tbuckley/cabot-search huggingface dataset:
“Hot Tongue and Mouth” on 18F-FDG PET/CT Due to Buccolingual Masticatory Syndrome, Caused by Metoclopramide Antiemetic Treatment
Authors: Mads Ryø Jochumsen, Stine Maria Jentoft Kramer
Journal: Clinical Nuclear Medicine (2024)

Abstract We present a case of a 66-year-old man, where 18 F-FDG PET/CT revealed intense FDG uptake in the tongue, lips, cheeks, and chewing musculature and distinct activation of the somatosensory and motor cortex corresponding to the mouth and tongue. The patient suffered from buccolingual masticatory syndrome, characterized by tardive dyskinesia, meaning uncontrollable, repetitive movements of the tongue, lips, cheeks, and masticatory musculature. In this case, the buccolingual masticatory syndrome was caused by metoclopramide antiemetic treatment. “Hot tongue” was previously described on 18 F-FDG PET/CT in patients with tardive dyskinesia due to antipsychotic treatment, but the distinct activation of the lower facial motor cortex makes the present case stand out.
CD70: An Emerging Anticancer Target in Renal Cell Carcinoma and Beyond
Authors: Peter D. Zang, Arkhjamil Angeles, Sumanta K. Pal
Journal: Annual Review of Medicine (2024)

CD70 is an emerging target for anticancer therapies. It is an ideal antigen target given its limited expression in normal physiologic tissues and propensity to be aberrantly expressed in a variety of malignancies, thus limiting off-target toxicities. It is also heavily involved in immune homeostasis, and disruption of this pathway can help overcome tumor-related immune cell exhaustion. Recent phase I/II trials using cellular therapies targeting CD70, such as chimeric antigen receptor-T cells, have shown promising effectiveness and safety in treating relapsed or refractory renal cell carcinoma. Noncellular therapies targeting CD70, such as antibody-drug conjugates, monoclonal antibodies, radionuclides, and cytokines, are currently under investigation, with early data showing encouraging results as well. Efforts are already underway to further improve and optimize CD70-based therapies.
Remarkable evolutionary rate variations among lineages and among genome compartments in malaria parasites of mammals
Authors: Hend Abu-Elmakarem, Oscar A MacLean, Frank Venter, Lindsey J Plenderleith, Richard L Culleton, Beatrice H Hahn, Paul M Sharp
Journal: Molecular Biology and Evolution (2024)

Abstract Genes encoded within organelle genomes often evolve at rates different from those in the nuclear genome. Here, we analyzed the relative rates of nucleotide substitution in the mitochondrial, apicoplast, and nuclear genomes in four different lineages of Plasmodium species (malaria parasites) infecting mammals. The rates of substitution in the three genomes exhibit substantial variation among lineages, with the relative rates of nuclear and mitochondrial DNA being particularly divergent between the Laverania (including Plasmodium falciparum) and Vivax lineages (including Plasmodium vivax). Consideration of synonymous and nonsynonymous substitution rates suggests that their variation is largely due to changes in mutation rates, with constraints on amino acid replacements remaining more similar among lineages. Mitochondrial DNA mutation rate variations among lineages may reflect differences in the long-term average lengths of the sexual and asexual stages of the life cycle. These rate variations have far-reaching implications for the use of molecular clocks to date Plasmodium evolution.
State-level disparities in cervical cancer prevention and outcomes in the U.S.: a modeling study
Authors: Fernando Alarid-Escudero, Valeria Gracia, Marina Wolf, Ran Zhao, Caleb W Easterly, Jane J Kim, Karen Canfell, Inge M C M de Kok, Ruanne V Barnabas, Shalini Kulasingam
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Despite HPV vaccines’ availability for over a decade, coverage across the US varies. While some states have tried to increase HPV vaccination coverage, most model-based analyses focus on national impacts. We evaluated hypothetical changes in HPV vaccination coverage at the national and state levels for California, New York, and Texas using a mathematical model. Methods We developed a new mathematical model of HPV transmission and cervical cancer, creating US and state-level models, incorporating country- and state-specific vaccination coverage and cervical cancer incidence and mortality. We quantified the national and state-level impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 on cervical cancer outcomes and the time to elimination defined as &amp;lt; 4 per 100k women. Results Increasing vaccination coverage to 80% in Texas over ten years could reduce cervical cancer incidence by 50.9% (95% credible interval [CrI]: 46.6-56.1%) by 2100, from 1.58 (CrI : 1.19-2.09) to 0.78 (CrI : 0.57-1.02) per 100,000 women. Similarly, New York could see a 27.3% (CrI : 23.9-31.5%) reduction, from 1.43 (CrI : 0.93-2.07) to 1.04 (Crl : 0.66-1.53) per 100,000 women, and California a 24.4% (CrI : 20.0-30.0%) reduction, from 1.01 (Crl : 0.66-1.44) to 0.76 (Crl : 0.50-1.09) per 100,000 women. Achieving 80% coverage in five years will provide slightly larger and sooner reductions. If the vaccination coverage levels in 2019 continue, cervical cancer elimination could occur nationally by 2051 (Crl : 2034-2064), but state timelines may vary by decades. Conclusion Targeting an HPV vaccination coverage of 80% by 2030 will disproportionately benefit states with low coverage and higher cervical cancer incidence. Geographically focused analyses can better inform priorities.
Sixty seconds on . . . medicinal cannabis
Authors: Elisabeth Mahase
Journal: BMJ (2024)

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Association of Insulin Resistance With Radiographic Lung Abnormalities and Incident Lung Disease: The Framingham Offspring Study
Authors: Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A. Staggers, Meredith McCormack, Dennis T. Villareal, Ivan O. Rosas, Nicola A. Hanania, Tianshi David Wu
Journal: Diabetes Care (2024)

OBJECTIVE Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study. RESEARCH DESIGN AND METHODS Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident lung disease was determined by a study examiner. The relationship of HOMA-IR to these outcomes was estimated in models adjusted for demographics, BMI, and lifetime smoking. RESULTS A total of 875 participants with longitudinal IR data and outcomes were identified. Their mean age was 51.5 years, and BMI was 26.7 kg/m2. HOMA-IR was temporally unstable, with a within-person SD approximately two-thirds of the between-person SD. In adjusted models, a 1 SD increase in log(HOMA-IR) z score was associated with higher odds of qualitative emphysema (odds ratio [OR] 1.33; 95% CI 1.04–1.70), ILAs (OR 1.35; 95% CI 1.05–1.74), and modest increases in airway wall thickness and wall area percentage. These radiographic findings were corroborated by a positive association of HOMA-IR with incident lung disease. CONCLUSIONS IR is associated with radiographic lung abnormalities and incident lung disease. Deeper phenotyping is necessary to define mechanisms of IR-associated lung injury.
Inflammatory Waldenström Macroglobulinemia is associated with clonal hematopoiesis: a multicentric cohort
Authors: Pierre-Edouard Debureaux, Stéphanie Poulain, Stephanie Harel, Marie Passet, Marie Templé, Chloe Friedrich, Nathalie Forgeard, Dikelele Elessa, William Plas, Laureen Chat, Gregory Lazarian, Lise Willems, Bruno Royer, Alexis Talbot, Tristan Vaugeois, Floriane Theves, Alexandre Terré, Anne C. Brignier, Marion Malphettes, Daphné Krzisch, Laurent Frenzel, Frédéric Davi, Clotilde Bravetti, Florence Nguyen-Khac, Jehan Dupuis, Wendy Cuccuini, Didier Bouscary, Olivier Hermine, Damien Roos-Weil, Olivier Kosmider, Emmanuelle Clappier, Marion Espéli, Karl Balabanian, Bertrand Arnulf
Journal: Blood (2024)
Out-of-area mental health placements are harming patients, warns safety agency
Authors: Gareth Iacobucci
Journal: BMJ (2024)

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Outcome and management of patients with hepatocellular carcinoma who achieved complete response to immunotherapy-based systemic therapy
Authors: Bernhard Scheiner, Beodeul Kang, Lorenz Balcar, Iuliana-Pompilia Radu, Florian P. Reiter, Gordan Adžić, Jiang Guo, Xu Gao, Xiao Yuan, Long Cheng, Joao Gorgulho, Michael Schultheiss, Frederik Peeters, Florian Hucke, Najib Ben Khaled, Ignazio Piseddu, Alexander Philipp, Friedrich Sinner, Antonio D’Alessio, Katharina Pomej, Anna Saborowski, Melanie Bathon, Birgit Schwacha-Eipper, Valentina Zarka, Katharina Lampichler, Naoshi Nishida, Pei-Chang Lee, Anja Krall, Anwaar Saeed, Vera Himmelsbach, Giulia Tesini, Yi-Hsiang Huang, Caterina Vivaldi, Gianluca Masi, Arndt Vogel, Kornelius Schulze, Michael Trauner, Angela Djanani, Rudolf Stauber, Masatoshi Kudo, Neehar D. Parikh, Jean-François Dufour, Juraj Prejac, Andreas Geier, Bertram Bengsch, Johann von Felden, Marino Venerito, Arndt Weinmann, Markus Peck-Radosavljevic, Fabian Finkelmeier, Jeroen Dekervel, Fanpu Ji, Hung-Wei Wang, Lorenza Rimassa, David J. Pinato, Mohamed Bouattour, Hong Jae Chon, Matthias Pinter
Journal: Hepatology (2024)

Background and Aims: The outcome of patients with HCC who achieved complete response (CR) to immune-checkpoint inhibitor (ICI)–based systemic therapies is unclear. Approach and Results: Retrospective study of patients with HCC who had CR according to modified Response Evaluation Criteria in Solid Tumors (CR-mRECIST) to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3933 patients with HCC treated with ICI-based noncurative systemic therapies, 174 (4.4%) achieved CR-mRECIST, and 97 (2.5%) had CR according to RECISTv1.1 (CR-RECISTv1.1) as well. The mean age of the total cohort (male, 85%; Barcelona-Clinic Liver Cancer-C, 70%) was 65.9±9.8 years. The majority (83%) received ICI-based combination therapies. Median follow-up was 32.2 (95% CI: 29.9–34.4) months. One- and 3-year overall survival rates were 98% and 86%. One- and 3-year recurrence-free survival rates were excellent in patients with CR-mRECIST-only and CR-RECISTv1.1 (78% and 55%; 70% and 42%). Among patients who discontinued ICIs for reasons other than recurrence, those who received immunotherapy for ≥6 months after the first mRECIST CR had a longer recurrence-free survival than those who discontinued immunotherapy earlier ( p =0.008). Of 9 patients who underwent curative surgical conversion therapy, 8 (89%) had pathological CR (CR-RECISTv1.1, n= 2/2; CR-mRECIST-only, n= 6/7). Conclusions: Overall survival and recurrence-free survival of patients with CR-mRECIST-only and CR-RECISTv1.1 were excellent, and 6 of 7 patients with CR-mRECIST-only who underwent surgical conversion therapy had pathological CR. Despite potential limitations, these findings support the use of mRECIST in the context of immunotherapy for clinical decision-making. When considering ICI discontinuation, treatment for at least 6 months beyond CR seems advisable.
Plasma FSTL-1 as a non-invasive diagnostic biomarker for patients with advanced liver fibrosis
Authors: Wenzhu Li, Yongquan Chi, Xuan Xiao, Junda Li, Mingmin Sun, Shanke Sun, Wei Xu, Long Zhang, Xiaoguo Li, Feng Cheng, Xiaolong Qi, Jianhua Rao
Journal: Hepatology (2024)

Background and Aims: Reliable novel noninvasive biomarkers for the diagnosis of advanced liver fibrosis are urgently needed in clinical practice. We aimed to investigate the accuracy of plasma Follistatin-like protein 1 (FSTL-1) in the diagnosis of advanced liver fibrosis in chronic liver diseases. Approach and Results:﻿ We collected cross-sectional clinical data for a derivation cohort (n = 86) and a validation cohort (n = 431), totaling 517 subjects with liver biopsy. Advanced liver fibrosis was defined by the METAVIR pathological score (F ≥3). Dual cutoff values for diagnosis were explored. In the derivation cohort, plasma FSTL-1 levels were significantly elevated in patients with advanced liver fibrosis, with an AUROC of 0.85 (95% CI, 0.75–0.96). In the validation cohort, plasma FSTL-1 maintained good diagnostic performance, with an AUROC of 0.88 (95% CI, 0.83–0.92). Plasma FSTL-1 levels were significantly associated with individual histological features of the METAVIR scoring system, including interface hepatitis, lobular necrosis, and hepatocellular ballooning ( p &lt; 0.0001). A cutoff value ≤ 0.43 ng/mL was the optimal rule-out threshold, with a sensitivity of 84.62% (95% CI, 76.46%–90.30%) and a specificity of 79.51% (95% CI, 74.81%–83.53%), while ≥0.50 ng/mL was the best rule-in threshold, with a specificity of 86.41% (95% CI, 81.06%–90.43%) and a sensitivity of 70.67% (95% CI, 64.41%–76.23%). Conclusions: Plasma FSTL-1 has high diagnostic accuracy and could potentially reduce the need for liver biopsy in identifying patients with advanced liver fibrosis.
Salcaprozate-based ionic liquids for GLP-1 gastric delivery: A mechanistic understanding of in vivo performance
Authors: René Rebollo, Zhigao Niu, Lasse Blaabjerg, Damiano La Zara, Trine Juel, Henrik Duelund Pedersen, Vincent Andersson, Michaela Benova, Camilla Krogh, Raphaël Pons, Tobias Palle Holm, Per-Olof Wahlund, Li Fan, Zhuoran Wang, Adam Kennedy, Rune Ehrenreich Kuhre, Philip Christophersen, Pierre-Louis Bardonnet, Philip Jonas Sassene
Journal: Journal of Controlled Release (2024)
Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer
Authors: Shan Liu, Xingda Zhang, Wenzheng Wang, Xue Li, Xue Sun, Yuqian Zhao, Qi Wang, Yingpu Li, Fangjie Hu, He Ren
Journal: Molecular Cancer (2024)

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving metabolic resistance in both primary and metastatic breast cancer, and how the unique metabolic environments in metastatic sites further complicate treatment. By targeting distinct metabolic vulnerabilities at both the primary and metastatic stages, new strategies could improve the efficacy of existing therapies and provide better outcomes for breast cancer patients.
A data-driven framework for identifying patient subgroups on which an AI/machine learning model may underperform
Authors: Adarsh Subbaswamy, Berkman Sahiner, Nicholas Petrick, Vinay Pai, Roy Adams, Matthew C. Diamond, Suchi Saria
Journal: npj Digital Medicine (2024)

Abstract A fundamental goal of evaluating the performance of a clinical model is to ensure it performs well across a diverse intended patient population. A primary challenge is that the data used in model development and testing often consist of many overlapping, heterogeneous patient subgroups that may not be explicitly defined or labeled. While a model’s average performance on a dataset may be high, the model can have significantly lower performance for certain subgroups, which may be hard to detect. We describe an algorithmic framework for identifying subgroups with potential performance disparities (AFISP), which produces a set of interpretable phenotypes corresponding to subgroups for which the model’s performance may be relatively lower. This could allow model evaluators, including developers and users, to identify possible failure modes prior to wide-scale deployment. We illustrate the application of AFISP by applying it to a patient deterioration model to detect significant subgroup performance disparities, and show that AFISP is significantly more scalable than existing algorithmic approaches.
Utilizing Neurons to Interrogate Cancer: Integrative Analysis of Cancer Omics Data with Deep Learning Models
Authors: Raid Halawani, Michael Buchert, Yi-Ping Phoebe Chen
Journal: IEEE Reviews in Biomedical Engineering (2024)

Genomics plays an essential role in the early detection, classification, and targeted cancer therapy based on the analysis of precise alterations at the molecular level. Using the most reliable approach is essential for the exact interrogation and cross-examination of complex and multi-high-dimensional "Multi-omics" cancer genomics data. In recent years, deep learning has been successfully utilized to deal with large cancer genomics data and has the potential to transform predictive biology. This review aims to explore the recent advancements in the application of deep learning models in basic cancer omics research, including different methodologies for the interrogation of bulk cancer omics data and the importance of cross-platform data integration. The paper provides insights into advantages, limitations, potential for improvement, research gaps, future direction, and an in-depth comparison of the models currently used in the field of cancer genomics, highlighting the crucial need for collaboration and interdisciplinary research in the field.
Letter to the Editor: Refining the role of HAF in hepatocellular carcinoma
Authors: Jiashu Han, Dan Shan
Journal: Hepatology (2024)

1Department of General Surgery, Peking Union Medical College Hospital, Beijing, China 2Department of Biobehavioral Sciences, Columbia University, New York, NY 10027, USA Correspondence Dan Shan, Department of Biobehavioral Sciences, Columbia University, 525 West 120th Street, New York, NY 10027, USA. Email: [email protected]
Reply: Refining the role of HAF in hepatocellular carcinoma
Authors: Scott A. Summers, Mei Yee Koh
Journal: Hepatology (2024)

1Department of Nutrition & Integrative Physiology, University of Utah, Salt Lake City, UT 84103 2Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84103 Correspondence Mei Yee Koh, Department of Pharmacology and Toxicology, University of Utah, 30S 2000E, Salt Lake City, UT 84112. Email: [email protected]
Nicotinamide mononucleotide protects STAT1 from oxidative stress‐induced degradation to prevent colorectal tumorigenesis
Authors: Ting Li, Chengting Luo, Zongyuan Liu, Jinyu Li, Meng Han, Ran Zhang, Yuling Chen, Haiteng Deng
Journal: MedComm (2024)

Abstract Colitis, accompanied by the accumulation of reactive oxygen species (ROS) in the intestinal tract, is a risk factor for colorectal cancer (CRC). Our previous studies indicate that nicotinamide mononucleotide (NMN) replenishment reduces chronic inflammation. In this study, we confirm that NMN supplementation reduces inflammatory cytokine levels and oxidative tissue damage in an azoxymethane/dextran sulfate sodium (AOM/DSS)‐induced colitis‐associated cancer (CAC) model. Mice treated with NMN developed fewer colon tumors than untreated animals under the same AOM/DSS treatment conditions. Quantitative proteomic analysis revealed a decrease in signal transducer and activator of transcription 1 (STAT1) expression in the CAC model. We demonstrate that STAT1 overexpression induces G1 arrest by downregulating CDK6 expression and suppressing tumor cell proliferation and migration. Of note, H 2 O 2 induced trioxidation of the STAT1 protein and promoted its degradation, which was partially reversed by NMN supplementation. Upon H 2 O 2 treatment, Cys155 in STAT1 was oxidized to sulfonic acid, whereas the mutation of Cys155 to alanine abolished ROS‐mediated STAT1 degradation. These results indicate that oxidative stress induces STAT1 degradation in tumor cells and possibly in CAC tissues, whereas supplementation with NMN protects STAT1 from oxidation‐induced degradation and prevents tumorigenesis. This study provides experimental evidence for the development of NMN‐mediated chemoprevention strategies for CRC.
Vaccine and therapeutic agents against the respiratory syncytial virus: resolved and unresolved issue
Authors: Qianqian Li, Huan Li, Zhihua Li, Youchun Wang
Journal: MedComm (2024)

Abstract Respiratory syncytial virus (RSV) is a predominant pathogen responsible for respiratory tract infections among infants, the elderly, and immunocompromised individuals. In recent years, significant progress has been made in innovative vaccines and therapeutic agents targeting RSV. Nevertheless, numerous challenges and bottlenecks persist in the prevention and treatment of RSV infections. This review will provide an overview of the resolved and unresolved issues surrounding the development of vaccines and therapeutic agents against RSV. As of September 2024, three RSV vaccines against acute lower respiratory infections (ALRI) have been approved globally. Additionally, there have been notable progress in the realm of passive immunoprophylactic antibodies, with the monoclonal antibody nirsevimab receiving regulatory approval for the prevention of RSV infections in infants. Furthermore, a variety of RSV therapeutic agents are currently under clinical investigation, with the potential to yield breakthrough advancements in the foreseeable future. This review delineates the advancements and challenges faced in vaccines and therapeutic agents targeting RSV. It aims to provide insights that will guide the development of effective preventive and control measures for RSV.
Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design
Authors: Alberto Bossi, Stéphanie Foulon, Xavier Maldonado, Paul Sargos, Ray MacDermott, Paul Kelly, Aude Fléchon, Bertrand Tombal, Stephane Supiot, Dominik Berthold, Philippe Ronchin, Gabriel Kacso, Naji Salem, Fabio Calabro, Jean-François Berdah, Ali Hasbini, Marlon Silva, Jihane Boustani, Hélène Ribault, Karim Fizazi
Journal: The Lancet (2024)