tbuckley/cabot-search huggingface dataset:
Real-world Uptake of Enfortumab Vedotin plus Pembrolizumab after US Food and Drug Administration Approval Among Patients with Advanced Urothelial Cancer
Authors: Ronac Mamtani, Ernesto Ulloa-Pérez, Ravi B Parikh, Khilna Patel, Blanca Homet Moreno, Chethan Ramamurthy, Haojie Li, Rebecca A Hubbard
Journal: European Urology (2024)
Re: Carlotta Nedbal, Patrick Juliebø-Jones, Eamonn Rogers, et al. Improving Patient Information and Enhanced Consent in Urology: The Impact of Simulation and Multimedia Tools. A Systematic Literature Review from the European Association of Urology Patient Office. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.04.009
Authors: Sandra P García Nader, Cesar A Díaz Ritter, Valentina Garcia Perez
Journal: European Urology (2024)
Enhancing Root Canal Therapy with NIR‐II Semiconducting Polymer AIEgen and Low‐Concentration Sodium Hypochlorite Synergy
Authors: Yuanzhu Zhou, Dan Li, Xin Yue, Yang Shi, Cong Li, Yuhan Wang, Yao Chen, Qian Liu, Dan Ding, Dong Wang, Jing Shen
Journal: Advanced Healthcare Materials (2024)

Despite significant efforts to eliminate bacterial biofilm within root canals, achieving effective disinfection remains challenging due to the complex anatomy and limitations of disinfectants. In this study, a second near-infrared (NIR-II) semiconducting polymer with aggregation-induced emission (AIE) properties, named PIDT-TBT, is deliberately designed and synthesized. This proposes an AIE luminogen-based sterilization strategy in synergy with a low concentration of sodium hypochlorite (NaClO). Water-dispersible PIDT-TBT nanoparticles (NPs) are prepared, demonstrating good biocompatibility, as well as photothermal and photodynamic properties. Subsequent antibacterial tests show that PIDT-TBT NPs exhibit excellent bactericidal effects against three bacterial strains: Staphylococcus aureus, Streptococcus mutans, and Enterococcus faecalis, upon 808 nm laser irradiation. In synergy with a low concentration of NaClO (0.5%) solution, PIDT-TBT NPs significantly improves the outcome of root canal treatment under 808 nm laser irradiation in a human extracted tooth root canal infection model. Additionally, it is found that PIDT-TBT NPs combine with a low concentration of NaClO solution could safely dissolve dentin debris and further increase the efficiency of root canal preparation by altering the elemental composition of the inner root canal wall.
RNA binding protein‐directed control of leukemic stem cell evolution and function
Authors: Pratik Joshi, Ava Keyvani Chahi, Lina Liu, Steven Moreira, Ana Vujovic, Kristin J. Hope
Journal: HemaSphere (2024)

Strict control over hematopoietic stem cell decision making is essential for healthy life-long blood production and underpins the origins of hematopoietic diseases. Acute myeloid leukemia (AML) in particular is a devastating hematopoietic malignancy that arises from the clonal evolution of disease-initiating primitive cells which acquire compounding genetic changes over time and culminate in the generation of leukemic stem cells (LSCs). Understanding the molecular underpinnings of these driver cells throughout their development will be instrumental in the interception of leukemia, the enabling of effective treatment of pre-leukemic conditions, as well as the development of strategies to target frank AML disease. To this point, a number of precancerous myeloid disorders and age-related alterations are proving as instructive models to gain insights into the initiation of LSCs. Here, we explore this myeloid dysregulation at the level of post-transcriptional control, where RNA-binding proteins (RBPs) function as core effectors. Through regulating the interplay of a myriad of RNA metabolic processes, RBPs orchestrate transcript fates to govern gene expression in health and disease. We describe the expanding appreciation of the role of RBPs and their post-transcriptional networks in sustaining healthy hematopoiesis and their dysregulation in the pathogenesis of clonal myeloid disorders and AML, with a particular emphasis on findings described in human stem cells. Lastly, we discuss key breakthroughs that highlight RBPs and post-transcriptional control as actionable targets for precision therapy of AML.
Biomarkers of outcome in patients undergoing CD19 CAR‐T therapy for large B cell lymphoma
Authors: Inna Y. Gong, Daisy Tran, Samuel Saibil, Rob C. Laister, John Kuruvilla
Journal: HemaSphere (2024)

CD19-directed autologous chimeric antigen receptor T cell (CAR-T) therapy has transformed the management of relapsed/refractory (R/R) large B cell lymphoma (LBCL). Initially approved in the third line and beyond setting, CAR-T is now standard of care (SOC) for second-line treatment in patients with refractory disease or early relapse (progression within 12 months) following primary chemoimmunotherapy. Despite becoming SOC, most patients do not achieve complete response, and long-term cure is only observed in approximately 40% of patients. Accordingly, there is an urgent need to better understand the mechanisms of treatment failure and to identify patients that are unlikely to benefit from SOC CAR-T. The field needs robust biomarkers to predict treatment outcome, as better understanding of prognostic factors and mechanisms of resistance can inform on the design of novel treatment approaches for patients predicted to respond poorly to SOC CAR-T. This review aims to provide a comprehensive overview of clinical, molecular, imaging, and cellular features that have been shown to influence outcomes of CAR-T therapy in patients with R/R LBCL.
Barriers to accessing mental health care for refugees and asylum seekers in high-income countries: A scoping review of reviews mapping demand and supply-side factors onto a conceptual framework
Authors: Lars Dumke, Sarah Wilker, Tobias Hecker, Frank Neuner
Journal: Clinical Psychology Review (2024)

This study undertakes a scoping review of reviews on barriers to accessing mental health care for refugees and asylum seekers in high-income countries. By assessing mental health care access using the Levesque's conceptual framework, we identify barriers along the patient care pathway and highlight research gaps. Following PRISMA-ScR guidelines, 10 relevant systematic and scoping reviews were identified and analyzed. Seven common barriers were identified, that could be located across different stages of the conceptual framework. Demand-side barriers included: (1) refugees' understanding of mental illness, (2) fear of stigma, (3) lack of awareness of services, (4) attitudes towards formal treatment; while supply-side barriers comprised: (5) language barriers, (6) practical and structural issues, and (7) providers' attitudes and competence. There was a focus on demand-side barriers as key determinants for low service use. We observed a paucity of quantitative studies linking barriers and indicators of access to care. In the context of well-established mental health care systems, previous research has largely explained low access through peculiarities of refugees and asylum seekers, thereby neglecting the role of supply-side factors (including system structures and attitudes of service providers). We discuss how future research can critically question prevailing assumptions and contribute to rigorous evidence.
Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis
Authors: Simone Margaard Offersen, Xiaotian Mao, Malene Roed Spiegelhauer, Frej Larsen, Viktoria Rose Li, Dennis Sandris Nielsen, Lise Aunsholt, Thomas Thymann, Anders Brunse
Journal: Gut Microbes (2024)

Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT) – particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects. However, this assumption remains unproven. To address this gap, we separated virus-like particles (30 kDa to 0.45 µm) of donor feces from the residual postbiotic fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring them to NEC-susceptible preterm piglets. Virome transfer was equally effective as FFT in reducing the severity of NEC-like pathology. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens. Virome transfer diversified gut viral communities with concomitant constraining effects on the bacterial composition. Unexpectedly, virome transfer, but not residual postbiotic fluid, led to earlier diarrhea. While diarrhea may be a minor concern in human infants, future work should identify ways of eliminating this side effect without losing treatment efficacy.
MOF‐818 Nanozyme Suppresses Calcium Oxalate Kidney Stones by Alleviating Oxidative Stress and Inflammatory Injury
Authors: Yuan Tian, Ziyu Ye, Xunrui Wang, Hantian Guan, Weifeng Liu, Xiaolu Duan, Yang Liu, Guohua Zeng, Hongxing Liu
Journal: Advanced Healthcare Materials (2024)

Abstract There remains a lack of effective drugs to alleviate the kidney stones caused by oxidative stress and inflammatory damage. The MOF‐818 nanozyme is utilized to lessen the generation of reactive oxygen species (ROS) effectively, restore the membrane potential of mitochondria, regulate the cell cycle, decrease cell death, hinder the recruitment of macrophages, and mitigate the release of inflammatory factors in macrophages. These effects are attributed to the nanozyme's ability to mimic the enzyme properties of catalase (CAT) and superoxide dismutase (SOD). It is demonstrated that this nanozyme can reduce kidney calcium oxalate crystal deposition by reducing the renal injury caused by high concentration oxalate, upregulate the expression levels of SOD and CAT in tissues, downregulate adhesion proteins and inflammatory factor IL‐6 and TNF‐α, and promote the polarization of macrophages from M1 to M2 phenotype in the rat model induced by ethylene glycol. Overall, MOF‐818 has the potential to effectively suppress oxidative stress and inflammatory harm caused by high levels of oxalate, hence lowering the likelihood of stone formation. MOF‐818 nanozyme is also expected to be used as an alternative drug for the treatment of calcium oxalate kidney stones and provide an experimental theoretical basis for the development of new nanomedicines.
Alterations in the Skin Microbiome in Dermatologic Diseases and with External Exposures: CME Part 2
Authors: Margaret A. MacGibeny, Susuana Adjei, Hunter Pyle, Christopher G. Bunick, Mahmoud Ghannoum, Ayman Grada, Tamia Harris-Tryon, Stephen K. Tyring, Heidi H. Kong
Journal: Journal of the American Academy of Dermatology (2024)
Targeting the liver clock improves fibrosis by restoring TGF-β signaling
Authors: Emilie Crouchet, Mayssa Dachraoui, Frank Jühling, Natascha Roehlen, Marine A. Oudot, Sarah C. Durand, Clara Ponsolles, Cloé Gadenne, Laura Meiss-Heydmann, Julien Moehlin, Romain Martin, Nicolas Brignon, Fabio Del Zompo, Yuji Teraoka, Hiroshi Aikata, Hiromi Abe-Chayama, Kazuaki Chayama, Antonio Saviano, Danijela Heide, Mihaela Onea, Lucas Geyer, Thibaut Wolf, Emanuele Felli, Patrick Pessaux, Mathias Heikenwälder, Pierre Chambon, Catherine Schuster, Joachim Lupberger, Atish Mukherji, Thomas F. Baumert
Journal: Journal of Hepatology (2024)
Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies
Authors: Cyrille Touzeau, Amrita Y Krishnan, Philippe Moreau, Aurore Perrot, Saad Z Usmani, Salomon Manier, Michele Cavo, Carmen Martinez Chamorro, Ajay K. Nooka, Thomas G Martin, Lionel Karlin, Xavier Leleu, Nizar J. Bahlis, Britta Besemer, Lixia Pei, Sarah Stein, Shun Xin Wang Lin, Danielle Trancucci, Raluca Verona, Suzette Girgis, Xin Miao, Clarissa Uhlar, Katherine Chastain, Alfred Garfall
Journal: Blood (2024)

Abstract Teclistamab is a B-cell maturation antigen (BCMA)–directed bispecific antibody approved for the treatment of patients with triple-class exposed relapsed/refractory multiple myeloma (R/RMM). In the phase 1/2 MajesTEC-1 study, a cohort of patients who had prior BCMA-targeted therapy (antibody-drug conjugate [ADC] or chimeric antigen receptor T-cell [CAR-T] therapy) was enrolled to explore teclistamab in patients previously exposed to anti-BCMA treatment. At a median follow-up of 28.0 months (range, 0.7-31.1), 40 patients with prior BCMA-targeted therapy had received subcutaneous 1.5 mg/kg weekly teclistamab. The median prior lines of treatment was 6 (range, 3-14). Prior anti-BCMA therapy included ADC (n = 29), CAR-T (n = 15), or both (n = 4). The overall response rate was 52.5%; 47.5% of patients achieved very good partial response or better, and 30.0% achieved complete response or better. The median duration of response was 14.8 months, the median progression-free survival was 4.5 months, and the median overall survival was 15.5 months. The most common treatment-emergent adverse events (TEAEs) were neutropenia, infections, cytokine release syndrome, and anemia; cytopenias and infections were the most common grade ≥3 TEAEs. Infections occurred in 28 patients (70.0%; maximum grade 3/4, n = 13 [32.5%]; grade 5, n = 4 [10%]). Before starting teclistamab, baseline BCMA expression and immune characteristics were unaffected by prior anti-BCMA treatment. The MajesTEC-1 trial cohort C results demonstrate favorable efficacy and safety of teclistamab in patients with heavily pretreated R/RMM and prior anti-BCMA treatment. This trial was registered at www.ClinicalTrials.gov as #NCT03145181 and #NCT04557098.
Spatial transcriptomics reveals profound subclonal heterogeneity and T-cell dysfunction in extramedullary myeloma
Authors: Mara John, Moutaz Helal, Johannes Duell, Greta Mattavelli, Emilia Stanojkovska, Nazia Afrin, Alexander Michael Leipold, Maximilian Johannes Steinhardt, Xiang Zhou, David Žihala, Anjana Anilkumar Sithara, Julia Mersi, Johannes M Waldschmidt, Christine Riedhammer, Sofie-Katrin Kadel, Marietta Truger, Rudolf A. Werner, Claudia Haferlach, Hermann Einsele, Kai Kretzschmar, Tomáš Jelínek, Andreas Rosenwald, K. Martin Kortüm, Angela Riedel, Leo Rasche
Journal: Blood (2024)
Fenamates: Forgotten treasure for cancer treatment and prevention: Mechanisms of action, structural modification, and bright future
Authors: Junfang Li, Xiaodong Wang, Honghua Zhang, Xiaoling Hu, Xue Peng, Weifan Jiang, Linsheng Zhuo, Yan Peng, Guo Zeng, Zhen Wang
Journal: Medicinal Research Reviews (2024)

Fenamates as classical nonsteroidal anti-inflammatory agents are widely used for relieving pain. Preclinical studies and epidemiological data highlight their chemo-preventive and chemotherapeutic potential for cancer. However, comprehensive reviews of fenamates in cancer are limited. To accelerate the repurposing of fenamates, this review summarizes the results of fenamates alone or in combination with existing chemotherapeutic agents. This paper also explores targets of fenamates in cancer therapy, including COX, AKR family, AR, gap junction, FTO, TEAD, DHODH, TAS2R14, ion channels, and DNA. Besides, this paper discusses other mechanisms, such as regulating Wnt/β-catenin, TGF-β, p38 MAPK, and NF-κB pathway, and the regulation of the expressions of Sp, EGR-1, NAG-1, ATF-3, ErbB2, AR, as well as the modulation of the tumor immune microenvironment. Furthermore, this paper outlined the structural modifications of fenamates, highlighting their potential as promising leads for anticancer drugs.
Genotyped RHD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D
Authors: Stella T. Chou, Julia Mewha, David F Friedman, VIctoia Lazariu, Shaimaa Makrm, Gorka Ochoa, Sunitha Vege, Connie Marie Westhoff
Journal: Blood (2024)
Targeting organ-specific mitochondrial dysfunction to improve biological aging
Authors: Corina T Madreiter-Sokolowski, Ursula Hiden, Jelena Krstic, Katrin Panzitt, Martin Wagner, Christian Enzinger, Michael Khalil, Mahmoud Abdellatif, Ernst Malle, Tobias Madl, Elena Osto, Markus Schosserer, Christoph J Binder, Andrea Olschewski
Journal: Pharmacology & Therapeutics (2024)

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function. The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics. We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues. In conclusion, this review highlights the therapeutic potential of addressing mitochondrial dysfunction to mitigate organ-specific aging, focusing on the skin, liver, lung, brain, skeletal muscle, and lung, as well as on the reproductive, immune, and cardiovascular systems. Based on a comprehensive understanding of the multifaceted roles of mitochondria, innovative therapeutic strategies may be developed and optimized to combat biological aging and promote healthy aging across diverse organ systems.
Proteolytic bacteria expansion during colitis amplifies inflammation through cleavage of the external domain of PAR2
Authors: Liam Emile Rondeau, Bruna Barbosa Da Luz, Alba Santiago, Miriam Bermudez-Brito, Amber Hann, Giada De Palma, Jennifer Jury, Xuanyu Wang, Elena Francisca Verdu, Heather Jean Galipeau, Corinne Rolland, Celine Deraison, Wolfram Ruf, Premysl Bercik, Nathalie Vergnolle, Alberto Caminero
Journal: Gut Microbes (2024)

Imbalances in proteolytic activity have been linked to the development of inflammatory bowel diseases (IBD) and experimental colitis. Proteases in the intestine play important roles in maintaining homeostasis, but exposure of mucosal tissues to excess proteolytic activity can promote pathology through protease-activated receptors (PARs). Previous research implicates microbial proteases in IBD, but the underlying pathways and specific interactions between microbes and PARs remain unclear. In this study, we investigated the role of microbial proteolytic activation of the external domain of PAR2 in intestinal injury using mice expressing PAR2 with a mutated N-terminal external domain that is resistant to canonical activation by proteolytic cleavage. Our findings demonstrate the key role of proteolytic cleavage of the PAR2 external domain in promoting intestinal permeability and inflammation during colitis. In wild-type mice expressing protease-sensitive PAR2, excessive inflammation leads to the expansion of bacterial taxa that cleave the external domain of PAR2, exacerbating colitis severity. In contrast, mice expressing mutated protease-resistant PAR2 exhibit attenuated colitis severity and do not experience the same proteolytic bacterial expansion. Colonization of wild-type mice with proteolytic PAR2-activating Enterococcus and Staphylococcus worsens colitis severity. Our study identifies a previously unknown interaction between proteolytic bacterial communities, which are shaped by inflammation, and the external domain of PAR2 in colitis. The findings should encourage new therapeutic developments for IBD by targeting excessive PAR2 cleavage by bacterial proteases.
Frequency of antimicrobial-resistant bloodstream infections in 111 hospitals in Thailand, 2022
Authors: Krittiya Tuamsuwan, Panida Chamawan, Phairam Boonyarit, Voranadda Srisuphan, Preeyarach Klaytong, Chalida Rangsiwutisak, Prapass Wannapinij, Trithep Fongthong, John Stelling, Paul Turner, Direk Limmathurotsakul
Journal: Journal of Infection (2024)

To evaluate the frequency of antimicrobial-resistant bloodstream infections (AMR BSI) in Thailand.
Surveillance of avian influenza viruses in Hebei Province of China from 2021 to 2023: Identification of a novel reassortant H3N3
Authors: Yanbai Li, Zhe Yin, Juan Wang, Yujuan Xu, Shanshan Huo, Yang Wu, Dou Dou, Qingan Han, Shibo Jiang, Feng Li, Peng Liu, Fei Yu
Journal: Journal of Infection (2024)
Trends in Children’s Exposure to Food and Beverage Advertising on Television
Authors: Lisa M. Powell, Julien Leider, Rebecca M. Schermbeck, Aline Vandenbroeck, Jennifer L. Harris
Journal: JAMA Network Open (2024)

Importance Reducing children’s exposure to advertisements promoting unhealthy foods and beverages has been recognized by the World Health Organization as a key strategy to improve children’s diets and reduce childhood obesity. Objective To examine changes in children’s exposure to food-related (food, beverage, and restaurant) television advertising, including for products high in nutrients to limit (NTL; ie, saturated fat, trans fat, total sugars, and sodium) based on federal Interagency Working Group guidelines, following changes in the voluntary industry self-regulatory Children’s Food and Beverage Advertising Initiative (CFBAI). Design, Setting, and Participants This repeated cross-sectional study used US television ratings data on advertising exposure from The Nielsen Company for 2013, 2014, 2015, 2018, and 2022. Food and beverage product advertisements were assessed for nutritional content. Participants included 2- to 5-year-old and 6-to 11-year-old children. Data analysis was performed from July 2023 to January 2024. Exposure Changes in CFBAI standards in 2014 and 2020. Main Outcomes and Measures The primary outcome was the number of food-related advertisements seen per year and percentage of food and beverage product advertisements high in NTL, on all programming and children’s programming (defined as ≥35% child audience share). Results From 2013 to 2022, total advertisements seen per year declined by 77.6% (from 4611 to 1035) for 2- to 5-year-olds and by 78.5% (from 4860 to 1046) for 6- to 11-year-olds. Advertisements seen on children’s programming decreased by 95.1% (from 1703 to 84 per year) for 2- to 5-year-olds and by 97.0% (from 1745 to 52 per year) for 6- to 11-year-olds. The percentages of advertisements for products high in NTL decreased from 2013 to 2022 but were still high: 68.9% for all programming and 63.9% for children’s programming for 2- to 5-year-olds, and 68.4% for all programming and 60.6% for children’s programming for 6- to 11-year-olds. The majority (51%-52%) of CFBAI-member food and beverage advertisements on children’s programming remained high in NTL. Black children saw more food-related television advertisements than White children (58% more for 2- to 5-year-olds and 72% more for 6- to 11-year-olds); however, the percentage of advertisements for food and beverage products high in NTL seen was similar by race. Conclusions and Relevance In this repeated cross-sectional study of children’s exposure to food-related television advertisements, exposure via children’s programming decreased substantially. However, most advertisements seen were still for unhealthy products, and exposure from all programming remained substantial. Findings of more than 90% of advertising exposure not from children’s programming and more than 1000 food-related advertisements seen per year suggest the need for government regulations based on time of day rather than programming.