tbuckley/cabot-search huggingface dataset:
Managing Osteoporosis in Dialysis—A Medical Catch-22
Authors: Pascale Khairallah, Thomas L. Nickolas
Journal: JAMA (2024)

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Efficient ultrasound-mediated drug delivery to orthotopic liver tumors – Direct comparison of doxorubicin-loaded nanobubbles and microbubbles
Authors: Pinunta Nittayacharn, Eric Abenojar, Michaela B. Cooley, Felipe M. Berg, Claire Counil, Amin Jafari Sojahrood, Muhammad Saad Khan, Celina Yang, Elizabeth Berndl, Marcin Golczak, Michael C. Kolios, Agata A. Exner
Journal: Journal of Controlled Release (2024)
Tolerability, safety, and immunogenicity of the novel oral polio vaccine type 2 in children aged 6 weeks to 59 months in an outbreak response campaign in The Gambia: an observational cohort study
Authors: Adedapo O Bashorun, Larry Kotei, Ousubie Jawla, Abdoulie F Jallow, Aisha J Saidy, Ma-Ansu Kinteh, Arafang Kujabi, Tijan Jobarteh, Francis John Kanu, Simon A Donkor, Esu Ezeani, Sidat Fofana, Mbye Njie, Lamin Ceesay, Basit Jafri, Amanda Williams, David Jeffries, Brezesky Kotanmi, Bernardo A Mainou, Michael Ooko, Ed Clarke
Journal: The Lancet Infectious Diseases (2024)
TRIB3–TRIM8 complex drives NAFLD progression by regulating HNF4α stability
Authors: Meng-Chao Xiao, Nan Jiang, Li-Lin Chen, Fang Liu, Shu-Qing Liu, Chen-Hong Ding, Si-Han Wu, Ke-Qi Wang, Yuan-Yuan Luo, Yu Peng, Fang-Zhi Yan, Xin Zhang, Hui Qian, Wei-Fen Xie
Journal: Journal of Hepatology (2024)
Human germline gain-of-function in STAT6: from severe allergic disease to lymphoma and beyond
Authors: Mehul Sharma, Narissara Suratannon, Daniel Leung, Safa Baris, Ichiro Takeuchi, Simran Samra, Kumiko Yanagi, Jaime S. Rosa Duque, Mehdi Benamar, Kate L. Del Bel, Mana Momenilandi, Vivien Béziat, Jean-Laurent Casanova, P. Martin van Hagen, Katsuhiro Arai, Ichiro Nomura, Tadashi Kaname, Pantipa Chatchatee, Hideaki Morita, Talal A Chatila, Yu Lung Lau, Stuart E Turvey
Journal: Trends in Immunology (2024)
Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by sodium–glucose cotransporter 2 inhibitors
Authors: Paul J M Wijnker, Rafeeh Dinani, Nico C van der Laan, Sila Algül, Bjorn C Knollmann, Arie O Verkerk, Carol Ann Remme, Coert J Zuurbier, Diederik W D Kuster, Jolanda van der Velden
Journal: Cardiovascular Research (2024)

Abstract Aims Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, often caused by pathogenic sarcomere mutations. Early characteristics of HCM are diastolic dysfunction and hypercontractility. Treatment to prevent mutation-induced cardiac dysfunction is lacking. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a group of antidiabetic drugs that recently showed beneficial cardiovascular outcomes in patients with acquired forms of heart failure. We here studied if SGLT2i represent a potential therapy to correct cardiomyocyte dysfunction induced by an HCM sarcomere mutation. Methods and results Contractility was measured of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) harbouring an HCM mutation cultured in 2D and in 3D engineered heart tissue (EHT). Mutations in the gene encoding β-myosin heavy chain (MYH7-R403Q) or cardiac troponin T (TNNT2-R92Q) were investigated. In 2D, intracellular [Ca2+], action potential and ion currents were determined. HCM mutations in hiPSC-CMs impaired relaxation or increased force, mimicking early features observed in human HCM. SGLT2i enhance the relaxation of hiPSC-CMs, to a larger extent in HCM compared to control hiPSC-CMs. Moreover, SGLT2i-effects on relaxation in R403Q EHT increased with culture duration, i.e. hiPSC-CMs maturation. Canagliflozin’s effects on relaxation were more pronounced than empagliflozin and dapagliflozin. SGLT2i acutely altered Ca2+ handling in HCM hiPSC-CMs. Analyses of SGLT2i-mediated mechanisms that may underlie enhanced relaxation in mutant hiPSC-CMs excluded SGLT2, Na+/H+ exchanger, peak and late Nav1.5 currents, and L-type Ca2+ current, but indicate an important role for the Na+/Ca2+ exchanger. Indeed, electrophysiological measurements in mutant hiPSC-CM indicate that SGLT2i altered Na+/Ca2+ exchange current. Conclusion SGLT2i (canagliflozin &amp;gt; dapagliflozin &amp;gt; empagliflozin) acutely enhance relaxation in human EHT, especially in HCM and upon prolonged culture. SGLT2i may represent a potential therapy to correct early cardiac dysfunction in HCM.
Donor respiratory multidrug-resistant bacteria and lung transplantation outcomes
Authors: Rayid Abdulqawi, Rana Ahmed Saleh, Reem Mahmoud Alameer, Haifa Aldakhil, Khaled Manae AlKattan, Reem Saad Almaghrabi, Sahar Althawadi, Mahmoud Hashim, Waleed Saleh, Amani Hassan Yamani, Eid Abdullah Al-Mutairy
Journal: Journal of Infection (2024)

RationaleRespiratory culture screening is mandatory for all potential lung transplant donors. There is limited evidence on the significance of donor multidrug-resistant (MDR) bacteria on transplant outcomes. Establishing the safety of allografts colonized with MDR bacteria has implications for widening an already limited donor pool.ObjectivesWe aimed to describe the prevalence of respiratory MDR bacteria among our donor population and to test for associations with posttransplant outcomes.MethodsThis retrospective observational study included all adult patients who underwent lung-only transplantation for the first time at King Faisal Specialist Hospital & Research Centre in Riyadh from January 2015 through May 2022. The study evaluated donor bronchoalveolar lavage and bronchial swab cultures.Main resultsSixty-seven of 181 donors (37%) had respiratory MDR bacteria, most commonly MDR Acinetobacter baumannii (n=24), methicillin-resistant Staphylococcus aureus (n=18), MDR Klebsiella pneumoniae (n=8), MDR Pseudomonas aeruginosa (n=7), and Stenotrophomonas maltophilia (n=6).Donor respiratory MDR bacteria were not significantly associated with allograft survival or chronic lung allograft dysfunction (CLAD) in adjusted hazard models. Sensitivity analyses revealed an increased risk for 90-day mortality among recipients of allografts with MDR Klebsiella pneumoniae (n=6 with strains resistant to a carbapenem and n=2 resistant to a third-generation cephalosporin only) compared to those receiving culture-negative allografts (25.0% versus 11.1%, p=0.04). MDR Klebsiella pneumoniae (aHR 3.31, 95%CI 0.95-11.56) and Stenotrophomonas maltophilia (aHR 5.35, 95%CI 1.26-22.77) were associated with an increased risk for CLAD compared to negative cultures.ConclusionOur data suggest the potential safety of using lung allografts with MDR bacteria in the setting of appropriate prophylaxis; however, caution should be exercised in the case of MDR Klebsiella pneumoniae.
ASCEND-Eye
Authors: Emily L. Sammons, Georgina Buck, Louise J. Bowman, William M. Stevens, Imen Hammami, Sarah Parish, Jane Armitage, Emily Sammons, Louise Bowman, William Stevens, Georgina Buck, Imen Hammami, Sarah Parish, Jane Armitage, R. Collins, J. Armitage, L. Bowman, S. Parish, R. Peto, J. Barton, D. Simpson, A. Adler, T. Aung, C. Baigent, H.J. Bodansky, A. Farmer, R. Haynes, R. McPherson, M. Mafham, H.A.W. Neil, N. Samani, P. Sleight, P. Weissberg, P. Sandercock, H. Gerstein, R. Gray, C. Hennekens, J. Barton, L. Fletcher, K. Murphy, S. Hurley, R. Lee, S. Pickworth, M. Willett, M. Wincott, J. Armitage, L. Bowman, M. Mafham, E. Sammons, M. Lay, S. Parish, G. Buck, A. Murawska, W. Stevens, K. Wallendszus, A. Young, I. Hammami, K. Melham, G. Brown, J. Latham-Mollart, A. Brewer, P. Scanlon, P. Patel, M. Olson, J. Kay, S. Banerjee, L. Evans, A. Davies, M. Griffiths, H. Clayton, P. Kirby, M. Pennington, D. Clarke, J. Anslow, A. Hallam, J. Witts, S. Egan, A. Wharton, A. Sachdev, A. Derbyshire, E. Williamson, K. Hepplestone, S. Mithra, S. Oliver, P. Wiatrak-Olszewska, T. Gazis, K. Alvey, E. Wu, H. Cook, N. Gregory, P. Parkinson, J. Anderson, L. Bolter, P. Maharajan, R. McFee, L. Allsop, D. Sowter, D. Hodgson, J. Thow, J. Featonby, R. Furnival, P. Scanlon, H. Lipinski, H. Benjamin, T. McAfee, E. Payne, L. Still
Journal: Ophthalmology (2024)
Investigating the efficacy of nasal administration for delivering magnetic nanoparticles into the brain for magnetic particle imaging
Authors: Satoshi Seino, Hiroto Ikehata, Mizuki Tanabe, Tomohiro Umeda, Takami Tomiyama, Akiko Tanaka, Tomoyuki Furubayashi, Toshiyasu Sakane, Toshihiko Kiwa, Masaomi Washino, Kota Nomura, Shun Tonooka, Akihiro Izawa, Yuki Okumura, Takashi Nakagawa
Journal: Journal of Controlled Release (2024)

This study explored the effectiveness of nasal administration in delivering magnetic nanoparticles into the brain for magnetic particle imaging of target regions. Successful delivery of iron oxide nanoparticles, which serve as contrast agents, to specific sites within the brain is crucial for achieving magnetic particle imaging. Nasal administration has gained attention as a method to bypass the blood-brain barrier and directly deliver therapeutics to the brain. In this study, we investigated surface modification techniques for administering magnetic nanoparticles into the nasal cavity, and provided experimental validation through in vivo studies. By compositing magnetic nanoparticles with gold nanoparticles, we enabled additional surface modification via AuS bonds without compromising their magnetic properties. The migration of the designed PEGylated magnetic nanoparticles into the brain following nasal administration was confirmed by magnetization measurements. Furthermore, we demonstrated the accumulation of these nanoparticles at specific target sites using probe molecules immobilized on the PEG terminus. Thus, the efficacy of delivering magnetic nanoparticles to the brain via nasal administration was demonstrated in this study. The findings of this research are expected to contribute significantly to the realization of magnetic particle imaging of target regions within the brain.
Tunable rigidity of PLGA shell-lipid core nanoparticles for enhanced pulmonary siRNA delivery in 2D and 3D lung cancer cell models
Authors: Hezhi Wang, Ye Yuan, Lu Qin, Mengmeng Yue, Jingwen Xue, Zhixiang Cui, Xuanguang Zhan, Jiayi Gai, Xin Zhang, Jian Guan, Shirui Mao
Journal: Journal of Controlled Release (2024)
Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3
Authors: Qun Wang, Jinxin Wang, Dianping Yu, Qing Zhang, Hongmei Hu, Mengting Xu, Hongwei Zhang, Saisai Tian, Guangyong Zheng, Dong Lu, Jiajia Hu, Mengmeng Guo, Minchen Cai, Xiangxin Geng, Yanyan Zhang, Jianhua Xia, Xing Zhang, Ang Li, Sanhong Liu, Weidong Zhang
Journal: Cell Reports Medicine (2024)

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockade has become a mainstay of cancer immunotherapy. Targeting the PD-1/PD-L1 axis with small molecules is an attractive approach to enhance antitumor immunity. Here, we identified a natural marine product, benzosceptrin C (BC), that enhances the cytotoxicity of T cells to cancer cells by reducing the abundance of PD-L1. Furthermore, BC exerts its antitumor effect in mice bearing MC38 tumors by activating tumor-infiltrating T cell immunity. Mechanistic studies suggest that BC can prevent palmitoylation of PD-L1 by inhibiting DHHC3 enzymatic activity. Subsequently, PD-L1 is transferred from the membrane to the cytoplasm and cannot return to the membrane via recycling endosomes, triggering lysosome-mediated degradation of PD-L1. Moreover, the combination of BC and anti-CTLA4 effectively enhances antitumor T cell immunity. Our findings reveal a previously unrecognized antitumor mechanism of BC and represent an alternative immune checkpoint blockade (ICB) therapeutic strategy to enhance the efficacy of cancer immunotherapy.
Construction of tumor organoids and their application to cancer research and therapy
Authors: Jiajing Lv, Xuan Du, Miaomiao Wang, Jiacan Su, Yan Wei, Can Xu
Journal: Theranostics (2024)

Cancer remains a severe public health burden worldwide.One of the challenges hampering effective cancer therapy is that the existing cancer models hardly recapitulate the tumor microenvironment of human patients.Over the past decade, tumor organoids have emerged as an in vitro 3D tumor model to mimic the pathophysiological characteristics of parental tumors.Various techniques have been developed to construct tumor organoids, such as matrix-based methods, hanging drop, spinner or rotating flask, nonadhesive surface, organ-on-a-chip, 3D bioprinting, and genetic engineering.This review elaborated on cell components and fabrication methods for establishing tumor organoid models.Furthermore, we discussed the application of tumor organoids to cancer modeling, basic cancer research, and anticancer therapy.Finally, we discussed current limitations and future directions in employing tumor organoids for more extensive applications.
Morphine- and foot shock-responsive neuronal ensembles in the VTA possess different connectivity and biased GPCR signaling pathway
Authors: Fan Wang, Chao-bao Liu, Yi Wang, Xi-xi Wang, Yuan-yao Yang, Chang-you Jiang, Qiu-min Le, Xing Liu, Lan Ma, Fei-fei Wang
Journal: Theranostics (2024)

Neurons in the ventral tegmental area (VTA) are sensitive to stress and their maladaptation have been implicated in the psychiatric disorders such as anxiety and addiction,
Tumor-draining lymph nodes: opportunities, challenges, and future directions in colorectal cancer immunotherapy
Authors: Yao Wang, Tingting Zhu, Qi Shi, Guanghui Zhu, Siwei Zhu, Fenggang Hou
Journal: Journal for ImmunoTherapy of Cancer (2024)

Tumor-draining lymph nodes (TDLNs) are potential immunotherapy targets that could expand the population of patients with colorectal cancer (CRC) who may benefit from immunotherapy. Currently, pathological detection of tumor cell infiltration limits the acquisition of immune information related to the resected lymph nodes. Understanding the immune function and metastatic risk of specific stages of lymph nodes can facilitate better discussions on the removal or preservation of lymph nodes, as well as the timing of immunotherapy. This review summarized the contribution of TDLNs to CRC responses to immune checkpoint blockade therapy, local immunotherapy, adoptive cell therapy, and cancer vaccines, and discussed the significance of these findings for the development of diagnostics based on TDLNs and the potential implications for guiding immunotherapy after a definitive diagnosis. Molecular pathology and immune spectrum diagnosis of TDLNs will promote significant advances in the selection of immunotherapy options and predicting treatment efficacy.
Impact of<i>Helicobacter pylori</i>infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors
Authors: Bingting Yu, Maikel Peppelenbosch, Gwenny Fuhler
Journal: Journal for ImmunoTherapy of Cancer (2024)

We have read with great interest the recent publication titled 'Impact of Helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors' by Magahis et al .[1][1] The study presents intriguing findings on the association
Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146
Authors: Vicky Makker, Matthew H Taylor, Carol Aghajanian, Allen L Cohn, Marcia S Brose, Christopher Di Simone, Zhu Alexander Cao, Leah Suttner, Andrey Loboda, Razvan Cristescu, Petar Jelinic, Robert Orlowski, Lea Dutta, Junji Matsui, Corina E Dutcus, Yukinori Minoshima, Mark J Messing
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 ( NCT02501096 ). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest. Methods Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell–inflamed gene expression profile (Tcell inf GEP) and 11 other gene signatures were evaluated by RNA sequencing. TMB, hotspot mutations in PIK3CA (oncogene), and deleterious mutations in PTEN and TP53 (tumor suppressor genes) were evaluated by whole-exome sequencing (WES). Results 93 and 79 patients were included in the RNA-sequencing-evaluable and WES-evaluable populations, respectively. No statistically significant associations were observed between any of the RNA-sequencing signature scores and objective response rate or progression-free survival. Area under the receiver operating characteristic curve values for response ranged from 0.39 to 0.54; all 95% CIs included 0.50. Responses were seen regardless of TMB (≥175 or &lt;175 mutations/exome) and mutation status. There were no correlations between Tcell inf GEP and TMB, Tcell inf GEP and microvessel density (MVD), or MVD and TMB. Conclusions This analysis demonstrated efficacy for lenvatinib plus pembrolizumab regardless of biomarker status. Results from this study do not support clinical utility of the evaluated biomarkers. Further investigation of biomarkers for this regimen is warranted. Trial registration number NCT02501096 .
Vasostatins: new molecular targets for atherosclerosis, post-ischemic angiogenesis and arteriogenesis
Authors: Rosalinda Madonna, Serena Barachini, Sandra Ghelardoni, Lin Lu, Wei-Feng Shen, Raffaele De Caterina
Journal: Cardiovascular Research (2024)

Abstract The chromogranin–secretogranin secretory proteins—granins—are acidic proteins localized in granules of endocrine cells and neurons. The chromogranin family includes chromogranins A (CgA) and B, as well as secretogranin II (once called chromogranin C). Members of this family undergo catalytic proteolysis to produce active peptides. The CgA-derived peptides vasostatin-1 and vasostatin-2, in particular, appear to protect against atherosclerosis, suppressing the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, as well as exerting vasodilatory effects by enhancing nitric oxide bioavailability. Vasostatin-1 also suppresses vasoconstriction and abnormal angiogenesis. Vasostatin-1 and vasostatin-2 may be novel therapeutic targets for atherosclerosis and coronary heart disease, also protecting the myocardium against ischaemic damage.
Response to Yu and Fuhler<i>et al</i>
Authors: Patrick Tiongco Magahis, Steven B Maron, David Faleck, Monika Laszkowska
Journal: Journal for ImmunoTherapy of Cancer (2024)

We thank Yu and Fuhler et al [1][1] for their interest and insightful comments regarding our recent study entitled ‘Impact of Helicobacter Pylori Infection Status on Outcomes among Patients with Advanced Gastric Cancer Treated with Immune Checkpoint Inhibitors’.[2][2] We agree with the
Oligomerization of drug transporters: Forms, functions, and mechanisms
Authors: Chunxu Ni, Mei Hong
Journal: Acta Pharmaceutica Sinica B (2024)

Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs. The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance. With our accumulating knowledge on the three-dimensional structure of drug transporters, their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification (PTM). In-depth studies of oligomeric complexes formed among drug transporters as well as their interactions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins, provide clues for the development of novel drugs, and improve the therapeutic efficacy. In this review, we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies, summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins, and discuss the regulatory mechanisms of oligomerization. Finally, we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharmaceutical application of this important drug transporter PTM.
Molecular force-induced liberation of transforming growth factor-beta remodels the spleen for ectopic liver regeneration
Authors: Zhenzhen Wang, Daping Xie, Jiayi Li, Ziyu Zhai, Zhuojian Lu, Xuejiao Tian, Yiming Niu, Qi Zhao, Peng Zheng, Lei Dong, Chunming Wang
Journal: Journal of Hepatology (2024)
Decoding real-world outcomes: Exploring clinical features associated with efficacy in patients treated with dupilumab
Authors: Zequn Tong, Kunli Zhou, Ying Zou, Zhenlan Wu, Jiawen Chen, Chenyao Xue, Zheyu Zhuang, Yifan Zhao, Liangqi Cai, Ting Gong, Chao Ji
Journal: Journal of the American Academy of Dermatology (2024)
Circulating biomarkers of airflow limitation across the life span
Authors: Jing Zhai, Nipasiri Voraphani, Medea Imboden, Dirk Keidel, Congjian Liu, Debra A. Stern, Claire Venker, Hans Petersen, Anthony Bosco, Duane L. Sherrill, Wayne J. Morgan, Yohannes Tesfaigzi, Nicole M. Probst-Hensch, Fernando D. Martinez, Marilyn Halonen, Stefano Guerra
Journal: Journal of Allergy and Clinical Immunology (2024)
PEGylated-liposomal astaxanthin ameliorates Aβ neurotoxicity and Alzheimer-related phenotypes by scavenging formaldehyde
Authors: Ziqi Gu, Hang Zhao, Yilan Song, Yiduo Kou, Wanting Yang, Ye Li, Xiang Li, Ling Ding, Zihui Sun, Jing Lin, Qi Wang, Xi Li, Xu Yang, Xuerong Huang, Chuang Yang, Zhiqian Tong
Journal: Journal of Controlled Release (2024)
Polyunsaturated fatty acid-binding protein FABP7, an attractive metabolic target for inhibition of glioblastoma stem cells
Authors: Yanfei Sun, Guangjing Mu, Zhiwei Xue, Shuai Wang, Xingang Li, Shilei Ni, Mingzhi Han
Journal: Neuro-Oncology (2024)

Polyunsaturated fatty acidbinding protein FABP7, an attractive