tbuckley/cabot-search huggingface dataset:
Recent advances in liposomes and peptide-based therapeutics for glioblastoma treatment
Authors: M-A Jourdain, J Eyer
Journal: Journal of Controlled Release (2024)

In the context of glioblastoma treatment, the penetration of drugs is drastically limited by the blood-brain-barrier (BBB). Emerging therapies have focused on the field of therapeutic peptides for their excellent BBB targeting properties that promote a deep tumor penetration. Peptide-based strategies are also renowned for their abilities of driving cargo such as liposomal system allowing an active targeting of receptors overexpressed on GBM cells. This review provides a detailed description of the internalization mechanisms of specific GBM homing and penetrating peptides as well as the latest in vitro/in vivo studies of liposomes functionalized with them. The purpose of this review is to summarize a selection of promising pre-clinical results that demonstrate the advantages of this nanosystem, including an increase of tumor cell targeting, triggering drug accumulation and thus a strong antitumor effect. Aware of the early stage of these studies, many challenges need to be overcome to promote peptide-directed liposome at clinical level. In particular, the lack of suitable production, the difficulty to characterize the nanosystem and therapeutic competition leaded by antibodies.
CT-FFR by expanding coronary tree with Newton–Krylov–Schwarz method to solve the governing equations of CFD
Authors: Weifeng Guo, Wei He, Yige Lu, Jiasheng Yin, Li Shen, Shan Yang, Hang Jin, Xinhong Wang, Jiang Jun, Xinyang Hu, Jianwen Liang, Wenbin Wei, Jiansheng Wu, Hua Zhang, Hao Zhou, Yanqing Wu, Renqiang Yang, Jinyu Huang, Guoxin Tong, Beibei Gao, Rongliang Chen, Jia Liu, Zhengzheng Yan, Zaiheng Cheng, Jianan Wang, Chenguang Li, Zhifeng Yao, Mengsu Zeng, Junbo Ge
Journal:  (2024)

A new model of computational fluid dynamics (CFD)-based algorithm for coronary CT angiography (CCTA)-derived fractional flow reserve (FFR) (CT-FFR) analysis by expanding the coronary tree to smaller-diameter lumen (0.8 mm) using Newton-Krylov-Schwarz (NKS) method to solve the three-dimensional time-dependent incompressible Navier-Stokes equations has been developed; however, the diagnostic performance of this new method has not been sufficiently investigated. The aim of this study was to determine the diagnostic performance of a novel CT-FFR technique by expanding the coronary tree in the CFD domain. Six centres enrolled 338 symptomatic patients with suspected or known coronary artery disease (CAD) who prospectively underwent CCTA and FFR. Stenosis assessment in CCTA and CT-FFR analysis were performed in independent core laboratories. Haemodynamically significant stenosis was defined by a CT-FFR and FFR ≤ 0.80, and anatomically obstructive CAD was defined as a CCTA with stenosis ≥ 50%. Diagnostic performance of CT-FFR was evaluated against invasive FFR using receiver operating characteristic (ROC) curve analysis. The correlation between CT-FFR and invasive FFR was analysed using the Spearman correlation coefficient and Bland-Altman analysis. Intra-observer and inter-observer agreements were evaluated utilizing the intraclass correlation coefficient (ICC). In this study, 338 patients with 422 targeted vessels were investigated, revealing haemodynamically significant stenosis in 31.1% (105/338) of patients and anatomically obstructive stenosis in 54.1% of patients. On a per-vessel basis, the area under the ROC curve for CT-FFR was 0.94 vs. 0.76 for CCTA (P < 0.001). Per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 89.8%, 89.3%, 90.0%, 79.0%, and 99.2%, respectively, for CT-FFR and were 68.4%, 82.8%, 62.3%, 48.1%, and 89.6%, respectively, for CCTA stenosis. CT-FFR and FFR were well correlated (r = 0.775, P < 0.001) with a Bland-Altman bias of 0.0011, and limits of agreement from -0.1509 to 0.1531 (P = 0.770). The ICCs with CT-FFR for intro- and inter-observer agreements were 0.919 (95% CI: 0.866-0.952) and 0.909 (95% CI: 0.851-0.945), respectively. The average computation time for CT-FFR analysis was maintained at 11.7 min. This novel CT-FFR model with the inclusion of smaller lumen provides high diagnostic accuracy in detecting haemodynamically significant CAD. Furthermore, the integration of the NKS method ensures that the computation time remains within an acceptable range for potential clinical applications in the future.
CRISPR-Based Therapy for Hereditary Angioedema
Authors: Danny M Cohn, Padmalal Gurugama, Markus Magerl, Constance H Katelaris, David Launay, Laurence Bouillet, Remy S Petersen, Karen Lindsay, Emel Aygören-Pürsün, David Maag, James S Butler, Mrinal Y Shah, Adele Golden, Yuanxin Xu, Ahmed M Abdelhady, David Lebwohl, Hilary J Longhurst
Journal: New England Journal of Medicine (2024)

BackgroundHereditary angioedema is a rare genetic disease characterized by severe and unpredictable swelling attacks. NTLA-2002 is an in vivo gene-editing therapy that is based on clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9. NTLA-2002 targets the gene encoding kallikrein B1 (KLKB1). A single dose of NTLA-2002 may provide lifelong control of angioedema attacks.MethodsIn this phase 2 portion of a phase 1–2 trial, we randomly assigned adults with hereditary angioedema in a 2:2:1 ratio to receive NTLA-2002 in a single dose of 25 mg or 50 mg or placebo. The primary end point was the number of angioedema attacks per month (the monthly attack rate) from week 1 through week 16. Secondary end points included safety, pharmacokinetics, and pharmacodynamics (i.e., the change from baseline in total plasma kallikrein protein level); exploratory end points included patient-reported outcomes.ResultsOf the 27 patients who underwent randomization, 10 received 25 mg of NTLA-2002, 11 received 50 mg, and 6 received placebo. From week 1 through week 16, the estimated mean monthly attack rate was 0.70 (95% confidence interval [CI], 0.25 to 1.98) with 25 mg of NTLA-2002, 0.65 (95% CI, 0.24 to 1.76) with 50 mg, and 2.82 (95% CI, 0.80 to 9.89) with placebo; the difference in the estimated mean attack rate with NTLA-2002 as compared with placebo was −75% with 25 mg and −77% with 50 mg. Among patients who received NTLA-2002, 4 of the 10 patients who received 25 mg (40%) and 8 of the 11 who received 50 mg (73%) were attack-free with no additional treatment during the period from week 1 through week 16. The most common adverse events among patients who received NTLA-2002 were headache, fatigue, and nasopharyngitis. The mean percent change in total plasma kallikrein protein levels from baseline to week 16 was −55% with 25 mg and −86% with 50 mg; levels remained unchanged with placebo.ConclusionsNTLA-2002 administered in a single dose of 25 mg or 50 mg reduced angioedema attacks and led to robust and sustained reduction in total plasma kallikrein levels in patients with hereditary angioedema. These results support continued investigation in a larger phase 3 trial. (Funded by Intellia Therapeutics; ClinicalTrials.gov number, NCT05120830; EudraCT number, 2021-001693-33.)
MAIT cells: Conserved watchers on the wall
Authors: Lilou Germain, Pablo Veloso, Olivier Lantz, François Legoux
Journal: The Journal of Experimental Medicine (2024)

MAIT cells are innate-like T cells residing in barrier tissues such as the lung, skin, and intestine. Both the semi-invariant T cell receptor of MAIT cells and the restricting element MR1 are deeply conserved across mammals, indicating non-redundant functions linked to antigenic specificity. MAIT cells across species concomitantly express cytotoxicity and tissue-repair genes, suggesting versatile functions. Accordingly, MAIT cells contribute to antibacterial responses as well as to the repair of damaged barrier tissues. MAIT cells recognize riboflavin biosynthetic pathway-derived metabolites, which rapidly cross epithelial barriers to be presented by antigen-presenting cells. Changes in gut ecology during intestinal inflammation drive the expansion of strong riboflavin and MAIT ligand producers. Thus, MAIT cells may enable real-time surveillance of microbiota dysbiosis across intact epithelia and provide rapid and context-dependent responses. Here, we discuss recent findings regarding the origin and regulation of MAIT ligands and the role of MAIT cells in barrier tissues. We speculate on the potential reasons for MAIT cell conservation during evolution.
The role and mechanism of gut-lung axis mediated bidirectional communication in the occurrence and development of chronic obstructive pulmonary disease
Authors: Xiaofan Song, Xina Dou, Jiajing Chang, Xiaonan Zeng, Qinhong Xu, Chunlan Xu
Journal: Gut Microbes (2024)

The current studies have shown that the occurrence and development of chronic obstructive pulmonary disease (COPD) are closely related to the changes in gut health and its microenvironment, and even some gut diseases have significant clinical correlation with COPD. The dysbiosis of gut microbiota observed in COPD patients also suggests a potential bidirectional interaction between the gut and lung. Communication between the gut and lung may occur through circulating inflammatory cells, gut microbial metabolites, and circulating inflammatory mediators, but the mechanism of bidirectional communication between the gut and lung in COPD is still under study. Therefore, more research is still needed in this area. In this review, we summarize recent clinical studies and animal models on the role of the gut-lung axis in the occurrence and development of COPD and its mechanisms, so as to provide ideas for further research in this field. In addition, we also summarized the negative effects of COPD medication on gut microbiota and the gut microbiota risk factors for COPD and proposed the potential prevention and treatment strategies.
Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state
Authors: Davide Mangani, Ayshwarya Subramanian, Linglin Huang, Hanning Cheng, S Harsha Krovi, Yufan Wu, Dandan Yang, Thais G Moreira, Giulia Escobar, Alexandra Schnell, Karen O Dixon, Rajesh K Krishnan, Vasundhara Singh, Raymond A Sobel, Howard L Weiner, Vijay K Kuchroo, Ana C Anderson
Journal: Immunity (2024)
Gut-first Parkinson’s disease is encoded by gut dysbiome
Authors: Mário F. Munoz-Pinto, Emanuel Candeias, Inês Melo-Marques, A. Raquel Esteves, Ana Maranha, João D. Magalhães, Diogo Reis Carneiro, Mariana Sant’Anna, A. Raquel Pereira-Santos, António E Abreu, Daniela Nunes-Costa, Susana Alarico, Igor Tiago, Ana Morgadinho, João Lemos, Pedro N. Figueiredo, Cristina Januário, Nuno Empadinhas, Sandra Morais Cardoso
Journal: Molecular Neurodegeneration (2024)

Abstract Background In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body - first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD - related neurodegeneration. Methods To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age - matched healthy donors to challenge the gut-immune-brain axis. Results This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood–brain-barrier, observed by an increase in mesencephalic Ig - G - positive microvascular leaks and by an increase of mesencephalic IL - 17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation. Conclusions We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain. Graphical Abstract
Hepatitis D virus infection markedly increases the risk of hepatocellular carcinoma in patients with viral B cirrhosis
Authors: Dominique Roulot, Richard Layese, Ségolène Brichler, Nathalie Ganne, Tarik Asselah, Fabien Zoulim, Emmanuel Gordien, Pierre Nahon, Françoise Roudot-Thoraval, Pierre Nahon, Nathalie Ganne, Zahia BenAbdesselam, Tarik Asselah, Fabien Zoulim, Dominique Guyader, Dominique Roulot, Stanislas Pol, Hélène Fontaine, Jean-Didier Grangé, Victor De Lédinghen, Bruno Roche, Thomas Decaens, Dominique Thabut, Albert Tran, Ghassan Riachi, Paul Calès, Olivier Chazouillères, Ariane Mallat, Jean-Frédéric Blanc, Denis Ouzan, Jean-Marie Péron, Laurent Alric, Louis d’Alteroche, Jean-Pierre Bronowicki, Sebastien Dharancy, Christophe Pilette, Christine Silvain
Journal: Clinical Gastroenterology and Hepatology (2024)
Prevalence of Chronic liver disease in Cholangiocarcinoma: a Meta-Analysis
Authors: Ethan Kai Jun Tham, Ryan Yanzhe Lim, Benjamin Koh, Darren Jun Hao Tan, Cheng Han Ng, Michelle Law, Elina Cho, Nicole Shu Ying Tang, Claire Shiying Tan, Benedix Kuan Loo Sim, En Ying Tan, Wen Hui Lim, Mei Chin Lim, Toru Nakamura, Pojsakorn Danpanichkul, Sakkarin Chirapongsathorn, Karn Wijarnpreecha, Hirokazu Takahashi, Asahiro Morishita, Ming-Hua Zheng, Alfred Kow, Mark Muthiah, Jia Hao Law, Daniel Q Huang
Journal: Clinical Gastroenterology and Hepatology (2024)
HLX07 alone or combined with serplulimab, cisplatin and 5‐fluorouracil for advanced esophageal squamous cell carcinoma: A phase 2 study
Authors: Yun Liu, Yanfeng Wang, Yanrong Zhu, Tao Wu, Zhenyang Liu, Jin Zhou, Yuan Yuan, Mudan Yang, Bo Liu, Zhenbo Tan, Wu Zhuang, Jiayan Chen, Ning Li, Ying Wang, Xuhui Hu, Lin Wang, Haoyu Yu, Qingyu Wang, Jun Zhu, Jing Huang
Journal: Cancer Communications (2024)

Abstract Background The combination of anti‐PD‐1 antibody serplulimab and chemotherapy is considered standard first‐line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later‐line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti‐EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. Methods This open‐label, non‐randomized, two‐cohort, phase 2 trial involved patients 18‐75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0‐1. Patients who had failed first‐line immuno‐chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m 2 , day 1) for up to 8 cycles and 5‐fluorouracil (1,200 mg/m 2 , days 1‐2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3‐4 treatment‐related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3‐4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab‐related pneumonitis. Conclusions HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. Trial registration This trial was registered at Clinicaltrials.gov (NCT05221658).
The Path to Genomic Screening—Far From Simple, but the Journey Has Begun
Authors: Jonathan S. Berg
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Cryo-EM structure of the human native plasma coagulation factor XIII complex
Authors: Sneha Singh, Gregor Hagelueken, Deniz Ugurlar, Samhitha Urs Ramaraje Urs, Amit Sharma, Manoranjan Mahapatra, Friedel Drepper, Diana Imhof, Pitter F Huesgen, Johannes Oldenburg, Matthias Geyer, Arijit Biswas
Journal: Blood (2024)
Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapies
Authors: Laurie H. Sehn, Nancy L. Bartlett, Matthew J. Matasar, Stephen J. Schuster, Sarit E. Assouline, Pratyush Giri, John Kuruvilla, Mazyar Shadman, Chan Y Cheah, Sascha Dietrich, Keith Fay, Matthew Ku, Loretta J. Nastoupil, Michael C. Wei, Shen Yin, Iris To, Derrick Kaufman, Antonia Kwan, Elicia Penuel, Christopher R. Bolen, Lihua Elizabeth Budde
Journal: Blood (2024)
A novel endoscopic artificial intelligence system to assist in the diagnosis of autoimmune gastritis: a multicenter study
Authors: Shurong Chen, Louzhe Xu, Lingling Yan, Jie Zhang, Xuefeng Zhou, Jiayi Wang, Tianlian Yan, Jinghua Wang, Xinjue He, Han Ma, Xuequn Zhang, Shenghua Zhu, Yi-zhen Zhang, Chengfu Xu, Jianguo Gao, Xia Ji, Dezhi Bai, Yuan Chen, Hongda Chen, Yini Ke, Lan Li, Chaohui Yu, Xinli Mao, Ting Li, Yi Chen
Journal: Endoscopy (2024)

Background &amp; Aims: Autoimmune gastritis (AIG), distinct from Helicobacter pylori-associated atrophic gastritis (HpAG), is underdiagnosed due to limited awareness. This multicenter study aims to develop a novel endoscopic artificial intelligence (AI) system assisting in AIG diagnosis. Methods: Patients diagnosed with AIG, as well as HpAG and non-atrophic gastritis (NAG), were retrospectively enrolled from six centers. Endoscopic images with relevant demographic and medical data, were collected for the development of AI-assisted system, SEER-SCOPE AI, based on multi-site feature fusion model. The diagnostic performance of SEER-SCOPE AI was evaluated in the internal and external datasets. Endoscopists’ performance with and without AI support was tested and compared using Mann-Whitney U test. Heatmap analysis was performed to interpret SEER-SCOPE AI. Results: 1 070 patients (294 AIG, 386 HpAG, 390 NAG) with 18 828 endoscopy images were collected. SEER-SCOPE AI achieved strong performance for identifying AIG, with 96.9% sensitivity, 92.2% specificity and an AUROC of 0.990 internally, and 90.3% sensitivity, 93.1% specificity and an AUROC of 0.973 externally. The performance of SEER-SCOPE AI (sensitivity 91.3%) was comparable to experts (87.3%) and significantly outperformed non-experts (70.0%). With AI support, the overall performance of endoscopists was improved (sensitivity: 90.3% [95% CI 86.0%-93.2%] vs. 78.7% [95% CI 73.6%-83.2%], p=0.008). Heatmap analysis revealed consistent focus of SEER-SCOPE AI on regions corresponding to atrophic areas. Conclusions: SEER-SCOPE AI demonstrated expert-level performance in identifying AIG, and enhanced the diagnostic ability of endoscopists. Its application holds promise as a potent endoscopy-assisted tool for guiding biopsy sampling and early detection of AIG.
Short-Term Clinical and Technical Outcomes of a Modified Zenker’s Peroral Endoscopic Myotomy (Z-POEM) With Mucosal Flap Incision
Authors: Jose Antonio Navarro Almario, Amit Mehta, Apurva Shrigiriwar, Farimah Fayyaz, Mohamed El-Sherbiny, Karim Essam, Hany Haggag, Kerolis Yousef, Abeer Abdallatef, Shaimaa Elkholy, Andrew Canakis, Raymond Eunho Kim, Dennis Yang, Miguel Puga-Tejada, Juan Alcivar Vasquez, Maria Egas-Izquierdo, Raquel Del Valle, Domenica Cunto, Jorge Baquerizo-Burgos, Martha Arevalo-Mora, Carlos Robles-Medranda, Aleksandra Borkowicz, Michał Filip Kamiński, Michael Lajin, Prashant Kedia, Mouen A Khashab
Journal: Endoscopy (2024)

BACKGROUND: Zenker’s diverticulum (ZD) per-oral endoscopic myotomy (Z-POEM) is an effective treatment for symptomatic (ZD). A modification to Z-POEM is the mucosal flap incision (MFI). We describe the technical and clinical success of patients who underwent Z-POEM with MFI. METHODS : We included patients who underwent Z-POEM with MFI for ZD at 8 international centers. The primary outcome was the rate of clinical success, assessed by post-procedure Kothari-Haber symptom score (KHSS) without retreatment. Secondary outcomes included technical success, serious adverse events, and clinical recurrence with need for retreatment. RESULTS : 36 patients (69% male, age 69 + 9 years) underwent Z-POEM with MFI for symptomatic ZD. Mean ZD size was 32 mm (+ 14). Clinical success was achieved in 35 (97%) cases. Median pre-procedure KHSS was 6 and median post-procedure KHSS was 1 (P &lt;0.0001). Technical success was achieved in all cases. Mean procedure time was 57 minutes (+ 32), median follow up time was 196 days (IQR 39-499). There was one adverse event (3%) which was treated endoscopically. CONCLUSION: Z-POEM with MFI has a high rate of technical and clinical success. Prospective evaluation is needed to further validate this technique in patients with large ZD.