tbuckley/cabot-search huggingface dataset:
Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity
Authors: Deeksha Deep, Herman Gudjonson, Chrysothemis C. Brown, Samuel A. Rose, Roshan Sharma, Yoselin A. Paucar Iza, Seunghee Hong, Saskia Hemmers, Michail Schizas, Zhong-Min Wang, Yuezhou Chen, Duane R. Wesemann, Virginia Pascual, Dana Pe’er, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (2024)

Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage. Specifically, a previously unappreciated population of naïve CD4+ T cells sensing environmental type I IFN exhibited distinct activation thresholds, suggesting that naïve CD4+ T cell differentiation potential may be influenced by environmental cues. This population was expanded in human viral infection and type I IFN response-lined autoimmunity. Understanding the relevance of naïve T cell heterogeneity to beneficial and maladaptive T cell responses may have therapeutic implications for adoptive T cell therapies in cancer immunotherapy and vaccination.
Association of Daily Doses of Buprenorphine With Urgent Health Care Utilization
Authors: Sarah Axeen, Rosalie Liccardo Pacula, Jessica S. Merlin, Adam J. Gordon, Bradley D. Stein
Journal: JAMA Network Open (2024)

Importance Higher buprenorphine doses may benefit the increasing number of individuals using fentanyl and other synthetic opioids, but there is little empirical evidence on the efficacy of such higher doses. Objective To examine the association between higher buprenorphine doses (above 16 mg and 24 mg) and subsequent emergency department (ED) or inpatient service use among patients diagnosed with opioid use disorder. Design, Setting, and Participants This cross-sectional study was a retrospective analysis of health data from Optum’s deidentified Clinformatics Data Mart Database from 2016 to 2021 for commercially insured individuals aged 18 years or older diagnosed with opioid use disorder (OUD). Eligible participants initiated buprenorphine after at least 90 days of enrollment and were dispensed at least a 14-day supply of buprenorphine. Data were analyzed from September 2023 through February 2024. Exposures Maximum buprenorphine dose received by a patient for 14 or more days: more than 24 mg, more than 16 mg to 24 mg, more than 8 mg to 16 mg, or 1 mg to 8 mg. Main Outcomes and Measures Days from initiation of the maximum buprenorphine dose to an ED or inpatient visit for a behavioral health diagnosis, controlling for patient demographics, comorbid conditions, time to reaching maximum dose, buprenorphine discontinuation, and pre-buprenorphine health care utilization. Results A total of 35 451 individuals with an OUD diagnosis who began buprenorphine treatment were identified (mean [SD] age, 46.2 [15.1] years; 20 983 male [59.2%]; 3326 Black [9.4%], 2411 Hispanic [6.8%], 26 712 White [75.3%]). The most common dose was more than 8 mg to 16 mg daily (14 802 patients [42.9%]), with 9669 patients (27.3%) in the 1 mg to 8 mg tier, 10 329 patients (29.1%) in the 8 mg to 16 mg tier, and 651 patients (1.8%) in the tier receiving more than 24 mg. Among all patients receiving buprenorphine, 12.5% experienced an ED or inpatient visit. Survival analysis shows patients receiving doses more than 24 mg and between 16 mg to 24 mg had longer times to ED or inpatient use than patients receiving from 8 mg to 16 mg (time ratio [TR], 1.11; 95% CI, 1.02 to 1.20) and more than 24 mg (TR, 1.37; 95% CI, 1.04 to 1.81). Findings for doses above 16 mg daily were consistent for observation windows as short as 365 days (more than 24 mg: TR, 1.48; 95% CI, 1.01-2.18; more than 16 mg to 24 mg: TR, 1.19; 95% CI, 1.06-1.32). Conclusions and Relevance These findings contribute to the sparse empirical research regarding potential benefits of higher-dose buprenorphine treatment of individuals with OUD. Clinicians should be aware of the potential effects of higher buprenorphine doses on health care utilization while policymakers work to ensure equitable access to individuals who could potentially benefit from higher doses.
Kidney Transplant Outcome Following Donation After Euthanasia
Authors: Julia S. Slagter, Hendrikus J. A. N. Kimenai, Jacqueline van de Wetering, Hanneke J. A. M. Hagenaars, Marlies E. J. Reinders, Wojciech G. Polak, Robert J. Porte, Robert C. Minnee
Journal: JAMA Surgery (2024)

In the Netherlands, organ donation after euthanasia (donation after circulatory death type V [DCD-V]) has been increasingly performed since 2012. However, the outcomes of DCD-V kidney grafts have not been thoroughly investigated. It is critical to assess the outcomes of these kidney grafts to ascertain whether DCD-V is a safe and valuable way to increase the kidney donor pool.
A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies
Authors: Jiaxi Wu, Nicolin Bloch, Aaron Y Chang, Ramandeep Bhavsar, Qingqing Wang, Alison Crawford, David J DiLillo, Kristin Vazzana, Katja Mohrs, Drew Dudgeon, Supriya Patel, Hassan Ahmed, Vidur Garg, Michael Amatulli, Olivia Q Antao, Yuetian Yan, Shunhai Wang, Willy Ramos, Pamela Krueger, Christina Adler, Min Ni, Yi Wei, Chunguang Guo, Lynn Macdonald, Tammy Huang, Erica Ullman, Aynur Hermann, George D Yancopoulos, Andrew J Murphy, Samuel Davis, William C Olson, John C Lin, Eric Smith, Tong Zhang
Journal: Cell Reports Medicine (2024)
Development and validation of a machine learning model to predict myocardial blood flow and clinical outcomes from patients’ electrocardiograms
Authors: Fares Alahdab, Maliazurina Binti Saad, Ahmed Ibrahim Ahmed, Qasem Al Tashi, Muhammad Aminu, Yushui Han, Jonathan B Moody, Venkatesh L Murthy, Jia Wu, Mouaz H Al-Mallah
Journal: Cell Reports Medicine (2024)
Asymptomatic vs Symptomatic Hypotension With Sacubitril/Valsartan in Heart Failure and Reduced Ejection Fraction in PARADIGM-HF
Authors: Shingo Matsumoto, Li Shen, Alasdair D Henderson, Michael Böhm, Akshay S Desai, Lars Køber, Martin P Lefkowitz, Milton Packer, Jean L Rouleau, Scott D Solomon, Karl Swedberg, Muthiah Vaduganathan, Orly Vardeny, Adriaan A Voors, Michael R Zile, Pardeep S Jhund, John J V McMurray
Journal: Journal of the American College of Cardiology (2024)
Label‐Free Exosome Analysis by Surface‐Enhanced Raman Scattering Spectroscopy with Laser‐Ablated Silver Nanoparticle Substrate
Authors: Jong‐Eun Park, Hyeono Nam, June Sik Hwang, Seunggyu Kim, Seong Jae Kim, Sanha Kim, Jessie S. Jeon, Minyang Yang
Journal: Advanced Healthcare Materials (2024)

Abstract Early diagnostics of breast cancer is crucial to reduce the risk of cancer metastasis and late relapse. Exosome, which contains distinct information of its origin, can be the target object as a liquid biopsy. However, its low sensitivity and inadequate diagnostic tools interfere with the point‐of‐care testing (POCT) of the exosome. Recently, Surface‐enhanced Raman Scattering (SERS) spectroscopy, which amplifies the Raman scattering, has been proved as a promising tool for exosome detection. However, the fabrication process of SERS probe or substrate is still inefficient and far from large‐scale production. This study proposes rapid and label‐free detection of breast cancer‐derived exosomes by statistical analysis of SERS spectra using silver‐nanoparticle‐based SERS substrate fabricated by selective laser ablation and melting (SLAM). Employing silver nanowires and optimizing laser process parameters enable rapid and low‐energy fabrication of SERS substrate. The functionalities including sensitivity, reproducibility, stability, and renewability are evaluated using rhodamine 6G as a probe molecule. Then, the feasibility of POCT is examined by the statistical analysis of SERS spectra of exosomes from malignant breast cancer cells and non‐tumorigenic breast epithelial cells. The presented framework is anticipated to be utilized in other biomedical applications, facilitating cost‐effective and large‐scale production performance.
An Advanced Mechanically Active Osteoarthritis‐on‐Chip Model to Test Injectable Therapeutic Formulations: The SYN321 Case Study
Authors: Cecilia Palma, Stefano Piazza, Roberta Visone, Rune Ringom, Ulf Björklund, Antonio Bermejo Gómez, Marco Rasponi, Paola Occhetta
Journal: Advanced Healthcare Materials (2024)

Abstract Current treatments for osteoarthritis (OA) often fail to address the underlying pathophysiology and may have systemic side effects, particularly associated with long‐term use of non‐steroidal anti‐inflammatory drugs (NSAIDs). Thus, researchers are currently directing their efforts toward innovative polymer‐drug combinations, such as mixtures of hyaluronic acid viscoelastic hydrogels and NSAIDs like diclofenac, to ensure sustained release of the NSAID within the joint following intra‐articular injection. However, the progress of novel injectable therapies for OA is hindered by the absence of preclinical models that accurately represent the pathology of the disease. The uBeat® MultiCompress platform is here presented as a novel approach for studying anti‐OA injectable therapeutics on human mechanically‐damaged OA cartilage microtissues, in a physiologically relevant environment. This platform can accommodate injectable therapeutic formulations and is successfully tested with SYN321, a novel diclofenac‐sodium hyaluronate conjugate under development as a treatment for knee OA. Results indicate the platform's effectiveness in evaluating therapeutic potential, showing downregulation of inflammatory markers and reduction in matrix degradation in OA cartilage micro‐tissues treated with SYN321. The uBeat® MultiCompress platform thus represents a valuable tool for OA research, offering a bridge between traditional in vitro studies and potential clinical applications, with implications for future drug discovery.
Autologous platelet concentrates after third molar extraction: A systematic review
Authors: S. A. M. Siawasch, J. Yu, A. B. Castro, A. Temmerman, W. Teughels, M. Quirynen
Journal: Periodontology 2000 (2024)

Abstract Surgical removal of impacted mandibular third molars is often followed by postoperative sequelae like pain, swelling, trismus, etc. This systematic review explored the benefits of applying different autologous platelet concentrates (APCs) in the extraction socket of third molars. For this systematic review, PubMed, EMBASE, Web of Science, and Scopus have been utilized, initially yielding 544 papers. The search was narrowed to randomized controlled trials (RCTs, n = 59) published before 2024, all comparing the outcome of applying APCs in the extraction socket of surgically removed impacted mandibular third molars with unassisted healing (blood clot). Most RCTs primarily assessed the impact of APCs on postoperative sequelae. Some RCTs looked at soft‐ and hard‐tissue healing. Eleven studies used PRP, three PRGF, and 45 L‐PRF. A detailed analysis revealed a large heterogeneity between studies rendering a meta‐analysis impossible. Moreover, the risk of bias was considered high. In the majority of RCTs, the application of an APC resulted in statistically significant reductions of postoperative sequelae (lower pain intensity, lower consumption of analgesics, less postoperative edema, and a lower incidence of trismus and alveolar osteitis), as well as a faster soft tissue healing, and qualitatively and quantitatively better bone healing. A minority of studies reported significant differences in periodontal parameters distally from the second molar.
An overview of the progress made in research into the Mpox virus
Authors: Yansheng Li, Lianrong Wang, Shi Chen
Journal: Medicinal Research Reviews (2024)

Abstract Mpox is a zoonotic illness caused by the Mpox virus (MPXV), a member of the Orthopoxvirus family. Although a few cases have been reported outside Africa, it was originally regarded as an endemic disease limited to African countries. However, the Mpox outbreak of 2022 was remarkable in that the infection spread to more than 123 countries worldwide, causing thousands of infections and deaths. The ongoing Mpox outbreak has been declared as a public health emergency of international concern by the World Health Organization. For a better management and control of the epidemic, this review summarizes the research advances and important scientific findings on MPXV by reviewing the current literature on epidemiology, clinical characteristics, diagnostic methods, prevention and treatment measures, and animal models of MPXV. This review provides useful information to raise awareness about the transmission, symptoms, and protective measures of MPXV, serving as a theoretical guide for relevant institutions to control MPXV.
Associations between Aircraft Noise, Sleep, and Sleep–Wake Cycle: Actimetric Data from the UK Biobank Cohort near Four Major Airports
Authors: Xiangpu Gong, Katie Eminson, Glory O. Atilola, Calvin Jephcote, Kathryn Adams, Gabriella Captur, Andrew P. Hall, Marta Blangiardo, John Gulliver, Alex V. Rowlands, Anna L. Hansell
Journal: Environmental Health Perspectives (2024)

Nighttime aircraft noise may affect people's sleep, yet large-scale evidence using objective and subjective measures remains limited.
Effect of Delayed Remote Ischemic Preconditioning on Acute Kidney Injury and Outcomes in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial
Authors: Ping Jia, Qiang Ji, Zhouping Zou, Qi Zeng, Ting Ren, Weize Chen, Zhixin Yan, Daoqi Shen, Yang Li, Fangyuan Peng, Ying Su, Jiarui Xu, Bo Shen, Zhe Luo, Chunsheng Wang, Xiaoqiang Ding
Journal: Circulation (2024)

BACKGROUND: Remote ischemic preconditioning (RIPC) has 2 time windows for organ protection: acute and delayed. Previous studies have mainly focused on the organoprotective effects of acute RIPC. We aimed to determine whether delayed RIPC can reduce the occurrence of acute kidney injury (AKI) and postoperative complications in patients undergoing cardiac surgery. METHODS: This prospective, single-center, double-blind, randomized controlled trial involved 509 patients at high risk for AKI who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass. Patients were randomized to receive RIPC (4 cycles of 5-minute inflation and 5-minute deflation on 1 upper arm with a blood pressure cuff) 24 hours before surgery or a sham condition (control group) that was induced by 4 cycles of 5-minute inflation to a pressure of 20 mm Hg followed by 5-minute cuff deflation. The primary end point was the incidence of AKI within the prior 7 days after cardiac surgery. The secondary end points included renal replacement therapy during hospitalization, change in urinary biomarkers of AKI and markers of myocardial injury, duration of intensive care unit stay and mechanical ventilation, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. RESULTS: A total of 509 patients (mean age, 65.2±8.2 years; 348 men [68.4%]) were randomly assigned to the RIPC group (n=254) or control group (n=255). AKI was significantly reduced in the RIPC group compared with the control group (69/254 [27.2%] versus 90/255 [35.3%]; odds ratio, 0.68 [95% CI, 0.47–1.00]; P =0.048). There were no significant between-group differences in the secondary end points of perioperative myocardial injury (assessed by the concentrations of cardiac troponin T, creatine kinase myocardial isoenzyme, and NT-proBNP [N-terminal pro-brain natriuretic peptide]), duration of stay in the intensive care unit and hospital, and occurrence of nonfatal myocardial infarction, stroke, and all-cause mortality by day 90. CONCLUSIONS: Among high-risk patients undergoing cardiac surgery, delayed RIPC significantly reduced the occurrence of AKI. REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR2000035568.
Inflammation indices in association with periodontitis and cancer
Authors: Kay‐Arne Walther, Sabine Gröger, Jonas Adrian Helmut Vogler, Bernd Wöstmann, Jörg Meyle
Journal: Periodontology 2000 (2024)

Abstract Inflammation is a complex physiological process that plays a pivotal role in many if not all pathological conditions, including infectious as well as inflammatory diseases, like periodontitis and autoimmune disorders. Inflammatory response to periodontal biofilms and tissue destruction in periodontitis is associated with the release of inflammatory mediators. Chronic inflammation can promote the development of cancer. Persistence of inflammatory mediators plays a crucial role in this process. Quantification and monitoring of the severity of inflammation in relation to cancer is essential. Periodontitis is mainly quantified based on the severity and extent of attachment loss and/or pocket probing depth, in addition with bleeding on probing. In recent years, studies started to investigate inflammation indices in association with periodontal diseases. To date, only few reviews have been published focusing on the relationship between blood cell count, inflammation indices, and periodontitis. This review presents a comprehensive overview of different systemic inflammation indices, their methods of measurement, and the clinical applications in relation to periodontitis and cancer. This review outlines the physiological basis of inflammation and the underlying cellular and molecular mechanisms of the parameters described. Key inflammation indices are commonly utilized in periodontology such as the neutrophil to lymphocyte ratio. Inflammation indices like the platelet to lymphocyte ratio, platelet distribution width, plateletcrit, red blood cell distribution width, lymphocyte to monocyte ratio, delta neutrophil index, and the systemic immune inflammation index are also used in hospital settings and will be discussed. The clinical roles and limitations, relationship to systemic diseases as well as their association to periodontitis and treatment response are described.
Measurable residual disease monitoring in <scp>AML</scp>: Prospects for therapeutic decision‐making and new drug development
Authors: Nicholas J. Short, Richard Dillon
Journal: American Journal of Hematology (2024)

Abstract Measurable residual disease (MRD) is strongly associated with risk of relapse and long‐term survival outcomes in patients with acute myeloid leukemia (AML). Apart from its clear prognostic impact, MRD information is also increasingly used to guide therapeutic decision‐making, including selection of appropriate patients for stem cell transplant, use of post‐transplant maintenance, and candidacy for non‐transplant maintenance therapies or MRD‐directed clinical trials. While much progress has been made in accurately assessing MRD and understanding its clinical importance, many questions remain about how to optimize MRD testing and guide treatment decisions for individual patients. In this review, we discuss the common methods to assess MRD in AML and the prognostic impact of MRD across common clinical scenarios. We also review emerging and investigational strategies to target MRD and discuss some of the important unanswered questions and challenges in the field.
Glucose Oxidase‐Immobilized Dually‐Crosslinked Nanogels for Rapid‐Responsive Insulin Delivery
Authors: Yuhong Ma, Jingru Yang, Yukun Ma, Rui Yang, Fuwei Han, Mujiao He, Wei Liu, Hongliang Qian, Wei Chen, Dechun Huang
Journal: Advanced Healthcare Materials (2024)

Abstract Despite the potential benefits of close‐looped insulin delivery systems in regulating glycemic homeostasis and effectively alleviating diabetes, they still encounter challenges such as limited effectiveness in preventing low glycemic episodes due to sluggish glucose response, and issues with the instability of enzymes and carriers. In this study, dually‐crosslinked and glucose oxidase (GOx)‐immobilized insulin nanogels (DC‐NGs@Ins) are developed for rapid‐responsive and sustained hypoglycemic therapy. The DC‐NGs@Ins with the phenylborate ester linker enabled the insulin release in a close‐looped fashion, and moreover, immobilized GOx‐generated hydrogen peroxide (H 2 O 2 ) by consuming the glucose, which can further bind to phenylborate ester for enhancing glucose response and accelerating the insulin release. The dually‐crosslinked structure (phenylboronic ester and UV‐crosslinking) effectively minimized the initial burst release of insulin, thus preventing the potential risk of hypoglycemia. More interestingly, GOx immobilized in the nanogels mitigated GOx leakage and enhanced its multiple utilization compared to free GOx. In vivo study demonstrated that DC‐NGs@Ins effectively maintained glycemic levels (BGLs) below 200 mg dL −1 for at least 8 h compared to singly‐crosslinked nanogels (SC‐NGs@Ins). Therefore, this intelligent insulin delivery system shows potential applications in diabetes treatment.
LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis)
Authors: María-Victoria Mateos, Katja Weisel, Valerio De Stefano, Hartmut Goldschmidt, Michel Delforge, Mohamad Mohty, Dominik Dytfeld, Emanuele Angelucci, Laure Vincent, Aurore Perrot, Reuben Benjamin, Niels W C J van de Donk, Enrique M Ocio, Tito Roccia, Jordan M Schecter, Silva Koskinen, Imène Haddad, Vadim Strulev, Lada Mitchell, Jozefien Buyze, Octavio Costa Filho, Hermann Einsele, Philippe Moreau
Journal: Leukemia (2024)
Translating the 2021 <scp>ESC</scp> heart failure guideline recommendations in daily practice: Results from a heart failure survey. A scientific statement of the <scp>ESC</scp> Council for Cardiology Practice and the Heart Failure Association of the <scp>ESC</scp>
Authors: Ruxandra Christodorescu, Oliviana Geavlete, Marc Ferrini, Thomas Kümler, Konstantinos Toutoutzas, Antoni Bayes‐Genis, Petar Seferovic, Marco Metra, Ovidiu Chioncel, Giuseppe M.C. Rosano, Gianluigi Savarese
Journal: European Journal of Heart Failure (2024)
Cardio‐ocular syndrome: Retinal microvascular changes in acutely decompensated heart failure
Authors: Amr Abdin, Alaa Din Abdin, Giuseppe Merone, Wissam Aljundi, Bernhard Haring, Yaser Abu Dail, Felix Mahfoud, Insa Emrich, Hussam Al Ghorani, Elsa Wilma Böhm, Berthold Seitz, Michael Böhm
Journal: European Journal of Heart Failure (2024)
MMP-9 responsive hydrogel promotes diabetic wound healing by suppressing ferroptosis of endothelial cells
Authors: Chuanlu Lin, Yiqiang Hu, Ze Lin, Longyu Du, Yixin Hu, Lizhi Ouyang, Xudong Xie, Peng Cheng, Jiewen Liao, Li Lu, Ruiyin Zeng, Ping Xia, Zhiyong Hou, Guohui Liu, Hankun Hu
Journal: Bioactive Materials (2024)