tbuckley/cabot-search huggingface dataset:
Recovery of Left Ventricular Function and Long-Term Outcomes in Patients With Takotsubo Syndrome
Authors: Manuel Almendro-Delia, Luis López-Flores, Aitor Uribarri, Oscar Vedia, Emilia Blanco-Ponce, María Del Carmen López-Flores, Antonio P Rivas-García, Clara Fernández-Cordón, Alessandro Sionis, Agustín C Martín-García, Ravi Vazirani, Miguel Corbí-Pascual, Jorge Salamanca, Alberto Pérez-Castellanos, Manuel Martínez-Sellés, Víctor Manuel Becerra, David Aritza-Conty, Javier López-País, Marta Guillén-Marzo, Carmen Lluch-Requerey, Juan C García-Rubira, Iván J Núñez-Gil
Journal: Journal of the American College of Cardiology (2024)
Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer
Authors: D E Rathkopf, M R Patel, A D Choudhury, D Rasco, N Lakhani, J E Hawley, S Srinivas, A Aparicio, V Narayan, K D Runcie, H Emamekhoo, Z R Reichert, M H Nguyen, A L Wells, R Kandimalla, C Liu, S Suryawanshi, J Han, J Wu, V K Arora, M Pourdehnad, A J Armstrong
Journal: Annals of Oncology (2024)

Metastatic castration-resistant prostate cancer (mCRPC) that progresses on androgen receptor pathway inhibitors (ARPIs) may continue to be driven by AR signaling. BMS-986365 is an orally administered ligand-directed degrader targeting the AR via a first-in-class dual mechanism of AR degradation and antagonism. CC-94676-PCA-001 (NCT04428788) is a phase I multicenter study of BMS-986365 in patients with progressive mCRPC.
Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: subgroup analysis from CIRCULATE-Japan GALAXY
Authors: K Kataoka, K Mori, Y Nakamura, J Watanabe, N Akazawa, K Hirata, M Yokota, K Kato, M Kotaka, K Yamazaki, Y Kagawa, S Mishima, K Ando, M Miyo, H Yukami, G Laliotis, S Sharma, C C Palsuledesai, M Rabinowitz, A Jurdi, M C Liu, A Aleshin, D Kotani, H Bando, H Taniguchi, I Takemasa, T Kato, T Yoshino, E Oki
Journal: Annals of Oncology (2024)

The prognostic role of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear.
First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase 1 dose exploration
Authors: J Rodon, H Prenen, A Sacher, M Villalona-Calero, N Penel, A El Helali, S Rottey, N Yamamoto, F Ghiringhelli, M E Goebeler, T Doi, S Postel-Vinay, C-C Lin, C Liu, C-H Chuang, K Keyvanjah, T Eggert, B H O'Neil
Journal: Annals of Oncology (2024)
Reversal of Pharmacologically Induced Mydriasis with Phentolamine Ophthalmic Solution
Authors: Jay S Pepose, David Wirta, David Evans, Barbara Withers, Kavon Rahmani, Audrey Lazar, Drey Coleman, Ronil Patel, Reda Jaber, Mina Sooch, Mitchell Brigell, Konstantinos Charizanis
Journal: Ophthalmology (2024)
Interactions of Obstructive Sleep Apnea With the Pathophysiology of Cardiovascular Disease, Part 1
Authors: Shahrokh Javaheri, Sogol Javaheri, Virend K Somers, David Gozal, Babak Mokhlesi, Reena Mehra, Walter T McNicholas, Phyllis C Zee, Francisco Campos-Rodriguez, Miguel Angel Martinez-Garcia, Peter Cistulli, Atul Malhotra
Journal: Journal of the American College of Cardiology (2024)
Treatment of OSA and its Impact on Cardiovascular Disease, Part 2
Authors: Shahrokh Javaheri, Sogol Javaheri, David Gozal, Francisco Campos-Rodriguez, Miguel Angel Martinez-Garcia, Babak Mokhlesi, Reena Mehra, Walter T McNicholas, Virend K Somers, Phyllis C Zee, Peter Cistulli, Atul Malhotra
Journal: Journal of the American College of Cardiology (2024)
Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system xc− in liver cancer: A non-ferroptotic approach
Authors: So-Yeol Yoo, Hyun Young Kim, Dong Hyun Kim, Wan Seob Shim, Sang Min Lee, Dong Hwan Lee, Jang Mo Koo, Ji Hoon Yoo, Seokjin Koh, Jong Chan Park, Jieun Yu, Jang Su Jeon, Min-Jun Baek, Dae-Duk Kim, Ji-Yoon Lee, Soo Jin Oh, Sang Kyum Kim, Jae-Young Lee, Keon Wook Kang
Journal: Journal of Controlled Release (2024)
Ipilimumab with Nivolumab in molecular-Selected patients with castration-resistant PRostate cancer: primary analysis of the Phase 2 INSPIRE trial
Authors: S van Wilpe, I S H Kloots, P H J Slootbeek, M den Brok, H Westdorp, M D Franken, M Coskunturk, T Osinga, H Bloemendal, G Adema, R J Smeenk, J Nagarajah, J van Ipenburg, L I Kroeze, M J L Ligtenberg, J Schalken, W R Gerritsen, N Mehra
Journal: Annals of Oncology (2024)

Metastatic castration-resistant prostate cancer (mCRPC) typically exhibits resistance to immune checkpoint inhibitors (ICIs). However, a subset of mCRPC patients displays a more immunogenic profile. This study examines efficacy and safety of dual ICI therapy in molecularly selected mCRPC.
Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis
Authors: N E Harrington, A Kottara, K Cagney, M J Shepherd, E M Grimsey, T Fu, R C Hull, C E Chong, K S Baker, D Z Childs, J L Fothergill, J D Chalmers, M A Brockhurst, S Paterson
Journal: Journal of Infection (2024)
A new therapeutic strategy for infectious diseases against intracellular multidrug-resistant bacteria
Authors: Zhao-Jie Wang, Yan-Yan Zhu, Li-Yu Bai, Dong-Mei Tang, Zhong-Shun Zhou, Mei-Zhen Wei, Jin-Biao He, None Yu-Duan, Xiao-Dong Luo
Journal: Journal of Controlled Release (2024)

Bacterial infections result in 7,700,000 deaths per year globally, with intracellular bacteria causing repeated and resistant infection. No drug is currently licenced for the treatment of intracellular bacteria. A new screening platform mimicking the host milieu has been established to explore phytochemical antibiotic adjuvants. Previously neglected isoprenylated flavonoids were found to be effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Specifically, the synergistic effect between glabrol and streptomycin against intracellular bacteria was observed for the first time. The glabrol-streptomycin combination targets bacterial inner membrane phospholipids, disrupts arginine biosynthesis, inhibits cell wall proteins and biofilm formation genes (agrA/B/C/D), and promotes ROS production, causing subsequent membrane and wall damage. To enhance the selective uptake of combination drug into infected cells, hyaluronic acid-streptomycin-lipoic acid-glabrol nanoparticles (HSLGS-S) were designed and synthesized to trigger the intracellular delivery of the glabrol-streptomycin combination. Thus, the treatment can be transported into the infected intracellular region and selectively release the glabrol-streptomycin combination to the bacterial at site. The bioactivity of HSLGS-S in clearing intracellular bacteria was 20-fold higher than that of the glabrol-streptomycin combination alone in vitro and 2- to 10-fold higher in vivo.
Switchable PAMAM megamers for deep tumor penetration and enhanced cell uptake
Authors: Effat Nekoueifard, Fatemeh Radmanesh, Ibrahim Zarkesh, Marzieh Ebrahimi, Mohamad Raoufi, Hamid Sadeghi Abandansari, Hossein Baharvand, Rassoul Dinarvand
Journal: Journal of Controlled Release (2024)
Thin-film freeze-drying of an influenza virus hemagglutinin mRNA vaccine in unilamellar lipid nanoparticles with blebs
Authors: Qin Li, Ruiqi Shi, Haiyue Xu, Khaled AboulFotouh, Molly M H Sung, Thomas H Oguin, Madeline Hayes, Chaeho Moon, Huy M Dao, Houping Ni, Sawittree Sahakijpijarn, Chris Cano, Gregory J Davenport, Robert O Williams, Jon Le Huray, Zhengrong Cui, Drew Weissman
Journal: Journal of Controlled Release (2024)
Lipid-Laden Macrophages Recycle Myelin to Feed Glioblastoma
Authors: Lizhi Pang, Fei Zhou, Peiwen Chen
Journal: Cancer Research (2024)

Tumor-associated microglia and macrophages (TAM) make up the largest immune cell population in the glioblastoma (GBM) tumor microenvironment. Given the heterogeneity and plasticity of TAMs in the GBM tumor microenvironment, understanding the context-dependent cancer cell-TAM symbiotic interaction is crucial for understanding GBM biology and developing effective therapies. In a recent issue of Cell, Kloosterman and colleagues identified a subpopulation of glycoprotein nonmetastatic melanoma protein Bhigh lipid-laden microglia and macrophages (LLM) in GBM. Mesenchymal-like GBM cells help generate the LLM phenotype. Reciprocally, LLMs are epigenetically rewired to recycle myelin and transfer the lipid from myelin to cancer cells, fueling mesenchymal-like GBM progression in a liver X receptor/ABCA1-dependent manner. Together, leveraging LLMs opens new therapeutic possibilities for rewiring the metabolism-mediated tumor-TAM interaction during GBM progression.
Antimicrobial Biomaterials Based on Physical and Physicochemical Action
Authors: Adrian G. Nowotnick, Zhongqian Xi, Zhaorui Jin, Sadaf Khalatbarizamanpoor, Delia S. Brauer, Bettina Löffler, Klaus D. Jandt
Journal: Advanced Healthcare Materials (2024)

Abstract Developing effective antimicrobial biomaterials is a relevant and fast‐growing field in advanced healthcare materials. Several well‐known (e.g., traditional antibiotics, silver, copper etc.) and newer (e.g., nanostructured, chemical, biomimetic etc.) approaches have been researched and developed in recent years and valuable knowledge has been gained. However, biomaterials associated infections (BAIs) remain a largely unsolved problem and breakthroughs in this area are sparse. Hence, novel high risk and potential high gain approaches are needed to address the important challenge of BAIs. Antibiotic free antimicrobial biomaterials that are largely based on physical action are promising, since they reduce the risk of antibiotic resistance and tolerance. Here, selected examples are reviewed such antimicrobial biomaterials, namely switchable, protein‐based, carbon‐based and bioactive glass, considering microbiological aspects of BAIs. The review shows that antimicrobial biomaterials mainly based on physical action are powerful tools to control microbial growth at biomaterials interfaces. These biomaterials have major clinical and application potential for future antimicrobial healthcare materials without promoting microbial tolerance. It also shows that the antimicrobial action of these materials is based on different complex processes and mechanisms, often on the nanoscale. The review concludes with an outlook and highlights current important research questions in antimicrobial biomaterials.
High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity
Authors: Sohyon Lee, Tobias Weiss, Marcel Bühler, Julien Mena, Zuzanna Lottenbach, Rebekka Wegmann, Miaomiao Sun, Michel Bihl, Bartłomiej Augustynek, Sven P Baumann, Sandra Goetze, Audrey van Drogen, Patrick G A Pedrioli, David Penton, Yasmin Festl, Alicia Buck, Daniel Kirschenbaum, Anna M Zeitlberger, Marian C Neidert, Flavio Vasella, Elisabeth J Rushing, Bernd Wollscheid, Matthias A Hediger, Michael Weller, Berend Snijder
Journal: Nature Medicine (2024)
Gene therapy for cardiac diseases: methods, challenges, and future directions
Authors: Luca Grisorio, Rossana Bongianino, Matteo Gianeselli, Silvia Giuliana Priori
Journal: Cardiovascular Research (2024)

Gene therapy is advancing at an unprecedented pace, and the recent success of clinical trials reinforces optimism and trust among the scientific community. Recently, the cardiac gene therapy pipeline, which had progressed more slowly than in other fields, has begun to advance, overcoming biological and technical challenges, particularly in treating genetic heart pathologies. The primary rationale behind the focus on monogenic cardiac diseases is the well-defined molecular mechanisms driving their phenotypes, directly linked to the pathogenicity of single genetic mutations. This aspect makes these conditions a remarkable example of "genetically druggable" diseases. Unfortunately, current treatments for these life-threatening disorders are few and often poorly effective, underscoring the need to develop therapies to modulate or correct their molecular substrates. In this review we examine the latest advancements in cardiac gene therapy, discussing the pros and cons of different molecular approaches and delivery vectors, with a focus on their therapeutic application in cardiac inherited diseases. Additionally, we highlight the key factors that may enhance clinical translation, drawing insights from previous trials and the current prospects of cardiac gene therapy.
Five-leaf generalizations of the <i>D</i>-statistic reveal the directionality of admixture
Authors: Kalle Leppälä, Flavio Augusto da Silva Coelho, Michaela Richter, Victor A Albert, Charlotte Lindqvist
Journal: Molecular Biology and Evolution (2024)

Abstract Over the past 15 years, the D-statistic, a four-taxon test for organismal admixture (hybridization, or introgression) which incorporates single nucleotide polymorphism data with allelic patterns ABBA and BABA, has seen considerable use. This statistic seeks to discern significant deviation from either a given species tree assumption, or from the balanced incomplete lineage sorting that could otherwise defy this species tree. However, while the D-statistic can successfully discriminate admixture from incomplete lineage sorting, it is not a simple matter to determine the directionality of admixture using only four-leaf tree models. As such, methods have been developed that use five leaves to evaluate admixture. Among these, the DFOIL method (“FOIL”, a mnemonic for “First-Outer-Inner-Last”), which tests allelic patterns on the “symmetric” tree S=(((1,2),(3,4)),5), succeeds in finding admixture direction for many five-taxon examples. However, DFOIL does not make full use of all symmetry, nor can DFOIL function properly when ancient samples are included because of the reliance on singleton patterns (such as BAAAA and ABAAA). Here, we take inspiration from DFOIL to develop a new and completely general family of five-leaf admixture tests, dubbed Δ-statistics, that can either incorporate or exclude the singleton allelic patterns depending on individual taxon and age sampling choices. We describe two new shapes that are also fully testable, namely the “asymmetric” tree A=((((1,2),3),4),5) and the “quasisymmetric” tree Q=(((1,2),3),(4,5)), which can considerably supplement the “symmetric” S=(((1,2),(3,4)),5) model used by DFOIL. We demonstrate the consistency of Δ-statistics under various simulated scenarios, and provide empirical examples using data from black, brown and polar bears, the latter also including two ancient polar bear samples from previous studies. Recently, DFOIL and one of these ancient samples was used to argue for a dominant polar bear → brown bear introgression direction. However, we find, using both this ancient polar bear and our own, that by far the strongest signal using both DFOIL and Δ-statistics on tree S is actually bidirectional gene flow of indistinguishable direction. Further experiments on trees A and Q instead highlight what were likely two phases of admixture: one with stronger brown bear → polar bear introgression in ancient times, and a more recent phase with predominant polar bear → brown bear directionality.
Myeloid beta-arrestin 2 depletion attenuates metabolic dysfunction-associated steatohepatitis via the metabolic reprogramming of macrophages
Authors: Xiaoli Wei, Dongqing Wu, Jing Li, Miaomiao Wu, Qianhui Li, Zhaodi Che, Xu Cheng, Qianying Cheng, Fan Yin, Hao Zhang, Xuefu Wang, Shabnam Abtahi, Li Zuo, Lei Hang, Lili Ma, Wei-Ting Kuo, Xiaoying Liu, Jerrold R Turner, Hua Wang, Jia Xiao, Fei Wang
Journal: Cell Metabolism (2024)
A fast and responsive voltage indicator with enhanced sensitivity for unitary synaptic events
Authors: Yukun A Hao, Sungmoo Lee, Richard H Roth, Silvia Natale, Laura Gomez, Jiannis Taxidis, Philipp S O'Neill, Vincent Villette, Jonathan Bradley, Zeguan Wang, Dongyun Jiang, Guofeng Zhang, Mengjun Sheng, Di Lu, Edward Boyden, Igor Delvendahl, Peyman Golshani, Marius Wernig, Daniel E Feldman, Na Ji, Jun Ding, Thomas C Südhof, Thomas R Clandinin, Michael Z Lin
Journal: Neuron (2024)
Resource Use and Care Quality Differences Among Medicare Beneficiaries Undergoing Chemotherapy
Authors: Yamini Kalidindi, Jeah Jung, Roger Feldman, Caroline Carlin, Ge Song, Aaron Mitchell
Journal: JAMA Network Open (2024)

Importance Medicare Advantage (MA) has grown significantly over the last decade; however, MA’s performance for patients with serious conditions, such as cancer, remains unclear. Objective To compare resource use and care quality between MA and traditional Medicare (TM) beneficiaries undergoing cancer chemotherapy. Design, Setting, and Participants This cohort study used TM claims and MA encounter records from January 2015 to December 2019. Participants were MA and TM beneficiaries who initiated cancer chemotherapy between January 2016 and December 2019. Inverse probability of treatment weighting balanced characteristics between MA and TM beneficiaries, and regression estimation was used. The analysis was conducted between August 2023 and May 2024. Exposure Chemotherapy initiation after a 1-year washout period. Main Outcomes and Measures Resource use and care quality were measured during a 6-month period following chemotherapy initiation. Resource use was measured using standardized prices for services in both MA and TM, covering hospital inpatient services, outpatient care, Part D drugs, and hospice services. Chemotherapy utilization was examined for Part B chemotherapy, Part B supportive drugs, and Part D chemotherapy. Quality measures included chemotherapy-related emergency department (ED) visits and hospitalizations, avoidable ED visits, preventable hospitalizations during the 6-month episode, and survival days up to 18 months from chemotherapy initiation. Results The study comprised 96 501 MA enrollees contributing to 98 872 episodes (mean [SD] age, 72.9 [7.6] years; 55 859 [56.5%] female; 7371 [7.5%] Hispanic, 14 778 [14.9%] non-Hispanic Black, and 75 130 [75.0%] non-Hispanic White participants) and 206 274 TM beneficiaries, contributing 212 969 episodes (mean [SD] age, 72.7 [8.3] years; 121 263 [56.9%] female; 8356 [3.9%] Hispanic, 16 693 [7.8%] non-Hispanic Black, and 182 228 [85.6%] non-Hispanic White participants). Adjusted total resource use per enrollee during the 6-month episode was $8718 (95% CI, $8343 to $9094) lower in MA than TM ($62 599 vs $71 317). Part B chemotherapy resource use accounted for most of the difference in total resource use, with MA enrollees having $5032 (95% CI, $4772 to $5293) lower use than TM beneficiaries. Lower resource use for Part B chemotherapy in MA was associated with both fewer chemotherapy visits (−1.06 visits; 95% CI, −1.10 to −1.02 visits) and less expensive chemotherapy per visit (−$277; 95% CI, −$275 to −$179). Findings on quality were mixed, but importantly, survival did not differ between MA and TM patients who initiated chemotherapy. Conclusions and Relevance In this cohort study of Medicare beneficiaries with cancer undergoing chemotherapy, MA enrollment was associated with lower resource use but not shorter survival.
Evolutionary innovations in conserved regulatory elements associate with developmental genes in mammals
Authors: Severin Uebbing, Acadia A Kocher, Marybeth Baumgartner, Yu Ji, Suxia Bai, Xiaojun Xing, Timothy Nottoli, James P Noonan
Journal: Molecular Biology and Evolution (2024)

Abstract Transcriptional enhancers orchestrate cell type- and time point-specific gene expression programs. Genetic variation within enhancer sequences is an important contributor to phenotypic variation including evolutionary adaptations and human disease. Certain genes and pathways may be more prone to regulatory evolution than others, with different patterns across diverse organisms, but whether such patterns exist has not been investigated at a sufficient scale. To address this question, we identified signatures of accelerated sequence evolution in conserved enhancer elements throughout the mammalian phylogeny at an unprecedented scale. While different genes and pathways were enriched for regulatory evolution in different parts of the tree, we found a striking overall pattern of pleiotropic genes involved in gene regulatory and developmental processes being enriched for accelerated enhancer evolution. These genes were connected to more enhancers than other genes, which was the basis for having an increased amount of sequence acceleration over all their enhancers combined. We provide evidence that sequence acceleration is associated with turnover of regulatory function. Detailed study of one acceleration event in an enhancer of HES1 revealed that sequence evolution led to a new activity domain in the developing limb that emerged concurrently with the evolution of digit reduction in hoofed mammals. Our results provide evidence that enhancer evolution has been a frequent contributor to regulatory innovation at conserved developmental signaling genes in mammals.
Long-lived lung megakaryocytes contribute to platelet recovery in thrombocytopenia models
Authors: Alison C Livada, Kathleen E McGrath, Michael W Malloy, Chen Li, Sara K Ture, Paul D Kingsley, Anne D Koniski, Leah A Vit, Katherine E Nolan, Deanne Mickelsen, Grace E Monette, Preeti Maurya, James Palis, Craig N Morrell
Journal: Journal of Clinical Investigation (2024)

Lung megakaryocytes (Mks) are largely extravascular with an immune phenotype (1). Because bone marrow (BM) Mks are short-lived it has been assumed that extravascular lung Mks are constantly 'seeded' from the BM. To investigate lung Mk origins and how that impacts their functions, we developed methods to specifically label lung Mks using CFSE dye and biotin delivered oropharyngeal. Labeled lung Mks were present for up to four months, while BM Mks had a <1 week lifespan. In a parabiosis model, lung Mks were partially replaced over 1-month from a circulating source. Unlike tissue-resident macrophages, using MDS1-Cre-ERT2 TdTomato mice, we found that lung Mks arise from hematopoietic stem cells. However, studies with FlkSwitch mTmG mice showed that lung Mks are derived from a Flt3-independent lineage that does not go through a multipotent progenitor. CFSE labeling to track lung Mk-derived platelets showed that about 10% of circulating platelets are lung resident Mk-derived at steady state, but in sterile thrombocytopenia this was doubled (about 20%). Lung-derived platelets were similarly increased in a malaria infection model (Plasmodium yoelii) typified by thrombocytopenia. These studies indicate that lung Mks arise from a Flt3-negative BM source, are long-lived, and contribute more platelets during thrombocytopenia.