tbuckley/cabot-search huggingface dataset:
KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression
Authors: Hao Zhang, Yujia Zheng, Zhen Wang, Lin Dong, Liyan Xue, Xiaolin Tian, Haiteng Deng, Qi Xue, Shugeng Gao, Yibo Gao, Chunxiang Li, Jie He
Journal: Drug Resistance Updates (2024)

Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.
Evaluation of droplet digital PCR by detecting cell-free DNA in pleural effusion for the diagnosis of tuberculous pleurisy: a multicenter cohort study
Authors: Fudong Xu, Weili Du, Chengjun Li, Ye Li, Zhihui Li, Wenge Han, Huimin Li, Jianqin Liang, Dongmei Zhao, Xinting Yang, Feng Wang, Chaolian Long, Xuya Xing, Jing Tan, Nana Zhang, Zuyu Sun, Nanying Che
Journal: Clinical Microbiology and Infection (2024)
Harmonizing efficacy and safety: The potentials of CAR-NK in effectively addressing severe toxicities of CAR-T therapy in mantle cell lymphoma
Authors: Xu Sun, Yijun Wu, He Li, Ailin Zhao, Ting Niu
Journal: International Journal of Surgery (2024)

Sun, Xu PhD; Wu, Yijun MD; Li, He MD; Zhao, Ailin MD; Niu, Ting MD, PhD Author Information
Comment on“Prognostic significance of circulating tumor DNA in urothelial carcinoma: A systematic review and meta-analysis”
Authors: Jingwen Zhao, Qiang Xu
Journal: International Journal of Surgery (2024)

aTianjin University of Traditional Chinese Medicine bSecond Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China cInstitute of Surgery of Traditional Chinese Medicine, Tianjin, China dInstitute of Sores and Ulcers, Tianjin University of Traditional Chinese Medicine, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China. Tel: (+86)-022-60637062. E-mail address: [email protected] (Q. Xu). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Decreased LDL-Cholesterol Exposure Following ANGPTL3 Inhibition Reduces Coronary Plaque Development in Homozygous Familial Hypercholesterolemia
Authors: Willemijn A.M. Schonck, M. Doortje Reijman, Albert Wiegman, Shirin Ibrahim, Willemijn E. Corpeleijn, R. Nils Planken, G. Kees Hovingh, Erik S.G. Stroes, Nick S. Nurmohamed, Laurens F. Reeskamp
Journal: JACC. Cardiovascular imaging (2024)
The association of body composition phenotypes before chemotherapy with epithelial ovarian cancer mortality
Authors: Evan W Davis, Kristopher Attwood, Joseph Prunier, Gyorgy Paragh, Janine M Joseph, André Klein, Charles Roche, Nancy Barone, John Lewis Etter, Andrew D Ray, Britton Trabert, Matthew B Schabath, Lauren C Peres, Rikki Cannioto
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. Methods Body composition from 500 women in the Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). Results Overweight or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50). Conclusions Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors.
Remission after CAR T‐cell therapy: Do lymphoma patients recover a normal life?
Authors: Alya Perthus, Fanny Colin, Emilie Charton, Amélie Anota, Faustine Lhomme, Guillaume Manson, Sophie De Guibert, Pierre Daufresne, Adeline Bellec, Laetitia Le Bars, Sandra De Barros, Loïc Ysebaert, Marianne Merceur, Mélanie Cogné, Thierry Lamy De La Chapelle, Roch Houot, Aline Moignet
Journal: HemaSphere (2024)

Abstract Chimeric antigen receptor T cells (CAR T cells) can induce prolonged remission in a substantial subset of patients with relapse/refractory lymphoma. However, little is known about patients' life after CAR T‐cell therapy. We prospectively assessed the multidimensional recovery of lymphoma patients in remission, before leukapheresis, before CAR T‐cell infusion, and 3, 6, and 12 months thereafter. Validated tools were used to measure lymphoma‐related and global health‐related quality of life (HRQoL; Functional Assessment of Cancer Therapy‐Lymphoma [FACT‐Lym] and EQ‐5D‐5L), cognitive complaint (FACT‐Cognition), fatigue (FACIT‐Fatigue subscale), psychological status (Hospital Anxiety and Depression Scale, Post‐Traumatic Check List Scale), and sexuality (Relationship and Sexuality Scale). Beyond 12 months of remission, we also surveyed physical, professional, sexual, and general life status. At 3, 6, and 12 months, 53, 35, and 23 patients were evaluable, respectively. Improvement in lymphoma‐related HRQoL was clinically relevant at 3, 6, and 12 months with a mean change from baseline of 10.9 (95% confidence interval [CI]: 5.8; 16.1), 12.2 (95% CI: 4.2; 20.1), and 11.72 (95% CI: 2.06; 21.38), respectively. Improvement in global HRQoL, fatigue, and anxiety was clinically relevant, but 20%–40% of patients experienced persistent fatigue, psychological distress, and cognitive complaints over time. Beyond 12 months after CAR T cells, 81.8% of 22 evaluable patients were satisfied with their daily life. Physical activity, professional, sexual, and global well‐being had returned to prediagnosis levels in nearly half of the patients. We found an improvement in HRQoL after CAR T‐cell therapy including anxiety, depression, sexual satisfaction, and general well‐being. However, not all patients recover a “normal life.” Further research is needed to determine which patients are at risk of quality‐of‐life impairment to improve recovery after CAR T‐cell infusion.
Long‐Term Follow‐Up of Anti‐Infliximab Antibodies in Patients With Radiographic Axial Spondyloarthritis: A Marker of Drug Survival and Tapering
Authors: Clarissa Q. Pimentel, Ana Cristina Medeiros‐Ribeiro, Andrea Y. Shimabuco, Percival D. Sampaio‐Barros, Júlio César B. Moraes, Claudia G. Schainberg, Celio Roberto Gonçalves, Elaine P. Leon, Léonard De Vinci K. Kupa, Sandra G. Pasoto, Nádia E. Aikawa, Clovis A. Silva, Eloisa Bonfa, Carla G. S. Saad
Journal: Arthritis & Rheumatology (2024)

The aim of this study was to evaluate the influence of anti-infliximab (IFX) antibodies on three different points of care: response/tolerance to IFX, tapering strategy, and in a subsequent treatment with a second tumor necrosis factor inhibitor (TNFi).
Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study
Authors: Tomas O Jensen, Thomas A Murray, Greg A Grandits, Mamta K Jain, Birgit Grund, Kathryn Shaw-Saliba, Michael A Matthay, Mahsa Abassi, Magdalena Ardelt, Jason V Baker, Peter Chen, Robin L Dewar, Anna L Goodman, Timothy J Hatlen, Helene C Highbarger, Mark Holodniy, Perrine Lallemand, Sylvain Laverdure, Bradley G Leshnower, David Looney, Charalampos D Moschopoulos, Henry Mugerwa, Daniel D Murray, Eleftherios Mylonakis, Stephanie Nagy-Agren, M Tauseef Rehman, Adam Rupert, Randy Stevens, Stuart Turville, Amy Weintrob, Katherine Wick, Jens Lundgren, Emily R Ko
Journal: The Lancet Microbe (2024)
Current Advances and Material Innovations in the Search for Novel Treatments of Phenylketonuria
Authors: Philippe Delbreil, Sofie Dhondt, Rita Maria Kenaan El Rahbani, Xavier Banquy, John J. Mitchell, Davide Brambilla
Journal: Advanced Healthcare Materials (2024)

Phenylketonuria (PKU) is a genetically inherited disease caused by a mutation of the gene encoding phenylalanine hydroxylase (PAH) and is the most common inborn error of amino acid metabolism. A deficiency of PAH leads to increased blood and brain levels of phenylalanine (Phe), which may cause permanent neurocognitive symptoms and developmental delays if untreated. Current management strategies for PKU consist of early detection through neonatal screening and implementation of a restrictive diet with minimal amounts of natural protein in combination with Phe-free supplements and low-protein foods to meet nutritional requirements. For milder forms of PKU, oral treatment with synthetic sapropterin (BH4), the cofactor of PAH, may improve metabolic control of Phe and allow for more natural protein to be included in the patient's diet. For more severe forms, daily injections of pegvaliase, a PEGylated variant of phenylalanine ammonia-lyase (PAL), may allow for normalization of blood Phe levels. However, the latter treatment has considerable drawbacks, notably a strong immunogenicity of the exogenous enzyme and the attached polymeric chains. Research for novel therapies of PKU makes use of innovative materials for drug delivery and state-of-the-art protein engineering techniques to develop treatments which are safer, more effective, and potentially permanent.
Dextran‐Based Antibacterial Hydrogel Dressings for Accelerating Infected Wound Healing by Reducing Inflammation Levels
Authors: Jianhao Liang, Junhong Ling, Deguan Sun, Guanhuai Wu, Xiao‐kun Ouyang, Nan Wang, Guocai Yang
Journal: Advanced Healthcare Materials (2024)

Infected wounds pose challenges such as exudate management, bacterial infections, and persistent inflammation, making them a significant challenge for modern dressings. To address these issues in infected wounds more effectively, aerogel-hydrogel biphase gels based on dextran are developed. The gel introduced in this study exhibits antibacterial and anti-inflammatory properties in the process of wound therapy, contributing to accelerated wound healing. The aerogel phase exhibits exceptional water-absorption capabilities, rapidly soaking up exudate from infected wound, thereby fostering a clean and hygienic wound healing microenvironment. Concurrently, the aerogel phase is enriched with hydrogen sulfide donors. Following water absorption and the formation of the hydrogel phase, it enables the sustained release of hydrogen sulfide around the wound sites. The experiments confirm that hydrogen sulfide, by promoting M2 macrophage differentiation and reducing the levels of inflammatory factors, effectively diminishes local inflammation levels at the wound site. Furthermore, the sodium copper chlorophyllin component within the hydrogel phase demonstrates effective antibacterial properties through photodynamic antimicrobial therapy, providing a viable solution to wound infection challenges.
Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma
Authors: Bruno Almeida Costa, Jessica Flynn, Noriko Nishimura, Sean M. Devlin, Tasmin Farzana, Sridevi Rajeeve, David J. Chung, Heather J. Landau, Oscar B. Lahoud, Michael Scordo, Gunjan L. Shah, Hani Hassoun, Kylee Maclachlan, Malin Hultcrantz, Neha Korde, Alexander M. Lesokhin, Urvi A. Shah, Carlyn R. Tan, Sergio A. Giralt, Saad Z. Usmani, Karthik Nath, Sham Mailankody
Journal: Blood Cancer Journal (2024)

Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.
Perinatal thymic-derived CD8αβ-expressing γδ T cells are innate IFN-γ producers that expand in IL-7R–STAT5B-driven neoplasms
Authors: Nital Sumaria, Gina J. Fiala, Daniel Inácio, Marta Curado-Avelar, Ana Cachucho, Rúben Pinheiro, Robert Wiesheu, Shunsuke Kimura, Lucien Courtois, Birte Blankenhaus, Julie Darrigues, Tobias Suske, Afonso R. M. Almeida, Susana Minguet, Vahid Asnafi, Ludovic Lhermitte, Charles G. Mullighan, Seth B. Coffelt, Richard Moriggl, João T. Barata, Daniel J. Pennington, Bruno Silva-Santos
Journal: Nature Immunology (2024)

Abstract The contribution of γδ T cells to immune responses is associated with rapid secretion of interferon-γ (IFN-γ). Here, we show a perinatal thymic wave of innate IFN-γ-producing γδ T cells that express CD8αβ heterodimers and expand in preclinical models of infection and cancer. Optimal CD8αβ + γδ T cell development is directed by low T cell receptor signaling and through provision of interleukin (IL)-4 and IL-7. This population is pathologically relevant as overactive, or constitutive, IL-7R–STAT5B signaling promotes a supraphysiological accumulation of CD8αβ + γδ T cells in the thymus and peripheral lymphoid organs in two mouse models of T cell neoplasia. Likewise, CD8αβ + γδ T cells define a distinct subset of human T cell acute lymphoblastic leukemia pediatric patients. This work characterizes the normal and malignant development of CD8αβ + γδ T cells that are enriched in early life and contribute to innate IFN-γ responses to infection and cancer.
Variation in TaSPL6-D confers salinity tolerance in bread wheat by activating TaHKT1;5-D while preserving yield-related traits
Authors: Meng Wang, Jie Cheng, Jianhui Wu, Jiefei Chen, Dan Liu, Chenyang Wang, Shengwei Ma, Weiwei Guo, Guangjie Li, Dongwei Di, Yumei Zhang, Dejun Han, Herbert J. Kronzucker, Guangmin Xia, Weiming Shi
Journal: Nature Genetics (2024)
NG2 glia protect against prion neurotoxicity by inhibiting microglia-to-neuron prostaglandin E2 signaling
Authors: Yingjun Liu, Jingjing Guo, Maja Matoga, Marina Korotkova, Per-Johan Jakobsson, Adriano Aguzzi
Journal: Nature Neuroscience (2024)

Oligodendrocyte-lineage cells, including NG2 glia, undergo prominent changes in various neurodegenerative disorders. Here, we identify a neuroprotective role for NG2 glia against prion toxicity. NG2 glia were activated after prion infection in cerebellar organotypic cultured slices (COCS) and in brains of prion-inoculated mice. In both model systems, depletion of NG2 glia exacerbated prion-induced neurodegeneration and accelerated prion pathology. Loss of NG2 glia enhanced the biosynthesis of prostaglandin E2 (PGE2) by microglia, which augmented prion neurotoxicity through binding to the EP4 receptor. Pharmacological or genetic inhibition of PGE2 biosynthesis attenuated prion-induced neurodegeneration in COCS and mice, reduced the enhanced neurodegeneration in NG2-glia-depleted COCS after prion infection, and dampened the acceleration of prion disease in NG2-glia-depleted mice. These data unveil a non-cell-autonomous interaction between NG2 glia and microglia in prion disease and suggest that PGE2 signaling may represent an actionable target against prion diseases.
Genome folding principles uncovered in condensin-depleted mitotic chromosomes
Authors: Han Zhao, Yinzhi Lin, En Lin, Fuhai Liu, Lirong Shu, Dannan Jing, Baiyue Wang, Manzhu Wang, Fengnian Shan, Lin Zhang, Jessica C. Lam, Susannah C. Midla, Belinda M. Giardine, Cheryl A. Keller, Ross C. Hardison, Gerd A. Blobel, Haoyue Zhang
Journal: Nature Genetics (2024)
Phylogenomic and comparative genomic analyses support a single evolutionary origin of flatfish asymmetry
Authors: Emanuell Duarte-Ribeiro, Ulises Rosas-Puchuri, Matt Friedman, Gavin C. Woodruff, Lily C. Hughes, Kent E. Carpenter, William T. White, John J. Pogonoski, Mark Westneat, Juan Martin Diaz de Astarloa, Jeffrey T. Williams, Mudjekeewis D. Santos, Omar Domínguez-Domínguez, Guillermo Ortí, Dahiana Arcila, Ricardo Betancur-R
Journal: Nature Genetics (2024)
Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease
Authors: Yong Huang, Minghui Wang, Haofei Ni, Jinglong Zhang, Aiqun Li, Bin Hu, Chrystian Junqueira Alves, Shalaka Wahane, Mitzy Rios de Anda, Lap Ho, Yuhuan Li, Sangjo Kang, Ryan Neff, Ana Kostic, Joseph D. Buxbaum, John F. Crary, Kristen J. Brennand, Bin Zhang, Hongyan Zou, Roland H. Friedel
Journal: Nature Neuroscience (2024)
Deep history of cultural and linguistic evolution among Central African hunter-gatherers
Authors: Cecilia Padilla-Iglesias, Javier Blanco-Portillo, Bogdan Pricop, Alexander G. Ioannidis, Balthasar Bickel, Andrea Manica, Lucio Vinicius, Andrea Bamberg Migliano
Journal: Nature Human Behaviour (2024)

Human evolutionary history in Central Africa reflects a deep history of population connectivity. However, Central African hunter-gatherers (CAHGs) currently speak languages acquired from their neighbouring farmers. Hence it remains unclear which aspects of CAHG cultural diversity results from long-term evolution preceding agriculture and which reflect borrowing from farmers. On the basis of musical instruments, foraging tools, specialized vocabulary and genome-wide data from ten CAHG populations, we reveal evidence of large-scale cultural interconnectivity among CAHGs before and after the Bantu expansion. We also show that the distribution of hunter-gatherer musical instruments correlates with the oldest genomic segments in our sample predating farming. Music-related words are widely shared between western and eastern groups and likely precede the borrowing of Bantu languages. In contrast, subsistence tools are less frequently exchanged and may result from adaptation to local ecologies. We conclude that CAHG material culture and specialized lexicon reflect a long evolutionary history in Central Africa.
Evolutionary–developmental (evo-devo) dynamics of hominin brain size
Authors: Mauricio González-Forero
Journal: Nature Human Behaviour (2024)

Brain size tripled in the human lineage over four million years, but why this occurred remains uncertain. Here, to study what caused this brain expansion, I mathematically model the evolutionary and developmental (evo-devo) dynamics of hominin brain size. The model recovers (1) the evolution of brain and body sizes of seven hominin species starting from brain and body sizes of the australopithecine scale, (2) the evolution of the hominin brain-body allometry and (3) major patterns of human development and evolution. I show that the brain expansion recovered is not caused by direct selection for brain size but by its genetic correlation with developmentally late preovulatory ovarian follicles. This correlation is generated over development if individuals experience a challenging ecology and seemingly cumulative culture, among other conditions. These findings show that the evolution of exceptionally adaptive traits may not be primarily caused by selection for them but by developmental constraints that divert selection.
Human ventromedial prefrontal cortex is necessary for prosocial motivation
Authors: Patricia L. Lockwood, Jo Cutler, Daniel Drew, Ayat Abdurahman, Deva Sanjeeva Jeyaretna, Matthew A. J. Apps, Masud Husain, Sanjay G. Manohar
Journal: Nature Human Behaviour (2024)

Ventromedial prefrontal cortex (vmPFC) is vital for decision-making. Functional neuroimaging links vmPFC to processing rewards and effort, while parallel work suggests vmPFC involvement in prosocial behaviour. However, the necessity of vmPFC for these functions is unknown. Patients with rare focal vmPFC lesions (n = 25), patients with lesions elsewhere (n = 15) and healthy controls (n = 40) chose between rest and exerting effort to earn rewards for themselves or another person. vmPFC damage decreased prosociality across behavioural and computational measures. vmPFC patients earned less, discounted rewards by effort more, and exerted less force when another person benefited, compared to both control groups. Voxel-based lesion mapping revealed dissociations between vmPFC subregions. While medial damage led to antisocial behaviour, lateral damage increased prosocial behaviour relative to patients with damage elsewhere. vmPFC patients also showed reduced effort sensitivity overall, but reward sensitivity was limited to specific subregions. These results reveal multiple causal contributions of vmPFC to prosocial behaviour, effort and reward.