tbuckley/cabot-search huggingface dataset:
A Transfusion Reaction due to Anti‐<scp>ER5</scp> in a Hyposplenic β<sup>0</sup> Thalassemia Major Patient
Authors: Arun Thomas, Kirstin Lund, Viviene Ballon, Barbara J. Bain
Journal: American Journal of Hematology (2025)

A 6-year-old boy of Libyan ethnic origin was referred to pediatric hematology 3 months after entering the United Kingdom as a refugee. The child was known to have thalassemia major. His parents were first cousins. He had previously been transfused every 4 weeks, received chelation therapy and had been splenectomized. More recently, transfusion requirement had increased to every 2 weeks and he had developed post-transfusion hemoglobinuria, which was not ameliorated by corticosteroids. He had not been transfused since arriving in the United Kingdom and his hemoglobin concentration (Hb) was 72 g/L. Anti-c and anti-E were present together with a panagglutinating antibody directed at the high frequency antigen, ER5. It was not possible to source ER5-negative blood and he was therefore transfused with Rh-typed red cells under cover of intravenous immunoglobulin, methylprednisolone, and eculizumab. Transfusion led to an initial rise of Hb to 96 g/L but, despite the precautions taken, by 3 days the Hb had fallen to 65 g/L. His mother reported that following the transfusion his urine had again become red. Post-transfusion his blood film (both images, ×100 objective) showed hypochromic red cells, target cells, Howell–Jolly bodies, Pappenheimer bodies, schistocytes, alpha chain inclusions within hypochromic erythrocytes (upper image), and nucleated red blood cells. In addition to the evidence of thalassemia and hyposplenism, there were also considerable numbers of spherocytes, indicating a transfusion reaction. The direct antiglobulin test was positive for immunoglobulin G (+). Molecular analysis showed homozygosity for β0 thalassemia, specifically NM_000518.4: c93-22_95del p.? In addition, there was homozygosity for the Xmn1 (−158) polymorphism of the HBG2 gene, which leads to some increase in hemoglobin F synthesis. ER5 is a recently recognized, high incidence antigen, antibodies to which can cause hemolytic disease of the fetus and newborn [1]. Future management of the child will be fraught with problems. The authors declare no conflicts of interest.
Every gain comes with loss: Ecological and physiological shifts associated with polyploidization in a pygmy frog
Authors: Qiheng Chen, Wei Zhu, Liming Chang, Meihua Zhang, Shouhong Wang, Jiongyu Liu, Ningning Lu, Cheng Li, Feng Xie, Bin Wang, Jianping Jiang
Journal: Molecular Biology and Evolution (2025)

Abstract Polyploidization plays a pivotal role in vertebrate evolution and diversification. However, the effects of polyploidization on animals across various biological levels, and how these differences drive ecological shifts, remain unclear. Through karyotype analysis and whole-genome sequencing, we identified an autotetraploid Microhyla fissipes from Hainan Island, which shows reproductive isolation and geographic differentiation from its diploid counterpart. Tetraploids exhibited larger cell size, improved tadpole growth rates, and greater whole-body size, along with reduced cell cycle activity. Rather than being simple scaled-up diploids, tetraploids showed shifts in physiological performance, organ allometry, gene expression profiles, and metabolic patterns. Tetraploid adults demonstrated superior jumping ability and increased reproductive investment (e.g., larger gonads and steeper slopes in the relationship between gonadal weight and body weight), suggesting a potential competitive advantage over diploids. However, tetraploids exhibited higher energy expenditure at elevated temperatures, reduced hepatic energy storage, and altered pulmonary regulatory metabolites at 25 oC. Males had smaller relative heart sizes, and females showed flatter slopes in the relationship between heart and lung weight and body weight, indicating reduced investment in cardiopulmonary system. These variations suggest an increased risk of metabolic constraints under heat stress, putting tetraploids at a disadvantage in warmer regions. Importantly, the physiological trade-offs associated with polyploidization help explain the geographical differentiation between diploids and tetraploids, which reflects a climatic boundary, with tetraploids occupying cooler northeastern areas. Our findings identify an autotetraploid frog, report the first autotetraploid genome in amphibians, and demonstrate how vertebrate polyploids physiologically and ecologically diverge from their diploid counterparts.
Outcomes of Relapsed or Refractory Diffuse Large B‐Cell Lymphoma Treated With R‐<scp>GemOx</scp>: A Multicenter Cohort Study
Authors: Samuel Yamshon, Jean L. Koff, Melissa C. Larson, Brad S. Kahl, Carla Casulo, Izidore S. Lossos, Sara Haddadi, Michele Stanchina, Dai Chihara, Amy Ayers, Thomas M. Habermann, Yucai Wang, Arushi Khurana, Grzegorz S. Nowakowski, Tanner W. Reicks, Umar Farooq, Brian K. Link, Jonathon B. Cohen, Peter Martin, Jia Li, Ashwini Shewade, Connie Lee Batlevi, Andrea Lo‐Rossi, David Fox, Anthony Masaquel, Yong Mun, James R. Cerhan, Christopher R. Flowers, Matthew J. Maurer, Loretta J. Nastoupil
Journal: American Journal of Hematology (2025)

ABSTRACT Rituximab, gemcitabine, and oxaliplatin (R‐GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), but there are limited real‐world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high‐grade B cell lymphoma treated with R‐GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy ( n = 100), those utilizing R‐GemOx as a bridge to ASCT or CAR T ( n = 83), and those aged 70 and older ( n = 71). Overall response rates (ORRs) for all patients treated with R‐GemOx were 45% with a complete response (CR) rate of 29%. The median event‐free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R‐GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R‐GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R‐GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R‐GemOx in the rapidly evolving landscape of R/R DLBCL therapies.
AI-driven histologic analysis of human Achilles tendinopathy provides a roadmap to unravel pathogenesis
Authors: Guillaume Planckaert, Arne Burssens, Flore Stappers, Julie Coudenys, Sofía Demolder, Irem Kaya, Malaïka Van der Linden, Amanda Gonçalves, Kelly Lemeire, Benjamin Pavie, Edwin Van Ovost, Peter Burssens, Amber Vanhaecke, Jo Van Dorpe, Lauren Pringels, Evi Wezenbeek, Jess Snedeker, Katrien De Bock, Fiona Bonar, Jill Cook, Jan Victor, Dirk Elewaut, Eric Gracey
Journal: Annals of the Rheumatic Diseases (2025)

Achilles tendinopathy is a common source of pain and dysfunction, yet its pathogenesis remains poorly understood. Research on human tendons is hampered by lack of standardisation in tissue sample validation, making interpretation of results challenging. We sought to develop an automated and operator-independent approach to histologically score human tendons. We assembled a cohort of 15 tendinopathic and 10 normal control Achilles tendon samples. We stained longitudinal sections with haematoxylin and eosin and Alcian blue and developed a low temperature epitope-retrieval protocol for immunostaining of blood vessels. Histologic sections were scored by pathologists using the current gold standard Bonar score. Whole sections were then analysed with open-source software (QuPath). Histologic features were automatically quantified across the entire section and summarised in the BonAIr score. Tissue from the same patients was subsequently analysed by quantitative polymerase chain reaction and flow cytometry to validate elements of the BonAIr score. We observed increased cell roundness, collagen disarrangement, ground substance, and vascularity in tendinopathy using both the Bonar and BonAIr scores. Increased cellularity was only detected by the BonAIr score. Cellular and transcriptomic analyses corroborated tendinopathic shifts in all elements of the BonAIr score and further identified elevated THY1/CD90 expression in tendinopathy. CD90+ cells were found to localise to areas of low collagen alignment. These results align with the concept of stromal cell dysregulation in tendinopathy. Automated analysis of whole tendon sections refines conventional histopathologic scoring and predicts cellular and molecular changes found in tendinopathy. The BonAIr score should be further developed for standardised assessment of tendons samples across other anatomical locations and different research centres.
Digital twins as global learning health and disease models for preventive and personalized medicine
Authors: Xinxiu Li, Joseph Loscalzo, A K M Firoj Mahmud, Dina Mansour Aly, Andrey Rzhetsky, Marinka Zitnik, Mikael Benson
Journal: Genome Medicine (2025)

Abstract Ineffective medication is a major healthcare problem causing significant patient suffering and economic costs. This issue stems from the complex nature of diseases, which involve altered interactions among thousands of genes across multiple cell types and organs. Disease progression can vary between patients and over time, influenced by genetic and environmental factors. To address this challenge, digital twins have emerged as a promising approach, which have led to international initiatives aiming at clinical implementations. Digital twins are virtual representations of health and disease processes that can integrate real-time data and simulations to predict, prevent, and personalize treatments. Early clinical applications of DTs have shown potential in areas like artificial organs, cancer, cardiology, and hospital workflow optimization. However, widespread implementation faces several challenges: (1) characterizing dynamic molecular changes across multiple biological scales; (2) developing computational methods to integrate data into DTs; (3) prioritizing disease mechanisms and therapeutic targets; (4) creating interoperable DT systems that can learn from each other; (5) designing user-friendly interfaces for patients and clinicians; (6) scaling DT technology globally for equitable healthcare access; (7) addressing ethical, regulatory, and financial considerations. Overcoming these hurdles could pave the way for more predictive, preventive, and personalized medicine, potentially transforming healthcare delivery and improving patient outcomes.
The clinical journey of belantamab mafodotin in relapsed or refractory multiple myeloma: lessons in drug development
Authors: Pralay Mukhopadhyay, Hesham A. Abdullah, Joanna B. Opalinska, Prani Paka, Eric Richards, Katja Weisel, Suzanne Trudel, Maria-Victoria Mateos, Meletios Athanasios Dimopoulos, Sagar Lonial
Journal: Blood Cancer Journal (2025)
Alterations in mucosa branched <i>N</i> -glycans lead to dysbiosis and downregulation of ILC3: a key driver of intestinal inflammation
Authors: Cláudia S. Rodrigues, Joana Gaifem, Márcia S. Pereira, Maria Francisca Alves, Mariana Silva, Nuno Padrão, Bruno Cavadas, Catarina Moreira-Barbosa, Inês Alves, Ricardo Marcos-Pinto, Joana Torres, Aonghus Lavelle, Jean-Frederic Colombel, Harry Sokol, Salomé S. Pinho
Journal: Gut Microbes (2025)

The perturbation of the symbiotic relationship between microbes and intestinal immune system contributes to gut inflammation and Inflammatory Bowel Disease (IBD) development. The host mucosa glycans (glycocalyx) creates a major biological interface between gut microorganisms and host immunity that remains ill-defined. Glycans are essential players in IBD immunopathogenesis, even years before disease onset. However, how changes in mucosa glycosylation shape microbiome and how this impact gut immune response and inflammation remains to be clarified. Here, we revealed that alterations in the expression of complex branched N-glycans at gut mucosa surface, modeled in glycoengineered mice, resulted in dysbiosis, with a deficiency in Firmicutes bacteria. Concomitantly, this mucosa N-glycan switch was associated with a downregulation of type 3 innate lymphoid cells (ILC3)-mediated immune response, leading to the transition of ILC3 toward an ILC1 proinflammatory phenotype and increased TNFα production. In addition, we demonstrated that the mucosa glycosylation remodeling through prophylactic supplementation with glycans at steady state was able to restore microbial-derived short-chain fatty acids and microbial sensing (by NOD2 expression) alongside the rescue of the expression of ILC3 module, suppressing intestinal inflammation and controlling disease onset. In a complementary approach, we further showed that IBD patients, often displaying dysbiosis, exhibited a tendency of decreased MGAT5 expression at epithelial cells that was accompanied by reduced ILC3 expression in gut mucosa. Altogether, these results unlock the effects of alterations in mucosa glycome composition in the regulation of the bidirectional crosstalk between microbiota and gut immune response, revealing host branched N-glycans/microbiota/ILC3 axis as an essential pathway in gut homeostasis and in preventing health to intestinal inflammation transition.
Effectiveness and Cost-Effectiveness of Expanded Targeted Testing and Treatment of Latent Tuberculosis Infection Among the Medicare Population in 2022
Authors: Yunfei Li, Suzanne M. Marks, Garrett R. Beeler Asay, Carla A. Winston, Dawn Pepin, Susan McClure, Nicole A. Swartwood, Ted Cohen, C. Robert Horsburgh, Joshua A. Salomon, Nicolas A. Menzies
Journal: Annals of Internal Medicine (2025)

In the United States, older adults have elevated prevalence of latent tuberculosis infection (LTBI) and incidence of tuberculosis (TB). To estimate the health benefits and cost-effectiveness of LTBI testing and treatment among the Medicare-eligible population. Model-based cost-effectiveness analysis. Nationally representative surveys and published evidence. Medicare-eligible persons aged 65 years or older with at least 1 of 15 factors associated with elevated TB risk, as identified by guidelines from the U.S. Preventive Services Task Force (USPSTF) and other organizations. Lifetime. Societal. One-time offer of LTBI testing and treatment versus no intervention. Lifetime TB cases and deaths averted, quality-adjusted life-years (QALYs) gained, costs, and incremental cost-effectiveness ratios (ICERs). In 2022, there were an estimated 29.9 million Medicare-eligible persons (95% uncertainty interval [UI], 28.4 to 31.6 million persons) aged 65 years or older with elevated TB risks, including 14.7 million (95% UI, 13.4 to 16.0 million) with USPSTF-recommended factors. In the target population, 4.9 million persons (95% UI, 4.0 to 5.8 million persons) (16.4% [95% UI, 13.9% to 19.1%]) were estimated to have LTBI. Testing and treatment of LTBI was estimated to prevent 10 946 TB cases (95% UI, 4684 to 20 579 cases) and 2579 TB deaths (95% UI, 1106 to 4882 deaths), with 13 234 lifetime QALYs (95% UI, 5343 to 25 519 lifetime QALYs) gained. For the overall target population and for persons with USPSTF-recommended factors, ICERs were $192 000 (95% UI, $92 000 to $503 000) and $155 000 (95% UI, $77 000 to $393 000) per QALY gained, respectively. The ICER was $109 000 (95% UI, $49 000 to $285 000) per QALY gained for 65-year-olds newly eligible for Medicare. Health benefits from averted post-TB sequelae were not estimated. Medicare-eligible persons represent approximately one third of all U.S. persons with LTBI. Testing and treatment of LTBI in this population could lead to substantial reductions in TB and TB-related mortality, particularly among 65-year-olds newly eligible for Medicare. Centers for Disease Control and Prevention.
Stromal KITL/SCF maintains pancreas tissue homeostasis and restrains tumor progression
Authors: M. Kathrina. Oñate, Chet Oon, Sohinee Bhattacharyya, Vivien Low, Canping Chen, Xiaofan Zhao, Frank Arnold, Ziqiao Yan, Sneha Pramod, Yan Hang, Yu-Jui Ho, Scott W. Lowe, Seung K. Kim, Zheng Xia, Mara H. Sherman
Journal: Cancer Discovery (2025)

Abstract Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor onset. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown. Here we show that healthy pancreatic mesenchyme expresses the paracrine signaling molecule KITL, also known as stem cell factor, and identify loss of stromal KITL during tumorigenesis as tumor-promoting. Genetic inhibition of mesenchymal KITL in the contexts of health, injury, and cancer together indicate a role for KITL signaling in maintenance of pancreas tissue architecture, such that loss of the stromal KITL pool increased tumor growth and reduced survival of tumor-bearing mice. Together, these findings implicate loss of mesenchymal KITL as a mechanism for establishing a tumor-permissive microenvironment.
The impact of bicuspid valve morphology on the selection of TAVI devices: an in-silico study
Authors: Benedetta Grossi, Giulia Luraghi, Sara Barati, Chiara Forte, Luca Gerosa, Ottavia Cozzi, Fabrizio D’Ascenzo, Gianluigi Condorelli, Francesco Migliavacca, Giulio Stefanini
Journal:  (2025)

Bicuspid aortic valve (BAV) represents a challenge for transcatheter aortic valve implantation (TAVI). Few data are reported about the procedural implications of BAV using different self-expandable devices. The aim of this study is to investigate how BAV and tricuspid aortic valve (TAV) morphologies influence device selection and their impact on the potential development of post-operative conduction disturbances, using a novel in silico approach. Five patients with BAV undergoing TAVI were enrolled. TAVs were virtually modelled within each BAV patient-specific anatomy, resulting in 10 virtual patients. Acurate Neo2 and Evolut R implantations were subsequently simulated across all cases. Post-implantation stresses exerted on both the stent and aortic root were measured, allowing a comparative analysis of the impact of the two valve morphologies. Comparing stent stresses between BAV and TAV configurations, the stress gap increased by 21.96 ± 5.35% (P = 0.01) in Acurate Neo2 cases (n = 6) compared with Evolut R cases (n = 4). The analysis of aortic root stresses showed no significant differences between BAV (n = 5) and TAV (n = 5) configurations, with a mean stress difference of 5.1 ± 8.17% (P > 0.05). Our patient-specific model shows that high radial force devices, such as Evolut R, demonstrate consistent expansion regardless of valve morphology, without increasing the risk of post-implantation conduction disturbances, hence resulting more suitable for BAV cases. Incorporating this methodology into pre-operative planning could support clinicians in selecting the most suitable device with a patient-specific approach.
Letter: considerations on nonsurgical risk factors for marginal ulcer following Roux-en-Y Gastric bypass for obesity
Authors: Qiang Yi, Gangfeng Zhu, Jinghua Zhong
Journal: International Journal of Surgery (2025)

aThe First Clinical Medical College, Gannan Medical University, Ganzhou, Jiangxi Province, China bDepartment of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi Province, China *Corresponding author. Address: Department of Oncology, The First Affiliated Hospital of Gannan Medical University, 128 Jinling Road, Ganzhou, Jiangxi Province, China, 341000. E-mail: [email protected] (J. Zhong). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. See the article "Nonsurgical risk factors for marginal ulcer following Roux-en-Y gastric bypass for obesity: a systematic review and meta-analysis of 14 cohort studies" in volume 110(3): 1793–1799. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
Roving histological imaging for navigation-confirmed glioma negative margin by handheld endomicroscopy: a parallel controlled study
Authors: Xin Zhang, Xing Xiao, Qiyuan Zhuang, B.S Ming Chen, Jing Lyu, Liang Chen, Fan Zhao, Xingfu Wang, Xiang Zou
Journal: International Journal of Surgery (2025)

Roving histopathological imaging in the navigation-confirmed tumor negative margin has not been achieved during neurosurgery procedures. This study aims to explore the diagnostic values of a novel intraoperative handheld endomicroscopy DiveScope (DS) for ex vivo glioma diagnosis and in vivo roving scan in navigation-confirmed glioma negative margin and to evaluate its safety. This prospective pilot study was conducted at [university/hospital name] from October 2021 to October 2023, and enrolled patients scheduled for glioma resection surgery. The diagnostic values of DS scanning were compared with the frozen section (FS). Hematoxylin-eosin (HE) staining was used as the gold standard for evaluation. The medical device adverse events (MDAE) were recorded for safety analysis. The previous 24 patients with 73 intraoperative isolated samples were included in the DS ex vivo assessments for glioma diagnosis, and the subsequent 40 patients with 52 samples were included in the DS in vivo assessments for navigation-confirmed tumor negative margin. The sensitivity, specificity, and accuracy of DS scanning were 100.0%, 81.6%, and 90.4% for ex vivo assessment by a pathologist, 100.0%, 76.3%, and 87.7% for ex vivo assessment by a neurosurgeon, and 100.0%, 85.0%, and 94.2% for in vivo assessment, respectively. DS in vivo roving scan showed a significantly improved area under the receiver-operating characteristic curve (AUC) compared to FS in assessing the navigation-confirmed tumor negative margin (AUC: 0.925 vs. 0.725, P = 0.003). There were no MDAEs. Time consuming for DS scanning for each sample was 75.77 ± 45.03 s and for each patient was 121.63 ± 94.04 s. DiveScope could provide safe, time-effective, and accurate roving histological imaging for navigation-confirmed glioma negative margin during surgery, which may guide the glioma resection process to achieve maximal safe resection and promote prognosis.