tbuckley/cabot-search huggingface dataset:
Comment on intranasal esketamine combined with oral midazolam provides adequate sedation for outpatient pediatric dental procedures
Authors: Kejia Chu, Haihui Wang, Zhijun Zheng, Juxiang Peng, Juan Gao
Journal: International Journal of Surgery (2024)

Chu, Kejia MD; Wang, Haihui MD; Zheng, Zhijun MD; Peng, Juxiang MD; Gao, Juan MD Author Information
Pembrolizumab for advanced urothelial carcinoma: exploratory ctDNA biomarker analyses of the KEYNOTE-361 phase 3 trial
Authors: Thomas Powles, Yen-Hwa Chang, Yoshiaki Yamamoto, Jose Munoz, Felipe Reyes-Cosmelli, Avivit Peer, Graham Cohen, Evan Y. Yu, Anja Lorch, Abhishek Bavle, Blanca Homet Moreno, Julia Markensohn, Mackenzie Edmondson, Cai Chen, Razvan Cristescu, Carol Peña, Jared Lunceford, Seyda Gunduz
Journal: Nature Medicine (2024)

Abstract Circulating tumor DNA (ctDNA) is emerging as a potential biomarker in early-stage urothelial cancer, but its utility in metastatic disease remains unknown. In the phase 3 KEYNOTE-361 study, pembrolizumab with and without chemotherapy was compared with chemotherapy alone in patients with metastatic urothelial cancer. The study did not meet prespecified efficacy thresholds for statistical significance. To identify potential biomarkers of response, we retrospectively evaluated the association of pre- and posttreatment ctDNA with clinical outcomes in a subset of patients who received pembrolizumab ( n = 130) or chemotherapy ( n = 130) in KEYNOTE-361. Baseline ctDNA was associated with best overall response (BOR; P = 0.009), progression-free survival ( P &lt; 0.001) and overall survival (OS; P &lt; 0.001) for pembrolizumab but not for chemotherapy (all; P &gt; 0.05). Chemotherapy induced larger ctDNA decreases from baseline to treatment cycle 2 than pembrolizumab; however, change with pembrolizumab ( n = 87) was more associated with BOR ( P = 4.39 × 10 −5 ) and OS ( P = 7.07 × 10 −5 ) than chemotherapy ( n = 102; BOR: P = 1.01 × 10 −4 ; OS: P = 0.018). Tumor tissue-informed versions of ctDNA change metrics were most associated with clinical outcomes but did not show a statistically significant independent value for explaining OS beyond radiographic change by RECIST v.1.1 when jointly modeled (pembrolizumab P = 0.364; chemotherapy P = 0.823). These results suggest distinct patterns in early ctDNA changes with immunotherapy and chemotherapy and differences in their association with long-term outcomes, which provide preliminary insights into the utility of liquid biopsies for treatment monitoring in metastatic urothelial cancer. Clinical trial registration: NCT02853305 .
Surgery versus no surgery in platinum-sensitive relapsed ovarian cancer: final overall survival analysis of the SOC-1 randomized phase 3 trial
Authors: Rong Jiang, Yanling Feng, Yulian Chen, Xi Cheng, Tingyan Shi, Wen Gao, Huixun Jia, Shiyang Jiang, Yi Guo, Xiao Huang, Dongsheng Tu, Yuqin Zhang, Huijuan Yang, Ping Zhang, Jihong Liu, Jianqing Zhu, Rongyu Zang
Journal: Nature Medicine (2024)
Microenvironment‐Responsive Targeted Nanomedicine for a Collaborative Integration of Tumor Theranostics and Bone Defect Repair
Authors: Wenxuan Wang, Weiwei Kang, Xin Zhang, Xiaochun Zheng, Yarong Jin, Zhuo Ma, Yuhang Wang, Rong Dai, Xun Ma, Ziliang Zheng, Ruiping Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Despite advancements in breast cancer treatment, bone metastases remain a significant concern for advanced breast cancer patients. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, this work develops an activatable targeted nanomedicine AuMnCO@BSA‐N 3 (AMCBN) to enable a novel collaborative integration of second near‐infrared (NIR‐II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employs a chemical coordination between noble metal complex and metal carbonyl (MnCO), with surface modification of azide groups to enhance tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone‐binding properties enable the efficient and controlled release of Mn 2+ ions and carbon monoxide (CO) in the bone microenvironment, thereby facilitating the expression of osteogenesis‐related proteins and establishing a novel synchronous theranostics process for tumor‐bone repair.
Efficacy and Safety of Taletrectinib in Chinese Patients With <i>ROS1+</i> Non–Small Cell Lung Cancer: The Phase II TRUST-I Study
Authors: Wei Li, Anwen Xiong, Nong Yang, Huijie Fan, Qitao Yu, Yanqiu Zhao, Yongsheng Wang, Xue Meng, Jingxun Wu, Ziping Wang, Yunpeng Liu, Xicheng Wang, Xintian Qin, Kaihua Lu, Wu Zhuang, Yizhong Ren, Xianyu Zhang, Bing Yan, Christine M. Lovly, Caicun Zhou
Journal: Journal of Clinical Oncology (2024)

Taletrectinib, a highly potent, CNS-active,
Disseminated tuberculosis mimicking pleural mesothelioma in a polycythemia vera patient treated with ruxolitinib
Authors: L. Gorospe, A. Lario-Arribas, C. López-Hernández, A. Caminoa-Lizarralde-Aiza, J. Fortún-Abete, O. Ajuria-Illarramendi
Journal: Pulmonology (2024)
Corrigendum to “Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients”
Authors: Franziska Roth‐Walter, Roberto Berni Canani, Liam O'Mahony, Diego Peroni, Milena Sokolowska, Emilia Vassilopoulou, Carina Venter
Journal: Allergy (2024)

To the Editor, In February 2024, we published a review article titled "Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients" in Allergy. 2024 (PMID: 38084827; doi: 10.1111/all.15972). Recently, an error was spotted in Figure 4A of this review, which was missed when the figures were re-designed in the Allergy format. We apologize for the oversight when checking the manuscript, which caused confusion to the readers. We sincerely apologize to the journal and readers of the journal. We have now corrected the Figure 4. In this corrigendum to the review article, we have included a revised Figure 4A to address the error in the review article. In panel Figure 4A, the labels "anti-inflammatory" and "inflammatory" were put in the wrong position and should be switched. The label over the M2 macrophage should state "anti-inflammatory" and over the M1 macrophages "inflammatory." All the authors are aware of the mistake and approved the amendment.
A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy
Authors: Na Li, Shinan Geng, Zhen-zhen Dong, Ying Jin, Hangjie Ying, Hung-Wing Li, Liyun Shi
Journal: Molecular Cancer (2024)

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability. Graphical Abstract
<scp>BRD4</scp> degraders may effectively counteract therapeutic resistance of leukemic stem cells in <scp>AML</scp> and <scp>ALL</scp>
Authors: Karin Bauer, Alexander Hauswirth, Karoline V. Gleixner, Georg Greiner, Johannes Thaler, Peter Bettelheim, Yüksel Filik, Elisabeth Koller, Gregor Hoermann, Philipp B. Staber, Wolfgang R. Sperr, Felix Keil, Peter Valent
Journal: American Journal of Hematology (2024)

Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are life-threatening hematopoietic malignancies characterized by clonal expansion of leukemic blasts in the bone marrow and peripheral blood. The epigenetic reader BRD4 and its downstream effector MYC have recently been identified as potential drug targets in human AML and ALL. We compared anti-leukemic efficacies of the small-molecule BET inhibitor JQ1 and the recently developed BRD4 degraders dBET1 and dBET6 in AML and ALL cells. JQ1, dBET1, and dBET6 were found to suppress growth and viability in all AML and ALL cell lines examined as well as in primary patient-derived AML and ALL cells, including CD34
Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS‐CoV‐2 Variants (Adv. Healthcare Mater. 14/2024)
Authors: Jaehyeon Hwang, Beom Kyu Kim, Seokoh Moon, Wonbeom Park, Kyeong Won Kim, Jeong Hyeon Yoon, Hyunseok Oh, Sangwon Jung, Youngseo Park, Suhyun Kim, Misoo Kim, Soomin Kim, Younghun Jung, Myungseo Park, Jun‐Ho Kim, Sang Taek Jung, Sang Jick Kim, Yong‐Sung Kim, Woo‐Jae Chung, Min‐Suk Song, Dae‐Hyuk Kweon
Journal: Advanced Healthcare Materials (2024)
Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen‐Based Nanomedicines (Adv. Healthcare Mater. 14/2024)
Authors: Yu Wu, Jieli Wang, Yuru Deng, Borislav Angelov, Takehiko Fujino, Md. Shamim Hossain, Angelina Angelova
Journal: Advanced Healthcare Materials (2024)
Thiolation‐Based Protein–Protein Hydrogels for Improved Wound Healing (Adv. Healthcare Mater. 14/2024)
Authors: Xing Liu, Zhao Guo, Jie Wang, Wenting Shen, Zhenzhen Jia, Shuang Jia, Limiao Li, Jieqi Wang, Liping Wang, Jiaqi Li, Yinan Sun, Yufang Chen, Min Zhang, Jia Bai, Liyao Wang, Xinyu Li
Journal: Advanced Healthcare Materials (2024)
Self‐Organization of Long‐Lasting Human Endothelial Capillary‐Like Networks Guided by DLP Bioprinting (Adv. Healthcare Mater. 14/2024)
Authors: Elsa Mazari‐Arrighi, Matthieu Lépine, Dmitry Ayollo, Lionel Faivre, Jérôme Larghero, François Chatelain, Alexandra Fuchs
Journal: Advanced Healthcare Materials (2024)
The Genesis of Schizophrenia: An Origin Story
Authors: Rebecca Birnbaum, Daniel R. Weinberger
Journal: American Journal of Psychiatry (2024)

Schizophrenia is routinely referred to as a neurodevelopmental disorder, but the role of brain development in a disorder typically diagnosed during early adult life is enigmatic. The authors revisit the neurodevelopmental model of schizophrenia with genomic insights from the most recent schizophrenia clinical genetic association studies, transcriptomic and epigenomic analyses from human postmortem brain studies, and analyses from cellular models that recapitulate neurodevelopment. Emerging insights into schizophrenia genetic risk continue to converge on brain development, particularly stages of early brain development, that may be perturbed to deviate from a typical, normative course, resulting in schizophrenia clinical symptomatology. As the authors explicate, schizophrenia genetic risk is likely dynamic and context dependent, with effects of genetic risk varying spatiotemporally, across the neurodevelopmental continuum. Optimizing therapeutic strategies for the heterogeneous collective of individuals with schizophrenia may likely be guided by leveraging markers of genetic risk and derivative functional insights, well before the emergence of psychosis. Ultimately, rather than a focus on therapeutic intervention during adolescence or adulthood, principles of prediction and prophylaxis in the pre- and perinatal and neonatal stages may best comport with the biology of schizophrenia to address the early-stage perturbations that alter the normative neurodevelopmental trajectory.
Strain‐Programmed Adhesive Patch for Accelerated Photodynamic Wound Healing
Authors: Seong‐Jong Kim, Mungu Kim, Seung Min Yang, Kwanghyeon Park, Sei Kwang Hahn
Journal: Advanced Healthcare Materials (2024)

Abstract As an alternative to tissue adhesives, photochemical tissue bonding is investigated for advanced wound healing. However, these techniques suffer from relatively slow wound healing with bleeding and bacterial infections. Here, the versatile attributes of afterglow luminescent particles (ALPs) embedded in dopamine‐modified hyaluronic acid (HA–DOPA) patches for accelerated wound healing are presented. ALPs enhance the viscoelastic properties of the patches, and the photoluminescence and afterglow luminescence of ALPs maximize singlet oxygen generation and collagen fibrillogenesis for effective healing in the infected wounds. The patches are optimized to achieve the strong and rapid adhesion in the wound sites. In addition, the swelling and shrinking properties of adhesive patches contribute to a nonlinear behavior in the wound recovery, playing an important role as a strain‐programmed patch. The protective patch prevents secondary infection and skin adhesion, and the patch seamlessly detaches during wound healing, enabling efficient residue clearance. In vitro, in vivo, and ex vivo model tests confirm the biocompatibility, antibacterial effect, hemostatic capability, and collagen restructuring for the accelerated wound healing. Taken together, this research collectively demonstrates the feasibility of HA–DOPA/ALP patches as a versatile and promoting solution for advanced accelerated wound healing, particularly in scenarios involving bleeding and bacterial infections.
Rational Design of NIR‐II Emitting Conjugated Polymer Derived Nanoparticles for Image‐Guided Cancer Interventions
Authors: Nikita Gill, Indrajit Srivastava, Joshua Tropp
Journal: Advanced Healthcare Materials (2024)

Due to the reduced absorption, light scattering, and tissue autofluorescence in the NIR-II (1000-1700 nm) region, significant efforts are underway to explore diverse material platforms for in vivo fluorescence imaging, particularly for cancer diagnostics and image-guided interventions. Of the reported imaging agents, nanoparticles derived from conjugated polymers (CPNs) offer unique advantages to alternative materials including biocompatibility, remarkable absorption cross-sections, exceptional photostability, and tunable emission behavior independent of cell labeling functionalities. Herein, the current state of NIR-II emitting CPNs are summarized and structure-function-property relationships are highlighted that can be used to elevate the performance of next-generation CPNs. Methods for particle processing and incorporating cancer targeting modalities are discussed, as well as detailed characterization methods to improve interlaboratory comparisons of novel materials. Contemporary methods to specifically apply CPNs for cancer diagnostics and therapies are then highlighted. This review not only summarizes the current state of the field, but offers future directions and provides clarity to the advantages of CPNs over other classes of imaging agents.
Treatment effect heterogeneity of cognitive behavioral therapy for insomnia – A meta-analysis
Authors: Lisa Steinmetz, Laura Simon, Harald Baumeister, Kai Spiegelhalder, Yannik Terhorst
Journal: Sleep Medicine Reviews (2024)

Investigation of the heterogeneity of the treatment effect (HTE) might guide the optimization of cognitive behavioral therapy for insomnia (CBT-I). This study examined HTE in CBT-I thereby analyzing if treatment setting, control group, different CBT-I components, and patient characteristics drive HTE. Randomized controlled trials investigating CBT-I were included. Bayesian random effect meta-regressions were specified to examine variances between the intervention and control groups regarding post-treatment symptom severity. Subgroup analyses analyzing treatment setting and control groups and covariate analysis analyzing treatment components and patient characteristics were specified. No significant HTE in CBT-I was found for the overall data set, settings and control groups. The covariate analyses yielded significant results for baseline severity and the treatment component relaxation therapy. Thus, this study identified potential causes for HTE in CBT-I for the first time, showing that it might be worthwhile to further examine possibilities for precision medicine in CBT-I.
Glutaryl-CoA dehydrogenase suppresses tumor progression and shapes an anti-tumor microenvironment in hepatocellular carcinoma
Authors: Yuanxiang Lao, Xiaohan Cui, Zhu Xu, Hongyao Yan, Zechuan Zhang, Zhenwei Zhang, Longpo Geng, Binghua Li, Yijun Lu, Qifei Guan, Xiaohong Pu, Suwen Zhao, Jiapeng Zhu, Xihu Qin, Beicheng Sun
Journal: Journal of Hepatology (2024)
Mapping SCORing of Atopic Dermatitis (SCORAD) and objective SCORAD to the Eczema Area and Severity Index to facilitate large-scale meta-analyses of molecular data
Authors: Matthias Hübenthal, Chengliang Dai, Sara J Brown, Luise Heinrich, Barbara Kind, Inken Harder, Jochen Schmitt, Thomas Werfel, Stephan Weidinger
Journal: British Journal of Dermatology (2024)

We used data from 1501 patients to build mathematical models for mapping between common measures of atopic dermatitis severity, including SCORing of Atopic Dermatitis (SCORAD), objective SCORAD (oSORAD) and the Eczema Area and Severity Index (EASI). These models can be used to facilitate progress in harmonizing patient data across studies, enabling important comparative analyses at scale.
An innovative single-cell approach for phenotyping and functional genotyping of CAR NK cells
Authors: Matthew Ryan Sullivan, Michael Finocchiaro, Yichao Yang, Judene Thomas, Alaa Ali, Isabel Kaplan, Yasmin Abdulhamid, Eden Bobilev, Michal Sheffer, Rizwan Romee, Tania Konry
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background To accelerate the translation of novel immunotherapeutic treatment approaches, the development of analytic methods to assess their efficacy at early in vitro stages is necessary. Using a droplet-based microfluidic platform, we have established a method for multiparameter quantifiable phenotypic and genomic observations of immunotherapies. Chimeric antigen receptor (CAR) natural killer (NK) cells are of increased interest in the current immunotherapy landscape and thus provide an optimal model for evaluating our novel methodology. Methods For this approach, NK cells transduced with a CD19 CAR were compared with non-transduced NK cells in their ability to kill a lymphoma cell line. Using our microfluidic platform, we were able to quantify the increase in cytotoxicity and synaptic contact formation of CAR NK cells over non-transduced NK cells. We then optimized our droplet sorter and successfully used it to separate NK cells based on target cell killing to perform transcriptomic analyses. Results Our data revealed expected improvement in cytotoxicity with the CD19 CAR but more importantly, provided unique insights into the factors involved in the cytotoxic mechanisms of CAR NK cells. This demonstrates a novel, improved system for accelerating the pre-clinical screening of future immunotherapy treatments. Conclusions This study provides a new potential approach for enhanced early screening of immunotherapies to improve their development, with a highly relevant cell model to demonstrate. Additionally, our validation studies provided some potential insights into transcriptomic determinants influencing CAR NK cytotoxicity.
Nivolumab plus relatlimab in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II CheckMate 142 study
Authors: Michael J Overman, Fabio Gelsomino, Massimo Aglietta, Mark Wong, Maria Luisa Limon Miron, Gregory Leonard, Pilar García-Alfonso, Andrew G Hill, Antonio Cubillo Gracian, Eric Van Cutsem, Bassel El-Rayes, Stephen M McCraith, Beilei He, Ming Lei, Sara Lonardi
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Programmed death-1 (PD-1) inhibitors, including nivolumab, have demonstrated long-term survival benefit in previously treated patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (CRC). PD-1 and lymphocyte-activation gene 3 (LAG-3) are distinct immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes and contribute to tumor-mediated T-cell dysfunction. Relatlimab is a LAG-3 inhibitor that has demonstrated efficacy in combination with nivolumab in patients with melanoma. Here, we present the results from patients with MSI-H/dMMR metastatic CRC treated with nivolumab plus relatlimab in the CheckMate 142 study. Methods In this open-label, phase II study, previously treated patients with MSI-H/dMMR metastatic CRC received nivolumab 240 mg plus relatlimab 160 mg intravenously every 2 weeks. The primary end point was investigator-assessed objective response rate (ORR). Results A total of 50 previously treated patients received nivolumab plus relatlimab. With median follow-up of 47.4 (range 43.9–49.2) months, investigator-assessed ORR was 50% (95% CI 36% to 65%) and disease control rate was 70% (95% CI 55% to 82%). The median time to response per investigator was 2.8 (range 1.3–33.1) months, and median duration of response was 42.7 (range 2.8–47.0+) months. The median progression-free survival per investigator was 27.5 (95% CI 5.3 to 43.7) months with a progression-free survival rate at 3 years of 38%, and median overall survival was not reached (95% CI 17.2 months to not estimable), with a 56% overall survival rate at 3 years. The most common any-grade treatment-related adverse events (TRAEs) were diarrhea (24%), asthenia (16%), and hypothyroidism (12%). Grade 3 or 4 TRAEs were reported in 14% of patients, and TRAEs of any grade leading to discontinuation were observed in 8% of patients. No treatment-related deaths were reported. Conclusions Nivolumab plus relatlimab provided durable clinical benefit and was well tolerated in previously treated patients with MSI-H/dMMR metastatic CRC. Trial registration number NCT02060188 .
Cytokine-armed oncolytic herpes simplex viruses: a game-changer in cancer immunotherapy?
Authors: Hongbin Wang, Mia Borlongan, Howard L Kaufman, Uyen Le, Hans J Nauwynck, Samuel D Rabkin, Dipongkor Saha
Journal: Journal for ImmunoTherapy of Cancer (2024)

Cytokines are small proteins that regulate the growth and functional activity of immune cells, and several have been approved for cancer therapy. Oncolytic viruses are agents that mediate antitumor activity by directly killing tumor cells and inducing immune responses. Talimogene laherparepvec is an oncolytic herpes simplex virus type 1 (oHSV), approved for the treatment of recurrent melanoma, and the virus encodes the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). A significant advantage of oncolytic viruses is the ability to deliver therapeutic payloads to the tumor site that can help drive antitumor immunity. While cytokines are especially interesting as payloads, the optimal cytokine(s) used in oncolytic viruses remains controversial. In this review, we highlight preliminary data with several cytokines and chemokines, including GM-CSF, interleukin 12, FMS-like tyrosine kinase 3 ligand, tumor necrosis factor α, interleukin 2, interleukin 15, interleukin 18, chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 4, or their combinations, and show how these payloads can further enhance the antitumor immunity of oHSV. A better understanding of cytokine delivery by oHSV can help improve clinical benefit from oncolytic virus immunotherapy in patients with cancer.