrotic Interstitial Lung Abnormalities
Authors: Yuchen Zhang, Huajing Wan, Luca Richeldi, Min Zhu, Yan Huang, Xiaofeng Xiong, Junzhe Liao, Wenjun Zhu, Lingli Mao, Linrui Xu, Dongfan Ye, Ling Chen, Jia Liu, Linxi Fu, Liangyuan Li, Lan Lan, Ping Li, Lixia Wang, Xiaoju Tang, Fengming Luo
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Interstitial lung abnormalities (ILAs) are being increasingly identified in clinical practice. In particular, for subpleural nonfibrotic ILAs, the risk of progression over time and the risk factors for progressive behavior are still largely unknown. Objectives: To determine the age band prevalence of ILAs and the risk of radiological progression of subpleural nonfibrotic ILAs over time in a large health checkup population and to identify how reticulation contributes to the risk of radiological progression. Methods: On the basis of the ILAs definition by the Fleischner Society, low-dose chest computed tomography images from the community-dwelling population who have undergone health checkups were evaluated for ILAs. Multivariable logistic regression was used to assess the risk of radiological progression. Measurements and Main Results: Among 155,539 individuals, 3,300 (2.1%) were confirmed to have ILAs: the vast majority (81.7%) were defined as subpleural nonfibrotic ILAs. The prevalence of ILAs increased linearly with age (P for trend < 0.0001). Of 454 individuals with subpleural nonfibrotic ILAs, 198 (43.6%) had radiological progression over 4 years. The presence of reticulation on initial imaging was an independent predictor of radiological progression (odds ratio, 1.9; 95% confidence interval, 1.2-3.0; P = 0.0040). No difference in radiological progression was identified between subpleural nonfibrotic ILAs with extensive reticulation and subpleural fibrotic ILAs (73.0% vs. 68.8%; P = 0.7626). Conclusions: The prevalence of ILAs increases linearly with age. Nearly half of subpleural nonfibrotic ILAs progress radiologically over 4 years. The presence of reticulation is a risk factor for radiological progression. Subpleural nonfibrotic ILAs with extensive reticulation are likely to be a feature of subpleural fibrotic ILAs.
Inhaled Iloprost Improves Right Ventricular Load–Independent Contractility in Pulmonary Hypertension
Authors: Khodr Tello, Nils Kremer, Manuel J. Richter, Henning Gall, Jonas Muenks, Ardeschir Ghofrani, Ralph Schermuly, Robert Naeije, Baktybek Kojonazarov, Werner Seeger
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Inhaled Iloprost Improves Right Ventricular Load–Independent Contractility in Pulmonary Hypertension." American Journal of Respiratory and Critical Care Medicine, 206(1), pp. 111–114
Implementation of a Standardized Clinical Definition of Opioid Withdrawal in the Neonate
Authors: Shahla M. Jilani, Hendrée E. Jones, Jonathan M. Davis
Journal: JAMA (2022)

This Viewpoint discusses increases in opioid use disorder among pregnant people during the US opioid crisis and recommendations to define, diagnose, and treat neonatal abstinence syndrome and neonatal opioid withdrawal syndrome.
Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in sickle cell disease: A phase 2, open‐label study
Authors: Myrthe J. van Dijk, Minke A. E. Rab, Brigitte A. van Oirschot, Jennifer Bos, Cleo Derichs, Anita W. Rijneveld, Marjon H. Cnossen, Erfan Nur, Bart J. Biemond, Marije Bartels, Judith J. M. Jans, Wouter W. van Solinge, Roger E. G. Schutgens, Richard van Wijk, Eduard J. van Beers
Journal: American Journal of Hematology (2022)

Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment
Authors: Sophia B. Georghiou, Timothy C. Rodwell, Alexei Korobitsyn, Said H. Abbadi, Kanchan Ajbani, Jan-Willem Alffenaar, David Alland, Nataly Alvarez, Sönke Andres, Elisa Ardizzoni, Alexandra Aubry, Rossella Baldan, Marie Ballif, Ivan Barilar, Erik C. Böttger, Soumitesh Chakravorty, Pauline M. Claxton, Daniela M. Cirillo, Iñaki Comas, Chris Coulter, Claudia M. Denkinger, Brigitta Derendinger, Edward P. Desmond, Jurriaan E.M. de Steenwinkel, Keertan Dheda, Andreas H. Diacon, David L. Dolinger, Kelly E. Dooley, Matthias Egger, Soudeh Ehsani, Maha R. Farhat, Lanfranco Fattorini, Iris Finci, Laure Fournier Le Ray, Victoria Furió, Ramona Groenheit, Tawanda Gumbo, Scott K. Heysell, Doris Hillemann, Harald Hoffmann, Po-Ren Hsueh, Yi Hu, Hairong Huang, Alamdar Hussain, Farzana Ismail, Kiyohiko Izumi, Tomasz Jagielski, John L. Johnson, Priti Kambli, Koné Kaniga, G.H.R. Eranga Karunaratne, Meenu Kaushal Sharma, Peter M. Keller, Ellis C. Kelly, Margarita Kholina, Mikashmi Kohli, Katharina Kranzer, Ian F. Laurenson, Jason Limberis, S-Y. Grace Lin, Yongge Liu, Alexandre López-Gavín, Anna Lyander, Diana Machado, Elena Martinez, Faisal Masood, Satoshi Mitarai, Nomonde R. Mvelase, Stefan Niemann, Vladyslav Nikolayevskyy, Florian P. Maurer, Matthias Merker, Paolo Miotto, Shaheed V. Omar, Ralf Otto-Knapp, Moisés Palaci, Juan José Palacios Gutiérrez, Sharon J. Peacock, Charles A. Peloquin, Jennifer Perera, Catherine Pierre-Audigier, Suporn Pholwat, James E. Posey, Therdsak Prammananan, Leen Rigouts, Jaime Robledo, Neesha Rockwood, Camilla Rodrigues, Max Salfinger, Marcos C. Schechter, Marva Seifert, Sarah Sengstake, Thomas Shinnick, Natalia Shubladze, Vitali Sintchenko, Frederick Sirgel, Sulochana Somasundaram, Timothy R. Sterling, Andrea Spitaleri, Elizabeth Streicher, Philip Supply, Erik Svensson, Elisa Tagliani, Sabira Tahseen, Akiko Takaki, Grant Theron, Gabriela Torrea, Armand Van Deun, Jakko van Ingen, Annelies Van Rie, Dick van Soolingen, Roger Vargas Jr, Amour Venter, Nicolas Veziris, Cristina Villellas, Miguel Viveiros, Robin Warren, Shu'an Wen, Jim Werngren, Robert J. Wilkinson, Caie Yang, F. Ferda Yılmaz, Tingting Zhang, Danila Zimenkov, Nazir Ismail, Claudio U. Köser, Thomas Schön
Journal: European Respiratory Journal (2022)

<b>Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.</b>https://bit.ly/3i43wb6
Searching for new therapeutic options for the uncommon pathogen Mycobacterium chimaera: an open drug discovery approach
Authors: Daire Cantillon, Aaron Goff, Stuart Taylor, Emad Salehi, Katy Fidler, Simon Stoneham, Simon J Waddell
Journal: The Lancet Microbe (2022)

Mycobacterium chimaera is a slowly growing non-tuberculous mycobacterium associated with outbreaks of fatal infections in patients after cardiac surgery, and it is increasingly being detected in patients with chronic lung conditions. M chimaera can cause disseminated disease, osteomyelitis, and chronic skin or soft-tissue infections. We aimed to find new inhibitory compounds and drug repurposing opportunities for M chimaera, as current therapeutic options often result in poor outcomes.
Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy
Authors: Oscar Demeulenaere, Zulma Sandoval, Philippe Mateo, Alexandre Dizeux, Olivier Villemain, Romain Gallet, Bijan Ghaleh, Thomas Deffieux, Charlie Deméné, Mickael Tanter, Clément Papadacci, Mathieu Pernot
Journal: JACC. Cardiovascular imaging (2022)
Defining the determinants of vaccine uptake and undervaccination in migrant populations in Europe to improve routine and COVID-19 vaccine uptake: a systematic review
Authors: Alison F Crawshaw, Yasmin Farah, Anna Deal, Kieran Rustage, Sally E Hayward, Jessica Carter, Felicity Knights, Lucy P Goldsmith, Ines Campos-Matos, Fatima Wurie, Azeem Majeed, Helen Bedford, Alice S Forster, Sally Hargreaves
Journal: The Lancet Infectious Diseases (2022)
Infertility and Risk of Heart Failure in the Women’s Health Initiative
Authors: Emily S. Lau, Dongyu Wang, Mary Roberts, Christy N. Taylor, Gayathree Murugappan, Aladdin H. Shadyab, Peter F. Schnatz, Leslie V. Farland, Malissa J. Wood, Nandita S. Scott, Charles B. Eaton, Jennifer E. Ho
Journal: Journal of the American College of Cardiology (2022)
Leptomeningeal metastases—What outcomes should we measure and how?
Authors: Rimas V Lukas
Journal: Neuro-Oncology (2022)

Journal Article Leptomeningeal metastases—What outcomes should we measure and how? Get access Rimas V Lukas Rimas V Lukas Department of Neurology, Northwestern University, Chicago, Illinois, USALou & Jean Malnati Brain Tumor Institute, Chicago, Illinois, USA Corresponding Author: Rimas V. Lukas, MD, Department of Neurology, Northwestern University, 710 N. Lake Shore Drive, Abbott Hall 1114, Chicago, IL 60611, USA (rimas.lukas@nm.org). Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 24, Issue 10, October 2022, Pages 1736–1737, https://doi.org/10.1093/neuonc/noac101 Published: 14 April 2022 Article history Published: 14 April 2022 Corrected and typeset: 29 April 2022
Correction: First-in-Class Anti-Immunoglobulin–like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors
Authors: Lillian L. Siu, Ding Wang, John Hilton, Ravit Geva, Drew Rasco, Ruth Perets, Anson K. Abraham, Douglas C. Wilson, Julia F. Markensohn, Jared Lunceford, Leah Suttner, Shabana Siddiqi, Rachel A. Altura, Corinne Maurice-Dror
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), the number of patients who had ORR to MK-4830 + pembrolizumab was correct in Table 2 (n = 8), but footnote “b” contained incorrect information regarding cancer types and the number of patients with each cancer type. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret the error.
Single-Hit Inactivation Drove Tumor Suppressor Genes Out of the X Chromosome during Evolution
Authors: Xiansong Wang, Wei Hu, Xiangchun Li, Dan Huang, Qing Li, Hung Chan, Judeng Zeng, Chuan Xie, Huarong Chen, Xiaodong Liu, Tony Gin, Maggie Haitian Wang, Alfred Sze Lok Cheng, Wei Kang, Ka-Fai To, Dariusz Plewczynski, Qingpeng Zhang, Xiaoting Chen, Danny Cheuk Wing Chan, Ho Ko, Sunny Hei Wong, Jun Yu, Matthew Tak Vai Chan, Lin Zhang, William Ka Kei Wu
Journal: Cancer Research (2022)

Cancer-related genes are under intense evolutionary pressure. In this study, we conjecture that X-linked tumor suppressor genes (TSG) are not protected by the Knudson's two-hit mechanism and are therefore subject to negative selection. Accordingly, nearly all mammalian species exhibited lower TSG-to-noncancer gene ratios on their X chromosomes compared with nonmammalian species. Synteny analysis revealed that mammalian X-linked TSGs were depleted shortly after the emergence of the XY sex-determination system. A phylogeny-based model unveiled a higher X chromosome-to-autosome relocation flux for human TSGs. This was verified in other mammals by assessing the concordance/discordance of chromosomal locations of mammalian TSGs and their orthologs in Xenopus tropicalis. In humans, X-linked TSGs are younger or larger in size. Consistently, pan-cancer analysis revealed more frequent nonsynonymous somatic mutations of X-linked TSGs. These findings suggest that relocation of TSGs out of the X chromosome could confer a survival advantage by facilitating evasion of single-hit inactivation.This work unveils extensive trafficking of TSGs from the X chromosome to autosomes during evolution, thus identifying X-linked TSGs as a genetic Achilles' heel in tumor suppression.
Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma
Authors: Mingzhi Zhang, Dan Chen, Xiaorui Fu, Huimin Meng, Feifei Nan, Zhenchang Sun, Hui Yu, Lei Zhang, Ling Li, Xin Li, Xinhua Wang, Min Wang, Fengtao You, Zhaoming Li, Yu Chang, Zhiyuan Zhou, Jiaqin Yan, Jiwei Li, Xiaolong Wu, Yu Wang, Yinyan Wang, Shufen Xiang, YuSheng Chen, Guifang Pan, Hanying Xu, Bozhen Zhang, Lin Yang
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Since CD7 may represent a potent target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) immunotherapy, this study aimed to investigate safety and efficacy of autologous CD7–chimeric antigen receptor (CAR) T cells in patients with relapsed and refractory (R/R) T-ALL/LBL, as well as its manufacturing feasibility. Patients and Methods: Preclinical phase was conducted in NPG mice injected with Luc+ GFP+CCRF-CEM cells. Open-label phase I clinical trial (NCT04004637) enrolled patients with R/R CD7-positive T-ALL/LBL who received autologous CD7-CAR T-cell infusion. Primary endpoint was safety; secondary endpoints included efficacy and pharmacokinetic and pharmacodynamic parameters. Results: CD7 blockade strategy was developed using tandem CD7 nanobody VHH6 coupled with an endoplasmic reticulum/Golgi-retention motif peptide to intracellularly fasten CD7 molecules. In preclinical phase CD7 blockade CAR T cells prevented fratricide and exerted potent cytolytic activity, significantly relieving leukemia progression and prolonged the median survival of mice. In clinical phase, the complete remission (CR) rate was 87.5% (7/8) 3 months after CAR T-cell infusion; 1 patient with leukemia achieved minimal residual disease–negative CR and 1 patient with lymphoma achieved CR for more than 12 months. Majority of patients (87.5%) only had grade 1 or 2 cytokine release syndrome with no T-cell hypoplasia or any neurologic toxicities observed. The median maximum concentration of CAR T cells was 857.2 cells/μL at approximately 12 days and remained detectable up to 270 days. Conclusions: Autologous nanobody-derived fratricide-resistant CD7-CAR T cells demonstrated a promising and durable antitumor response in R/R T-ALL/LBL with tolerable toxicity, warranting further studies in highly aggressive CD7-positive malignancies.
Bottom-up assembly of target-specific cytotoxic synthetic cells
Authors: Jochen Estebano Hernandez Bücher, Oskar Staufer, Lukas Ostertag, Ulrike Mersdorf, Ilia Platzman, Joachim Pius Spatz
Journal: Biomaterials (2022)

Immune vigilance ensures body integrity by eliminating malignant cells through the complex but coordinated cooperation of highly diversified lymphocytes populations. The sheer complexity of the immune system has slowed development of immunotherapies based on top-down genetic engineering of lymphocytes. In contrast, bottom-up assembly of synthetic cell compartments has contributed novel engineering strategies to reverse engineer and understand cellular phenomena as molecularly defined systems. Towards reducing the complexity of immunological systems, herein, a bottom-up approach for controlled assembly of fully-synthetic immune-inspired cells from predefined molecular components based on giant unilamellar vesicles is described. For construction of target-specific cytotoxic immune cells, the Fas-ligand-based apoptosis-inducing immune cell module is combined with an antibody-mediated cellular cytotoxicity-inspired system. The designed immune cells identify leukemia cells by specific surface antigens. Subsequently, they form stable attachments sites and eliminate their targets by induction of apoptosis. A structural and functional characterization of the synthetic immune cells by means of microfluidics, live cell, confocal and electron microscopy, dynamic light scattering as well as flow cytometry is presented. This study demonstrates the bioinspired construction of effector immune cells from defined molecular building blocks, enabling learning-by-building approaches in synthetic immunology.
Elevated Lipoprotein(a) and Risk of Atrial Fibrillation
Authors: Pedrum Mohammadi-Shemirani, Michael Chong, Sukrit Narula, Nicolas Perrot, David Conen, Jason D. Roberts, Sébastien Thériault, Yohan Bossé, Matthew B. Lanktree, Marie Pigeyre, Guillaume Paré
Journal: Journal of the American College of Cardiology (2022)

Atrial fibrillation (AF) is a cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality. However, preventative therapies are needed with ancillary benefits on its cardiovascular comorbidities. Lipoprotein(a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), which itself increases AF risk, but it remains unknown whether Lp(a) is a causal mediator of AF independent of ASCVD.This study investigated the role of Lp(a) in AF and whether it is independent of ASCVD.Measured and genetically predicted Lp(a) levels were tested for association with 20,432 cases of incident AF in the UK Biobank (N = 435,579). Mendelian randomization analyses were performed by using summary-level data for AF from publicly available genome-wide association studies (N = 1,145,375).In the UK Biobank, each 50 nmol/L (23 mg/dL) increase in Lp(a) was associated with an increased risk of incident AF using measured Lp(a) (HR: 1.03; 95% CI: 1.02-1.04 ; P = 1.65 × 10-8) and genetically predicted Lp(a) (OR: 1.03; 95% CI: 1.02-1.05; P = 1.33 × 10-5). Mendelian randomization analyses using independent data replicated the effect (OR: 1.04 per 50 nmol/L Lp[a] increase; 95% CI: 1.03-1.05 per 50 nmol/L Lp[a] increase; P = 9.23 × 10-10). There was no evidence of risk-conferring effect from low-density lipoprotein cholesterol or triglycerides, and only 39% (95% CI: 27%-73%) of Lp(a) risk was mediated through ASCVD, suggesting that Lp(a) partly influences AF independent of its known effects on ASCVD.Our findings implicate Lp(a) as a potential causal mediator in the development of AF which show that the effects of Lp(a) extend across myocardial tissues. Ongoing clinical trials for Lp(a)-lowering therapies should evaluate effects on AF prevention.
Letter to the editor: Cautious use of multistate modeling in prognosis analysis of HCC
Authors: Shi‐Tao Jiang, Jun‐Wei Zhang, Xin Lu, Yi‐Yao Xu
Journal: Hepatology (2022)

To the editor, In a retrospective single‐center analysis, Ivanics et al. reviewed 486 patients with HCC who were treated with curative intent liver resection.[1] The results were impressive. They demonstrated that in contrast to standard single time‐to‐event estimates, multistate modeling considers transitions between different health states after surgery in patients with HCC, which was more in line with the real situation of such patients. However, the findings should be interpreted with caution given the following aspects. Except for the risk factors for recurrence mentioned by the authors, a few points were worth noting. First, the authors did not mention the preoperative viral load of patients with HBV or HCV infection and whether they received antiviral therapy.[2] Second, surgery‐related characteristics such as whether the surgical margin was > 1 cm, the duration of the operation, and whether the hepatic hilum was blocked during the operation were also not considered in this research. Because all of the above factors may contribute to postoperative recurrence, they should be included in the analysis. In addition, according to the Barcelona Clinic Liver Cancer staging system, patients with stage B were recommended to undergo transarterial chemoembolization (TACE), transarterial radioembolization, or liver transplantation.[3] This study included 43 patients with stage B who underwent hepatectomy with curative intent, which the authors should reasonably explain in the article. Meanwhile, whether or not patients received recurrence‐preventing treatments such as TACE after surgery also needed to be specified. The authors listed in their table 3 the treatment regimens that the patients received after postoperative recurrence. We found that treatment modalities were highly heterogeneous. This somewhat limited the credibility of the recurrence patterns reported in this paper. Because the treatment after a relapse may vary by medical institution, region, and country, this further reduced the generalizability of the findings. Finally, there were a few more things to be aware of when it comes to using multistate modeling correctly. Firstly, the authors did not define death precisely. Censoring competing risk events introduced bias (overestimation of cancer‐related deaths).[4] Secondly, it was necessary to verify whether the survival data satisfy the proportional hazards assumption. In addition, because of the possibility of transition from distant to local metastasis, the construction of the direction of progression needed to be considered. Funding information Supported by the CAMS Innovation Fund for Medical Sciences (2020‐I2M‐CT‐B‐026). CONFLICT OF INTEREST Nothing to report.