tbuckley/cabot-search huggingface dataset:
Eltrombopag improves platelet engraftment after haploidentical bone marrow transplantation: Results of a Phase <scp>II</scp> study
Authors: Sairah Ahmed, Qaiser Bashir, Roland L. Bassett, Fauzia Ullah, Fleur Aung, Benigno C. Valdez, Amin M. Alousi, Chitra Hosing, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Muzaffar H. Qazilbash, Katayoun Rezvani, Rohtesh Mehta, Elizabeth J. Shpall, Stefan Ciurea, Borje S. Andersson, Richard E. Champlin, Uday R. Popat
Journal: American Journal of Hematology (2024)

Abstract Slow platelet recovery frequently occurs after haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) with bone marrow graft and post‐transplant cyclophosphamide (PCy)‐based graft‐versus‐host disease (GVHD) prophylaxis. Improved platelet recovery may reduce the need for transfusions and improve outcomes. We investigated the safety and efficacy of eltrombopag, a thrombopoietin receptor agonist, at enhancing platelet recovery post‐haplo‐HSCT. The prospective study included patients ≥18 years of age who received haplo‐HSCT with bone marrow graft and PCy. Patients received eltrombopag 300 mg/day starting on Day +5. The primary objective was to estimate platelet engraftment (&gt;50 000/μL by Day 60). In a post hoc analysis, they were compared to a contemporary matched control group who did not receive eltrombopag. One hundred ten patients were included in the analysis (30 eltrombopag and 80 control). Seventy‐three percent and 50% of patients in the eltrombopag group and control group, respectively, attained &gt;50 000/μL platelet count by Day 60 ( p = .043). No eltrombopag‐related grade ≥4 adverse events were observed. Median time to platelet recovery (&gt;20 000/μL) was 29 days with eltrombopag and 31 days for controls ( p = .022), while its cumulative incidence was 90% (95% confidence interval [CI]: 78%–100%) with eltrombopag versus 67.5% (95% CI: 57%–78%) for controls ( p = .014). Number of platelet transfusions received, overall survival, progression‐free survival, GVHD rate, relapse rate, and non‐relapse mortality were similar between groups. Overall, eltrombopag is safe and improves platelet recovery in patients undergoing haplo‐HSCT with bone marrow graft and PCy.
Development and therapeutic potential of GSPT1 molecular glue degraders: A medicinal chemistry perspective
Authors: Xiujin Chang, Fangui Qu, Chunxiao Li, Jingtian Zhang, Yanqing Zhang, Yuanyuan Xie, Zhongpeng Fan, Jinlei Bian, Jubo Wang, Zhiyu Li, Xi Xu
Journal: Medicinal Research Reviews (2024)

Abstract Unprecedented therapeutic targeting of previously undruggable proteins has now been achieved by molecular‐glue‐mediated proximity‐induced degradation. As a small GTPase, G1 to S phase transition 1 (GSPT1) interacts with eRF1, the translation termination factor, to facilitate the process of translation termination. Studied demonstrated that GSPT1 plays a vital role in the acute myeloid leukemia (AML) and MYC‐driven lung cancer. Thus, molecular glue (MG) degraders targeting GSPT1 is a novel and promising approach for treating AML and MYC‐driven cancers. In this Perspective, we briefly summarize the structural and functional aspects of GSPT1, highlighting the latest advances and challenges in MG degraders, as well as some representative patents. The structure‐activity relationships, mechanism of action and pharmacokinetic features of MG degraders are emphasized to provide a comprehensive compendium on the rational design of GSPT1 MG degraders. We hope to provide an updated overview, and design guide for strategies targeting GSPT1 for the treatment of cancer.
Distinguishing heart failure with reduced ejection fraction from heart failure with preserved ejection fraction: A phenomics approach
Authors: Bart J. van Essen, Ganash N. Tharshana, Wouter Ouwerkerk, Poh Suan Daniel Yeo, David Sim, Fazlur Jaufeerally, Hean Yee Ong, Lieng Hsi Ling, Dinna Kar Nee Soon, Shao Guang Sheldon Lee, Gerard Leong, Seet Yoong Loh, Ru San Tan, Chrishan J. Ramachandra, Derek J. Hausenloy, Oi Wai Liew, Jenny Chong, Adriaan A. Voors, Carolyn S.P. Lam, A. Mark Richards, Jasper Tromp
Journal: European Journal of Heart Failure (2024)

Pathophysiological differences between patients with heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction (EF) remain unclear. Therefore we used a phenomics approach, integrating selected proteomics data with patient characteristics and cardiac structural and functional parameters, to get insight into differential pathophysiological mechanisms and identify potential treatment targets.
Decoding Sjögren syndrome: A comprehensive approach to multiparametric diagnosis: comment on the article by Bettacchioli et al
Authors: Ranjeet Singh Mahla
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Incorporation of Decidual Stromal Cells Derived Exosomes in Sodium Alginate Hydrogel as an Innovative Therapeutic Strategy for Advancing Endometrial Regeneration and Reinstating Fertility
Authors: Yuxiang Liang, Qizhi Shuai, Xiao Zhang, Shanshan Jin, Yuqian Guo, Zhaowei Yu, Xinrui Xu, Ruifang Ao, Zhiwei Peng, Huimin Lv, Sheng He, Chunfang Wang, Guohua Song, Zhizhen Liu, Hong Zhao, Qilong Feng, Ruochen Du, Bin Zheng, Zhaoyang Chen, Jun Xie
Journal: Advanced Healthcare Materials (2024)

Abstract Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity‐reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC‐derived exosomes (DSC‐exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal‐to‐epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC‐exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.
The impact of outdoor pollution and extreme temperatures on asthma‐related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma
Authors: Ioana Agache, Carlos Canelo‐Aybar, Isabella Annesi‐Maesano, Lorenzo Cecchi, David Rigau, L. Yesenia Rodríguez‐Tanta, Wendy Nieto‐Gutierrez, Yang Song, Yahveth Cantero‐Fortiz, Marta Roqué, Juan Carlos Vasquez, Ivan Sola, Benedetta Biagioni, Fan Chung, Gennaro D'Amato, Athanasios Damialis, Stefano del Giacco, Leticia de las Vecillas, Javier Dominguez‐Ortega, Carmen Galàn, Stefanie Gilles, Mattia Giovannini, Stephen Holgate, Mohamed Jeebhay, Kari Nadeau, Nikolaos Papadopoulos, Santiago Quirce, Joaquin Sastre, Claudia Traidl‐Hoffmann, Jolanta Walusiak‐Skorupa, Bernardo Sousa‐Pinto, Pablo Alonso‐Coello, Josefina Salazar, Marek Jutel, Cezmi A. Akdis
Journal: Allergy (2024)

Abstract Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma‐related outcomes of short‐term exposure to outdoor air pollutants (PM2.5, PM10, NO 2 , SO 2 , O 3 , and CO), heavy traffic, outdoor pesticides, and extreme temperatures. Additionally, the SR evaluated the impact of the efficacy of interventions reducing outdoor pollutants. The risk of bias was assessed using ROBINS‐E tools and the certainty of the evidence by using GRADE. Short‐term exposure to PM2.5, PM10, and NO 2 probably increases the risk of asthma‐related hospital admissions (HA) and emergency department (ED) visits (moderate certainty evidence). Exposure to heavy traffic may increase HA and deteriorate asthma control (low certainty evidence). Interventions reducing outdoor pollutants may reduce asthma exacerbations (low to very low certainty evidence). Exposure to fumigants may increase the risk of new‐onset asthma in agricultural workers, while exposure to 1,3‐dichloropropene may increase the risk of asthma‐related ED visits (low certainty evidence). Heatwaves and cold spells may increase the risk of asthma‐related ED visits and HA and asthma mortality (low certainty evidence).
Collagen Scaffolds Functionalized by Cu<sup>2+</sup>‐Chelated EGCG Nanoparticles with Anti‐Inflammatory, Anti‐Oxidation, Vascularization, and Anti‐Bacterial Activities for Accelerating Wound Healing
Authors: Lei Ma, Yunfei Tan, Qiulan Tong, Xiaoyu Cao, Danni Liu, Xiaomin Ma, Xian Jiang, Xudong Li
Journal: Advanced Healthcare Materials (2024)

Skin injury is a common health problem worldwide, and the highly complex healing process poses critical challenges for its management. Therefore, wound dressings with salutary effects are urgently needed for wound care. However, traditional wound dressing with a single function often fails to meet the needs of wound repair, and the integration of multiple functions has been required for wound repair. Herein, Cu2+-chelated epigallocatechin gallate nanoparticles (EAC NPs), with radical scavenging, inflammation relieving, bacteria restraining, and vascularization accelerating capacities, are adopted to functionalize collagen scaffold, aiming to promote wound healing. Radical scavenging experiments verify that EAC NPs could efficiently scavenge radicals. Additionally, EAC NPs could effectively remove Escherichia coli and Staphylococcus aureus. H2O2 stimuli-responsive EAC NPs show slow and sustained release properties of Cu2+. Furthermore, EAC NPs exhibit protective effects against H2O2-induced oxidative-stress damage and anti-inflammatory activity in vivo. Physicochemical characterizations show that the introduction of EAC NPs does not disrupt the gelation behavior of collagen, and the composite scaffolds (CS) remain porous structure similar to collagen scaffold. Animal experiments demonstrate that CS could promote wound healing through improving the thickness of renascent epidermis and number of new vessels. CS with multiple salutary functions is a promising dressing for wound care.
Advances towards genome‐based acute myeloid leukemia classification: A comparative analysis of <scp>WHO‐HAEM4R</scp>, <scp>WHO‐HAEM5</scp>, and International Consensus Classification
Authors: Xue Chen, Lili Yuan, Yang Zhang, Fang Wang, Xiaoli Ma, Jiancheng Fang, Panxiang Cao, Yijun Liu, Zhixiu Liu, Ming Liu, Jiaqi Chen, Xiaosu Zhou, Mingyue Liu, David Jin, Tong Wang, Peihua Lu, Hongxing Liu
Journal: American Journal of Hematology (2024)

Abstract Two recent guidelines, the 5th edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO‐HAEM5) and the International Consensus Classification (ICC), were published to refine the diagnostic criteria of acute myeloid leukemia (AML). They both consider genomic features more extensively and expand molecularly defined AML subtypes. In this study, we compared the classifications of 1135 AML cases under both criteria. According to WHO‐HAEM5 and ICC, the integration of whole transcriptome sequencing, targeted gene mutation screening, and conventional cytogenetic analysis identified defining genetic abnormalities in 89% and 90% of AML patients, respectively. The classifications displayed discrepancies in 16% of AML cases after being classified using the two guidelines, respectively. Both new criteria significantly reduce the number of cases defined by morphology and differentiation. However, their clinical implementation heavily relies on comprehensive and sophisticated genomic analysis, including genome and transcriptome levels, alongside the assessment of pathogenetic somatic and germline variations. Discrepancies between WHO‐HAEM5 and ICC, such as the assignment of RUNX1 mutations, the rationality of designating AML with mutated TP53 as a unique entity, and the scope of rare genetic fusions, along with the priority of concurrent AML‐defining genetic abnormalities, are still pending questions requiring further research for more elucidated insights.
Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries—The @IT.2020 multicenter study
Authors: S. Dramburg, U. Grittner, E. Potapova, A. Travaglini, S. Tripodi, S. Arasi, S. Pelosi, A. Acar Şahin, X. Aggelidis, A. Barbalace, A. Bourgoin, B. Bregu, M. A. Brighetti, E. Caeiro, S. Caglayan Sozmen, L. Caminiti, D. Charpin, M. Couto, L. Delgado, A. Di Rienzo Businco, C. Dimier, M. V. Dimou, J. A. Fonseca, O. Goksel, D. Hernandez, C. J. Hernandez Toro, T. M. Hoffmann, D. T. Jang, F. Kalpaklioglu, B. Lame, R. Llusar, M. Makris, A. Mazon, E. Mesonjesi, A. Nieto, A. B. Öztürk, L. Pahus, G. Pajno, I. Panasiti, N. G. Papadopoulos, E. Pellegrini, A. M. Pereira, M. Pereira, N. M. Pinar, A. Priftanji, F. Psarros, C. Sackesen, I. Sfika, J. Suarez, M. Thibaudon, U. Uguz, V. Verdier, V. Villella, P. Xepapadaki, D. Yazici, P. M. Matricardi
Journal: Allergy (2024)

Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach.
Therapeutic vaccine-induced plasma cell differentiation is defective in the presence of persistently high HBsAg levels
Authors: Ruoyao Qi, Rao Fu, Xing Lei, Jinhang He, Yao Jiang, Liang Zhang, Yangtao Wu, Siling Wang, Xueran Guo, Feng Chen, Meifeng Nie, Man Yang, Yiyi Chen, Jing Zeng, Jingjing Xu, Hualong Xiong, Mujin Fang, Yuqiong Que, Youliang Yao, Yingbin Wang, Jiali Cao, Huiming Ye, Yali Zhang, Zizheng Zheng, Tong Cheng, Jun Zhang, Xu Lin, Quan Yuan, Tianying Zhang, Ningshao Xia
Journal: Journal of Hepatology (2024)
Increased Siglec-9/Siglec-9L interactions on NK cells predict poor HCC prognosis and present a targetable checkpoint for immunotherapy
Authors: Rong Xiao, Ye Tian, Jiwei Zhang, Na Li, Mei Qi, Ling Liu, Jianping Wang, Zhenyu Li, Jie Zhang, Fabao Zhao, Tixiao Wang, Siyu Tan, Chunyang Li, Zhuanchang Wu, Mingyan Yu, Xuemei Jiang, Peng Zhan, Lifen Gao, Bo Han, Xinyong Liu, Xiaohong Liang, Chunhong Ma
Journal: Journal of Hepatology (2024)
Glycolysis-Mediated Activation of v-ATPase by Nicotinamide Mononucleotide Ameliorates Lipid-Induced Cardiomyopathy by Repressing the CD36-TLR4 Axis
Authors: Shujin Wang, Yinying Han, Ruimin Liu, Mengqian Hou, Dietbert Neumann, Jun Zhang, Fang Wang, Yumeng Li, Xueya Zhao, Francesco Schianchi, Chao Dai, Lizhong Liu, Miranda Nabben, Jan F.C. Glatz, Xin Wu, Xifeng Lu, Xi Li, Joost J.F.P. Luiken
Journal: Circulation Research (2024)

Chronic overconsumption of lipids followed by their excessive accumulation in the heart leads to cardiomyopathy. The cause of lipid-induced cardiomyopathy involves a pivotal role for the proton-pump vacuolar-type H+-ATPase (v-ATPase), which acidifies endosomes, and for lipid-transporter CD36, which is stored in acidified endosomes. During lipid overexposure, an increased influx of lipids into cardiomyocytes is sensed by v-ATPase, which then disassembles, causing endosomal de-acidification and expulsion of stored CD36 from the endosomes toward the sarcolemma. Once at the sarcolemma, CD36 not only increases lipid uptake but also interacts with inflammatory receptor TLR4 (Toll-like receptor 4), together resulting in lipid-induced insulin resistance, inflammation, fibrosis, and cardiac dysfunction. Strategies inducing v-ATPase reassembly, that is, to achieve CD36 reinternalization, may correct these maladaptive alterations. For this, we used NAD+ (nicotinamide adenine dinucleotide)-precursor nicotinamide mononucleotide (NMN), inducing v-ATPase reassembly by stimulating glycolytic enzymes to bind to v-ATPase. Rats/mice on cardiomyopathy-inducing high-fat diets were supplemented with NMN and for comparison with a cocktail of lysine/leucine/arginine (mTORC1 [mechanistic target of rapamycin complex 1]-mediated v-ATPase reassembly). We used the following methods: RNA sequencing, mRNA/protein expression analysis, immunofluorescence microscopy, (co)immunoprecipitation/proximity ligation assay (v-ATPase assembly), myocellular uptake of [3H]chloroquine (endosomal pH), and [14C]palmitate, targeted lipidomics, and echocardiography. To confirm the involvement of v-ATPase in the beneficial effects of both supplementations, mTORC1/v-ATPase inhibitors (rapamycin/bafilomycin A1) were administered. Additionally, 2 heart-specific v-ATPase-knockout mouse models (subunits V1G1/V0d2) were subjected to these measurements. Mechanisms were confirmed in pharmacologically/genetically manipulated cardiomyocyte models of lipid overload. NMN successfully preserved endosomal acidification during myocardial lipid overload by maintaining v-ATPase activity and subsequently prevented CD36-mediated lipid accumulation, CD36-TLR4 interaction toward inflammation, fibrosis, cardiac dysfunction, and whole-body insulin resistance. Lipidomics revealed C18:1-enriched diacylglycerols as lipid class prominently increased by high-fat diet and subsequently reversed/preserved by lysine/leucine/arginine/NMN treatment. Studies with mTORC1/v-ATPase inhibitors and heart-specific v-ATPase-knockout mice further confirmed the pivotal roles of v-ATPase in these beneficial actions. NMN preserves heart function during lipid overload by preventing v-ATPase disassembly.
Front Cover Image, Volume 44, Issue 2
Authors: Kang Wang, Yuecan Zhang, Guangji Wang, Haiping Hao, Hong Wang
Journal: Medicinal Research Reviews (2024)

The cover image is based on the Review Article FXR agonists for MASH therapy: Lessons and perspectives from obeticholic acid by Kang Wang et al., https://doi.org/10.1002/med.21991
Inside Front Cover Image, Volume 44, Issue 2
Authors: Yu Zheng, Yuke Li, Mao Li, Rujing Wang, Yuhong Jiang, Mengnan Zhao, Jun Lu, Rui Li, Xiaofang Li, Sanjun Shi
Journal: Medicinal Research Reviews (2024)

The cover image is based on the Review Article COVID-19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms by Yu Zheng et al., https://doi.org/10.1002/med.21997
Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells
Authors: Jing Wang, Shuqin Liu, Xinxiu Meng, Xuan Zhao, Tianhui Wang, Zhiyong Lei, H. Immo Lehmann, Guoping Li, Pilar Alcaide, Yihua Bei, Junjie Xiao
Journal: Circulation Research (2024)

Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection.
Bioinspired Bioinks for the Fabrication of Chemomechanically Relevant Standalone Disease Models of Hepatic Steatosis
Authors: Giuseppe Guagliano, Cristina Volpini, Lorenzo Sardelli, Francesco Briatico Vangosa, Livia Visai, Paola Petrini
Journal: Advanced Healthcare Materials (2024)

Hepatotoxicity-related issues are poorly predicted during preclinical experimentation, as its relevance is limited by the inadequacy to screen all the non-physiological subclasses of the population. These pitfalls can be solved by implementing complex in vitro models of hepatic physiology and pathologies in the preclinical phase. To produce these platforms, extrusion-based bioprinting is focused on, since it allows to manufacture tridimensional cell-laden constructs with controlled geometries, in a high-throughput manner. Different bioinks, whose formulation is tailored to mimic the chemomechanical environment of hepatic steatosis, the most prevalent hepatic disorder worldwide, are proposed. Internally crosslinked alginate hydrogels are chosen as structural components of the inks. Their viscoelastic properties (G' = 512-730 Pa and G″ = 94-276 Pa, depending on frequency) are tuned to mimic those of steatotic liver tissue. Porcine hepatic ECM is introduced as a relevant biochemical cue. Sodium oleate is added to recall the accumulation of lipids in the tissue. Downstream analyses on 14-layered bioprinted structures cultured for 10 days reveal the establishment of steatotic-like features (intracellular lipid vesicles, viability decrease up to ≈50%) without needing external conditionings. The presented bioinks are thus suitable to fabricate complex models of hepatic steatosis to be implemented in a high-throughput experimental frame.
Clinical Images: A Strange Reaction After a Hyaluronic Acid Injection
Authors: Marie Piroth, Youta Fanjat, Nathalie Cardot‐Leccia, Christian Roux, Thierry Passeron
Journal: Arthritis & Rheumatology (2024)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Where is the PrEP for migrants?
Authors: Rebecca Irons
Journal: BMJ (2024)

Where is the PrEP for migrants?Displaced Venezuelans and other refugee populations are at risk of HIV infection.Providing PrEP and tackling stigma are critical to preventing this, writes Rebecca Irons Rebecca Irons senior research fellowWith more than seven million people displaced, the Venezuelan refugee crisis-fuelled by political, economic, and social instability-is on a similar scale to that of Ukraine and Syria, yet it remains out of international headlines. 1Despite Venezuela's health system reaching near collapse, 2 medical and humanitarian aid have steadily declined in recent years, with an acceleration in 2021 as international agencies redirected funds towards Ukraine.
cGAS‐STING pathway agonists are promising vaccine adjuvants
Authors: Xinyu Tian, Jiayuan Ai, Xiaohe Tian, Xiawei Wei
Journal: Medicinal Research Reviews (2024)

Adjuvants are of critical value in vaccine development as they act on enhancing immunogenicity of antigen and inducing long-lasting immunity. However, there are only a few adjuvants that have been approved for clinical use, which highlights the need for exploring and developing new adjuvants to meet the growing demand for vaccination. Recently, emerging evidence demonstrates that the cGAS-STING pathway orchestrates innate and adaptive immunity by generating type I interferon responses. Many cGAS-STING pathway agonists have been developed and tested in preclinical research for the treatment of cancer or infectious diseases with promising results. As adjuvants, cGAS-STING agonists have demonstrated their potential to activate robust defense immunity in various diseases, including COVID-19 infection. This review summarized the current developments in the field of cGAS-STING agonists with a special focus on the latest applications of cGAS-STING agonists as adjuvants in vaccination. Potential challenges were also discussed in the hope of sparking future research interests to further the development of cGAS-STING as vaccine adjuvants.