tbuckley/cabot-search huggingface dataset:
Peptide-based PET tracer targeting LAG-3 for evaluating the efficacy of immunotherapy in melanoma
Authors: Peizhe Yuan, Yu Long, Nannan Wei, Yan Wang, Ziyang Zhu, Jinquan Han, Dawei Jiang, Xiaoli Lan, Yongkang Gai
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Lymphocyte activation gene 3 (LAG-3) is expressed on activated immune cells and has emerged as a promising target for immune checkpoints blockade. However, conflicting findings have been reported regarding the association between LAG-3 expression in tumors and patient prognosis, indicating the need for further investigation into the significance of LAG-3 expression levels in tumor therapies. In this study, 68 Ga-NOTA-XH05, a novel peptide-based positron emission tomography (PET) tracer targeting LAG-3, was constructed to non-invasively detect LAG-3 expression in melanoma after CpG oligonucleotide (CpG) treatment and explore the relationship between LAG-3 expression and therapeutic effect. Methods The tracer 68 Ga-NOTA-XH05 was identified by high-performance liquid chromatography after being prepared and purified. Cell uptake and blocking essays were performed to verify the specificity of the tracer in vitro. The expression of LAG-3 in B16-F10 subcutaneous tumors was monitored by flow cytometry, and its correlation with the tracer uptake was analyzed to evaluate the tracer specificity. PET imaging and biodistribution studies were conducted after CpG treatment of unilateral or bilateral B16-F10 subcutaneous tumor models to assess the ability of 68 Ga-NOTA-XH05 in monitoring immunotherapy efficacy and the abscopal effect of CpG. Results Following purification, 68 Ga-NOTA-XH05 exhibited high radiochemical purity and specificity. Flow cytometry analysis revealed a positive correlation between LAG-3 expression in tumors and the uptake of 68 Ga-NOTA-XH05. In B16-F10 bearing mice treated with CpG, PET imaging using 68 Ga-NOTA-XH05 demonstrated a higher tumor to blood ratio (TBR) compared with the control group. Furthermore, TBR values obtained from CpG-treated mice allowed for differentiation between responders and non-responders. In a bilateral subcutaneous tumor model where only right-sided tumors were treated with intratumoral injection of CpG, TBR values of left-sided tumors were significantly higher than those in the control group, indicating that 68 Ga-NOTA-XH05 could effectively monitor the systemic effect of local CpG injection. Conclusion Our findings highlight the detection capability of 68 Ga-NOTA-XH05 in assessing LAG-3 expression levels within tumors and evaluating response to immunotherapy, thereby suggesting promising clinical translational prospects.
A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/angiogenesis and recruitment
Authors: Shiyuan Yang, Yan Zhu, Chunxiao Ji, Huimin Zhu, An Lao, Ran Zhao, Yue Hu, Yuning Zhou, Jia Zhou, Kaili Lin, Yuanjin Xu
Journal: Bioactive Materials (2024)

Periodontitis is a chronic inflammatory disease caused by plaque that destroys the alveolar bone tissues, resulting in tooth loss. Poor eradication of pathogenic microorganisms, persistent malignant inflammation and impaired osteo-/angiogenesis are currently the primary challenges to control disease progression and rebuild damaged alveolar bone. However, existing treatments for periodontitis fail to comprehensively address these issues. Herein, an injectable composite hydrogel (SFD/CS/ZIF-8@QCT) encapsulating quercetin-modified zeolitic imidazolate framework-8 (ZIF-8@QCT) is developed. This hydrogel possesses thermo-sensitive and adhesive properties, which can provide excellent flowability and post-injection stability, resist oral fluid washout as well as achieve effective tissue adhesion. Inspirationally, it is observed that SFD/CS/ZIF-8@QCT exhibits a rapid localized hemostatic effect following implantation, and then by virtue of the sustained release of zinc ions and quercetin exerts excellent collective functions including antibacterial, immunomodulation, pro-osteo-/angiogenesis and pro-recruitment, ultimately facilitating excellent alveolar bone regeneration. Notably, our study also demonstrates that the inhibition of osteo-/angiogenesis of PDLSCs under the periodontitis is due to the strong inhibition of energy metabolism as well as the powerful activation of oxidative stress and autophagy, whereas the synergistic effects of quercetin and zinc ions released by SFD/CS/ZIF-8@QCT are effective in reversing these biological processes. Overall, our study presents innovative insights into the advancement of biomaterials to regenerate alveolar bone in periodontitis.
Podocyte density as a predictor of long-term kidney outcome in obesity-related glomerulopathy
Authors: Kotaro Haruhara, Yusuke Okabayashi, Takaya Sasaki, Eisuke Kubo, Vivette D. D'Agati, John F. Bertram, Nobuo Tsuboi, Takashi Yokoo
Journal: Kidney International (2024)

Glomerulomegaly and focal segmental glomerulosclerosis are histopathological hallmarks of obesity-related glomerulopathy (ORG). Podocyte injury and subsequent depletion are regarded as key processes in the development of these glomerular lesions in patients with ORG, but their impact on long-term kidney outcome is undetermined. Here, we correlated clinicopathological findings and podocyte depletion retrospectively in patients with ORG. Relative (podocyte density) and absolute (podocyte number per glomerulus) measures of podocyte depletion were estimated using model-based stereology in 46 patients with ORG. The combined endpoint of kidney outcomes was defined as a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure. Patients with lower podocyte density were predominantly male and had larger body surface area, greater proteinuria, fewer non-sclerotic glomeruli, larger glomeruli and higher single-nephron eGFR. During a median follow-up of 4.1 years, 18 (39%) patients reached endpoint. Kidney survival in patients with lower podocyte density was significantly worse than in patients with higher podocyte density. However, there was no difference in kidney survival between patient groups based on podocyte number per glomerulus. Cox hazard analysis showed that podocyte density, but not podocyte number per glomerulus, was associated with the kidney outcomes after adjustment for clinicopathological confounders. Thus, our study demonstrates that a relative depletion of podocytes better predicts long-term kidney outcomes than does absolute depletion of podocytes. Hence, the findings implicate mismatch between glomerular enlargement and podocyte number as a crucial determinant of disease progression in ORG.
Metastatic hormone-naïve prostate cancer: a distinct biological entity
Authors: Jon Corres-Mendizabal, Francesca Zacchi, Natalia Martín-Martín, Joaquin Mateo, Arkaitz Carracedo
Journal: Trends in cancer (2024)

Metastatic hormone-naïve prostate cancer (mHNPC) is often the initial form of presentation for metastatic prostate cancer and encompasses a heterogeneous patient population with high inter-patient heterogeneity in prognosis and response to therapy. A more precise treatment of mHNPC, guided by evidence-based biomarkers, remains an unmet medical need. In addition, the limited number of representative laboratory models of mHNPC hampers the translation of basic research into clinical applications. We provide a comprehensive overview of the clinical and biological features that characterize mHNPC, highlight molecular data that could explain the unique prognostic characteristics of mHNPC, and identify key open questions.
A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK–Irish A-STAR register
Authors: Helen Alexander, Rayka Malek, David Prieto-Merino, Elizaveta Gribaleva, Manisha Baden, Paula Beattie, Sara Brown, Tim Burton, Shona Cameron, Bola Coker, Michael J Cork, Ross Hearn, John R Ingram, Alan D Irvine, Graham A Johnston, Alice Lambert, Mark Lunt, Irene Man, Louise Newell, Graham Ogg, Prakash Patel, Mandy Wan, Richard B Warren, Richard Woolf, Zenas Z N Yiu, Nick Reynolds, Michael R Ardern-Jones, Carsten Flohr
Journal: British Journal of Dermatology (2024)

The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA.
Impact of racial disparities in follow-up and quality of colonoscopy on colorectal cancer outcomes
Authors: Oguzhan Alagoz, Folasade P May, Chyke A Doubeni, A Mark Fendrick, Vahab Vahdat, Chris Estes, Travelle Ellis, Paul J Limburg, Durado Brooks
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The benefits of colorectal cancer (CRC) screening programs rely on completing follow-up colonoscopy when a noncolonoscopy test is abnormal and on quality of colonoscopy screening as measured by the endoscopists’ adenoma detection rate. Existing data demonstrate substantially lower follow-up colonoscopy rates and adenoma detection rate for Black Americans than White Americans. However, the contributions of racial differences in follow-up colonoscopy and adenoma detection rate on CRC outcomes have not been rigorously evaluated. Methods We used established and validated CRC-Adenoma Incidence and Mortality (CRC-AIM) model as our analysis platform, with inputs from published literature that report lower follow-up colonoscopy rates and adenoma detection rate in Black adults compared with White adults (15% and 10% lower, respectively). We simulated screening with annual fecal immunochemical test, triennial multitarget stool DNA, and colonoscopy every 10 years between ages 45 and 75 years using real-world utilization of the screening modalities vs no screening. We reported lifetime outcomes per 1000 Black adults. Results Elimination of Black-White disparities in follow-up colonoscopy rates would reduce CRC incidence and mortality by 5.2% and 9.3%, respectively, and improve life-years gained with screening by 3.4%. Elimination of Black-White disparities in endoscopists’ adenoma detection rate would reduce CRC incidence and mortality by 9.4% and improve life-years gained by 3.7%. Elimination of both disparities would reduce CRC incidence and mortality by 14.6% and 18.7%, respectively, and improve life-years gained by 7.1%. Conclusions This modeling study predicts eliminating racial differences in follow-up colonoscopy rates, and quality of screening colonoscopy would substantially reduce Black-White disparities in CRC incidence and mortality.
Paris air quality monitoring for the 2024 Olympics and Paralympics: focus on air pollutants and pollen
Authors: Valerie Bougault, Richard Valorso, Roland Sarda-Esteve, Dominique Baisnee, Nicolas Visez, Gilles Oliver, Jordan Bureau, Fatine Abdoussi, Veronique Ghersi, Gilles Foret
Journal: British Journal of Sports Medicine (2024)

Background Exposure to air pollution can affect the health of individuals with respiratory disease, but may also impede the health and performance of athletes. This is potentially relevant for people travelling to and competing in the Olympic and Paralympic Games (OPG) in Paris. We describe anticipated air quality in Paris based on historical monitoring data and describe the impact of the process on the development of monitoring strategies for future international sporting events. Methods Air pollutant data for July to September 2020–2023 and pollen data for 2015–2022 were provided by Airparif (particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ) and ozone (O 3 )) and RNSA stations in the Paris region. Airparif’s street-level numerical modelling provided spatial data for the OPG venues. Results The maximum daily mean PM 2.5 was 11±6 µg/m 3 at traffic stations, below the WHO recommended daily air quality threshold (AQT). Daily NO 2 concentrations ranged from 5±3 µg/m 3 in rural areas to 17±14 µgm 3 in urban areas. Near traffic stations, this rose to 40±24 µg/m 3 exceeding the WHO AQT. Both peaked around 06:00 and 20:00 UTC (coordinated universal time). The ambient O 3 level exceeded the AQT on 20 days per month and peaked at 14:00 UTC. The main allergenic taxa from June to September was Poaceae (ie, grass pollen variety). Conclusion Air pollutant levels are expected to be within accepted air quality thresholds at the Paris OPG. However, O 3 concentrations may be significantly raised in very hot and clear conditions and grass pollen levels will be high, prompting a need to consider and manage this risk in susceptible individuals.
Non-invasive mapping of brown adipose tissue activity with magnetic resonance imaging
Authors: Zimeng Cai, Qiaoling Zhong, Yanqiu Feng, Qian Wang, Zuoman Zhang, Cailv Wei, Zhinan Yin, Changhong Liang, Chong Wee Liew, Lawrence Kazak, Aaron M. Cypess, Zaiyi Liu, Kejia Cai
Journal: Nature Metabolism (2024)

Thermogenic brown adipose tissue (BAT) has a positive impact on whole-body metabolism. However, in vivo mapping of BAT activity typically relies on techniques involving ionizing radiation, such as [
Effect of Transcutaneous Electrical Nerve Stimulation Based on Wrist-Ankle Acupuncture Theory for Pain Relief during Non-Anesthetic Colonoscopy: A Randomized Controlled Trial
Authors: fanfu fang, Xiaonan Huang, Hao Wang, Lei Shi, Li-Fan Xu, Can Lv, Wen-Juan Song, Le-Le Huang, Fei-Hu Yan, Ping Shi, Meng-Cheng Cai
Journal: Endoscopy (2024)

Colonoscopy is essential for diagnosing colorectal diseases but can cause pain during the procedure. This study explored the analgesic effects of transcutaneous electrical nerve stimulation based on wrist-ankle acupuncture theory (TENS-WAA) in colonoscopy without anesthesia.
Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications
Authors: Tomoko Akaike, Manisha Thakuria, Ann W. Silk, Daniel S. Hippe, Song Youn Park, Naomi A. So, Nolan J. Maloney, Lindsay Gunnell, Alec Eschholz, Emily Y. Kim, Sumi Sinha, Evan Thomas Hall, Shailender Bhatia, Sunil Reddy, Angel Augusto Rodriguez, Alexey Aleshin, Jacob S. Choi, Kenneth Y. Tsai, Sue S. Yom, Siegrid S. Yu, Jaehyuk Choi, Sunandana Chandra, Paul Nghiem, Lisa C. Zaba
Journal: Journal of Clinical Oncology (2024)

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence.
Roles of Individual Human Cytochrome P450 Enzymes in Drug Metabolism
Authors: F. Peter Guengerich
Journal: Pharmacological Reviews (2024)

Our knowledge of the roles of individual cytochrome P450 (P450, CYP) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for "phenotyping" of metabolism reactions with new drug candidates. Endogenous biomarkers are being used for non-invasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining "orphan" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating inter-species differences in drug metabolism, particularly in the context of "metabolism in safety testing" (MIST) regulatory issues ("disproportionate (human) metabolites"). <b>Significance Statement</b> Cytochrome P450 enzymes are the major catalysts involved in drug metabolism. The characterization of their individual roles has major implications in drug development and clinical practice.
15-Gene Expression Profile and <i>PRAME</i> as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1)
Authors: J. William Harbour, Zelia M. Correa, Amy C. Schefler, Prithvi Mruthyunjaya, Miguel A. Materin, Thomas A. Aaberg, Alison H. Skalet, David A. Reichstein, Ezekiel Weis, Ivana K. Kim, Timothy S. Fuller, Hakan Demirci, Kisha D. Piggott, Basil K. Williams, Eugene Shildkrot, Antonio Capone, Scott C. Oliver, Scott D. Walter, John Mason, Devron H. Char, Michael Altaweel, Jill R. Wells, Jay S. Duker, Peter G. Hovland, Dan S. Gombos, Tony Tsai, Cameron Javid, Brian P. Marr, Ang Gao, Christina L. Decatur, James J. Dollar, Stefan Kurtenbach, Song Zhang
Journal: Journal of Clinical Oncology (2024)

PURPOSEValidated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and
IBAT inhibitors in pediatric cholestatic liver diseases: Transformation on the horizon?
Authors: Harry Sutton, Ronald J. Sokol, Binita M. Kamath
Journal: Hepatology (2024)

Historically, the therapeutic options available to hepatologists managing cholestasis have been limited. Apart from bile acid--binding resins and the choleretic ursodeoxycholic acid, the medical management of cholestasis in children has been predominately focused on managing the complications of cholestasis, namely pruritus, malnutrition, fat-soluble vitamin deficiencies, and portal hypertension. As such, invasive surgical procedures such as biliary diversion and liver transplantation may become the only options for progressive and unremitting cases of cholestasis. Particularly in the pediatric population, where debilitating pruritus is a common indication for a liver transplant, effective anti-cholestatic medications have the potential to prolong native liver survival without the need for biliary diversion. Ileal bile acid transporter (IBAT) inhibitors are a relatively new class of drugs which that target the ileal re-uptake of bile acids, thus interrupting the enterohepatic circulation and reducing the total bile acid pool size and exposure of the liver. Oral, minimally absorbed IBAT inhibitors have been demonstrated to reduce serum bile acid levels and pruritus with a minimal side effect profile in clinical trials in Alagille Ssyndrome and progressive familial intrahepatic cholestasis, leading to FDA and EMA approval. The indications for IBAT inhibitors will likely expand in the coming years as clinical trials in other adult and pediatric cholestatic conditions are ongoing. This review will summarize the published clinical and pre-clinical data on IBAT inhibitors and offer providers guidance on their practical use.
Association Between State Medicaid Policies and Accrual of Black or Hispanic Patients to Cancer Clinical Trials
Authors: William L. Schpero, Samuel U. Takvorian, Daniel Blickstein, Afrah Shafquat, Jingshu Liu, Arnaub K. Chatterjee, Elizabeth B. Lamont, Paula Chatterjee
Journal: Journal of Clinical Oncology (2024)

It is unknown whether Medicaid expansion under the Affordable Care Act (ACA) or state-level policies mandating Medicaid coverage of the routine costs of clinical trial participation have ameliorated longstanding racial and ethnic disparities in cancer clinical trial enrollment.
US Food and Drug Administration's Directive to Deal With Delayed Confirmatory Trials: Lessons From Pralatrexate and Belinostat for T-Cell Lymphoma
Authors: Edward R. Scheffer Cliff, David A. Russler-Germain, C. Joseph Ross Daval, Aaron S. Kesselheim
Journal: Journal of Clinical Oncology (2024)

The FDA's directive to deal with delayed confirmatory trials: lessons from pralatrexate and belinostat for T-cell lymphoma
Comment on Kaminski et al. Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes. Diabetes Care 2024;47:267–271
Authors: Ray Wang, Rahul D. Barmanray, Mervyn Kyi, Spiros Fourlanos
Journal: Diabetes Care (2024)
Response to Comment on Kaminski et al. Assessment of Glycemic Control by Continuous Glucose Monitoring, Hemoglobin A1c, Fructosamine, and Glycated Albumin in Patients With End-Stage Kidney Disease and Burnt-Out Diabetes. Diabetes Care 2024;47:267–271
Authors: Priyathama Vellanki, Guillermo E. Umpierrez
Journal: Diabetes Care (2024)
The crosstalk between efflux pump and resistance gene mutation in <i>Helicobacter pylori</i>
Authors: Xiaoling Gong, Youhua Wang, Ying An, Zhen Li, Dongsheng Liu, Xie Yong
Journal: Gut Microbes (2024)

Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in Helicobacter pylori. Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.