tbuckley/cabot-search huggingface dataset:
Reversing cancer immunoediting phases with a tumor-activated and optically reinforced immunoscaffold
Authors: Xinchao Li, Xiuqi Liang, Wangxian Fu, Rui Luo, Miaomiao Zhang, Xiaorong Kou, Yi Zhang, Yingjie Li, Dongxue Huang, Yanjie You, Qinjie Wu, Changyang Gong
Journal: Bioactive Materials (2024)

vaccine (ISV) is a promising immunotherapeutic tactic due to its complete tumoral antigenic repertoire. However, its efficiency is limited by extrinsic inevitable immunosuppression and intrinsic immunogenicity scarcity. To break this plight, a tumor-activated and optically reinforced immunoscaffold (TURN) is exploited to trigger cancer immunoediting phases regression, thus levering potent systemic antitumor immune responses. Upon response to tumoral reactive oxygen species, TURN will first release RGX-104 to attenuate excessive immunosuppressive cells and cytokines, and thus immunosuppression falls and immunogenicity rises. Subsequently, intermittent laser irradiation-activated photothermal agents (PL) trigger abundant tumor antigens exposure, which causes immunogenicity springs and preliminary infiltration of T cells. Finally, CD137 agonists from TURN further promotes the proliferation, function, and survival of T cells for durable antitumor effects. Therefore, cancer immunoediting phases reverse and systemic antitumor immune responses occur. TURN achieves over 90 % tumor growth inhibition in both primary and secondary tumor lesions, induces potent systemic immune responses, and triggers superior long-term immune memory
ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection
Authors: Clara Bredow, Fabien Thery, Eva Katrin Wirth, Sarah Ochs, Meike Kespohl, Gunnar Kleinau, Nicolas Kelm, Niclas Gimber, Jan Schmoranzer, Martin Voss, Karin Klingel, Joachim Spranger, Kostja Renko, Markus Ralser, Michael Mülleder, Arnd Heuser, Klaus-Peter Knobeloch, Patrick Scheerer, Jennifer Kirwan, Ulrike Brüning, Nikolaus Berndt, Francis Impens, Antje Beling
Journal: Cardiovascular Research (2024)

Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signalling, cardiomyocytes counteract infection by various effector processes, with the IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification with ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular aspects how the ISG15 system affects the functional properties of respective protein substrates in the heart are unknown.
Adaptive Capacity of a DNA Polymerase Clamp-loader ATPase Complex
Authors: Subu Subramanian, Weilin Zhang, Siddharth Nimkar, Mazzin Kamel, Michael O’Donnell, John Kuriyan
Journal: Molecular Biology and Evolution (2024)

The ability of mutations to facilitate adaptation is central to evolution. To understand how mutations can lead to functional adaptation in a complex molecular machine, we created a defective version of the T4 clamp-loader complex, which is essential for DNA replication. This variant, which is ∼5,000-fold less active than the wild type, was made by replacing the catalytic domains with those from another phage. A directed-evolution experiment revealed that multiple substitutions to a single negatively charged residue in the chimeric clamp loader-Asp 86-restore fitness to within ∼20-fold of wild type. These mutations remove an adventitious electrostatic repulsive interaction between Asp 86 and the sliding clamp. Thus, the fitness decrease of the chimeric clamp loader is caused by a reduction in affinity between the clamp loader and the clamp. Deep mutagenesis shows that the reduced fitness of the chimeric clamp loader is also compensated for by lysine and arginine substitutions of several DNA-proximal residues in the clamp loader or the sliding clamp. Our results demonstrate that there is a latent capacity for increasing the affinity of the clamp loader for DNA and the sliding clamp, such that even single-point mutations can readily compensate for the loss of function due to suboptimal interactions elsewhere.
Maximizing scarce colonoscopy resources: the crucial role of stool-based tests
Authors: Gloria D Coronado, Leslie Bienen, Andrea Burnett-Hartman, Jeffrey K Lee, Carolyn M Rutter
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract During the COVID-19 pandemic, health systems, including federally qualified health centers, experienced disruptions in colorectal cancer (CRC) screening. National organizations called for greater use of at-home stool-based testing followed by colonoscopy for those with abnormal test results to limit (in-person) colonoscopy exams to people with acute symptoms or who were high risk. This stool-test-first strategy may also be useful for adults with low-risk adenomas who are due for surveillance colonoscopy. We argue that colonoscopy is overused as a first-line screening method in low- and average-risk adults and as a surveillance tool among adults with small adenomas. Yet, simultaneously, many people do not receive much-needed colonoscopies. Delivering the right screening tests at intervals that reduce the risk of CRC, while minimizing patient inconvenience and procedural risks, can strengthen health-care systems. Risk stratification could improve efficiency of CRC screening, but because models that adequately predict risk are years away from clinical use, we need to optimize use of currently available technology—that is, low-cost fecal testing followed by colonoscopy for those with abnormal test results. The COVID-19 pandemic highlighted the urgent need to adapt to resource constraints around colonoscopies and showed that increased use of stool-based testing was possible. Learning how to adapt to such constraints without sacrificing patients’ health, particularly for patients who receive care at federally qualified health centers, should be a priority for CRC prevention research.
CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression
Authors: Wen Wang, Qian Wang, Shiying Sun, Pengfei Zhang, Yuyu Li, Weimin Lin, Qiwen Li, Xiao Zhang, Zhe Ma, Haiyan Lu
Journal: International Journal of Oral Science (2024)

Abstract Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing. However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation; while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion, our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.
Effect of surgery versus chemotherapy in pancreatic cancer patients: a target trial emulation
Authors: Jakob Kirkegård, Charles Gaber, Uffe Heide-Jørgensen, Claus Wilki Fristrup, Jennifer L Lund, Deirdre Cronin-Fenton, Frank Viborg Mortensen
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background To estimate the causal effect of surgery vs chemotherapy on survival in patients with T1-3NxM0 pancreatic cancer in a rigorous framework addressing selection bias and immortal time bias. Methods We used population-based Danish health-care registries to conduct a cohort study emulating a hypothetical randomized trial to estimate the absolute difference in survival, comparing surgery with chemotherapy. We included pancreatic cancer patients diagnosed during 2008-2021. Exposure was surgery or chemotherapy initiated within a 16-week grace period after diagnosis. At the time of diagnosis, data of each patient were duplicated; one copy was assigned to the surgery protocol, and one copy to the chemotherapy protocol of the hypothetical trial. Copies were censored when the assigned treatment deviated from the observed treatment. To account for informative censoring, uncensored patients were weighted according to confounders. For comparison, we also applied a more conventional analysis using propensity score-based inverse probability weighting. Results We included 1744 patients with a median age of 68 years: 73.6% underwent surgery, and 18.6% had chemotherapy without surgery; 7.8% received no treatment. The 3-year survival was 39.7% (95% confidence interval [CI] = 36.7% to 42.6%) after surgery and 22.7% (95% CI = 17.7% to 28.4%) after chemotherapy, corresponding to an absolute difference of 17.0% (95% CI = 10.8% to 23.1%). In the conventional survival analysis, this difference was 23.0% (95% CI = 17.0% to 29.0%). Conclusion Surgery was superior to chemotherapy in achieving long-term survival for pancreatic cancer. The difference comparing surgery and chemotherapy was substantially smaller when using the clone-censor-weight approach than conventional survival analysis.
Comparison of the Antibacterial Activity of Selected Deep Eutectic Solvents (DESs) and Deep Eutectic Solvents Comprising Organic Acids (OA‐DESs) Toward Gram‐Positive and Gram‐Negative Species
Authors: Tomasz Swebocki, Aleksandra M. Kocot, Alexandre Barras, Helena Arellano, Leila Bonnaud, Kamel Haddadi, Anne‐Laure Fameau, Sabine Szunerits, Magdalena Plotka, Rabah Boukherroub
Journal: Advanced Healthcare Materials (2024)

Abstract Deep eutectic solvents (DESs) have been intensively investigated in recent years for their antibacterial properties, with DESs that comprise organic acids (OA‐DESs) showing promising antibacterial action. However a majority of the reports focused only on a limited number strains and techniques, which is not enough to determine the antibacterial potential of a substance. To bridge this gap, the antibacterial activity of classical DESs and OA‐DESs is assessed on twelve Gram‐negative and Gram‐positive bacteria strains, with some of them exhibiting specific resistance toward antibiotics. The investigated formulations of OA‐DESs comprise glycolic, malic, malonic, and oxalic acids as representatives of this group. Using a range of microbiological assays as well as physicochemical characterization methods, a major difference of the effectiveness between the two groups is demonstrated, with OA‐DESs exhibiting, as expected, greater antibacterial effectiveness than classical DESs. Most interestingly, slight differences in the minimum inhibitory and bactericidal concentration values as well as time‐kill kinetics profiles are observed between Gram‐positive and Gram‐negative strains. Transmission electron microscopy analysis reveals the effect of the treatment of the bacteria with the representatives of both groups of DESs, which allows us to better understand the possible mechanism‐of‐action of these novel materials.
The International Association for the Study of Lung Cancer Staging Project for Lung Cancer: Proposals for the Revision of the M Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer
Authors: Kwun M. Fong, Adam Rosenthal, Dorothy J. Giroux, Katherine K. Nishimura, Jeremy Erasmus, Yolande Lievens, Mirella Marino, Edith M. Marom, Paul Martin Putora, Navneet Singh, Francisco Suárez, Ramon Rami-Porta, Frank Detterbeck, Wilfried E.E. Eberhardt, Hisao Asamura
Journal: Journal of Thoracic Oncology (2024)
Biomarkers for Personalizing IBD Therapy: The Quest Continues
Authors: Raja Atreya, Markus F. Neurath
Journal: Clinical Gastroenterology and Hepatology (2024)

Despite recent advances in the understanding of the pathogenesis of inflammatory bowel diseases (IBD) and advent of multiple targeted therapies, approximately one-third of patients are primary non-responders to initiated treatment, and half of patients lose response over time. There is currently a lack of available biomarkers that would prognosticate therapeutic effectiveness of these advanced therapies. This is partly explained by insufficient characterization of the functional roles assumed by the chosen molecular targets during disease treatment. There is a dire need for validated objective biomarkers, which could be indicators of a biological process, that can be applied in clinical practice to assist us in assigning therapies to patients with the highest probability of response. An appropriate molecular and cellular characterization that accounts for the interindividual differences in drug efficacy and potential side effects would help to guide clinicians in the management of patients with IBD and represent a major step to tailor a more personalized approach to treatment. An appropriate combination of complementing biomarkers should ideally incorporate a multimodal analysis in which genetic, microbial, transcriptional, proteomic, metabolic, and immunologic data are combined to enable a truly personalized approach. This would classify patients into disease subgroups according to molecular characteristics, which would enable us to initiate the most appropriate therapeutic substance. Emergence of single-cell technologies to map the intestinal cellular landscape and multiomic approaches have helped to further dissect the pathogenic mechanisms of mucosal inflammation, but the clinical translation of potential biomarkers remains cumbersome, and an ongoing concerted effort by the IBD community is required.
HCCDB v2.0: Decompose Expression Variations by Single-cell RNA-seq and Spatial Transcriptomics in HCC
Authors: Ziming Jiang, Yanhong Wu, Yuxin Miao, Kaige Deng, Fan Yang, Shuhuan Xu, Yupeng Wang, Renke You, Lei Zhang, Yuhan Fan, Wenbo Guo, Qiuyu Lian, Lei Chen, Xuegong Zhang, Yongchang Zheng, Jin Gu
Journal: Genomics Proteomics & Bioinformatics (2024)

Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma (HCC). Integrated 15 transcriptomic datasets of HCC clinical samples, the first version of HCC database (HCCDB v1.0) was released in 2018. Through the meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets, it provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and robustness. With four years having passed, the database now needs integration of recently published datasets. Furthermore, the latest single-cell and spatial transcriptomics have provided a great opportunity to decipher complex gene expression variations at the cellular level with spatial architecture. Here, we present HCCDB v2.0, an updated version that combines bulk, single-cell, and spatial transcriptomic data of HCC clinical samples. It dramatically expands the bulk sample size by adding 1656 new samples from 11 datasets to the existing 3917 samples, thereby enhancing the reliability of transcriptomic meta-analysis. A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections, respectively. A novel single-cell level and 2-dimension (sc-2D) metric is proposed as well to summarize cell type-specific and dysregulated gene expression patterns. Results are all graphically visualized in our online portal, allowing users to easily retrieve data through a user-friendly interface and navigate between different views. With extensive clinical phenotypes and transcriptomic data in the database, we show two applications for identifying prognosis-associated cells and tumor microenvironment. HCCDB v2.0 is available at http://lifeome.net/database/hccdb2.
NeoTCR: an immunoinformatic database of experimentally-supported functional neoantigen-specific TCR sequences
Authors: Weijun Zhou, Wenting Xiang, Jinyi Yu, Zhihan Ruan, Yichen Pan, Kankan Wang, Jian Liu
Journal: Genomics Proteomics & Bioinformatics (2024)

Neoantigen-based immunotherapy has demonstrated long-lasting antitumor activity. The recognition of neoantigens by T cell receptors (TCRs) is considered a trigger for antitumor responses. Due to the overwhelming number of TCR repertoires in the human genome, pinpointing neoantigen-specific TCRs is a formidable challenge. Recent studies have identified a number of functional neoantigen-specific TCRs, but the corresponding information is scattered across published literature and is difficult to retrieve. To improve access to these data, we developed an immunoinformatic database (NeoTCR) containing a unified description of publicly available neoantigen-specific TCR sequences, as well as relevant information on targeted neoantigens, from experimentally supported studies across 18 cancer subtypes. A user-friendly web interface allows interactive browsing and running of complex database queries. To facilitate rapid identification of neoantigen-specific TCRs from raw sequencing data, NeoTCR offers a one-stop analysis for annotation and visualization of TCR clonotypes, discovery of existing neoantigen-specific TCRs, and exclusion of bystander viral-associated TCRs. NeoTCR represents a unique tool to expedite future studies of neoantigen-specific TCRs and the development of neoantigen-based immunotherapy. NeoTCR is available at http://neotcrdb.bioaimed.com/ and https://github.com/lyotvincent/NeoTCR.
Fibroblast growth factor receptor 1 inhibition suppresses pancreatic cancer chemoresistance and chemotherapy-driven aggressiveness
Authors: Qingxiang Lin, Andrea Serratore, Jin Niu, Shichen Shen, Tista Roy Chaudhuri, Wen Wee Ma, Jun Qu, Eugene S. Kandel, Robert M. Straubinger
Journal: Drug Resistance Updates (2024)
Controlled human infection study underpins efficacy of the tetravalent live-attenuated dengue vaccine TV005
Authors: Annelies Wilder-Smith
Journal: Journal of Clinical Investigation (2024)

Dengue fever, caused by four distinct serotypes of the dengue virus (DENV1–4), poses a public health concern for much of the world. The NIH's Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) has developed a series of single-dose, live-attenuated tetravalent DENV vaccines, including TV005. However, phase III trials require a lengthy three-to-five year follow-up. In contrast, controlled human infection models (CHIMs) offer a faster means to assess vaccine efficacy for any of the four serotypes. In this issue of the JCI, Pierce, Durbin, and colleagues conducted a CHIM study with attenuated DENV2 and DENV3 challenge viruses in individuals six months after vaccination with TV005. The TV005 vaccine was well tolerated and effectively protected all vaccinated individuals from viremia and rash during challenges with DENV2 or DENV3. Notably, vaccine recipients also showed serotype-specific efficacy. While long-term studies are still needed, these findings represent an important step in providing protection against dengue virus.
Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial
Authors: Yuanyuan Wang, Rong Li, Rui Yang, Danni Zheng, Lin Zeng, Ying Lian, Yimin Zhu, Junli Zhao, Xiaoyan Liang, Wen Li, Jianqiao Liu, Li Tang, Yunxia Cao, Guimin Hao, Huichun Wang, Hua Zhang, Rui Wang, Ben W Mol, Hefeng Huang, Jie Qiao
Journal: The Lancet (2024)
Performance of models for predicting 1-year to 3-year mortality in older adults: a systematic review of externally validated models
Authors: Leonard Ho, Carys Pugh, Sohan Seth, Stella Arakelyan, Nazir I Lone, Marcus J Lyall, Atul Anand, Jacques D Fleuriot, Paola Galdi, Bruce Guthrie
Journal: The Lancet Healthy Longevity (2024)

Mortality prediction models support identifying older adults with short life expectancy for whom clinical care might need modifications. We systematically reviewed external validations of mortality prediction models in older adults (ie, aged 65 years and older) with up to 3 years of follow-up. In March, 2023, we conducted a literature search resulting in 36 studies reporting 74 validations of 64 unique models. Model applicability was fair but validation risk of bias was mostly high, with 50 (68%) of 74 validations not reporting calibration. Morbidities (most commonly cardiovascular diseases) were used as predictors by 45 (70%) of 64 of models. For 1-year prediction, 31 (67%) of 46 models had acceptable discrimination, but only one had excellent performance. Models with more than 20 predictors were more likely to have acceptable discrimination (risk ratio [RR] vs <10 predictors 1·68, 95% CI 1·06–2·66), as were models including sex (RR 1·75, 95% CI 1·12–2·73) or predicting risk during comprehensive geriatric assessment (RR 1·86, 95% CI 1·12–3·07). Development and validation of better-performing mortality prediction models in older people are needed.
Randomized Trial of Effect of Bariatric Surgery on Blood Pressure After 5 Years
Authors: Carlos A. Schiavon, Alexandre B. Cavalcanti, Juliana D. Oliveira, Rachel H.V. Machado, Eliana V. Santucci, Renato N. Santos, Julia S. Oliveira, Lucas P. Damiani, Débora Junqueira, Helio Halpern, Frederico de L.J. Monteiro, Patricia M. Noujaim, Ricardo V. Cohen, Marcio G. de Sousa, Luiz A. Bortolotto, Otavio Berwanger, Luciano F. Drager
Journal: Journal of the American College of Cardiology (2024)
Suicide Attempts After a Diagnosis of Polycystic Ovary Syndrome
Authors: Tien-Wei Hsu, Yu-Chen Kao, Shih-Jen Tsai, Ya-Mei Bai, Tung-Ping Su, Tzeng-Ji Chen, Chih-Sung Liang, Mu-Hong Chen
Journal: Annals of Internal Medicine (2024)

Limited evidence exists about suicide risk in persons with polycystic ovary syndrome (PCOS).