tbuckley/cabot-search huggingface dataset:
Ultrasound-induced immune responses in tumors: A systematic review and meta-analysis
Authors: Anne Rix, Helen Heinrichs, Céline Porte, Cathalijn Leenaars, André Bleich, Fabian Kiessling
Journal: Journal of Controlled Release (2024)

Ultrasound is widely used in the diagnosis and therapy of cancer. Tumors can be treated by thermal or mechanical tissue ablation. Furthermore, tumors can be manipulated by hyperthermia, sonodynamic therapy and sonoporation, e.g., by increasing tumor perfusion or the permeability of biological barriers to enhance drug delivery. These treatments induce various immune responses in tumors. However, conflicting data and high heterogeneity between experimental settings make it difficult to generalize the effects of ultrasound on tumor immunity. Therefore, we performed a systematic review to answer the question: "Does ultrasound alter the immune reaction of peripheral solid tumors in humans and animals compared to control conditions without ultrasound?" A systematic literature search was performed in PubMed, EMBASE, and Web of Science and 24,401 potentially relevant publications were identified. Of these, 96 publications were eligible for inclusion in the systematic review. Experiments were performed in humans, rats, and mice and focused on different tumor types, primarily breast and melanoma. We collected data on thermal and non-thermal ultrasound settings, the use of sono-sensitizers or sono-enhancers, and anti-tumor therapies. Six meta-analyses were performed to quantify the effect of ultrasound on tumor infiltration by T cells (cytotoxic, helper, and regulatory T cells) and on blood cytokines (interleukin-6, interferon-γ, tumor necrosis factor-α). We provide robust scientific evidence that ultrasound alters T cell infiltration into tumors and increases blood cytokine concentrations. Furthermore, we identified significant differences in immune cell infiltration based on tumor type, ultrasound settings, and mouse age. Stronger effects were observed using hyperthermia in combination with sono-sensitizers and in young mice. The latter may impair the translational impact of study results as most cancer patients are older. Thus, our results may help refining ultrasound parameters to enhance anti-tumor immune responses for therapeutic use and to minimize immune effects in diagnostic applications.
Peripheral blood stem cell versus bone marrow graft for patients ≥60 years undergoing reduced intensity conditioning haploidentical transplantation for acute myeloid leukemia in complete remission: An analysis of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
Authors: Raynier Devillier, Jacques‐Emmanuel Galimard, Didier Blaise, Anna Maria Raiola, Stefania Bramanti, Giovanni Grillo, Rocco Pastano, Régis Peffault de Latour, Alessandro Busca, Lucía López‐Corral, Arancha Bermúdez Rodríguez, Christoph Schmid, Edouard Forcade, Jan Vydra, Carlos Solano, Gesine Bug, Andreas Neubauer, Amandine Charbonnier, Eolia Brissot, Arnon Nagler, Fabio Ciceri, Mohamad Mohty
Journal: American Journal of Hematology (2024)

Abstract In the context of T‐cell replete haploidentical stem cell transplantation (Haplo‐SCT) using post‐transplantation cyclophosphamide (PT‐Cy), it is still unknown whether peripheral blood (PB) or bone marrow (BM) is the best graft source. While PB is associated with a higher incidence of graft‐versus‐host disease (GVHD), it may induce a stronger graft‐versus‐leukemia effect compared to BM, notably in acute myeloid leukemia (AML). From the EBMT registry database, we compared T‐cell replete PB ( n = 595) versus BM ( n = 209) grafts in a large cohort of 804 patients over the age of 60 years who underwent Haplo‐SCT with PT‐Cy for an AML in first or second complete remission. The risk of acute GVHD was significantly higher in the PB group (Grade II‐IV: HR = 1.67, 95% CI [1.10–2.54], p = 0.01; Grade III‐IV: HR = 2.29, 95% CI [1.16–4.54], p = 0.02). No significant difference was observed in chronic GVHD or non‐relapse mortality. In the PB group, the risk of relapse was significantly lower in the PB group (HR = 0.65, 95% CI [0.45–0.94], p = 0.02) and leukemia‐free survival was significantly better (HR = 0.76, 95% CI [0.59–0.99], p = 0.04), with a trend toward better overall survival (HR = 0.78, 95% CI [0.60–1.01], p = 0.06). We conclude that in the specific context of Haplo‐SCT with PT‐Cy, PB grafts represent a valid option to decrease the risk of relapse and improve outcome of older AML patients who usually do not benefit from conditioning intensification.
Immunostimulatory CKb11 gene combined with immune checkpoint PD-1/PD-L1 blockade activates immune response and simultaneously overcomes the immunosuppression of cancer
Authors: Wen Nie, Yihong He, Xue Mi, Shi He, Jing Chen, Yunchu Zhang, Bilan Wang, Songping Zheng, Zhiyong Qian, Xiang Gao
Journal: Bioactive Materials (2024)

Immunosuppression tumor microenvironment (TME) seriously impedes anti-tumor immune response, resulting in poor immunotherapy effect of cancer. This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells, resulting in high CKb11 secretion from tumor cells, successfully activating immune cells and increasing cytokine secretion to reshape the TME, and ultimately delaying tumor progression. The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME. It can cause high expression of IFN-γ, which is a double-edged sword that inhibits tumor growth while causing an increase in the expression of PD-L1 on tumor cells. Therefore, combining CKb11 with PD-L1 inhibitors can counterbalance the suppressive impact of PD-L1 on anti-cancer defense, leading to a collaborative anti-tumor outcome. Thus, utilizing nanotechnology to achieve targeted delivery of immune stimulatory chemokines and immune checkpoint inhibitors to tumor sites, thereby reshaping immunosuppressive TME for cancer treatment, has great potential as an immunogene therapy in clinical applications.
A rechargeable coating with temporal-sequence antibacterial activity and soft tissue sealing
Authors: Fang Wang, Shiwei Guan, Min Xing, Wenhao Qian, Jiajun Qiu, Xuanyong Liu
Journal: Bioactive Materials (2024)

Transcutaneous implants that penetrate through skin or mucosa are susceptible to bacteria invasion and lack proper soft tissue sealing. Traditional antibacterial strategies primarily focus on bacterial eradication, but excessive exposure to bactericidal agents can induce noticeable tissue damage. Herein, a rechargeable model (HPI-Ti) was constructed using perylene polyimide, an aqueous battery material, achieving temporal-sequence regulation of bacterial killing and soft tissue sealing. Charge storage within HPI-Ti is achieved after galvanostatic charge, and chemical discharge is initiated when immersed in physiological environments. During the early discharge stage, post-charging HPI-Ti demonstrates an antibacterial rate of 99.96 ± 0.01 % for 24 h, preventing biofilm formation. Contact-dependent violent electron transfer between bacteria and the material causes bacteria death. In the later discharge stage, the attenuated discharging status creates a gentler electron-transfer micro-environment for fibroblast proliferation. After discharge, the antibacterial activity can be reinstated by recharge against potential reinfection. The antibacterial efficacy and soft tissue compatibility were verified in vivo. These results demonstrate the potential of the charge-transfer-based model in reconciling antibacterial efficacy with tissue compatibility.
An iron-based metal-organic framework nanoplatform for enhanced ferroptosis and oridonin delivery as a comprehensive antitumor strategy
Authors: Mengru Cai, Tingting Fu, Rongyue Zhu, Panxiang Hu, Jiahui Kong, Shilang Liao, Yuji Du, Yongqiang Zhang, Changhai Qu, Xiaoxv Dong, Xingbin Yin, Jian Ni
Journal: Acta Pharmaceutica Sinica B (2024)

Ferroptosis is a recently discovered pathway for regulated cell death pathway. However, its efficacy is affected by limited iron content and intracellular ion homeostasis. Here, we designed a metal-organic framework (MOF)-based nanoplatform that incorporates calcium peroxide (CaO
In vivo adenine base editing rescues adrenoleukodystrophy in a humanized mouse model
Authors: Ramu Gopalappa, MinYoung Lee, Globinna Kim, Eul Sik Jung, Hanahrae Lee, Hye-Yeon Hwang, Jong Geol Lee, Su Jung Kim, Hyun Ju Yoo, Young Hoon Sung, Daesik Kim, In-Jeoung Baek, Hyongbum Henry Kim
Journal: Molecular Therapy (2024)
Lipid conjugate dissociation analysis improves the in vivo understanding of lipid-based nanomedicine
Authors: Winant L. van Os, Laura Wielaert, Claudio Alter, David Davidović, Radek Šachl, Thomas Kock, Urimare Ugueto González, Gabriela Arias-Alpizar, Fernando Lozano Vigario, Renzo A. Knol, Rick Kuster, Stefan Romeijn, Nestor Lopez Mora, Pascal Detampel, Martin Hof, Jörg Huwyler, Alexander Kros
Journal: Journal of Controlled Release (2024)

Lipid conjugates have advanced the field of lipid-based nanomedicine by promoting active-targeting (ligand, peptide, antibody), stability (PEGylation), controlled release (lipoid prodrug), and probe-based tracking (fluorophore). Recent findings indicate lipid conjugates dissociating from nanomedicine upon encountering a biological environment. Yet, implications for (pre)clinical outcomes remain unclear. In this study, using the zebrafish model (Danio rerio), we investigated the fate of liposome-incorporated lipid fluorophore conjugates (LFCs) after intravenous (IV) administration. LFCs having a bilayer mismatch and relatively polar fluorophore revealed counter-predictive outcomes for Caelyx/Doxil (clearance vs. circulating) and AmBisome-like liposomes (scavenger endothelial cell vs. macrophage uptake). Findings on LFC (mis)match for Caelyx/Doxil-like liposomes were supported by translational intravital imaging studies in mice. Importantly, contradicting observations suggest to originate from LFC dissociation in vivo, which was investigated by Asymmetric Flow Field-Flow Fractionation (AF4) upon liposome-serum incubation in situ. Our data suggests that LFCs matching with the liposome bilayer composition - that did not dissociate upon serum incubation - revealed improved predictive outcomes for liposome biodistribution profiles. Altogether, this study highlights the critical importance of fatty acid tail length and headgroup moiety when selecting lipid conjugates for lipid-based nanomedicine.
When sex is demanded as payment for health-care services
Authors: Michele L Coleman, Manuela Colombini, Sarah Bandali, Tom Wright, Maryam Chilumpha, Dina Balabanova
Journal: The Lancet Global Health (2024)

Sexual corruption or sextortion has gained recent attention in the anti-corruption space. It occurs when a sexual favour is used as the currency for a bribe. Sexual corruption is a manifestation of gender-based violence, is inherently a human rights violation, and is a grave public health concern because of its effects on the physical, emotional, and mental wellbeing of the person who has experienced sexual corruption. It impacts health systems' abilities to achieve universal health coverage and deliver services in the most effective, high-quality manner. Despite the health consequences, limited evidence exists on sexual corruption occurring in the health sector. This Viewpoint briefly reviews the literature on sexual corruption occurring within health systems focusing mainly on low-income to middle-income countries, with a concentration on its prevalence, the driving forces associated with it, and recommendations to address it.
Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment
Authors: Wei Guo, Min Ji, Yingjie Li, Min Qian, Yanhui Qin, Wenshuai Li, Huifang Nie, Wenxin Lv, Guangwei Jiang, Rong Huang, Chenteng Lin, Hongyuan Li, Rongqin Huang
Journal: Biomaterials (2024)
Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage
Authors: Jingyou Rao, Ruiqi Xin, Christian Macdonald, Matthew K. Howard, Gabriella O. Estevam, Sook Wah Yee, Mingsen Wang, James S. Fraser, Willow Coyote-Maestas, Harold Pimentel
Journal: Genome biology (2024)

Abstract Deep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p -values cannot be correctly calibrated when treating variants independently. We propose , a Bayesian framework for analyzing growth-based DMS data. leverages amino acid position information to increase power and control the false discovery rate by sharing information across parameters via shrinkage. We also developed for simulating the distributional properties of DMS. We show that is robust to the violation of model assumptions and is more powerful than existing tools.
Effect of genomic and cellular environments on gene expression noise
Authors: Clarice K. Y. Hong, Avinash Ramu, Siqi Zhao, Barak A. Cohen
Journal: Genome biology (2024)

Abstract Background Individual cells from isogenic populations often display large cell-to-cell differences in gene expression. This “noise” in expression derives from several sources, including the genomic and cellular environment in which a gene resides. Large-scale maps of genomic environments have revealed the effects of epigenetic modifications and transcription factor occupancy on mean expression levels, but leveraging such maps to explain expression noise will require new methods to assay how expression noise changes at locations across the genome. Results To address this gap, we present Single-cell Analysis of Reporter Gene Expression Noise and Transcriptome (SARGENT), a method that simultaneously measures the noisiness of reporter genes integrated throughout the genome and the global mRNA profiles of individual reporter-gene-containing cells. Using SARGENT, we perform the first comprehensive genome-wide survey of how genomic locations impact gene expression noise. We find that the mean and noise of expression correlate with different histone modifications. We quantify the intrinsic and extrinsic components of reporter gene noise and, using the associated mRNA profiles, assign the extrinsic component to differences between the CD24+ “stem-like” substate and the more “differentiated” substate. SARGENT also reveals the effects of transgene integrations on endogenous gene expression, which will help guide the search for “safe-harbor” loci. Conclusions Taken together, we show that SARGENT is a powerful tool to measure both the mean and noise of gene expression at locations across the genome and that the data generatd by SARGENT reveals important insights into the regulation of gene expression noise genome-wide.
When I use a word . . . The languages of medicines—International Nonproprietary Names (INNs)
Authors: Jeffrey K Aronson
Journal: BMJ (2024)

The system of names for medicines known as International Nonproprietary Names (INNs) was introduced by the World Health Organization (WHO) in the 1950s. No nomenclatural system is perfect, and the INN system is no different from any other in that respect. However, despite inconsistencies, the system has proved useful in bringing a degree of uniformity to the way in which drugs are named internationally. Over the years the INNs have gradually been adopted as standard by many countries, and they may have been helpful in reducing the risks of medication errors, in addition to introducing uniformity of nomenclature, making communication easier.
Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials
Authors: Changsong Qi, Panpan Zhang, Chang Liu, Jun Zhang, Jun Zhou, Jiajia Yuan, Dan Liu, Miao Zhang, Jifang Gong, Xicheng Wang, Jian Li, Xiaotian Zhang, Ning Li, Xiaohui Peng, Zhen Liu, Daijing Yuan, Raffaele Baffa, Yumeng Wang, Lin Shen
Journal: Journal of Clinical Oncology (2024)

CT041 is a chimeric antigen receptor (CAR)-modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC).
Leveraging AI to improve evidence synthesis in conservation
Authors: Oded Berger-Tal, Bob B.M. Wong, Carrie Ann Adams, Daniel T. Blumstein, Ulrika Candolin, Matthew J. Gibson, Alison L. Greggor, Malgorzata Lagisz, Biljana Macura, Catherine J. Price, Breanna J. Putman, Lysanne Snijders, Shinichi Nakagawa
Journal: Trends in Ecology & Evolution (2024)
Re: Roxana Ramos, Ethan Ferguson, Mahmoud Abou Zeinab, et al. Single-port Transvesical Robot-assisted Simple Prostatectomy: Surgical Technique and Clinical Outcomes. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2023.11.012
Authors: Jas Singh
Journal: European Urology (2024)
Publisher Correction: Clonally expanded memory CD8+ T cells accumulate in atherosclerotic plaques and are pro-atherogenic in aged mice
Authors: Daniel J. Tyrrell, Kathleen M. Wragg, Judy Chen, Hui Wang, Jianrui Song, Muriel G. Blin, Chase Bolding, Donald Vardaman, Kara Giles, Harrison Tidwell, Md Akkas Ali, Abhinav Janappareddi, Sherri C. Wood, Daniel R. Goldstein
Journal: Nature Aging (2024)
Modifiable risk factors for asthma exacerbations during the COVID-19 pandemic: a population-based repeated cross-sectional study using the Research and Surveillance Centre primary care database
Authors: Mome Mukherjee, Cecilia Okusi, Gavin Jamie, Rachel Byford, Filipa Ferreira, Utkarsh Agarwal, David Weatherill, Monica Fletcher, Jennifer K Quint, Mohammad Romel Bhuia, Simon de Lusignan, Sir Aziz Sheikh
Journal: The Lancet Regional Health - Europe (2024)
Spatial and functional targeting of intratumoral Tregs reverses CD8+ T cell exhaustion and promotes cancer immunotherapy
Authors: Lei Zhou, Maria Velegraki, Yi Wang, J K Mandula, Yuzhou Chang, Weiwei Liu, No-Joon Song, Hyunwoo Kwon, Tong Xiao, Chelsea Bolyard, Feng Hong, Gang Xin, Qin Ma, Mark P. Rubinstein, Haitao Wen, Zihai Li
Journal: Journal of Clinical Investigation (2024)

Intratumoral regulatory T cells (Tregs) are key mediators of cancer immunotherapy resistance, including anti-PD-(L)1 immune checkpoint blockade (ICB). The mechanisms driving Treg infiltration into the tumor microenvironment (TME) and the consequence on CD8+ T cell exhaustion remains elusive. Herein, we report that heat shock protein gp96 (GRP94) is indispensable for Treg tumor infiltration, primarily through gp96's roles in chaperoning integrins. Among various gp96-dependent integrins, we found that only LFA-1 (αL integrin) but not αV, CD103 (αE) or β7 integrin was required for Treg tumor homing. Loss of Treg infiltration into the TME by genetically deleting gp96/LFA-1 potently induces rejection of multiple ICB-resistant murine cancer models in a CD8+ T cell-dependent manner without loss of self-tolerance. Moreover, gp96 deletion impeded Treg activation primarily by suppressing IL-2/STAT5 signaling, which also contributes to tumor regression. By competing for intratumoral IL-2, Tregs prevent activation of CD8+ tumor-infiltrating lymphocytes (TILs), drive TOX induction and induce bona fide CD8+ T cell exhaustion. By contrast, Treg ablation leads to striking CD8+ T cell activation without TOX induction, demonstrating clear uncoupling of the two processes. Our study reveals that the gp96/LFA-1 axis plays a fundamental role in Treg biology and suggests that Treg-specific gp96/LFA-1 targeting represents a valuable strategy for cancer immunotherapy without inflicting autoinflammatory conditions.
Single cell RNA sequencing of human eosinophils from nasal polyps reveals eosinophil heterogeneity in chronic rhinosinusitis tissue
Authors: Naruhito Iwasaki, Julie A. Poposki, Aiko Oka, Masanori Kidoguchi, Aiko I. Klingler, Lydia A. Suh, Junqin Bai, Whitney W. Stevens, Anju T. Peters, Leslie C. Grammer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Robert P. Schleimer, Robert C. Kern, Bruce S. Bochner, Bruce K. Tan, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2024)
A digital twin model incorporating generalized metabolic fluxes to identify and predict chronic kidney disease in type 2 diabetes mellitus
Authors: Naveenah Udaya Surian, Arsen Batagov, Andrew Wu, Wen Bin Lai, Yan Sun, Yong Mong Bee, Rinkoo Dalan
Journal: npj Digital Medicine (2024)

Abstract We have developed a digital twin-based CKD identification and prediction model that leverages generalized metabolic fluxes (GMF) for patients with Type 2 Diabetes Mellitus (T2DM). GMF digital twins utilized basic clinical and physiological biomarkers as inputs for identification and prediction of CKD. We employed four diverse multi-ethnic cohorts ( n = 7072): a Singaporean cohort (EVAS, n = 289) and a North American cohort (NHANES, n = 1044) for baseline CKD identification, and two multi-center Singaporean cohorts (CDMD, n = 2119 and SDR, n = 3627) for 3-year CKD prediction and risk stratification. We subsequently conducted a comprehensive study utilizing a single dataset to evaluate the clinical utility of GMF for CKD prediction. The GMF-based identification model performed strongly, achieving an AUC between 0.80 and 0.82. In prediction, the GMF generated with complete parameters attained high performance with an AUC of 0.86, while with incomplete parameters, it achieved an AUC of 0.75. The GMF-based prediction model utilizing complete inputs is the standard implementation of our algorithm: HealthVector Diabetes®. We have established the GMF digital twin-based model as a robust clinical tool capable of predicting and stratifying the risk of future CKD within a 3-year time horizon. We report the correlation of GMF with basic input parameters, their ability to differentiate between future health states and medication status at baseline, and their capability to quantify CKD progression rates. This holistic methodology provides insights into patients’ health states and CKD progression rates based on GMF metabolic profile differences, enabling personalized care plans.
Digital Engagement Strategy and Health Care Worker Mental Health
Authors: Anish K. Agarwal, Lauren Southwick, Rachel E. Gonzales, Lisa M. Bellini, David A. Asch, Judy A. Shea, Nandita Mitra, Lin Yang, Michael Josephs, Michael Kopinksy, Rachel Kishton, Mohan Balachandran, Courtney Benjamin Wolk, Emily M. Becker-Haimes, Raina M. Merchant
Journal: JAMA Network Open (2024)

The health care workforce continues to experience high rates of depression and anxiety. Finding ways to effectively support the mental health and well-being of health care workers is challenging.
Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases
Authors: Camille Rolin, Jacques Zimmer, Carole Seguin-Devaux
Journal: Cellular and Molecular Immunology (2024)

Abstract By binding to multiple antigens simultaneously, multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass of antibody-based constructs, consist of engineered structures designed to bridge immune effector cells to their target, thereby redirecting the immune response toward the tumor cells or infected cells. The increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and infections. In this review, we discuss how different immune cell types (T and natural killer lymphocytes, as well as myeloid cells) can be bound by immune cell engagers in immunotherapy for cancer and infectious diseases. Furthermore, we explore the preclinical and clinical advancements of these constructs, and we discuss the challenges in translating the current knowledge from cancer to the virology field. Finally, we speculate on the promising future directions that immune cell engagers may take in cancer treatment and antiviral therapy.