tbuckley/cabot-search huggingface dataset:
Hypereosinophilia and Hypereosinophilic Syndromes: First Findings From a Nationwide Multicenter Cohort
Authors: Guillaume Lefèvre, Séverine Bleuse, Mathieu Puyade, Guillaume Moulis, Antoine Néel, Noémie Abisror, Antoine Baudet, Bernard Bonnotte, Jérémie Dion, Antoine Dossier, Maximilien Grall, François Lifermann, Nicolas Limal, Bertrand Lioger, Irène Machelart, Catherine Mohr, Roderau Outh, Viviane Queyrel‐Moranne, Borhane Slama, Ludovic Tréfond, Wadih Abou Chahla, Félix Ackerman, Nabil Belfeki, Alice Berezne, Jean‐Sébastien Blade, Mohammed Azzedine Bouderbala, Safia Chebrek, Vincent Cottin, Sébastien De Almeida, Adèle De Masson, Frédéric Dezoteux, Tiphaine Goulenok, Vincent Jachiet, Mathieu Jouvray, Irina Latu, Emmanuel Ledoult, Amélie Leurs, Maxime Lugosi, Michael Martin, Sara Melboucy‐Belkhir, Chafika Morati‐Hafsaoui, Thomas Quemeneur, Julien Rohmer, Frédérique Roy‐Peaud, Sébastien Sanges, Nicolas Schleinitz, Delphine Staumont‐Salle, Camille Taillé, Louis Terriou, Nathalie Tieulie, Japhete Darline Elenga Koenga, Laurent Schwarb, Kewin Panel, Jean‐Emmanuel Kahn, Matthieu Groh
Journal: Allergy (2025)

Hypereosinophilic syndromes (HES) are a heterogenous group of eosinophilic disorders. To date, only retrospective studies of limited sample-size and/or follow-up duration are available. The COHESion study is a national prospective multicenter multidisciplinary cohort recruiting both adults or children with the spectrum of eosinophilic disorders (including reactive HE/HES [HE/HES-R], idiopathic HES [HES-I], lymphocytic HES [HES-L], neoplastic HE/HES [HE/HES-N], HE of unknown significance [HE-US], as well as IgG4-related disease [IgG4RD] or ANCA-negative eosinophilic granulomatosis with polyangiitis [EGPA] overlaps). Patients are followed-up yearly. All data about final diagnosis, organ involvement assessments, and outcome profiles in HES-I were captured and analyzed centrally by HES expert centers. From May 2019 to November 2023, 779 patients were included. For this preliminary analysis, 550 cases were available for centralized review (mean ± SD age: 56 ± 18 years, 42% of female patients). The final diagnoses were HES-I (47%), HE/HES-R (16%), HE-US (15%), HE/HES-N (7%), HE/HES-L (6%), IgG4RD (2%), and ANCA-negative EGPA (7%). In the 258 HES-I patients, outcome profiles were classified as follows: 16.3% had a "single-flare" without further relapse, 28.3% had a "relapsing-remitting" disease when there was at least a 6-month period free of symptoms between two flares, 46.1% had a "persistent disease" requiring continuous treatment to avoid relapses (9.3% remained unclassified because of insufficient follow-up). The COHESion cohort is the first nationwide prospective multicenter study collecting data on the full spectrum of HE/HES disorders. This preliminary analysis confirms that idiopathic HES patients have various outcome profiles, suggesting different underlying pathophysiological mechanisms and the need of patient-specific management. ClinicalTrials.gov identifier: NCT04018118.
Polycationic γ‐Cyclodextrin with Amino Side Chains for a Highly Efficient Anti‐Heparin Coagulant
Authors: Wen‐Jin An, Zhuo Lei, Xiao‐Yong Yu, Chu‐Han Liu, Chen Zhang, Yong Chen, Yu Liu
Journal: Advanced Healthcare Materials (2025)

Multicharged cyclodextrins have attracted significant attention because of their applications in biology and pharmaceuticals. This study reports an aminoethoxy-phenyl-pyridinium-modified γ-cyclodextrin (PyA-γ-CD) as a highly efficient coagulant for heparin through multivalent interactions. The UV titration experiment is performed to obtain apparent binding constants (K
Limited Benefit of Routine Clinical Follow‐Up for Relapse Detection in Diffuse Large B‐Cell Lymphoma Patients in Complete Remission Following First‐Line Treatment
Authors: Therese Lassen, Torsten H. Nielsen, Annika von Heymann, Lene K. Nielsen, Morten K. Larsen, Anne O. Gang, Christoffer Johansen, Lars M. Pedersen
Journal: American Journal of Hematology (2025)

ABSTRACT Despite advances in treatment, approximately 15% of patients with diffuse large B‐cell lymphoma (DLBCL) who achieve complete remission (CR) after first‐line therapy will experience a relapse. However, there is no consensus on the optimal follow‐up strategies for detecting relapse after achieving CR. This population‐based study, based on the Danish Lymphoma Registry (LYFO), identified a total of 1634 patients diagnosed with DLBCL between 2010 and 2017, including 105 patients who achieved CR following first‐line R‐CHOP‐like therapy and subsequently relapsed. The median follow‐up time was 6 years (range 3–8 years). Most cases of relapse were symptomatic (83%), with B symptoms and peripheral lymphadenopathy being the most common. Asymptomatic relapses were identified through physical examination (1%), blood tests (3%), or imaging findings (13%). The proportion of relapses identified outside routine visits was 70%. Only 5% of scheduled routine visits led to a relapse diagnosis, whereas 74% of unscheduled visits initiated by the patient outside routine follow‐up resulted in relapse detection. Our findings highlight that systematic, scheduled monitoring of patients in remission after first‐line treatment contributes only modestly to the early detection of disease recurrence. Future studies should explore alternative methods of relapse surveillance rather than relying solely on pre‐scheduled clinical follow‐up.
Beyond dysphoria and stress: a theory of gender euphoria and gender fulfillment
Authors: Judith Leitch, Van Nguyen, Sam Potter
Journal: International Journal of Transgender Health (2025)

Background This qualitative study inductively draws on interviews with transgender and gender nonconforming (TGNC) people about positive emotional experiences related to their TGNC identities. Applying grounded theory tradition, this study provides an understanding of TGNC people's pathways to gender fulfillment and euphoria and presents a positive framework to understand TGNC gender experiences.
Enhancement of Osseointegration via Endogenous Electric Field by Regulating the Charge Microenvironments around Implants
Authors: Fangfang Xu, Guangbin Zhao, Yuxin Gong, Xiang Liang, Ming Yu, Hao Cui, Linyang Xie, Nan Zhu, Xuan Zhu, Xiaoxi Shao, Kun Qi, Bingheng Lu, Junbo Tu, Sijia Na
Journal: Advanced Healthcare Materials (2025)

The regulation of the charged microenvironment around implants is an effective way to promote osseointegration. Although homeostasis of the charged microenvironment plays an integral role in tissues, current research is externally invasive and unsuitable for clinical applications. In this study, functional materials with different surface potential differences are prepared by changing the spatial layout of Ta and Ag on the surface of a Ti-6Al-4V alloy (TC4). This naturally formed an endogenous electric field (EEF) with a negatively charged cell membrane after in vivo implantation and promoted osseointegration at the interface between the bone and implant through the upregulation of Ca
Hyper‐<scp>CVAD</scp> and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome‐Negative B‐Cell Acute Lymphoblastic Leukemia
Authors: Hagop Kantarjian, Nicholas J. Short, Nitin Jain, Fadi G. Haddad, Tapan Kadia, Musa Yilmaz, Alessandra Ferrajoli, Koji Sasaki, Yesid Alvarado, Naveen Pemmaraju, Jayastu Senapati, Rebecca Garris, Farhad Ravandi, Elias Jabbour
Journal: American Journal of Hematology (2025)

Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.3 mg/m2 was added on Days 1 and 8 to two cycles of high-dose methotrexate and cytarabine, and two cycles of blinatumomab. The primary endpoint was the relapse-free survival (RFS) rate. Seventy-five patients were treated (median age of 33 years; range, 18-59), of whom 37 (49%) received hyper-CVAD with blinatumomab and InO (cohort 2). Measurable residual disease (MRD) negativity by next-generation sequencing (sensitivity: 1 × 10-6) was achieved in 79% of patients in cohort 2. The median follow-up was 44 months (range, 13-90) overall, and 26 months (range, 8-39) in cohort 2. For the entire cohort, the estimated 3-year RFS rate was 82% and the 3-year overall survival rate was 90%. These rates were 90% versus 74% (p = 0.06) and 100% versus 82% (p = 0.01) in patients who did or did not receive InO, respectively. No sinusoidal obstruction syndrome was observed. In summary, hyper-CVAD with blinatumomab and InO improved the outcomes of patients with newly diagnosed B-ALL.
Responsive Degradable Bottlebrush Polymers Enable Drugs With Superior Efficacy and Minimal Systemic Toxicity
Authors: Liming Shao, Hongrui Zhang, Lei Sun, Lubin Ning, Xiuying Sun, Chaoke Qin, Wenhua Xu, Rui Xu, Fei Jia
Journal: Advanced Healthcare Materials (2025)

Bottlebrush polymers (BBPs) have garnered significant attention as advanced drug delivery systems, capable of transporting a diverse range of therapeutic agents, including both chemical drugs and biologics. Despite their effectiveness, the empty BBP vectors post-drug release may pose long-term safety risks due to their difficult systemic clearance. Here, a responsive degradable BBP platform for cancer therapy is developed, featuring a poly(disulfide) backbone grafted with fluorine-terminated zwitterionic side chains. Anti-cancer drugs are tethered to the backbone via a clinically approved valine-citrulline (VC) linker. This design leverages the tumor's reductive environment and Cathepsin B overexpression for BBP rapid degradation and precise drug release restricted within tumor cells, thereby addressing systemic safety concerns over synthetic BBP and expanding the therapeutic window of anti-cancer drugs simultaneously. Surface fluorination of BBP further enhances tumor accumulation and deep penetration. In vivo studies with monomethyl auristatin E (MMAE)-loaded BBP in tumor-bearing mice demonstrate substantial tumor suppression with minimal side effects. Together, these findings highlight the potential of responsive degradable BBP as a versatile unimolecular platform for cancer drug delivery, addressing existing challenges associated with synthetic BBP nanomedicines.
Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions
Authors: Tiantian Wang, Dong Zhou, Zhen Hong
Journal: MedComm (2025)

Abstract Sarcopenia is defined as a muscle‐wasting syndrome that occurs with accelerated aging, while cachexia is a severe wasting syndrome associated with conditions such as cancer and immunodeficiency disorders, which cannot be fully addressed through conventional nutritional supplementation. Sarcopenia can be considered a component of cachexia, with the bidirectional interplay between adipose tissue and skeletal muscle potentially serving as a molecular mechanism for both conditions. However, the underlying mechanisms differ. Recognizing the interplay and distinctions between these disorders is essential for advancing both basic and translational research in this area, enhancing diagnostic accuracy and ultimately achieving effective therapeutic solutions for affected patients. This review discusses the muscle microenvironment's changes contributing to these conditions, recent therapeutic approaches like lifestyle modifications, small molecules, and nutritional interventions, and emerging strategies such as gene editing, stem cell therapy, and gut microbiome modulation. We also address the challenges and opportunities of multimodal interventions, aiming to provide insights into the pathogenesis and molecular mechanisms of sarcopenia and cachexia, ultimately aiding in innovative strategy development and improved treatments.
Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism
Authors: Felix Pfister, Lucas R. Carnell, Lisa Löffler, Philipp Boosz, Niels Schaft, Jan Dörrie, René Stein, Malte Lenz, Erdmann Spiecker, Christian M. Huber, Sami Haddadin, Carola Berking, Christoph Alexiou, Christina Janko
Journal: MedComm (2025)

Abstract Therapies against hematological malignancies using chimeric antigen receptors (CAR)‐T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer‐specific solid tumor antigens. Therefore, the enrichment of tumor‐antigen specific CAR‐T cells in the desired region is critical for improving therapy efficacy and reducing systemic on‐target/off‐tumor side effects. Here, we functionalized human CAR‐T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site‐directed targeting. SPION‐loaded CAR‐T cells maintained their specific cytolytic capacity against melanoma cells expressing the CAR‐specific antigen chondroitin sulfate proteoglycan (CSPG4). Importantly, SPIONs suppressed cytokine release in the loaded CAR‐T cells, shifting the cell death phenotype in the tumor cells from pyroptosis to apoptosis. Furthermore, SPION‐loaded CAR‐T cells could be enriched in a dynamic flow model through an external magnetic field and be detected in MRI. These results demonstrate that lytic cytotoxicity is retained after SPION‐functionalization and provides a basis for future site‐specific immunotherapies against solid tumors with reduced systemic adverse side effects.
The Current Progress in the Quest for Vaccines Against the Semliki Forest Virus Complex
Authors: Dorothy Hui Juan Cheong, Bowen Yi, Yi Hao Wong, Justin Jang Hann Chu
Journal: Medicinal Research Reviews (2025)

The Semliki Forest virus (SFV) complex comprises of arboviruses that are transmitted by arthropod vectors and cause acute febrile illness in humans. In the last seven decades, re-emergence of these viruses has resulted in numerous outbreaks globally, affecting regions including Africa, Americas, Asia, Europe and the Caribbean. These viruses are transmitted to humans by the bite of infected mosquitoes. Symptoms of infection include high fever, severe joint pain, skin rash, muscle pain and headache. Fatal cases were reported, and mortality rate increased during the epidemic of these viruses. There is therefore a need to control the spread of these emerging arboviruses. Given that vaccination is one of the most effective ways to protect populations against viral outbreaks, efforts have been made to develop and test potential vaccine candidates. However, there are still no licensed vaccines available against the medically important viruses in the SFV complex. This review first summarizes the current knowledge of the SFV complex disease pathogenesis. Next, seven strategies that have been applied in vaccine development against these viruses are reviewed, indicating the immune response and efficacies of these vaccine candidates in in vivo models of infection. Finally, the more promising candidates that have entered clinical trials are discussed and insights into the future development of vaccines for viruses of the SFV complex are given.
Spatiotemporal Control Over Circadian Rhythms With Light
Authors: Dušan Kolarski, Wiktor Szymanski, Ben L. Feringa
Journal: Medicinal Research Reviews (2025)

Circadian rhythms are endogenous biological oscillators that synchronize internal physiological processes and behaviors with external environmental changes, sustaining homeostasis and health. Disruption of circadian rhythms leads to numerous diseases, including cardiovascular and metabolic diseases, cancer, diabetes, and neurological disorders. Despite the potential to restore healthy rhythms in the organism, pharmacological chronotherapy lacks spatial and temporal resolution. Addressing this challenge, chrono-photopharmacology, the approach that employs small molecules with light-controlled activity, enables the modulation of circadian rhythms when and where needed. Two approaches-relying on irreversible and reversible drug activation-have been proposed for this purpose. These methodologies are based on photoremovable protecting groups and photoswitches, respectively. Designing photoresponsive bioactive molecules requires meticulous structural optimization to obtain the desired chemical and photophysical properties, and the design principles, detailed guidelines and challenges are summarized here. In this review, we also analyze all the known circadian modulators responsive to light and dissect the rationale following their construction and application to control circadian biology from the protein level to living organisms. Finally, we present the strength of a reversible approach in allowing the modulation of the circadian period and the phase.
Aberrant splicing in Huntington’s disease accompanies disrupted TDP-43 activity and altered m6A RNA modification
Authors: Thai B. Nguyen, Ricardo Miramontes, Carlos Chillon-Marinas, Roy Maimon, Sonia Vazquez-Sanchez, Alice L. Lau, Nicolette R. McClure, Zhuoxing Wu, Keona Q. Wang, Whitney E. England, Monika Singha, Jennifer T. Stocksdale, Marie Heath, Ki-Hong Jang, Sunhee Jung, Karen Ling, Paymann Jafar-nejad, Jharrayne I. McKnight, Leanne N. Ho, Osama Al Dalahmah, Richard L. M. Faull, Joan S. Steffan, Jack C. Reidling, Cholsoon Jang, Gina Lee, Don W. Cleveland, Clotilde Lagier-Tourenne, Robert C. Spitale, Leslie M. Thompson
Journal: Nature Neuroscience (2025)
Genome-wide CRISPR-Cas 9 screens identify BCL family members as modulators of response to regorafenib in experimental glioma
Authors: Lara Annina Haeusser, Hannes Becker, Laurence Kuhlburger, Marcello Zago, Bianca Walter, Foteini Tsiami, Sarah Erdmann, Jil Trampert, Surender Surender, Aaron Stahl, Markus Templin, Eileen Wegner, Tobias Schmidt, Christian Schmees, Nicolas Casadei, Lisa Sevenich, Manfred Claassen, Sven Nahnsen, Susanne Beck, Daniel Josef Merk, Ghazaleh Tabatabai
Journal: Neuro-Oncology (2025)

Abstract Background Registered systemic treatment options for glioblastoma patients are limited. The phase II REGOMA trial suggested an improvement of median overall survival in progressive glioblastoma by the multi-tyrosine kinase inhibitor regorafenib. This has not been confirmed by GBM AGILE. So far, regorafenib has been administered as monotherapy or as an addition to standard of care in newly diagnosed glioblastoma. Rational combination therapies involving regorafenib might be a reasonable strategy. Here, we aimed at identifying functionally instructed combination therapies involving regorafenib. Methods We applied a genome-wide CRISPR-Cas9-based functional genomics target discovery approach using activation and knockout screens followed by genetic, pharmacological, functional validations. Regorafenib-induced molecular alterations were assessed by RNA sequencing and DigiWest. We investigated selected functionally instructed combination therapies in three orthotopic glioma mouse models in vivo (syngeneic SMA560/VM/Dk model and two xenograft models) and performed immunohistochemistry of post-treatment brains. Results We identified potential modifiers of regorafenib response, including BCL2, BCL2L1, ITGB3, FOXC1, SERAC1, ARAF, and PLCE1. The combination of regorafenib with Bcl-2/Bcl-xL inhibition was superior to both monotherapies alone in vitro, ex vivo, and in vivo. We identified regorafenib-induced regulations of the Bcl-2 downstream target chemokine receptor 1 (CCR1) as one potential underlying molecular mediator. Furthermore, regorafenib led to changes in the myeloid compartment of the glioma-associated microenvironment. Conclusions This preclinical study uses a functional genomics-based target discovery approach with subsequent validations involving regorafenib. It serves as a biological rationale for clinical translation. Particularly, an investigation of the combination of regorafenib plus navitoclax within a clinical trial is warranted.
G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials
Authors: Aina Bellver‐Sanchis, Marta Ribalta‐Vilella, Alba Irisarri, Pinky Gehlot, Bhanwar Singh Choudhary, Abhisek Jana, Vivek Kumar Vyas, Deb Ranjan Banerjee, Mercè Pallàs, Ana Guerrero, Christian Griñán‐Ferré
Journal: Medicinal Research Reviews (2025)

ABSTRACT This review provides a comprehensive overview of the role of G9a/EHMT2, focusing on its structure and exploring the impact of its pharmacological and/or gene inhibition in various neurological diseases. In addition, we delve into the advancements in the design and synthesis of G9a/EHMT2 inhibitors, which hold promise not only as a treatment for neurodegeneration diseases but also for other conditions, such as cancer and malaria. Besides, we presented the discovery of dual therapeutic approaches based on G9a inhibition and different epigenetic enzymes like histone deacetylases, DNA methyltransferases, and other lysine methyltransferases. Hence, findings offer valuable insights into developing novel and promising therapeutic strategies targeting G9a/EHMT2 for managing these neurological conditions.
Engineered IL‐21‐Expressing Nanovesicles for Co‐Delivery of GOX and Ferrocene to Induce Synergistic Anti‐Tumor Effects
Authors: Chao Li, Mengyang Zhou, Yang Li, Haojie Jia, Lin Huang
Journal: Advanced Healthcare Materials (2025)

Glucose oxidase (GOX)-induced starvation is a safe treatment for tumor. However, the non-specific targeting of GOX and the plasticity of tumor metabolism lead to toxic side effects and low tumor mortality. Thus, it is necessary to develop a synergistic strategy with high tumor targeting specificity to enhance the mortality of GOX. In this study, a genetically engineered CD44 targeting peptide (CP) and IL-21 fusion protein-displaying nanovesicles platform (mCP@IL21-Fc-GOX) are designed to efficiently encapsulate GOX and ferrocene (Fc). After reaching the tumor site, IL-21 can be precisely released and targeted to NK cells through the cleavage of MMP-2, thus achieving precise anti-tumor immunotherapy of IL-21. Second, the exposed CP enable mCP-Fc-GOX to be further targeted to tumor cells, completing the synergistic anti-cancer effects of starvation and chemodynamic therapy (CDT) triggered by GOX and Fc. In situ breast cancer models, the results show that mCP@IL21-Fc-GOX not only enhances NK and T cells aggregation in tumor tissue but also achieves precise nutrition deprivation and abundant reactive oxygen species production, thus significantly inhibits tumor growth based on the synergistic function of the immunotherapy, starvation and CDT. Therefore, this work provides a smart nanovesicle platform for achieving precise and safe synergistic anti-tumor therapy.