tbuckley/cabot-search huggingface dataset:
Conductive Microgel Annealed Scaffolds Enhance Myogenic Potential of Myoblastic Cells
Authors: Alena Casella, Jeremy Lowen, Katherine H. Griffin, Nathan Shimamoto, David H. Ramos‐Rodriguez, Alyssa Panitch, J. Kent Leach
Journal: Advanced Healthcare Materials (2023)

Abstract Conductive biomaterials may capture native or exogenous bioelectric signaling, but incorporation of conductive moieties is limited by cytotoxicity, poor injectability, or insufficient stimulation. Microgel annealed scaffolds are promising as hydrogel‐based materials due to their inherent void space that facilitates cell migration and proliferation better than nanoporous bulk hydrogels. Conductive microgels are generated from poly(ethylene) glycol (PEG and poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT: PSS) to explore the interplay of void volume and conductivity on myogenic differentiation. PEDOT: PSS increases microgel conductivity two‐fold while maintaining stiffness, annealing strength, and viability of associated myoblastic cells. C2C12 myoblasts exhibit increases in the late‐stage differentiation marker myosin heavy chain as a function of both porosity and conductivity. Myogenin, an earlier marker, is influenced only by porosity. Human skeletal muscle‐derived cells exhibit increased Myod1 , insulin like growth factor‐1, and insulin‐like growth factor binding protein 2 at earlier time points on conductive microgel scaffolds compared to non‐conductive scaffolds. They also secrete more vascular endothelial growth factor at early time points and express factors that led to macrophage polarization patterns observe during muscle repair. These data indicate that conductivity aids myogenic differentiation of myogenic cell lines and primary cells, motivating the need for future translational studies to promote muscle repair.
It’s all about the base: stromal cells are central orchestrators of metastasis
Authors: Lea Monteran, Yael Zait, Neta Erez
Journal: Trends in cancer (2023)

The tumor microenvironment (TME) is an integral part of tumors and plays a central role in all stages of carcinogenesis and progression. Each organ has a unique and heterogeneous microenvironment, which affects the ability of disseminated cells to grow in the new and sometimes hostile metastatic niche. Resident stromal cells, such as fibroblasts, osteoblasts, and astrocytes, are essential culprits in the modulation of metastatic progression: they transition from being sentinels of tissue integrity to being dysfunctional perpetrators that support metastatic outgrowth. Therefore, better understanding of the complexity of their reciprocal interactions with cancer cells and with other components of the TME is essential to enable the design of novel therapeutic approaches to prevent metastatic relapse.
Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect: A secondary analysis of NRG CC001
Authors: Hua-Ren R Cherng, Kai Sun, Søren Bentzen, Terri S Armstrong, Vinai Gondi, Paul D Brown, Minesh Mehta, Mark V Mishra
Journal: Neuro-Oncology (2023)

Abstract Background Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT. Methods An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated. Results The benefit of HA-WBRT on decreasing NCFF was seen in patients living ≥ 4 months (HR 0.75, 95% CI: 0.58–0.97, P = .03), whereas patients living &amp;lt; 4 months derived no significant neurocognitive benefit. A significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P = .03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR = 0.64, 95% CI: 0.48–0.85, P = .002) compared to those with highest MDASI-BT scores (HR = 1.24, 95% CI: 0.76–2.04, P = .39). Tumor histology also had a significant interaction (P = .01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR = 0.58, 95% CI: 0.43–0.77, P = .0007) from HA-WBRT, in contrast to nonlung primary histology patients (HR = 1.15, 95% CI: 0.78–1.50, P = .48). Conclusions Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving ≥ 4 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.
Phylloxera and Aphids Show Distinct Features of Genome Evolution Despite Similar Reproductive Modes
Authors: Zheng Li, Allen Z Xue, Gerald P Maeda, Yiyuan Li, Paul D Nabity, Nancy A Moran
Journal: Molecular Biology and Evolution (2023)

Abstract Genomes of aphids (family Aphididae) show several unusual evolutionary patterns. In particular, within the XO sex determination system of aphids, the X chromosome exhibits a lower rate of interchromosomal rearrangements, fewer highly expressed genes, and faster evolution at nonsynonymous sites compared with the autosomes. In contrast, other hemipteran lineages have similar rates of interchromosomal rearrangement for autosomes and X chromosomes. One possible explanation for these differences is the aphid's life cycle of cyclical parthenogenesis, where multiple asexual generations alternate with 1 sexual generation. If true, we should see similar features in the genomes of Phylloxeridae, an outgroup of aphids which also undergoes cyclical parthenogenesis. To investigate this, we generated a chromosome-level assembly for the grape phylloxera, an agriculturally important species of Phylloxeridae, and identified its single X chromosome. We then performed synteny analysis using the phylloxerid genome and 30 high-quality genomes of aphids and other hemipteran species. Unexpectedly, we found that the phylloxera does not share aphids’ patterns of chromosome evolution. By estimating interchromosomal rearrangement rates on an absolute time scale, we found that rates are elevated for aphid autosomes compared with their X chromosomes, but this pattern does not extend to the phylloxera branch. Potentially, the conservation of X chromosome gene content is due to selection on XO males that appear in the sexual generation. We also examined gene duplication patterns across Hemiptera and uncovered horizontal gene transfer events contributing to phylloxera evolution.
Acute <scp>NETosis</scp> from organophosphate poisoning
Authors: Bingwen Eugene Fan, Guo Feng Abel Teo, Kian Guan Eric Lim, Shiun Woei Wong, Yin Wen Lai, Ponnudurai Kuperan, Siu Ling Wong
Journal: American Journal of Hematology (2023)

We declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Upregulation of CoQ shifts ferroptosis dependence from GPX4 to FSP1 in acquired radioresistance
Authors: Xu Lin, Qingyi Zhang, Qi Li, Jun Deng, Shuying Shen, Muhu Tang, Xianghua Ye, Cong Ji, Yuhong Yang, Yuxiao Chen, Liping Zeng, Jiangang Zhao, M.B.N. Kouwenhoven, Don Eliseo Lucero-Prisno, Junjie Huang, Yangling Li, Bo Zhang, Jian Hu
Journal: Drug Resistance Updates (2023)

Acquired radioresistance is the primary contributor to treatment failure of radiotherapy, with ferroptosis is identified as a significant mechanism underlying cell death during radiotherapy. Although resistance to ferroptosis has been observed in both clinical samples of radioresistant cells and cell models, its mechanism remains unidentified. Herein, our investigation revealed that radioresistant cells exhibited greater tolerance to Glutathione Peroxidase 4 (GPX4) inhibitors and, conversely, increased sensitivity to ferroptosis suppressor protein 1 (FSP1) inhibitors compared to their sensitive counterparts. This observation suggested that FSP1 might play a dominant role in the development of radioresistance. Notably, the knockout of FSP1 demonstrated considerably superior efficacy in resensitizing cells to radiotherapy compared to the knockout of GPX4. To elucidate the driving force behind this functional shift, we conducted a metabolomic assay, which revealed an upregulation of Coenzyme Q (CoQ) synthesis and a downregulation of glutathione synthesis in the acquired radioresistance cells. Mechanistically, CoQ synthesis was found to be supported by aarF domain containing kinase 3-mediated phosphorylation of CoQ synthases, while the downregulation of Solute carrier family 7 member 11 led to decreased glutathione synthesis. Remarkably, our retrospective analysis of clinical response data further validated that the additional administration of statin during radiotherapy, which could impede CoQ production, effectively resensitized radioresistant cells to radiation. In summary, our findings demonstrate a dependency shift from GPX4 to FSP1 driven by altered metabolite synthesis during the acquisition of radioresistance. Moreover, we provide a promising therapeutic strategy for reversing radioresistance by inhibiting the FSP1-CoQ pathway.
Airway hyperresponsiveness correlates with airway TSLP in asthma independent of eosinophilic inflammation
Authors: Louise Munkholm Andreasson, Nanna Dyhre-Petersen, Morten Hvidtfeldt, Gustav Ørting Jørgensen, Anna Von Bülow, Ditte Kjærsgaard Klein, Lena Uller, Jonas Erjefält, Celeste Porsbjerg, Asger Sverrild
Journal: Journal of Allergy and Clinical Immunology (2023)
A Dual‐Function Hemicyanine Material with Highly Efficient Photothermal and Photodynamic Effect Used for Tumor Therapy
Authors: Minglu Zhang, Shuo Wang, Yueping Bai, Danyang Wang, Yu Fu, Zongyi Su, Guoqiang Zhang, Meng Meng, Fan Yu, Bing Wang, Hongzhen Jin, Wei Zhao
Journal: Advanced Healthcare Materials (2023)

Small molecular organic optical agents with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), hold credible promise for anti-tumor therapy by overcoming individual drawbacks and enhancing photon utilization efficiency. However, developing effective dual-function PTT-PDT photosensitizers (PSs) for efficient synergistic phototherapy remains challenging. Here, a benz[c,d]indolium-substituted hemicyanine named Rh-BI, which possesses a high photothermal conversion efficiency of 41.67% by exhaustively suppressing fluorescence emission, is presented. Meanwhile, the rotating phenyl group at meso-site induces charge recombination to enhance the molar extinction coefficient up to 13.58 × 10
Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry
Authors: Benjamin de Valence, Marion Delaune, Yann Nguyen, Vincent Jachiet, Mael Heiblig, Alexis Jean, Stanislas Riescher Tuczkiewicz, Pierrick Henneton, Philippe Guilpain, Nicolas Schleinitz, Guillaume Le Guenno, Hervé Lobbes, Valentin Lacombe, Samuel Ardois, Estibaliz Lazaro, Vincent Langlois, Roderau Outh, Julien Vinit, Jean-Philippe Martellosio, Paul Decker, Thomas Moulinet, Yannick Dieudonné, Adrien Bigot, Louis Terriou, Alexandre Vlakos, Baptiste de Maleprade, Guillaume Denis, Jonathan Broner, Marie Kostine, Sebastien Humbert, Francois Lifermann, Maxime Samson, Susann Pechuzal, Achille Aouba, Olivier Kosmider, Jeremie Dion, Sylvie Grosleron, Rim Bourguiba, Benjamin Terrier, Sophie Georgin-Lavialle, Olivier Fain, Arsène Mekinian, Marjolaine Morgand, Thibault Comont, Jerome Hadjadj, Isabelle Melki, Pierre Fenaux, Lionel Ades, Alexandra Audemard, Mikael Ebbo, Yvan Jamilloux, Odile Beyne Rauzy, Alexandre Belot, Raphaël Borie, Alexis Mathian, Laurent Arnaud, François Chasset, Jean-David Bouaziz, Pierre Sujobert, Ygal Benhamou, Gaetan Sauvetre, Khalil El-Karoui, François Rodrigues
Journal: Annals of the Rheumatic Diseases (2023)

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors. Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models. Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV-2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5-7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections. VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.
Birth Cohort Colorectal Cancer (CRC): Implications for Research and Practice
Authors: Samir Gupta, Folasade P. May, Sonia S. Kupfer, Caitlin C. Murphy
Journal: Clinical Gastroenterology and Hepatology (2023)

Colorectal cancer (CRC) epidemiology is changing due to a birth cohort effect, first recognized by increasing incidence of early onset CRC (EOCRC, age < 50 years). In this paper, we define "birth cohort CRC" as the observed phenomenon, among individuals born 1960 and later, of increasing CRC risk across successive birth cohorts, rising EOCRC incidence, increasing incidence among individuals age 50-54 years, and flattening of prior decreasing incidence among individuals age 55-74 years. We demonstrate birth cohort CRC is associated with unique features, including increasing rectal cancer (greater than colon) and distant (greater than local) stage CRC diagnosis, and increasing EOCRC across all racial/ethnic groups. We review potential risk factors, etiologies, and mechanisms for birth cohort CRC, using EOCRC as a starting point and describing importance of viewing these through the lens of birth cohort. We also outline implications of birth cohort CRC for epidemiologic and translational research, as well as current clinical practice. We postulate that recognition of birth cohort CRC as an entity - including and extending beyond rising EOCRC - can advance understanding of risk factors, etiologies, and mechanisms, and address the public health consequences of changing CRC epidemiology.
Long-term follow-up of patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation after primary induction failure
Authors: Miriam Mozaffari Jovein, Gabriele Ihorst, Jesús Duque-Afonso, Ralph Wäsch, Hartmut Bertz, Claudia Wehr, Justus Duyster, Robert Zeiser, Jürgen Finke, Florian Scherer
Journal: Blood Cancer Journal (2023)

Abstract Primary induction failure (PIF) in acute myeloid leukemia (AML) patients is associated with poor outcome, with allogeneic hematopoietic stem cell transplantation (HCT) being the sole curative therapeutic option. Here, we retrospectively evaluated long-term outcomes of 220 AML patients undergoing allogeneic HCT after PIF who never achieved remission, and identified clinical and molecular risk factors associated with treatment response and ultimate prognosis. In this high-risk population, disease-free survival was 25.2% after 5 years and 18.7% after 10 years, while overall survival rates were 29.8% and 21.6% after 5 and 10 years of HCT, respectively. 10-year non-relapse mortality was 32.5%, and 48.8% of patients showed disease relapse within 10 years after allogeneic HCT. Adverse molecular risk features determined at initial diagnosis, poor performance status at the time of allogeneic HCT, and long diagnosis-to-HCT intervals were associated with unfavorable prognosis. Collectively, our data suggests that immediate allogeneic HCT after PIF offers long-term survival and cure in a substantial subset of cases and that high-risk AML patients who never achieved complete response during induction might benefit from early donor search.
Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues
Authors: Jia Song, Hai Wang, Zhe-Zheng Wang, Cui-Lian Guo, Wen-Xuan Xiang, Jing-Xian Li, Zhi-Chao Wang, Ji-Xin Zhong, Kun Huang, Robert P. Schleimer, Yin Yao, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2023)
Prospective Comparison of Attenuation Imaging and Controlled Attenuation Parameter for Liver Steatosis Diagnosis in Patients With Nonalcoholic Fatty Liver Disease and Type 2 Diabetes
Authors: Marco Dioguardi Burgio, Laurent Castera, Mehdi Oufighou, Pierre-Emmanuel Rautou, Valérie Paradis, Pierre Bedossa, Riccardo Sartoris, Maxime Ronot, Sylvain Bodard, Philippe Garteiser, Bernard Van Beers, Dominique Valla, Valérie Vilgrain, Jean Michel Correas
Journal: Clinical Gastroenterology and Hepatology (2023)
Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease
Authors: Frederik Teicher Kirk, Ditte Emilie Munk, Eugene Scott Swenson, Adam Michael Quicquaro, Mikkel Holm Vendelbo, Agnete Larsen, Michael L. Schilsky, Peter Ott, Thomas Damgaard Sandahl
Journal: Journal of Hepatology (2023)

Background & AimsIn Wilson Disease (WD), copper accumulates in the liver and brain causing disease. Bis-choline tetrathiomolybdate (TTM) is a potent copper chelator that may have a lower risk of inducing paradoxical neurological worsening than conventional therapy for neurologic WD. To better understand the mode of action of TTM, we investigated the effects of TTM on copper absorption and biliary excretion.MethodsIn a double-blind randomized setting, hepatic 64Cu activity after orally administered 64Cu was examined by PET/CT in 16 healthy volunteers before and after 7 days of TTM treatment (15 mg/d) or placebo. Oral 64Cu was administered 1 h after final TTM dose. Changes in hepatic 64Cu activity reflected changes in intestinal 64Cu uptake. Additionally, in four WD patients, distribution of 64Cu in venous blood, liver, gallbladder, kidney, and brain were followed after i.v. 64Cu dosing for up to 68 hours before and after seven days of TTM (15 mg/d), using PET/MRI. Increased gallbladder 64Cu activity was taken as evidence of increased biliary 64Cu excretion.ResultsIn healthy subjects TTM reduced intestinal 64Cu uptake by 82% 15 hours after the oral 64Cu dose. In WD patients, gallbladder 64Cu activity was negligible before and after TTM, while TTM effectively retained 64Cu in the blood, significantly reduced hepatic 64Cu activity at all time points and significantly reduced cerebral 64Cu activity 2 h after the intravenous 64Cu dose.ConclusionsWhile we did not show an increase in biliary excretion of 64Cu following TTM administration, we demonstrated that TTM effectively inhibited most intestinal 64Cu uptake and retained 64Cu in the blood stream, limiting 64Cu exposure to organs like the liver and the brain.Impact and implicationsBis-choline tetrathiomolybdate (TTM) is an investigational copper chelator for treatment of Wilson Disease. In animal studies of Wilson Disease models, TTM has been shown to facilitate biliary copper excretion.In the present human study, TTM surprisingly did not facilitate biliary copper excretion but instead reduced intestinal copper uptake to a clinically significant degree.Our study improves the understanding of human copper metabolism and the mechanism of action of TTM.Clinical trial numberData is presented from two clinical trials:Absorption study: EudraCT 2020-005832-31Excretion study: EudraCT 2021-000102-25.
Much work to do about measuring work
Authors: Cathy J Bradley, Sara Kitchen, Kelsey M Owsley
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Work ability is a critical economic and well-being indicator in cancer care. Yet, work ability is understudied in clinical trials and observational research and is often undocumented in medical records. Despite agreement on the importance of work from well-being, health insurance, and financial perspectives, standardized approaches for collecting, measuring, and analyzing work outcomes are lacking in the health-care setting. The necessary components for closing the gap in patient and caregiver employment research in health-care settings involve a common set of measures, including those that replace or translate generic measures of mental and physical functioning into work outcomes in observational and clinical trial research, standardized approaches to data collection and documentation, and the use of longitudinal data to understand the consequences of reduced work ability over time. We present a conceptual framework for the inclusion of work ability in outcomes research. We cover constructs for employment and work ability measurement that can be adopted in research, recorded as patient-level data, and used to guide treatment decisions. The inclusion of return to work and hours worked, productivity, and ability to perform in a similar job can support conversations that guide treatment decisions and minimize economic consequences. Our hope is that by considering impact on work ability, improved treatments will be developed, health inequities reduced, and resources directed toward aiding patients and their caregivers in balancing work and health demands.
Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, in patients with refractory or relapsed peripheral T-cell lymphoma (JACKPOT8 Part B): a single-arm, multinational, phase 2 study
Authors: Yuqin Song, Luis Malpica, Qingqing Cai, Weili Zhao, Keshu Zhou, Jianqiu Wu, Huilai Zhang, Neha Mehta-Shah, Kaiyang Ding, Yao Liu, Zengjun Li, Liling Zhang, Meifang Zheng, Jie Jin, Haiyan Yang, Yuerong Shuang, Dok Hyun Yoon, Sujun Gao, Wenyu Li, Zhimin Zhai, Liqun Zou, Yaming Xi, Youngil Koh, Fei Li, Miles Prince, Hui Zhou, Lie Lin, Hui Liu, Pamela Allen, Fernando Roncolato, Zhenfan Yang, Won-Seog Kim, Jun Zhu
Journal: The Lancet Oncology (2023)
Noninvasive treatment of cutaneous neurofibromas (cNFs): Results of a randomized prospective, direct comparison of four methods
Authors: Patricia Richey, Margaret Funk, Fernanda Sakamoto, Scott Plotkin, Ina Ly, Justin Jordan, Alona Muzikansky, Josh Roberts, William Farinelli, Yakir Levin, Lilit Garibyan, Jaishri O. Blakeley, R.Rox Anderson
Journal: Journal of the American Academy of Dermatology (2023)
Association of Sociodemographic Characteristics with Pediatric Vision Screening and Eye Care
Authors: Bani Antonio-Aguirre, Sandra S. Block, Afua O. Asare, Kira Baldanado, Elise B. Ciner, Rachel A. Coulter, Dawn K. DeCarlo, Carolyn Drews-Botsch, Donna Fishman, E. Eugenie Hartmann, Olivia J. Killeen, Jenay Yuen, Megan E. Collins
Journal: Ophthalmology (2023)