tbuckley/cabot-search huggingface dataset:
cGAS-activated endothelial cell–T cell cross-talk initiates tertiary lymphoid structure formation
Authors: Ruibo Zhao, Jinghe Zhang, Jialu Ma, Yali Qu, Zhenrong Yang, Zhinan Yin, Fengyin Li, Zhongjun Dong, Qinmiao Sun, Shu Zhu, Zhijian J. Chen, Daxing Gao
Journal: Science Immunology (2024)

Aberrant activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS-STING) pathway causes autoimmunity in humans and mice; however, the exact mechanism by which the cGAS-STING pathway initiates adaptive immunity and tissue pathology is still not fully understood. Here, we used a cGAS knockin (KI) mouse model that develops systemic autoimmunity. In the lungs of cGAS-KI mice, blood vessels were enclosed by organized lymphoid tissues that resemble tertiary lymphoid structures (TLSs). Cell-intrinsic cGAS induction promoted up-regulation of CCR5 in CD8 + T cells and led to CCL5 production in vascular endothelial cells. Peripheral CD8 + T cells were recruited to the lungs and produced CXCL13 and interferon-γ. The latter triggered endothelial cell death, potentiated CCL5 production, and was essential for TLS establishment. Blocking CCL5 or CCR5, or depleting CD8 + T cells, impaired TLS formation. cGAS-mediated TLS formation also enhanced humoral and antitumor responses. These data demonstrate that cGAS signaling drives a specialized lymphoid structure that underlies autoimmune tissue pathology.
NG2 is a target gene of MLL-AF4 and underlies glucocorticoid resistance in MLL-r B-ALL by regulating NR3C1 expression
Authors: Belén Lopez-Millan, Alba Rubio-Gayarre, Meritxell Vinyoles, Juan L. Trincado, Mario F. Fraga, Narcís Fernandez-Fuentes, Mercedes Guerrero-Murillo, Alba Martinez, Talia Velasco-Hernandez, Aïda Falgàs, Carla Panisello, Gemma Valcarcel, José Luis Sardina, Paula López-Martí, Biola M. Javierre, Beatriz Del Valle-Pérez, Antonio García de Herreros, Franco Locatelli, Rob Pieters, Michela Bardini, Giovanni Cazzaniga, Juan Carlos Rodríguez-Manzaneque, Thomas Hanewald, Rolf Marschalek, Thomas A. Milne, Ronald W. Stam, Juan Ramón Tejedor, Pablo Menendez, Clara Bueno
Journal: Blood (2024)
Epigenetic agents plus anti-PD-1 reshapes tumor microenvironment and restores antitumor efficacy in Hodgkin lymphoma
Authors: Jing Nie, Chunmeng Wang, Liangtao Zheng, Yang Liu, Chengcheng Wang, Yixin Chang, Yudi Hu, Bing Guo, Yuting Pan, Qingming Yang, Xueda Hu, Weidong Han
Journal: Blood (2024)
Five decades of clinical ABO-incompatible liver transplantation research: a bibliometric analysis
Authors: Maiwulanjiang Maimaiti, Alimujiang Mamuti, Yilizhati Azhati, Aliya Tulading, Yun-Fei Zhang, Jing Wu, Abudusalamu Tuersunmaimaiti, Chun-Hui Lv, Gang Yao, Amina Aierken, Tao Li, Tuerganaili Aji, Ying-Mei Shao, Hao Wen, Tuerhongjiang Tuxun
Journal: International Journal of Surgery (2024)

Maimaiti, Maiwulanjiang MSc; Mamuti, Alimujiang MSc; Azhati, Yilizhati MSc; Tulading, Aliya BSc; Zhang, Yun-Fei MSc; Wu, Jing MD; Tuersunmaimaiti, Abudusalamu MSc; Lv, Chun-Hui MSc; Yao, Gang MSc; Aierken, Amina MSc; Li, Tao PhD; Aji, Tuerganaili PhD; Shao, Ying-Mei PhD; Wen, Hao MD, PhD; Tuxun, Tuerhongjiang MD, PhD Author Information
The correlation between TRPV1 and pain during urethrocystoscopy: a prospective observational study
Authors: Zebin Deng, Zhichao Huang, Yinhuai Wang, Qi Xiong, Shunhua Cheng, Xu Cheng
Journal: International Journal of Surgery (2024)

Deng, Zebin; Huang, Zhichao; Wang, Yinhuai; Xiong, Qi; Cheng, Shunhua; Cheng, Xu Author Information
Effectiveness and feasibility of nerve real-time monitoring and intermittent monitoring in endoscopic thyroidectomy: A multicenter retrospective cohort study of 1621 patients
Authors: Xing Yu, Ruiying Zhu, Peifeng Zhu, Yu Du, Cheerly Tanu, Zhenyi Han, Neng Jiang, Lei Pan, Chaoran Xie, Qunzi Zhao, Yong Wang
Journal: International Journal of Surgery (2024)

Background: Protecting recurrent laryngeal nerve (RLN) and external branch of the superior laryngeal nerve (EBSLN), a crucial indicator for assessing the quality of thyroid surgery, poses a challenge in endoscopic thyroidectomy. The aim of this study was to investigate the effectiveness and feasibility of nerve real-time monitoring and intermittent monitoring in endoscopic thyroidectomy. Methods: In this retrospective cohort study, patients underwent endoscopic thyroidectomy were included, and the characteristics and outcomes of real-time monitoring and intermittent monitoring groups were compared. Thereafter, the outcomes of four surgical types (unilateral lobectomy, total thyroidectomy, unilateral lobectomy + lymph node dissection (LND), and total thyroidectomy + LND) were compared in both groups. Results: A total of 1621 patients were enrolled. Compared to intermittent monitoring group, real-time monitoring group significantly shortened operation durations in the four surgical types (30.8 ± 6.1 min vs. 35.7 ± 5.7 min, 54.7 ± 4.4 min vs. 59.1 ± 5.2 min, 39.3 ± 4.6 min vs. 42.0 ± 4.7 min, 59.1 ± 4.9 min vs. 66.0 ± 5.8 min, respectively). As for surgical complications, compared to intermittent monitoring group, real-time monitoring group had lower rates of transient vocal cord paralysis among the four surgical types (0.0% vs. 3.3%, 0.0% vs. 4.0%, 0.8% vs. 3.2%, 2.8% vs. 6.7%, respectively), and lower rates of EBSLN injury (1.1% vs. 4.4%, 0.0% vs. 12.0%, 0.8% vs. 3.8%, 0.9% vs. 4.8%, respectively). Clinicopathologic characteristics and postoperative inflammatory reactions were similarly paralleled in both groups. Conclusion: Implementation of real-time monitoring in endoscopic thyroidectomy effectively protects the RLN and EBSLN while shortening operation duration, demonstrating its feasibility and efficacy in enhancing nerve protection and surgical efficiency.
Genetic background and intraoperative haemodynamic instability in patients with pheochromocytoma and paraganglioma: a multicenter retrospective study
Authors: Minghao Li, Jing Zhang, Yingxian Pang, Yao He, Yanting Shen, Jing Wang, Xiaowen Xu, Jiahao Liu, Kai Cheng, Zhi Li, Yujun Liu, Xin Gao, Graeme Eisenhofer, Jingjing Jiang, Longfei Liu
Journal: International Journal of Surgery (2024)

Background: Perioperative management to maintain intraoperative haemodynamic stability is crucial during surgical treatment of pheochromocytomas and paragangliomas (PPGLs). Although approximately 70% of PPGLs carry pathogenic variants (PVs) in susceptibility genes, whether intraoperative haemodynamic instability (IHI) is associated with genetic background remains unclear. This study aimed to analyse IHI in patients with PPGL due to PVs in different genes. Materials and Methods: This retrospective study recruited 756 patients with abdominal PPGL from two tertiary care centres. Clinical information including sex, age, catecholamine-associated signs and symptoms (CAS), tumour location and size, biochemistry, and perioperative characteristics were collected. Genetic mutations were investigated using next-generation sequencing. Results: Among the 671 patients included in the analysis, 61.8% (415/671) had IHI. IHI was significantly associated with genetic background in patients with PPGL. Most (80.9%, 89/110) patients with PPGL due to PVs in HRAS suffered IHI. In contrast, only half (31/62) of patients with PPGL due to PVs in VHL had IHI. In the multivariate regression analysis, compared to those with negative genetic testing results, patients with PPGL due to PVs in HRAS (OR 3.82, 95% CI 2.187-6.679, P &lt;0.001), the other cluster 2 genes (OR 1.95, 95% CI 1.287-2. 569, P &lt; 0.05), and cluster 1 genes other than VHL (OR 2.35, 95% CI 1.338-4.111, P &lt;0.05) were independent risk factors for IHI, while PVs in VHL was not independent risk factor (OR 1.09, 95% CI 0.605-1.953, P &gt;=0.05). In addition, age at diagnosis of primary tumour, presenting of CAS, and tumour size were identified as independent factors for IHI. The nomogram illustrated that genetic background as sharing the largest contribution to IHI, followed by tumour size, age, and presenting of CAS. Conclusion: IHI is associated with the genetic background in patients with PPGL. The perioperative management of patients with PPGL can be personalized according to their genetic backgrounds, tumour size, age, and presenting of CAS.
Association of positive airway pressure termination with mortality and non-fatal cardiovascular events in patients with obstructive sleep apnoea
Authors: AbdelKebir Sabil, Claire Launois, Wojchiech Trzepizur, François Goupil, Thierry Pigeanne, Sandrine Launois, Laurène Leclair-Visonneau, Philippe Masson, Acya Bizieux-Thaminy, Sandrine Kerbat, Sebastien Bailly, Frédéric Gagnadoux
Journal: Thorax (2024)

Background and aims The recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether PAP termination is associated with an increased incidence of major adverse CV events (MACE) compared with adherent PAP continuation. Methods Data from the Pays de la Loire Sleep Cohort were linked to the French national health insurance database to identify incident MACE (composite outcome of mortality, stroke and cardiac diseases), and CV active drug (lipid-lowering, antihypertensive and antiplatelet drugs, beta-blockers) adherence (medication possession ratio ≥80%). The association of PAP termination with MACE was evaluated using a time-dependent survival Cox model, with adjustment for confounders including CV active drug status. Results After a median follow-up of 8 years, 969 of 4188 included patients (median age 58 years, 69.6% men) experienced MACE, 1485 had terminated PAP while 2703 continued PAP with at least 4 hours/night use. 38% of patients were adherent to all CV drugs in the PAP continuation group versus 28% in the PAP termination group (p&lt;0.0001). After adjustment for confounders, PAP termination was associated with an increased risk of MACE (HR (95% CI): 1.39 (1.20 to 1.62); p&lt;0.0001). PAP termination was not associated with incident heart failure and coronary artery disease. Conclusions In this multicentre clinical-based cohort involving 4188 patients with OSA, PAP termination compared with adherent PAP continuation was associated with an increased risk of MACE. More research is needed to determine whether support programmes on PAP adherence could improve CV outcomes.
Airway proteomics reveals broad residual anti-inflammatory effects of prednisolone in mepolizumab-treated asthma
Authors: Imran Howell, Freda Yang, Vanessa Brown, Jennifer Cane, Emanuele Marchi, Adnan Azim, John Busby, Pamela J McDowell, Sarah E Diver, Catherine Borg, Liam G Heaney, Ian D Pavord, Christopher E Brightling, Rekha Chaudhuri, Timothy S C Hinks
Journal: Journal of Allergy and Clinical Immunology (2024)

Graphical abstractAbstractBackgroundMepolizumab is an anti-IL-5 mAb treatment for severe eosinophilic asthma that reduces asthma exacerbations. Residual airway inflammation with mepolizumab therapy may lead to persistent exacerbations. Oral corticosteroids remain the main treatment for these residual exacerbations.ObjectiveOur study aimed to explore the corticosteroid responsiveness of airway inflammation after mepolizumab treatment to find potentially treatable inflammatory mechanisms beyond the IL-5 pathway.MethodsThe MAPLE trial was a multicenter, randomized, double-blind, placebo-controlled, crossover study of 2 weeks of high-dose oral prednisolone treatment at stable state in 27 patients treated with mepolizumab for severe eosinophilic asthma. We analyzed paired sputum (n = 16) and plasma (n = 25) samples from the MAPLE trial using high-throughput Olink proteomics. We analyzed additional sputum proteins using ELISA.ResultsIn patients receiving mepolizumab, prednisolone significantly downregulated sputum proteins related to type 2 inflammation and chemotaxis including IL-4, IL-5, IL-13, CCL24, CCL26, EDN, CCL17, CCL22, OX40 receptor, FCER2, and the ST2 receptor. Prednisolone also downregulated cell adhesion molecules, prostaglandin synthases, mast cell tryptases, MMP1, MMP12, and neuroimmune mediators. Neutrophilic pathways were upregulated. Type 2 proteins were also downregulated in plasma, combined with IL-12, IFN-γ, and IP-10. IL-10 and amphiregulin were upregulated.ConclusionsAt stable state, prednisolone has broad anti-inflammatory effects on top of mepolizumab. These effects are heterogeneous and may be clinically relevant in residual exacerbations.
Eye tracking insights into physician behaviour with safe and unsafe explainable AI recommendations
Authors: Myura Nagendran, Paul Festor, Matthieu Komorowski, Anthony C. Gordon, Aldo A. Faisal
Journal: npj Digital Medicine (2024)

Abstract We studied clinical AI-supported decision-making as an example of a high-stakes setting in which explainable AI (XAI) has been proposed as useful (by theoretically providing physicians with context for the AI suggestion and thereby helping them to reject unsafe AI recommendations). Here, we used objective neurobehavioural measures (eye-tracking) to see how physicians respond to XAI with N = 19 ICU physicians in a hospital’s clinical simulation suite. Prescription decisions were made both pre- and post-reveal of either a safe or unsafe AI recommendation and four different types of simultaneously presented XAI. We used overt visual attention as a marker for where physician mental attention was directed during the simulations. Unsafe AI recommendations attracted significantly greater attention than safe AI recommendations. However, there was no appreciably higher level of attention placed onto any of the four types of explanation during unsafe AI scenarios (i.e. XAI did not appear to ‘rescue’ decision-makers). Furthermore, self-reported usefulness of explanations by physicians did not correlate with the level of attention they devoted to the explanations reinforcing the notion that using self-reports alone to evaluate XAI tools misses key aspects of the interaction behaviour between human and machine.
Global Case Fatality of Bacterial Meningitis During an 80-Year Period
Authors: Cornelis N. van Ettekoven, Fabian D. Liechti, Matthijs C. Brouwer, Merijn W. Bijlsma, Diederik van de Beek
Journal: JAMA Network Open (2024)

Importance The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain. Objective To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis. Data Sources Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality . Study Selection Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care–associated meningitis, tuberculous meningitis, or missing outcome were excluded. Data Extraction and Synthesis Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period’s year as an estimator variable were used. Main Outcome and Measure Case fatality ratios of bacterial meningitis. Results This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157 656 episodes. Of the 33 295 episodes for which the patients’ sex was reported, 13 452 (40%) occurred in females. Causative pathogens were reported in 104 598 episodes with Neisseria meningitidis in 26 344 (25%) episodes, Streptococcus pneumoniae in 26 035 (25%) episodes, Haemophilus influenzae in 22 722 (22%), other bacteria in 19 161 (18%) episodes, and unidentified pathogen in 10 336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli , or Streptococcus agalactiae ( P &amp;amp;lt; .001). Conclusions and Relevance In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained.
Biodistribution and Radiation Dosimetry for 68Ga-DOTA-CCK-66, a Novel CCK2R-Targeting Compound for Imaging of Medullary Thyroid Cancer
Authors: Oliver Viering, Andreas Rinscheid, Nadine Holzleitner, Alexander Dierks, Malte Kircher, Georgine Wienand, Marianne Patt, Hans-Jürgen Wester, Ralph A. Bundschuh, Thomas Günther, Constantin Lapa, Christian H. Pfob
Journal: Clinical Nuclear Medicine (2024)

Abstract Cholecystokinin 2 receptor (CCK 2 R) is a promising target for imaging and treatment of medullary thyroid cancer due to its overexpression in over 90% of tumor cells. 68 Ga-DOTA-CCK-66 is a recently introduced PET tracer selective for CCK 2 R, which has shown favorable pharmacokinetics in vivo in preclinical experiments. In order to further investigate safety and suitability of this tracer in the human setting, whole-body distribution and radiation dosimetry were evaluated. Patients and Methods Six patients with a history of medullary thyroid cancer were injected intravenously with 169 ± 19 MBq of 68 Ga-DOTA-CCK-66. Whole-body PET/CT scans were acquired at 10 minutes, 1 hour, 2 hours, and 4 hours after tracer injection. Time-activity curves per organ were determined, and mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. Results Injection of a standard activity of 150 MBq of 68 Ga-DOTA-CCK-66 results in an effective dose of 4.5 ± 0.9 mSv. The highest absorbed organ doses were observed in the urinary bladder wall (40 mGy) and the stomach (15 mGy), followed by the kidneys (6 mGy), as well as the liver and the spleen (3 mGy each). CCK 2 R-expressing tumor manifestations could be detected in 2 of the 6 patients, including lymph node, bone, and liver metastases. Conclusions 68 Ga-DOTA-CCK-66 exhibits a favorable dosimetry. Beyond physiologic receptor expression of the stomach, no other relevant tracer accumulation could be observed, rendering this organ at risk in case of subsequent radioligand therapy using 177 Lu-DOTA-CCK-66.
Prenatal RSV Vaccine Not Tied to Higher Risk of Preterm Births
Authors: Emily Harris
Journal: JAMA (2024)

Moeun Son, MD, MSCI; Laura E. Riley, MD; Anna P. Staniczenko, MD, MSc; Julia Cron, MD; Steven Yen, MS; Charlene Thomas, MS; Evan Sholle, MS; Lauren M. Osborne, MD; Heather S. Lipkind, MD, MS
A False-Negative 123I-MIBG SPECT/CT With True-Positive 68Ga-DOTATATE PET/CT in a Patient With Neuroblastoma Following 177Lu-DOTATATE Therapy
Authors: Siqi Li, Yanfeng Xu, Xia Lu, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2024)

Abstract A 10-year-old girl with high-risk neuroblastoma underwent 123 I-MIBG SPECT/CT and 68 Ga-DOTATE PET/CT, which both showed multiple bone metastases. However, following 177 Lu-DOTATATE therapy, only 68 Ga-DOTATATE PET/CT identified residual lesions with negative 123 I-MIBG SPECT/CT results. The case emphasized the complementary role of 68 Ga-DOTATATE PET/CT and 123 I-MIBG SPECT/CT after 177 Lu-DOTATATE therapy.
Systematic Review: Problems With Smell Tied to Increased Frailty Risk
Authors: Emily Harris
Journal: JAMA (2024)

Brian Sheng Yep Yeo, MBBS (Singapore); Jun He Chan, MBBS (Singapore); Benjamin Kye Jyn Tan, MBBS (Hons) (Singapore); Xuandao Liu, MBBS (Singapore), MMed (ORL); Laura Tay, MBBS (Singapore), MMed (Internal Medicine), MCI (Singapore); Neville Wei Yang Teo, MBBS (Singapore), MMed (ORL); Tze Choong Charn, MBBS (Singapore), GDFM (Singapore), MMed (ORL), DOHNS (England)
EHR Data Suggest Tirzepatide Outdoes Semaglutide for Weight Loss
Authors: Emily Harris
Journal: JAMA (2024)

Patricia J. Rodriguez, PhD; Brianna M. Goodwin Cartwright, MS; Samuel Gratzl, PhD; Rajdeep Brar, MD; Charlotte Baker, DrPH; Ty J. Gluckman, MD; Nicholas L. Stucky, MD
177Lu-PSMA With Olaparib Radiosensitization Potentiates Response and Toxicity in Extensive Castration-Resistant Metastatic Prostate cancer
Authors: Yung Hsiang Kao, Nadia Falzone, Michael Pearson, David Pook, Dinesh Sivaratnam
Journal: Clinical Nuclear Medicine (2024)

A patient with widespread intensely prostate-specific membrane antigen-expressing, BRCA gene mutation-positive bone metastases at the time of prostate cancer diagnosis had progressed on multiple lines of standard therapy. He received 177 Lu-prostate-specific membrane antigen 8.5 GBq augmented by a short course of olaparib radiosensitization and achieved 90% decrease in serum PSA level after a single treatment. His tumor response was much better than expected by predictive dosimetry. However, his marrow radiotoxicity was worse than anticipated and required hospitalization. This suggests radiosensitizing agents to be a double-edged sword that must be carefully considered and balanced during activity prescription.
Weight Loss Drugs Linked With Lower Risk of 10 Cancers
Authors: Emily Harris
Journal: JAMA (2024)

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The Power of Community Engagement and Patient Voices
Authors: Arshiya A. Baig
Journal: JAMA Network Open (2024)

Mark L. Wieland, MD, MPH; Katherine Diaz Vickery, MD, MSc; Valentina Hernandez, MS; Becky R. Ford, PhD; Crystal Gonzalez, MS; Silvio Kavistan, BS; Sheila Iteghete, BA; Christi A. Patten, PhD; Jane W. Njeru, MBChB; Abby M. Lohr, PhD, MPH; Jamie O'Byrne, BS; Paul J. Novotny, MS; Davinder P. Singh, MBBS; Linda K. Larkey, PhD; Miriam Goodson, MS; Graciela Porraz Capetillo; Irene G. Sia, MD, MSc
More Data About Risks, Benefits Might Change Breast Cancer Screening Choice
Authors: Emily Harris
Journal: JAMA (2024)

US Preventive Services Task Force; Wanda K. Nicholson, MD, MPH, MBA; Michael Silverstein, MD, MPH; John B. Wong, MD; Michael J. Barry, MD; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Esa M. Davis, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Marie Krousel-Wood, MD, MSPH; Sei Lee, MD, MAS; Li Li, MD, PhD, MPH; Carol M. Mangione, MD, MSPH; Goutham Rao, MD; John M. Ruiz, PhD; James J. Stevermer, MD, MSPH; Joel Tsevat, MD, MPH; Sandra Millon Underwood, PhD, RN; Sarah Wiehe, MD, MPH