tbuckley/cabot-search huggingface dataset:
Medical imaging utilization in migrants compared with nonmigrants in a universal healthcare system: A population-based matched cohort study
Authors: Giancarlo Di Giuseppe, Rinku Sutradhar, Priscila Pequeno, Marilyn L Kwan, Diana L Miglioretti, Rebecca Smith-Bindman, Jason D Pole
Journal: PLoS Medicine (2024)

Background Medical imaging is an integral part of healthcare. Globalization has resulted in increased mobilization of migrants to new host nations. The association between migration status and utilization of medical imaging is unknown. Methods and findings A retrospective population-based matched cohort study was conducted in Ontario, Canada from April 1, 1995 to December 31, 2016. A total of 1,848,222 migrants were matched 1:1 to nonmigrants in the year of migration on age, sex, and geography. Utilization of computed tomography (CT), magnetic resonance imaging (MRI), radiography, and ultrasonography was determined. Rate differences per 1,000 person-years comparing migrants to nonmigrants were calculated. Relative rates were calculated using a recurrent event framework, adjusting for age, sex, and time-varying socioeconomic status, comorbidity score, and access to a primary care provider. Estimates were stratified by migration age: children and adolescents (≤19 years), young adults (20 to 39), adults (40 to 59), and older adults (≥60). Utilization rates of CT, MRI, and radiography were lower for migrants across all age groups compared with Ontario nonmigrants. Increasing age at migration was associated with larger differences in utilization rates. Older adult migrants had the largest gap in imaging utilization. The longer the time since migration, the larger the gap in medical imaging use. In multivariable analysis, the relative rate of imaging was approximately 20% to 30% lower for migrants: ranging from 0.77 to 0.88 for CT and 0.72 to 0.80 for MRI imaging across age groups. Radiography relative rates ranged from 0.84 to 0.90. All migrant age groups, except older adults, had higher rates of ultrasonography. The indication for imaging was not captured, thus it was not possible to determine if the imaging was necessary. Conclusions Migrants utilized less CT, MRI, and radiography but more ultrasonography. Older adult migrants used the least amount of imaging compared with nonmigrants. Future research should evaluate whether lower utilization is due to barriers in healthcare access or health-seeking behaviors within a universal healthcare system.
Recent and recurrent autopolyploidization fueled diversification of snow carp on the Tibetan Plateau
Authors: Xinxin Li, Min Wang, Ming Zou, Xiaotong Guan, Shaohua Xu, Weitao Chen, Chongnv Wang, Yiyu Chen, Shunping He, Baocheng Guo
Journal: Molecular Biology and Evolution (2024)

Abstract Whole-genome duplication (WGD), or polyploidization, is a major contributor to biodiversity. However, the establishment and survival of WGDs are often considered to be stochastic, since elucidating the processes of WGD establishment remains challenging. In the current study, we explored the processes leading to polyploidy establishment in snow carp (Cyprinidae: Schizothoracinae), a predominant component of the ichthyofauna of the Tibetan Plateau and its surrounding areas. Using large-scale genomic data from isoform sequencing, we analyzed ohnolog genealogies and divergence in hundreds to thousands of gene families across major snow carp lineages. Our findings demonstrated that independent autopolyploidization subsequent to speciation was prevalent, while autopolyploidization followed by speciation also occurred in the diversification of snow carp. This was further supported by matrilineal divergence and drainage evolution evidence. Contrary to the long-standing hypothesis that ancient polyploidization preceded the diversification of snow carp, we determined that polyploidy in extant snow carp was established by recurrent autopolyploidization events during the Pleistocene. These findings indicate that the diversification of extant snow carp resembles a coordinated duet: first, the uplift of the Tibetan Plateau orchestrated the biogeography and diversification of their diploid progenitors; then, the extensive Pliocene–Pleistocene climate changes acted as relay runners, further fueling diversification through recurrent autopolyploidization. Overall, this study not only reveals a hitherto unrecognized recent WGD lineage in vertebrates but also advances current understanding of WGD processes, emphasizing that WGD establishment is a nonstochastic event, emerging from numerous adaptations to environmental challenges and recurring throughout evolutionary history rather than merely in plants.
Association of childhood obesity or weight change with early-onset follicular occlusion triad among children
Authors: Seong Rae Kim, Seong-Joon Koh, Hyunsun Park
Journal: British Journal of Dermatology (2024)

Abstract Background The effects of childhood obesity or weight gain on the development of early-onset follicular occlusion triad (FOT) among children, which includes hidradenitis suppurativa (HS), acne conglobata (AC), and dissecting cellulitis of the scalp (DCS), remain unknown. Objectives To investigate the association between body mass index (BMI) or its changes and early-onset FOT development. Methods This nationwide population-based longitudinal cohort study included a cohort of 2,012,928 Korean children who underwent two consecutive health examinations at 30–36 months and 42–48 months of age between 2009 and 2020. The BMI and its changes derived during health screenings at 30–36 and 42–48 months. We performed multivariate Cox proportional hazards regression analyses to estimate the risk of early-onset FOT, including HS, AC, and DCS. Results During the follow-up, 1,283 FOT, including 143 HS, 1,068 AC, and 72 DCS, events were identified. Children with obesity were at an elevated risk of early-onset FOT compared to those with a normal weight (FOT: adjusted hazard ratio [aHR] 1.49, 95% confidence interval [CI] 1.21–1.84; HS: aHR 2.30, 95% CI 1.39–3.82; AC: aHR 1.36, 95% CI 1.07–1.73). BMI gain was correlated with an elevated risk of early-onset FOT, particularly HS, whereas BMI loss was linked to a decreased risk of early-onset FOT, especially HS. Children who became obese had an increased early-onset FOT risk (aHR 1.51, 95% CI 1.07–2.14) compared to those who maintained a normal weight. Children who reduced from obese to normal weight exhibited a decreased risk of early-onset FOT (FOT: aHR 0.41, 95% CI 0.17–0.96, P for trend=0.02; HS: P for trend=0.05) compared to obese children who retained their weight. Conclusions Childhood obesity was associated with an elevated risk of early-onset FOT, including HS and AC. Weight gain was correlated with an increased risk of early-onset FOT, especially HS, while weight loss was associated with a decreased risk of early-onset FOT, particularly HS. Implementing purposeful weight-reduction strategies may be helpful in preventing early-onset FOT development.
Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in patients from China mainland, Taiwan, and South Korea with moderate to severe plaque psoriasis: a phase 3 randomized clinical trial
Authors: Jianzhong Zhang, Yangfeng Ding, Ping Wang, Linfeng Li, Weili Pan, Yan Lu, Hao Cheng, Xian Jiang, Ji-Chen Ho, Shuping Guo, Leona Liu, Arkendu Chatterjee, Renata M Kisa, Subhashis Banerjee
Journal: British Journal of Dermatology (2024)

Abstract Background Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the United States, European Union, Japan, South Korea, China, and other countries for treatment of moderate-to-severe plaque psoriasis. Objective To evaluate the efficacy and safety of deucravacitinib in Asian patients with moderate to severe plaque psoriasis. Methods In the 52-week, blinded, phase 3 POETYK PSO-3 trial (NCT04167462), patients were randomized 1 : 2 to placebo (n = 74) or deucravacitinib 6 mg once daily (n = 146) for 16 weeks followed by deucravacitinib alone. Coprimary endpoints were achievement of ≥ 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) at Week 16. Efficacy and safety were evaluated throughout. Results At Week 16, significantly higher proportions of patients receiving deucravacitinib versus placebo achieved PASI 75 (68.8% vs. 8.1%; P &amp;lt; 0.0001) and sPGA 0/1 (55.6% vs. 6.8%; P &amp;lt; 0.0001). Response rates with deucravacitinib were maintained through Week 52. Common adverse events included upper respiratory tract infection and nasopharyngitis. Serious adverse event and discontinuation rates were low. Conclusions Deucravacitinib was efficacious and well tolerated in Asian patients with moderate to severe plaque psoriasis.
Evaluation of proximod, a selective agonist of sphingosine-1-phosphate receptor-1, in healthy volunteers and patients with rheumatoid arthritis: a phase 1, double-blind, randomised, placebo-controlled, ascending dose trial
Authors: Hong Zhang, Qianqian Li, Cuiyun Li, Min Wu, Hong Chen, Yang Li, Feng You, Yanshi Zhao, Jing Jin, Xiaoguang Chen, Yanhua Ding
Journal: The Lancet Rheumatology (2024)
COVID-19 vaccine effectiveness against SARS-CoV-2-confirmed hospitalisation in the eastern part of the WHO European Region (2022–2023): a test-negative case-control study from the EuroSAVE network
Authors: Mark A Katz, Sandra Cohuet, Silvia Bino, Olgha Tarkhan-Mouravi, Besfort Kryeziu, Dinagul Otorbaeva, Kristina Stavridis, Maja Stosic, Jonilda Sulo, Ann Machablishvili, Ariana Kalaveshi, Abdyldaeva Sayragul Zhusupovna, Katerina Kjirkovikj Kolevska, Dragana Plavsa, Iris Hasibra, Khatuna Zakhashvili, Zana Kaçaniku-Deva, Uzakbaeva Aynura Zarylbekovna, Elizabeta Jancheska, Verica Jovanovic, James Humphreys, Jennifer Howard, Kirill Stolyarov, Oksana Artemchuk, Marc-Alain Widdowson, Iris Finci, Angela M C Rose, Richard Pebody
Journal: The Lancet Regional Health - Europe (2024)

Understanding COVID-19 vaccine effectiveness (VE) in preventing severe disease is critical to inform vaccine policy. We used the test-negative design to estimate VE against SARS-CoV-2-confirmed hospitalisation in adults ≥18 years in the eastern WHO European Region.
Zinc Sulfide Nanoparticles Serve as Gas Slow-release Bioreactors for H2S Therapy of Ischemic Stroke
Authors: Guangqiang Li, Ruolin Zhang, Keyu Chen, Jiawen Dong, Zhihao Yang, Hangyu Chen, Haipeng Wang, Hui Wang, Huali Lei, Wendai Bao, Min Zhang, Zhidong Xiao, Liang Cheng, Zhiqiang Dong
Journal: Biomaterials (2024)
Albumins Constrainting the Conformation of Mitochondria-targeted Photosensitizers for Tumor-specific Photodynamic Therapy
Authors: Bin Fang, Hua Bai, Jiaxin Zhang, Limin Wang, PanPan Li, Yihao Ge, Hui Yang, Hui Wang, Bo Peng, Wenbo Hu, Huili Ma, Xi Chen, Li Fu, Lin Li
Journal: Biomaterials (2024)
Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma
Authors: Erin McGillivray, Karam Ashouri, Eftychia Chatziioannou, Jesús Antonio Ocejo Gallegos, Jabra Zarka, Jacob Kechter, Angelina S Hwang, Kevin Zhang, Milton Barros, Justin Yeh, Ian Okazaki, Andrew B Crocker, Takuya Maeda, Soo J Park, Jacob Choi, Mia Andreoli, Tarneem Darwish, David J Savage, Kevin B Kim, Jayant Gupta, James Shen, Keisuke Shirai, April Choi, Lori Pai, Vinicius de Lima Vazquez, Justin Moser, Teresa Amaral, Leonel F Hernandez Aya, Jose Lutzky, Yana G Najjar, Collin M Costello, Aaron R Mangold, Shailender Bhatia, Geoffrey T Gibney, Jeffrey M Farma, Gregory A Daniels, Jeffrey Sosman, Sunandana Chandra, Ankit Mangla, Kathryn Bollin, Patrícia Abrão Possik, Carla Daniela Robles Espinoza, Fumito Ito, Gino K In
Journal: British Journal of Dermatology (2024)

Abstract Background Combination immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) leads to high response rates and improved survival in patients with advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). Objectives To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a diverse, real-world population of patients with ALM. Methods This multi-institutional retrospective study analysed patients with histologically confirmed ALM treated with a combination of PD-1 and CTLA-4 inhibitors between 2010 and 2022. The primary objective of the study was the objective response rate (ORR) as per the RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). Results In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n = 81; 74.3%). The ORR for the entire cohort was 18.3% [95% confidence interval (CI) 11.6–26.9], with 9 (8.3%) complete and 11 (10.1%) partial responses. A further 22 patients (20.2%) had stable disease, and the disease control rate was 38.5%. Median PFS was 4.2 months (95% CI 3.25–5.62), while median OS was 17 months (95% CI 12.4–23.1). Ninety-five patients (87.2%) had a treatment-related adverse event, with 40.4% (n = 44/109) experiencing at least one grade 3 or 4 toxicity. Elevated lactate dehydrogenase (P = 0.04), ≥ 2 lines of prior treatment (P = 0.03) and Asian ethnicity (P = 0.04) were associated with worse OS, while Hispanic/Latino ethnicity was associated with better OS (P = 0.02). Conclusions Combination PD-1 and CTLA-4 blockade is less effective for ALM than for CM, despite similar toxicity. In particular, Asian patients appear to derive less benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.
Iatrogenic infection associated with positive airway pressure therapy: A review of precedent, epidemiology, bioaerosols and risk mitigation.
Authors: Olivia A McGuiness, Sheila Sivam, Collette Menadue, Rania O Salama, Sebastiaan Van Hal, Brendon J Yee, Amanda J Piper
Journal: Sleep Medicine Reviews (2024)

Currently, evidence-based guidelines about cleaning positive airway pressure devices for maintenance or reprocessing for a new user do not exist. There is no strong evidence of harm caused by contaminated positive airway pressure equipment. Future research opportunities exist to streamline cleaning processes, assure hygiene, and reduce waste.
Ubiquitin regulatory X (UBX) domain-containing protein 6 is essential for autophagy induction and inflammation control in macrophages
Authors: Young Jae Kim, Sung-Gwon Lee, So Young Park, Sang Min Jeon, Soo In Kim, Kyung Tae Kim, Taylor Roh, Sang-Hee Lee, Min Joung Lee, Jinyoung Lee, Hyeon Ji Kim, So Eui Lee, Jin Kyung Kim, Jun Young Heo, In Soo Kim, Chungoo Park, Seungwha Paik, Eun-Kyeong Jo
Journal: Cellular and Molecular Immunology (2024)

Abstract Ubiquitin regulatory X (UBX) domain-containing protein 6 (UBXN6) is an essential cofactor for the activity of the valosin-containing protein p97, an adenosine triphosphatase associated with diverse cellular activities. Nonetheless, its role in cells of the innate immune system remains largely unexplored. In this study, we report that UBXN6 is upregulated in humans with sepsis and may serve as a pivotal regulator of inflammatory responses via the activation of autophagy. Notably, the upregulation of UBXN6 in sepsis patients was negatively correlated with inflammatory gene profiles but positively correlated with the expression of Forkhead box O3, an autophagy-driving transcription factor. Compared with those of control mice, the macrophages of mice subjected to myeloid cell-specific UBXN6 depletion exhibited exacerbated inflammation, increased mitochondrial oxidative stress, and greater impairment of autophagy and endoplasmic reticulum-associated degradation pathways. UBXN6-deficient macrophages also exhibited immunometabolic remodeling, characterized by a shift to aerobic glycolysis and elevated levels of branched-chain amino acids. These metabolic shifts amplify mammalian target of rapamycin pathway signaling, in turn reducing the nuclear translocation of the transcription factor EB and impairing lysosomal biogenesis. Together, these data reveal that UBXN6 serves as an activator of autophagy and regulates inflammation to maintain immune system suppression during human sepsis.
Discovery of a novel AhR–CYP1A1 axis activator for mitigating inflammatory diseases using an in situ functional imaging assay
Authors: Feng Zhang, Bei Zhao, Yufan Fan, Lanhui Qin, Jinhui Shi, Lin Chen, Leizhi Xu, Xudong Jin, Mengru Sun, Hongping Deng, Hairong Zeng, Zhangping Xiao, Xin Yang, Guangbo Ge
Journal: Acta Pharmaceutica Sinica B (2024)

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.
Identification of a Novel CRF01_AE/CRF07_BC (CRF163_0107) Circulating Recombinant Form in Shenyang city, the economic center of Northeast China
Authors: Wenjun Xing, Minghui An, Bin Zhao, Lin Wang, Hui Zhang, QingHai Hu, Haibo Ding, Hong Shang, Xiaoxu Han
Journal: Journal of Infection (2024)
Inborn errors of immunity are associated with increased COVID-19-related hospitalization and intensive care compared to the general population
Authors: Hannes Lindahl, Fredrik Kahn, Åsa Nilsdotter-Augustinsson, Mats Fredrikson, Pontus Hedberg, Isabela Killander Möller, Lotta Hansson, Lisa Blixt, Sandra Eketorp Sylvan, Anders Österborg, Soo Aleman, Christina Carlander, Sofia Nyström, Peter Bergman
Journal: Journal of Allergy and Clinical Immunology (2024)
The DLEU2/miR-15a/miR-16-1 cluster shapes the immune microenvironment of chronic lymphocytic leukemia
Authors: Ronghua Zhang, Priyanka Khare, Priyanka Banerjee, Cristina Ivan, Sarah Schneider, Federica Barbaglio, Karen Clise-Dwyer, Vanessa Behrana Jensen, Erika Thompson, Marisela Mendoza, Nicholas Chiorazzi, Shih-Shih Chen, Xiao-Jie Joy Yan, Nitin Jain, Paolo Ghia, Federico Caligaris-Cappio, Rima Mendonsa, Sashi Kasimsetty, Ryan Swoboda, Recep Bayraktar, William Wierda, Varsha Gandhi, George A. Calin, Michael J. Keating, Maria Teresa Sabrina Bertilaccio
Journal: Blood Cancer Journal (2024)

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2−/−γc−/− MEC1-based xenotransplantation model. The DLEU2/miR-16 locus was found downmodulated in monocytes/macrophages of leukemic mice. To validate the role of this cluster in the tumor immune microenvironment, we generated a mouse model that simultaneously mimics the overexpression of hTCL1 and the germline deletion of the minimal deleted region (MDR) encoding the DLEU2/miR-15a/miR-16-1 cluster. This model provides an innovative and faster CLL system where monocyte differentiation and macrophage polarization are exacerbated, and T-cells are dysfunctional. MDR deletion inversely correlates with the levels of predicted target proteins including BCL2 and PD1/PD-L1 on murine CLL cells and immune cells. The inverse correlation of miR-15a/miR-16-1 with target proteins has been confirmed on patient-derived immune cells. Forced expression of miR-16-1 interferes with monocyte differentiation into tumor-associated macrophages, indicating that selected ncRNAs drive the protumor phenotype of non-malignant immune cells.
Sensitive Detection of Urothelial Cancer via High-volume Urine DNA Analysis
Authors: Jussi Nikkola, Lauri Ryyppö, Juuso Vuorinen, Heini Kallio, Hanna Selin, Pyry Jämsä, Jonne Åkerla, Tuomo Virtanen, Tarmo Pekkarinen, Antti Kaipia, Johanna Pulkkinen, Gillian Vandekerkhove, David C Müller, Alexander W Wyatt, Peter C Black, Matti Nykter, Thea Veitonmäki, Matti Annala
Journal: European Urology (2024)
A phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed/refractory acute myeloid leukemia
Authors: Yuchen Liu, Dominique R Bollino, Osman M Bah, Erin T Strovel, Tien Van Le, Jinoos Zarrabi, Sunita Philip, Rena G Lapidus, Maria R Baer, Sandrine Niyongere, Vu H. Duong, Christine C Dougherty, Jan Hendrik Beumer, Katherine D Caprinolo, Farin Kamangar, Ashkan Emadi
Journal: Blood (2024)

Glutamine dependency has been shown to be a metabolic vulnerability in acute myeloid leukemia (AML). Prior studies using several in vivo AML models showed that depletion of plasma glutamine induced by the long-acting crisantaspase (pegcrisantaspase or PegC) was synergistic with the BCL-2 inhibitor venetoclax (Ven), resulting in significantly reduced leukemia burden and enhanced survival. Here, we report a phase 1 study (NCT04666649) of Ven and PegC combination (VenPegC) for treating adult patients with relapsed or refractory AML, including patients who had previously received Ven. The primary endpoints were incidence of regimen limiting toxicities (RLT) and maximum tolerated dose (MTD). Twenty-five patients received at least one PegC dose with Ven and 18 efficacy-evaluable patients completed at least one VenPegC cycle; 12 (67%) had previously received Ven. Hyperbilirubinemia was the RLT and occurred in 60% of patients treated with VenPegC; 20% had Grade ≥3 bilirubin elevations. MTD was determined to be Ven 400 mg daily with biweekly PegC 750 IU/m2. The most common treatment-related adverse events of any Grade in 25 patients who received VenPegC included antithrombin III decrease (52%), elevated transaminases (36-48%), fatigue (28%), and hypofibrinogenemia (24%). No thromboembolic or hemorrhagic adverse events or clinical pancreatitis were observed. The overall complete remission rate in efficacy-evaluable patients was 33%. Response correlated with alterations in proteins involved in mRNA translation. In patients with RUNX1 mutations, the composite complete rate was 100%.
Genetic iron overload aggravates and pharmacological iron restriction improves MDS pathophysiology in a preclinical study
Authors: Ada Antypiuk, Steven Vance, Richa Sharma, Sara T. Passos, Michela Asperti, Shobana Navaneethabalakrishnan, Franz Durrenberger, Vania Manolova, Francesca Vinchi
Journal: Blood (2024)