tbuckley/cabot-search huggingface dataset:
A systematic review and network meta-analysis of population-level interventions to tackle smoking behaviour
Authors: Shamima Akter, Md. Mizanur Rahman, Thomas Rouyard, Sarmin Aktar, Raïssa Shiyghan Nsashiyi, Ryota Nakamura
Journal: Nature Human Behaviour (2024)

This preregistered systematic review and meta-analysis (PROSPERO: CRD 42022311392) aimed to synthesize the effectiveness of all available population-level tobacco policies on smoking behaviour. Our search across 5 databases and leading organizational websites resulted in 9,925 records, with 476 studies meeting our inclusion criteria. In our narrative summary and both pairwise and network meta-analyses, we identified anti-smoking campaigns, health warnings and tax increases as the most effective tobacco policies for promoting smoking cessation. Flavour bans and free/discounted nicotine replacement therapy also showed statistically significant positive effects on quit rates. The network meta-analysis results further indicated that smoking bans, anti-tobacco campaigns and tax increases effectively reduced smoking prevalence. In addition, flavour bans significantly reduced e-cigarette consumption. Both the narrative summary and the meta-analyses revealed that smoking bans, tax increases and anti-tobacco campaigns were associated with reductions in tobacco consumption and sales. On the basis of the available evidence, anti-tobacco campaigns, smoking bans, health warnings and tax increases are probably the most effective policies for curbing smoking behaviour. In this systematic review and meta-analysis of population-level tobacco control policies, Akter et al. find that anti-tobacco campaigns, smoking bans, health warnings and tax increases are effective measures for curbing smoking behaviour.
Author Correction: GPR34 is a metabolic immune checkpoint for ILC1-mediated antitumor immunit
Authors: Jiaxian Yan, Chi Zhang, Yueli Xu, Zonghui Huang, Qingyuan Ye, Xiaojun Qian, Liang Zhu, Guangming Huang, Xiaqiong Wang, Wei Jiang, Rongbin Zhou
Journal: Nature Immunology (2024)
In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma
Authors: S. John Liu, Christopher Zou, Joanna Pak, Alexandra Morse, Dillon Pang, Timothy Casey-Clyde, Ashir A. Borah, David Wu, Kyounghee Seo, Thomas O’Loughlin, Daniel A. Lim, Tomoko Ozawa, Mitchel S. Berger, Roarke A. Kamber, William A. Weiss, David R. Raleigh, Luke A. Gilbert
Journal: Genome biology (2024)

Genetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking.
Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors
Authors: Annapoorna Venkatachalam, Cristina Correia, Kevin L. Peterson, Xianon Hou, Paula A. Schneider, Annabella R. Strathman, Karen S. Flatten, Chance C. Sine, Emily A. Balczewski, Cordelia D. McGehee, Melissa C. Larson, Laura N. Duffield, X. Wei Meng, Nicole D. Vincelette, Husheng Ding, Ann L. Oberg, Fergus J. Couch, Elizabeth M. Swisher, Hu Li, S. John Weroha, Scott H. Kaufmann
Journal: Molecular Cancer (2024)

Recent studies indicate that replication checkpoint modulators (RCMs) such as inhibitors of CHK1, ATR, and WEE1 have promising monotherapy activity in solid tumors, including platinum-resistant high grade serous ovarian cancer (HGSOC). However, clinical response rates are generally below 30%. While RCM-induced DNA damage has been extensively examined in preclinical and clinical studies, the link between replication checkpoint interruption and tumor shrinkage remains incompletely understood. Here we utilized HGSOC cell lines and patient-derived xenografts (PDXs) to study events leading from RCM treatment to ovarian cancer cell death. These studies show that RCMs increase CDC25A levels and CDK2 signaling in vitro, leading to dysregulated cell cycle progression and increased replication stress in HGSOC cell lines independent of homologous recombination status. These events lead to sequential activation of JNK and multiple BH3-only proteins, including BCL2L11/BIM, BBC3/PUMA and the BMF, all of which are required to fully initiate RCM-induced apoptosis. Activation of the same signaling pathway occurs in HGSOC PDXs that are resistant to poly(ADP-ribose) polymerase inhibitors but respond to RCMs ex vivo with a decrease in cell number in 3-dimensional culture and in vivo with xenograft shrinkage or a significantly diminished growth rate. These findings identify key cell death-initiating events that link replication checkpoint inhibition to antitumor response in ovarian cancer.
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017–2021
Authors: Mackenzie Price, Christine Ballard, Julia Benedetti, Corey Neff, Gino Cioffi, Kristin A Waite, Carol Kruchko, Jill S Barnholtz-Sloan, Quinn T Ostrom
Journal: Neuro-Oncology (2024)

Abstract The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2017 and 2021, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 25.34 per 100,000 population (malignant AAAIR=6.89 and non-malignant AAAIR=18.46). This overall rate was higher in females compared to males (28.77 versus 21.78 per 100,000) and non-Hispanic Black persons compared to persons who were non-Hispanic White (26.60 versus 25.72 per 100,000), non-Hispanic American Indian/Alaska Native (23.48 per 100,000), non-Hispanic Asian or Pacific Islander (19.86 per 100,000), and Hispanic persons of all races (22.37 per 100,000). Gliomas accounted for 22.9% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.9% of all tumors and 51.5% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (41.7% of all tumors and 56.8% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.02 per 100,000 population. There were 87,053 deaths attributed to malignant brain and other CNS tumors between 2017 and 2021. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 17,411 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 35.7%. For a non-malignant brain or other CNS tumor the five-year relative survival rate was 92.0%.
Testicular large B‐cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL
Authors: Alfredo Rivas‐Delgado, Cristina López, Guillem Clot, Ferran Nadeu, Marta Grau, Gerard Frigola, Jan Bosch‐Schips, Josefine Radke, Naveed Ishaque, Miguel Alcoceba, Gustavo Tapia, Luis Luizaga, Carmen Barcena, Nicholas Kelleher, Neus Villamor, Tycho Baumann, Ana Muntañola, Juan M. Sancho‐Cia, Alejandro M. García‐Sancho, Eva Gonzalez‐Barca, Estella Matutes, Jordi A. Brito, Kennosuke Karube, Itziar Salaverria, Anna Enjuanes, Stefan Wiemann, Frank L. Heppner, Reiner Siebert, Fina Climent, Elías Campo, Eva Giné, Armando López‐Guillermo, Silvia Beà
Journal: HemaSphere (2024)

Abstract Testicular large B‐cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune‐privileged site and has recently been recognized as a distinct entity from diffuse large B‐cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B‐cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next‐generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations ( p &lt; 0.04) but more somatic variants ( p &lt; 0.02) than nodal DLBCL and had more frequent 18q21.32‐q23 ( BCL2 ) gains and 6q and 9p21.3 ( CDKN2A/B ) deletions. PIM1 , MYD88 L265P , CD79B , TBL1XR1 , MEF2B , CIITA , EP300, and ETV6 mutations were more frequent in TLBCL, and BCL10 mutations in nodal DLBCL. There were no major genetic differences between TLBCL and PCNSL. Localized or disseminated TLBCL displayed similar genomic profiles. Using LymphGen, the majority of cases were classified as MCD. However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.
Safe and potent anti‐CD19 CAR T‐cells with shRNA‐IL‐6 gene silencing element in patients with refractory or relapsed B‐cell acute lymphoblastic leukemia
Authors: Jin‐Feng Ma, Jia‐Wei Yan, Mei‐Jing Liu, Chun‐Long Yan, Xiao‐Wen Tang, Hui‐Ying Qiu, Miao Miao, Yue Han, Li‐Min Li, Li‐Qing Kang, Nan Xu, Zhou Yu, Jing‐Wen Tan, Hong‐Jia Zhu, Xu Jia, Zhi‐Zhi Zhang, Miao Wang, Hai‐Ping Dai, Lei Yu, Sheng‐Li Xue, De‐Pei Wu, Wen‐Jie Gong
Journal: HemaSphere (2024)

Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (
Ablation Strategies for Repeat Procedures in Atrial Fibrillation Recurrences Despite Durable Pulmonary Vein Isolation: The Prospective Randomized ASTRO AF Multicenter Trial
Authors: Boris Schmidt, Stefano Bordignon, Andreas Metzner, Philipp Sommer, Daniel Steven, Tilmann Dahme, Matthias Busch, Roland Richard Tilz, David Schaack, Andreas Rillig, Christian Sohns, Arian Sultan, Karolina Weinmann-Emhardt, Astrid Hummel, Julia Vogler, Thomas Fink, Jakob Lueker, Alexander Pott, Christian Heeger, K.-R. Julian Chun
Journal: Circulation (2024)

BACKGROUND: Ablation strategies for patients with symptomatic atrial fibrillation and isolated pulmonary veins vary and their effects on arrhythmia recurrence remain unclear. A prospective randomized German multicenter trial sought to compare 2 ablation strategies in this patient cohort. METHODS: Patients with atrial fibrillation despite durable pulmonary vein isolation were randomly assigned at 7 centers to undergo low-voltage area ablation using 3-dimensional mapping and irrigated radiofrequency current ablation (group A) or empirical left atrial appendage isolation (LAAI) using the cryoballoon followed by staged interventional left atrial appendage closure (group B). The primary end point was freedom from atrial tachyarrhythmias between 91 and 365 days after index ablation. The study was powered for superiority of LAAI compared with low-voltage area. RESULTS: Patients (40% women; mean age, 68.8±8 years) with paroxysmal (32%) or persistent atrial fibrillation (68%) were randomized to undergo low-voltage area ablation (n=79) or cryoballoon-guided LAAI (n=82). After a planned interim analysis, enrollment was halted for futility on January 10, 2023. In the LAAI group, 77 of 82 left atrial appendages were successfully isolated with subsequent left atrial appendage closure in 57 patients. Procedure-related complications occurred in 4 (5%) and 11 (13.5%) patients in group A and B, respectively ( P =0.10). The median follow-up was 367 days (interquartile range, 359–378). The Kaplan-Meier point estimate for freedom from atrial tachyarrhythmias was 51.7% (CI, 40.9%–65.4%) for group A and 55.5% (CI, 44.4%–69.2%; P =0.8069) for group B. CONCLUSIONS: The current study did not detect superiority of cryoballoon-guided LAAI over low-voltage area ablation in patients with atrial fibrillation despite durable PVI. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04056390
The epithelial barrier theory and its associated diseases
Authors: Na Sun, Ismail Ogulur, Yasutaka Mitamura, Duygu Yazici, Yagiz Pat, Xiangting Bu, Manru Li, Xueyi Zhu, Huseyn Babayev, Sena Ardicli, Ozge Ardicli, Paolo D'Avino, Ayca Kiykim, Milena Sokolowska, Willem van de Veen, Lukas Weidmann, Deniz Akdis, Banu Goker Ozdemir, Marie Charlotte Brüggen, Luc Biedermann, Alex Straumann, Andrea Kreienbühl, Emma Guttman‐Yassky, Alexandra F. Santos, Stefano Del Giacco, Claudia Traidl‐Hoffmann, David J. Jackson, De‐Yun Wang, Antti Lauerma, Heimo Breiteneder, Luo Zhang, Liam O'Mahony, Oliver Pfaar, Robyn O'Hehir, Thomas Eiwegger, Wytske J. Fokkens, Beatriz Cabanillas, Cevdet Ozdemir, Walter Kistler, Mahmut Bayik, Kari C. Nadeau, Maria J. Torres, Mübeccel Akdis, Marek Jutel, Ioana Agache, Cezmi A. Akdis
Journal: Allergy (2024)

Abstract The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.
Long‐term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase 3 open‐label extension study
Authors: Avner Reshef, Connie Hsu, Constance H. Katelaris, Philip H. Li, Markus Magerl, Keiko Yamagami, Mar Guilarte, Paul K. Keith, Jonathan A. Bernstein, John‐Philip Lawo, Harsha Shetty, Maressa Pollen, Lolis Wieman, Tim J. Craig
Journal: Allergy (2024)

Hereditary angioedema (HAE) is a chronic, unpredictable disease. Long-term prophylactic treatments that offer durable efficacy, safety, and convenience are required to assist patients in achieving complete disease control, per international guidelines. We report an interim analysis of an ongoing phase 3 (VANGUARD) open-label extension (OLE) study evaluating the long-term safety and efficacy of garadacimab for HAE prophylaxis. Adults and adolescents aged ≥12 years with HAE previously participating in phase 2 and pivotal phase 3 (VANGUARD) studies were rolled over to an OLE, alongside newly enrolled patients. Patients received garadacimab 200 mg subcutaneously, once monthly for ≥12 months. The primary endpoint was treatment-emergent adverse events (TEAEs) in patients with C1 inhibitor deficiency/dysfunction. At data cut-off (February 13, 2023; N = 161), median (interquartile range) exposure was 13.8 months (11.9-16.3). For the primary endpoint, 133/159 patients experienced ≥1 TEAE (524 events), equivalent to 0.23 events/administration and 2.84 events/patient-year. Garadacimab-related TEAEs (13% of patients, 52 events) were most commonly injection-site reactions (ISRs). No deaths occurred. One patient discontinued treatment due to garadacimab-related moderate ISR. Most TEAEs were mild/moderate; three events were serious (COVID-19, two events; abdominal HAE attack, one event) and not garadacimab related. No abnormal bleeding, thromboembolic, severe hypersensitivity, or anaphylactic events were observed. Mean HAE attack rate decreased by 95% from the run-in period; 60% of patients were attack-free. Almost all patients (93%) rated their response to garadacimab as "good" or "excellent." Garadacimab has a favorable safety profile suitable for long-term use and provides durable protection against HAE attacks.
Mapping individual cortico–basal ganglia–thalamo–cortical circuits integrating structural and functional connectome: implications for upper limb motor impairment poststroke
Authors: Xin Xue, Jia‐Jia Wu, Xiang‐Xin Xing, Jie Ma, Jun‐Peng Zhang, Yun‐Ting Xiang, Mou‐Xiong Zheng, Xu‐Yun Hua, Jian‐Guang Xu
Journal: MedComm (2024)

This study investigated alterations in functional connectivity (FC) within cortico-basal ganglia-thalamo-cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single-target stimulation. We delineated individual-specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles-based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas-based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome-based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual-specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual-specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl-Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas-based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual-specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease-related circuits is essential for understanding poststroke brain reorganization.
Next‐generation spatial transcriptomics: unleashing the power to gear up translational oncology
Authors: Nan Wang, Weifeng Hong, Yixing Wu, Zhe‐Sheng Chen, Minghua Bai, Weixin Wang, Ji Zhu
Journal: MedComm (2024)

The growing advances in spatial transcriptomics (ST) stand as the new frontier bringing unprecedented influences in the realm of translational oncology. This has triggered systemic experimental design, analytical scope, and depth alongside with thorough bioinformatics approaches being constantly developed in the last few years. However, harnessing the power of spatial biology and streamlining an array of ST tools to achieve designated research goals are fundamental and require real-world experiences. We present a systemic review by updating the technical scope of ST across different principal basis in a timeline manner hinting on the generally adopted ST techniques used within the community. We also review the current progress of bioinformatic tools and propose in a pipelined workflow with a toolbox available for ST data exploration. With particular interests in tumor microenvironment where ST is being broadly utilized, we summarize the up-to-date progress made via ST-based technologies by narrating studies categorized into either mechanistic elucidation or biomarker profiling (translational oncology) across multiple cancer types and their ways of deploying the research through ST. This updated review offers as a guidance with forward-looking viewpoints endorsed by many high-resolution ST tools being utilized to disentangle biological questions that may lead to clinical significance in the future.
Synthesis, Biological Evaluation and Reversal of Sulfonated Di‐ and Triblock Copolymers as Novel Parenteral Anticoagulants
Authors: Justyna Swieton, Joanna Miklosz, Natalia Bielicka, Aleksandra Frackiewicz, Karol Depczynski, Marta Stolarek, Piotr Bonarek, Kamil Kaminski, Piotr Rozga, Shin‐Ichi Yusa, Anna Gromotowicz‐Poplawska, Krzysztof Szczubialka, Dariusz Pawlak, Andrzej Mogielnicki, Bartlomiej Kalaska
Journal: Advanced Healthcare Materials (2024)

Abstract Despite targeting different coagulation cascade sites, all Food and Drug Administration‐approved anticoagulants present an elevated risk of bleeding, including potentially life‐threatening intracranial hemorrhage. Existing studies have not thoroughly investigated the efficacy and safety of sulfonate polymers in animal models and fully elucidate the precise mechanisms by which these polymers act. The activity and safety of sulfonated di‐ and triblock copolymers containing poly(sodium styrenesulfonate) (PSSS), poly(sodium 2‐acrylamido‐2‐methylpropanesulfonate) (PAMPS), poly(ethylene glycol) (PEG), poly(sodium methacrylate) (PMAAS), poly(acrylic acid) (PAA), and poly(sodium 11‐acrylamidoundecanoate) (PAaU) blocks are synthesized and assessed. PSSS‐based copolymers exhibit greater anticoagulant activity than PAMPS‐based ones. Their activity is mainly affected by the total concentration of sulfonate groups and molecular weight. PEG‐containing copolymers demonstrate a better safety profile than PAA‐containing ones. The selected copolymer PEG 47 ‐PSSS 32 exhibits potent anticoagulant activity in rodents after subcutaneous and intravenous administration. Heparin Binding Copolymer (HBC) completely reverses the anticoagulant activity of polymer in rat and human plasma. No interaction with platelets is observed. Selected copolymer targets mainly factor XII and fibrinogen, and to a lesser extent factors X, IX, VIII, and II, suggesting potential application in blood‐contacting biomaterials for anticoagulation purposes. Further studies are needed to explore its therapeutic applications fully.