tbuckley/cabot-search huggingface dataset:
Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction
Authors: Ting Gong, You-Tan Liu, Jie Fan
Journal: Military Medical Research (2024)

Abstract Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.
Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel
Authors: Guido Ghilardi, Luca Paruzzo, Vrutti Patel, Jakub Svoboda, Emeline R. Chong, Eugenio Fardella, Elise A. Chong, Giulia Gabrielli, Sunita D. Nasta, Daniel J. Landsburg, Jordan Carter, Raymone Pajarillo, Stefan K. Barta, Griffin White, Elizabeth Weber, Ellen Napier, David L. Porter, Alfred L. Garfall, Stephen J. Schuster, Marco Ruella
Journal: Journal of Hematology & Oncology (2024)

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.
Programmed death receptor-1 and programmed death ligand-1 checkpoint inhibition-associated bullous pemphigoid: a propensity-matched retrospective cohort study
Authors: Katelyn Sarkovics, Joanna A Kolodney, Michael S Kolodney
Journal: British Journal of Dermatology (2024)

We provide a comparison of the bullous pemphigoid (BP)-free survival probability in patients starting PD-1/PD-L1 inhibitors and DPP-4 inhibitors that has not been previously demonstrated in other studies. A propensity-matched retrospective cohort study performed with TriNetX participants revealed a significantly increased risk of BP in patients starting PD-1/PD-L1 inhibitors, especially in male patients and those aged &amp;gt; 65 years.
Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycaemia
Authors: Changsheng Chen, Yinyin Qin, Yidan Xu, Xiaoning Wang, Wei Lei, Xiaozhong Shen, Lixun Chen, Linnong Wang, Jie Gong, Yongming Wang, Shijun Hu, Dong Liu
Journal: Cardiovascular Research (2024)

In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive.
Superior COL7A1 and TGM1 gene expression in difficult-to-transfect skin cell mediated by highly branched poly(β-amino esters) through stepwise fractionation
Authors: Chaolan Pan, Chenfei Wang, Yitong Zhao, Tao Bo, Liping Han, Dingjin Yao, Yumeng Wang, Xiaoxiao Wang, Linjing Shi, Anqi Zhao, Qiaoyu Cao, Fuying Chen, Wei He, Ying Ye, Si Zhang, Ming Li
Journal: Journal of Controlled Release (2024)
Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system
Authors: Xiaoqian Ma, Qing Yang, Nuo Lin, Yushuo Feng, Yaqing Liu, Peifei Liu, Yiru Wang, Huaping Deng, Haizhen Ding, Hongmin Chen
Journal: Journal of Controlled Release (2024)
‘Substantial clinical benefit’ and ‘substantial clinical worsening’ cutoff of Vitiligo Impact Scale (VIS)-22 change scores
Authors: Vishal Gupta, Neha Taneja, Hem Chandra Sati, Vishnubhatla Sreenivas, M Ramam
Journal: British Journal of Dermatology (2024)

Patient-centric outcome measures focus on clinically meaningful change in various aspects of disease, including severity, quality of life and psychological distress. The minimal important change (MIC) is a commonly used threshold of patient-reported outcome measures, representing the smallest difference that is considered significant by the patient and/or physician. However, it has been suggested that MIC is too low a bar for determining treatment success, and alternative thresholds such as substantial clinical benefit (SCB) and patient acceptable symptom state (PASS) may be preferred.
Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk
Authors: Natalie S. Callander, Rebecca Silbermann, Jonathan L. Kaufman, Kelly N. Godby, Jacob Laubach, Timothy M. Schmidt, Douglas W. Sborov, Eva Medvedova, Brandi Reeves, Binod Dhakal, Cesar Rodriguez, Saurabh Chhabra, Ajai Chari, Susan Bal, Larry D. Anderson, Bhagirathbhai R. Dholaria, Nitya Nathwani, Parameswaran Hari, Nina Shah, Naresh Bumma, Sarah A. Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M. Wildes, Robert Z. Orlowski, Kenneth H. Shain, Andrew J. Cowan, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S. Lin, Smith Giri, Luciano J. Costa, Saad Z. Usmani, Paul G. Richardson, Peter M. Voorhees
Journal: Blood Cancer Journal (2024)

Abstract In the MASTER study (NCT03224507), daratumumab+carfilzomib/lenalidomide/dexamethasone (D-KRd) demonstrated promising efficacy in transplant-eligible newly diagnosed multiple myeloma (NDMM). In GRIFFIN (NCT02874742), daratumumab+lenalidomide/bortezomib/dexamethasone (D-RVd) improved outcomes for transplant-eligible NDMM. Here, we present a post hoc analysis of patients with high-risk cytogenetic abnormalities (HRCAs; del[17p], t[4;14], t[14;16], t[14;20], or gain/amp[1q21]). Among 123 D-KRd patients, 43.1%, 37.4%, and 19.5% had 0, 1, or ≥2 HRCAs. Among 120 D-RVd patients, 55.8%, 28.3%, and 10.8% had 0, 1, or ≥2 HRCAs. Rates of complete response or better (best on study) for 0, 1, or ≥2 HRCAs were 90.6%, 89.1%, and 70.8% for D-KRd, and 90.9%, 78.8%, and 61.5% for D-RVd. At median follow-up (MASTER, 31.1 months; GRIFFIN, 49.6 months for randomized patients/59.5 months for safety run-in patients), MRD-negativity rates as assessed by next-generation sequencing (10 –5 ) were 80.0%, 86.4%, and 83.3% for 0, 1, or ≥2 HRCAs for D-KRd, and 76.1%, 55.9%, and 61.5% for D-RVd. PFS was similar between studies and superior for 0 or 1 versus ≥2 HRCAs: 36-month PFS rates for D-KRd were 89.9%, 86.2%, and 52.4%, and 96.7%, 90.5%, and 53.5% for D-RVd. These data support the use of daratumumab-containing regimens for transplant-eligible NDMM with HCRAs; however, additional strategies are needed for ultra-high–risk disease (≥2 HRCAs).
Age-stratified analysis reveals arterial thrombosis as a predictor for gender-related second cancers in myeloproliferative neoplasms: a case-control study
Authors: Arianna Ghirardi, Alessandra Carobbio, Paola Guglielmelli, Alessandro Rambaldi, Valerio De Stefano, Alessandro M. Vannucchi, Ayalew Tefferi, Tiziano Barbui
Journal: Blood Cancer Journal (2024)

Age-stratified analysis reveals arterial thrombosis as a
Real-time near infrared artificial intelligence using scalable non-expert crowdsourcing in colorectal surgery
Authors: Garrett Skinner, Tina Chen, Gabriel Jentis, Yao Liu, Christopher McCulloh, Alan Harzman, Emily Huang, Matthew Kalady, Peter Kim
Journal: npj Digital Medicine (2024)

Abstract Surgical artificial intelligence (AI) has the potential to improve patient safety and clinical outcomes. To date, training such AI models to identify tissue anatomy requires annotations by expensive and rate-limiting surgical domain experts. Herein, we demonstrate and validate a methodology to obtain high quality surgical tissue annotations through crowdsourcing of non-experts, and real-time deployment of multimodal surgical anatomy AI model in colorectal surgery.
Ki-67 is necessary during DNA replication for fork protection and genome stability
Authors: Konstantinos Stamatiou, Florentin Huguet, Lukas V. Serapinas, Christos Spanos, Juri Rappsilber, Paola Vagnarelli
Journal: Genome biology (2024)

Abstract Background The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle. Results Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested. Conclusions We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.
Inhibition of METTL3 in macrophages provides protection against intestinal inflammation
Authors: Huilong Yin, Zhuan Ju, Xiang Zhang, Wenjie Zuo, Yuhang Yang, Minhua Zheng, Xiaofang Zhang, Yuning Liu, Yingran Peng, Ying Xing, Angang Yang, Rui Zhang
Journal: Cellular and Molecular Immunology (2024)
Impact of autologous platelet concentrates on the osseointegration of dental implants
Authors: Sašo Ivanovski, Ryan S. B. Lee, Tulio Fernandez‐Medina, Nelson Pinto, Catherine Andrade, Marc Quirynen
Journal: Periodontology 2000 (2024)

Abstract Osseointegration is defined as the direct deposition of bone onto biomaterial devices, most commonly composed from titanium, for the purpose of anchoring dental prostheses. The use of autologous platelet concentrates (APC) has the potential to enhance this process by modifying the interface between the host and the surface of the titanium implant. The rationale is to modify the implant surface and implant–bone interface via “biomimicry,” a process whereby the deposition of the host's own proteins and extracellular matrix enhances the biocompatibility of the implant and hence accelerates the osteogenic healing process. This review of the available evidence reporting on the effect of APC on osseointegration explores in vitro laboratory studies of the interaction of APC with different implant surfaces, as well as the in vivo and clinical effects of APC on osseointegration in animal and human studies. The inherent variability associated with using autologous products, namely the unique composition of each individual's blood plasma, as well as the great variety in APC protocols, combination of biomaterials, and clinical/therapeutic application, makes it is difficult to make any firm conclusions about the in vivo and clinical effects of APC on osseointegration. The available evidence suggests that the clinical benefits of adding PRP and the liquid form of L‐PRF (liquid fibrinogen) to any implant surface appear to be limited. The application of L‐PRF membranes in the osteotomy site, however, may produce positive clinical effects at the early stage of healing (up to 6 weeks), by promoting early implant stability and reducing marginal bone loss, although no positive longer term effects were observed. Careful interpretation and cautious conclusions should be drawn from these findings as there were various limitations in methodology. Future studies should focus on better understanding of the influence of APCs on the biomaterial surface and designing controlled preclinical and clinical studies using standardized APC preparation and application protocols.
Strontium/Silicon/Calcium‐Releasing Hierarchically Structured 3D‐Printed Scaffolds Accelerate Osteochondral Defect Repair
Authors: Cheng Ji Li, Jeong‐Hui Park, Gang Shi Jin, Nandin Mandakhbayar, Donghyeon Yeo, Jun Hee Lee, Jung‐Hwan Lee, Hye Sung Kim, Hae‐Won Kim
Journal: Advanced Healthcare Materials (2024)

Abstract Articular cartilage defects are a global challenge, causing substantial disability. Repairing large defects is problematic, often exceeding cartilage's self‐healing capacity and damaging bone structures. To tackle this problem, a scaffold‐mediated therapeutic ion delivery system is developed. These scaffolds are constructed from poly(ε‐caprolactone) and strontium (Sr)‐doped bioactive nanoglasses (SrBGn), creating a unique hierarchical structure featuring macropores from 3D printing, micropores, and nanotopologies due to SrBGn integration. The SrBGn‐embedded scaffolds (SrBGn‐µCh) release Sr, silicon (Si), and calcium (Ca) ions, which improve chondrocyte activation, adhesion, proliferation, and maturation‐related gene expression. This multiple ion delivery significantly affects metabolic activity and maturation of chondrocytes. Importantly, Sr ions may play a role in chondrocyte regulation through the Notch signaling pathway. Notably, the scaffold's structure and topological cues expedite the recruitment, adhesion, spreading, and proliferation of chondrocytes and bone marrow‐derived mesenchymal stem cells. Si and Ca ions accelerate osteogenic differentiation and blood vessel formation, while Sr ions enhance the polarization of M2 macrophages. The findings show that SrBGn‐µCh scaffolds accelerate osteochondral defect repair by delivering multiple ions and providing structural/topological cues, ultimately supporting host cell functions and defect healing. This scaffold holds great promise for osteochondral repair applications.
Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents
Authors: Chintan V. Dave, Yongmei Li, Michael A. Steinman, Sei J. Lee, Xiaojuan Liu, Bocheng Jing, Laura A. Graham, Zachary A. Marcum, Kathy Z. Fung, Michelle C. Odden
Journal: JAMA Internal Medicine (2024)

Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents.
Breast Milk Enema and Meconium Evacuation Among Preterm Infants
Authors: Liqiang Zheng, Li Gai, Yani Wu, Chaonan Kong, Fangli Sun, Jinyue Gao, Wei Yuan, Min Liu, Hong Jiang, Nan Tuo, Fan Yang
Journal: JAMA Network Open (2024)

Importance Delayed meconium evacuation and delayed achievement of full enteral feeding among premature infants are associated with poor short- and long-term outcomes. Identifying a more effective and safer enema for meconium evacuation is imperative for improving neonatal care. Objective To examine whether breast milk enemas can shorten the time to complete meconium evacuation and achievement of full enteral feeding for preterm infants. Design, Setting, and Participants This randomized, open-label, parallel-group, single-center clinical trial was conducted from September 1, 2019, to September 30, 2022, among 286 preterm infants with a gestational age of 23 to 30 weeks in the neonatal ward of the Shengjing Hospital of China Medical University in Shenyang. Interventions Preterm infants were randomly assigned to receive either breast milk enemas or normal saline enemas 48 hours after birth. Main Outcome and Measures The primary outcomes were time to complete meconium evacuation and time to achieve full enteral feeding. Secondary outcomes were duration of hospitalization, weight at discharge, and duration of total parenteral nutrition. Intention-to-treat and per-protocol analyses were conducted. Results In total, 286 preterm infants (mean [SD] gestational age, 198.8 [7.9] days; 166 boys [58.0%]) were eligible and included in this study. A total of 145 infants were randomized to the normal saline group, and 141 were randomized to the breast milk group. The time to achieve complete meconium evacuation was significantly shorter in the breast milk group than in the normal saline group (–2.2 days; 95% CI, −3.2 to −1.2 days). The time to achieve full enteral feeding was also significantly shorter in the breast milk group than in the normal saline group (−4.6 days; 95% CI, −8.0 to −1.2 days). The duration of total parenteral nutrition was significantly shorter in the breast milk group than in the normal saline group (−4.6 days; 95% CI, −8.6 to −1.0 days). There were no clinically notable differences in any other secondary or safety outcomes between the 2 groups. Conclusions and Relevance In this randomized clinical trial testing the effects of breast milk enema on meconium evacuation, breast milk reduced the time to achieve complete meconium evacuation and achieve full enteral feeding for preterm infants with a gestational age of 23 to 30 weeks. Subgroup analyses highlight the need for tailored interventions based on gestational age considerations. Trial Registration isrctn.org Identifier: ISRCTN17847514
Measuring Equity in Readmission as an Assessment of Hospital Performance
Authors: Robert J. Gallo, Christine Santiago
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 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
Universal Tobacco Screening and Opt-Out Treatment Referral Strategy Among Patients Diagnosed With Cancer by Race and Ethnicity
Authors: Gleneara E. Bates-Pappas, Elizabeth Schofield, Lou-Anne R. Chichester, Chris Kotsen, Lisa Carter-Bawa, Graham W. Warren, Jamie S. Ostroff
Journal: JAMA Network Open (2024)

This quality improvement study examines whether a universal screening and opt-out referral model could promote racial and ethnic equity in access and use of tobacco treatment among patients with cancer.
Enhancing the Interpretation of Continuous Outcomes and Subgroup Analyses in Systematic Reviews—Reply
Authors: Tianji Zhou, Yuanhui Luo, Jingping Zhang
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal