tbuckley/cabot-search huggingface dataset:
Distinct pattern of genomic breakpoints in CML and BCR::ABL1-positive ALL: analysis of 971 patients
Authors: Lenka Hovorkova, Lucie Winkowska, Justina Skorepova, Manuela Krumbholz, Adela Benesova, Vaclava Polivkova, Julia Alten, Michela Bardini, Claus Meyer, Rathana Kim, Toby N. Trahair, Emmanuelle Clappier, Sabina Chiaretti, Michelle Henderson, Rosemary Sutton, Lucie Sramkova, Jan Stary, Katerina Machova Polakova, Rolf Marschalek, Markus Metzler, Giovanni Cazzaniga, Gunnar Cario, Jan Trka, Marketa Zaliova, Jan Zuna
Journal: Molecular Cancer (2024)

Abstract Background The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively. Methods By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed “Break-App” web tool to allow visualization and various analyses of the breakpoints. Pearson’s Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses. Results Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications. Conclusions Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs.
Anxiety and depression are associated with heightened risk of incident deep vein thrombosis: Mediation through stress‐related neural mechanisms
Authors: Rachel P. Rosovsky, Kenechukwu Mezue, Charbel Gharios, Giovanni Civieri, Alexander Cardeiro, Hadil Zureigat, Hui Chong Lau, Roger K. Pitman, Lisa Shin, Shady Abohashem, Michael T. Osborne, Farouc A. Jaffer, Ahmed Tawakol
Journal: American Journal of Hematology (2024)

Controversy exists as to whether anxiety and depression increase deep vein thrombosis (DVT) risk, and the mechanisms mediating potential links remain unknown. We aimed to evaluate the association between anxiety and depression and DVT risk and determine whether upregulated stress-related neural activity (SNA), which promotes chronic inflammation, contributes to this link. Our retrospective study included adults (N = 118 871) enrolled in Mass General Brigham Biobank. A subset (N = 1520) underwent clinical
Characterization of a Novel Pathogenic <scp><i>PLCG2</i></scp> Variant Leading to APLAID Syndrome Responsive to a TNF Inhibitor
Authors: Zhaohui Yang, Panfeng Tao, Xu Han, Anna Kozlova, Tingyan He, Egor Volchkov, Zoya Nesterenko, Dmitryi Pershin, Elena Raykina, Timur Fatkhudinov, Anastasia Korobeynikova, Ivona Aksentijevich, Jun Yang, Anna Shcherbina, Qing Zhou, Xiaomin Yu
Journal: Arthritis & Rheumatology (2024)

Autoinflammation and phospholipase C (PLC) γ2-associated antibody deficiency and immune dysregulation (APLAID) syndrome is an autoinflammatory disease caused by gain-of-function variants in PLCG2. This study investigates the pathogenic mechanism of a novel variant of PLCG2 in a patient with APLAID syndrome.
<scp>ERG</scp> Regulates Lymphatic Vessel Specification Genes and Its Deficiency Impairs Wound Healing‐Associated Lymphangiogenesis
Authors: Takashi Yamashita, Ulas Kaplan, Adri Chakraborty, Grace Marden, Sami Gritli, Daniel Roh, Andreea Bujor, Marcin Trojanowski, Giovanni Ligresti, Jeffrey L. Browning, Maria Trojanowska
Journal: Arthritis & Rheumatology (2024)

Objective Rarefaction of blood and lymphatic vessels in the skin has been reported in systemic sclerosis (SSc) (scleroderma). E26 transformation–specific–related factor (ERG) and Friend leukemia virus–induced erythroleukemia 1 (FLI‐1) are important regulators of angiogenesis, but their role in lymphatic vasculature is lesser known. The goal of this study was to determine the role of ERG and FLI‐1 in postnatal lymphangiogenesis and SSc lymphatic system defects. Methods Immunofluorescence was used to detect ERG and FLI‐1 in skin biopsy samples from patients with SSc and healthy controls. Transcriptional analysis of ERG or FLI‐1–silenced human dermal lymphatic endothelial cells (LECs) was performed using microarrays. Effects of ERG and FLI‐1 deficiency on in vitro tubulogenesis in human dermal LECs were examined using a Matrigel assay. ERG and FLI‐1 endothelial–specific knockouts and ERG lymphatic–specific knockouts were generated to examine vessel regeneration in mice. Results ERG and FLI‐1 protein levels were reduced in the blood and lymphatic vasculature in SSc skin biopsy samples. ERG levels were shown to regulate genes involved in lymphatic vessel specification, including vascular endothelial growth factor receptor 3/FLT‐4, lymphatic vessel endothelial hyaluronan receptor 1, SOX‐18, and prospero homeobox 1 (PROX‐1), whereas FLI‐1 enhanced the function of ERG. The ERG–FLT‐4 pathway regulated in vitro tubulogenesis in human LECs. Deficiency of ERG or FLI‐1 similarly impaired the function of blood vessels in mice. However, only ERG deficiency affected the regeneration of lymphatic vessels during wound healing. Conclusion ERG and FLI‐1 are essential regulators of blood and lymphatic vessel regeneration. Deficiency of ERG and FLI‐1 in SSc endothelial cells may contribute to the impairment of blood and lymphatic vasculature in patients with SSc. image
Lung Cancer in Ghana
Authors: Jane S Afriyie-Mensah, Mary-Ann Dadzie, Verna D N K Vanderpuye, Benedict Calys-Tagoe, Hafisatu Gbadamosi, Patrick Kafui Akakpo, Kow Entsua-Mensah, Adamu Issaka, Alex A Adjei
Journal: Journal of Thoracic Oncology (2024)
Periodontal pathogens and cancer development
Authors: Yuxi Zhou, Joerg Meyle, Sabine Groeger
Journal: Periodontology 2000 (2024)

Abstract Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti‐apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.
Understanding gut dysbiosis for hepatocellular carcinoma diagnosis and treatment
Authors: Jingjing Yu, Xiaoping Chen, Xiangliang Yang, Bixiang Zhang
Journal: Trends in Endocrinology and Metabolism (2024)

The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and for assessing the efficacy of immunotherapy in unresectable HCC. This review examines how gut microbiota dysbiosis, with varied functional profiles, contributes to HCCs of different etiologies. We discuss therapeutic strategies to modulate the gut microbiome including diets, antibiotics, probiotics, fecal microbiota transplantation, and nano-delivery systems, and underscore their potential as an adjunctive treatment modality for HCC.
Non-coding RNAs as regulators of autophagy in chondrocytes: Mechanisms and implications for osteoarthritis
Authors: Chenyu Zhu, Lingli Zhang, Xiaoqing Ding, Wei Wu, Jun Zou
Journal: Ageing Research Reviews (2024)

Osteoarthritis (OA) is a chronic degenerative joint disease with multiple causative factors such as aging, mechanical injury, and obesity. Autophagy is a complex dynamic process that is involved in the degradation and modification of intracellular proteins and organelles under different pathophysiological conditions. Autophagy, as a cell survival mechanism under various stress conditions, plays a key role in regulating chondrocyte life cycle metabolism and cellular homeostasis. Non-coding RNAs (ncRNAs) are heterogeneous transcripts that do not possess protein-coding functions, but they can act as effective post-transcriptional and epigenetic regulators of gene and protein expression, thus participating in numerous fundamental biological processes. Increasing evidence suggests that ncRNAs, autophagy, and their crosstalk play crucial roles in OA pathogenesis. Therefore, we summarized the complex role of autophagy in OA chondrocytes and focused on the regulatory role of ncRNAs in OA-associated autophagy to elucidate the complex pathological mechanisms of the ncRNA-autophagy network in the development of OA, thus providing new research targets for the clinical diagnosis and treatment of OA.
Inhibition of mast cell degranulation by novel small molecule MRGPRX2 antagonists
Authors: Joshua Wollam, Michelle Solomon, Christiane Villescaz, Marion Lanier, Samantha Evans, Corinne Bacon, David Freeman, Alexis Vasquez, Alan Vest, Jim Napora, Brittney Charlot, Christine Cavarlez, Andrew Kim, Lisa Dvorak, Brandon Selfridge, Liming Huang, Andres Nevarez, Harry Dedman, Jennifer Brooks, Stefan Frischbutter, Martin Metz, Nadine Serhan, Nicolas Gaudenzio, Gregg Timony, Esther Martinborough, Marcus F. Boehm, Veena Viswanath
Journal: Journal of Allergy and Clinical Immunology (2024)

Mas-related G protein-coupled receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent degranulation and has been implicated in multiple mast cell-mediated disorders, including chronic urticaria, atopic dermatitis, and pain disorders. Although it is a promising therapeutic target, few potent, selective, small molecule antagonists have been identified, and functional effects of human MRGPRX2 inhibition have not been evaluated in vivo.
Positive results of intense pulsed light-photodynamic therapy for moderate-to-severe rosacea: A prospective, single-arm study
Authors: Yun Wu, Yu Yan, Linglin Zhang, Xiaojing Liu, Jin Yang, Yajing Cao, Qihang Chang, Jia Yan, Qingyu Zeng, Peiru Wang, Xiuli Wang
Journal: Journal of the American Academy of Dermatology (2024)
Integration of genetics and MRD to define low risk patients with B-cell precursor acute lymphoblastic leukaemia with intermediate MRD levels at the end of induction
Authors: Anthony V. Moorman, Amir Enshaei, Daniel Murdy, Melvin Joy, Judith M. Boer, Monique L. den Boer, Rob Pieters, Valerie de Haas, Martin A. Horstmann, Gabriele Escherich, Bertil Johansson, Hanne V. Marquart, Kjeld Schmiegelow, Jeremy Hancock, John Moppett, Mats Heyman
Journal: Leukemia (2024)

Successful treatment of acute lymphoblastic leukaemia (ALL) relies on assigning patients to appropriate risk groups.Modern protocols use a combination of age, white cell count (WCC), CNS involvement, immunophenotype, genetics and treatment response to assign patients to different treatment pathways which determines chemo-intensity, randomisations offered and eligibility for transplant or CAR-T.Measurable residual disease (MRD) at the end of induction (EOI) is recognised as the single most important risk factor in ALL.Patients with B-cell precursor (BCP) ALL and undetectable MRD at the EOI have an excellent outcome with risk of relapse (RR) and overall survival (OS) at 5 years of ~5% and ~99% respectively [1,2].At the other end of the spectrum, patients with EOI MRD ≥ 5% had a poor outcome with 5 year event free survival (EFS) < 70% and these patients are invariably defined and treated as high-risk [3][4][5].Patients with high-risk genetics [KMT2A fusions, near-haploidy, low hypodiploidy, iAMP21, TCF3::HLF, and ABL-class fusions] or CNS disease at diagnosis also have an inferior outcome even when treated with intensive chemotherapy [6][7][8][9].Collectively patients with excellent MRD response, high-risk or CNS disease account for roughly onethird of BCP-ALL patients and their risk classification is straightforward.However, the risk classification of the remaining twothirds of BCP-ALL patients with intermediate MRD levels (MRD-IR cohort) is debatable.Analysis of UKALL2003 demonstrated that genotype-specific MRD thresholds improves the prediction of relapse and that the copy-number profiles of key genes was strongly linked with outcome [2,10].We sought to determine whether integrating MRD and genetics could identify clinically relevant subgroups within the MRD-IR cohort which might be suitable for treatment
The preferred surgical choice for intermediate-risk papillary thyroid cancer: total thyroidectomy or lobectomy? A systematic review and meta-analysis
Authors: Mingyu Cao, Tiexin Yu, Xingyu Miao, Zhijing Wu, Wenlong Wang
Journal: International Journal of Surgery (2024)

Background: The optimal surgical approach for intermediate-risk papillary thyroid carcinoma (IR-PTC) (according to ATA definition), whether total thyroidectomy (TT) or lobectomy (LT), has remained a contentious clinical grey area for several decades. This systematic review and meta-analysis aim to provide robust evidence and address this clinical dilemma comprehensively. Materials and Methods: A comprehensive literature search was conducted in Pubmed, Embase, Web of Science, and the Cochrane Library from 1 st January 2009 to 29 th December 2023 to evaluate the impact of different surgical options (TT or LT) on patients with IR-PTC. The primary outcomes included survival, recurrence rates, and postoperative complications. I 2 and sensitivity analysis was used to explore the heterogeneity. Results: A total of 8 studies involving 2984 participants were included in this meta-analysis and systematic review. The results indicated that LT was a superior choice for mitigating complications compared to TT (RR, 0.32; 95%CI, 0.24-0.44, P &lt;0.01), particularly for transient complications (RR, 0.24; 95%CI, 0.08-0.65, P &lt;0.01), such as the transient parathyroid dysfunction (RR, 0.04; 95%CI, 0.01-0.15, P &lt;0.01). However, TT did not increase the risk of recurrent laryngeal nerve palsy (RR, 0.78; 95%CI, 0.24-2.47, P =0.67), hemorrhage/seroma (RR, 0.77; 95%CI, 0.48-1.25, P =0.30) and permanent complications (RR, 0.18; 95%CI, 0.02-1.42, P =0.10). Besides, both LT and TT presented similar effect on survival outcomes (Overall Survival: RR, 1.00; 95%CI, 0.97-1.03, P =0.92, Disease-Specific Survival: RR, 0.99; 95%CI, 0.97-1.02, P =0.69, Recurrence-Free Survival: RR, 1.00; 95%CI, 0.96-1.05, P =0.86), recurrence (RR, 1.05; 95%CI, 0.76-1.46, P =0.76). Conclusion: The present meta-analysis revealed that TT did not yield improved outcomes in IR-PTC patients, but was associated with an increased incidence of temporary complications. In light of these findings, it may be advisable to consider LT as the optimal choice for IR-PTC patients.
A bioinspired doxorubicin-carried albumin Nanocage against aggressive Cancer via systemic targeting of tumor and lymph node metastasis
Authors: Haroon Iqbal, Anam Razzaq, Fan Liu, Fangrui Zhang, Jing Tao, Ting Li, Yingqian Jiang, Zhenduo Zhao, Mengting Qin, Xuehua Lin, Hengte Ke, Huabing Chen, Yibin Deng
Journal: Journal of Controlled Release (2024)
Ovarian cancer risk factors in relation to family history
Authors: Guoqiao Zheng, Louise Baandrup, Jiangrong Wang, Rasmus Hertzum-Larsen, Charlotte Gerd Hannibal, Mette Tuxen Faber, Karin Sundström, Susanne K Kjær
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Women with a family history of breast and/or ovarian cancer have an increased ovarian cancer risk. Yet it remains uncertain if common ovarian cancer risk factors—especially those that are modifiable—affect this high-risk population similarly to the general population. Methods Using the Danish and Swedish nationwide registers, we established 2 nested case-control study populations in women with a family history of breast and/or ovarian cancer (2138 ovarian cancers, 85 240 controls) and women without (10 730 ovarian cancers, 429 200 controls). The overall and histology-specific associations were assessed with conditional logistic regression. The country-specific estimates were combined based on a fixed-effect assumption. Results Multiparity, hysterectomy, tubal ligation, salpingectomy, and oral contraceptive (OC) use were associated with a reduced risk of ovarian cancer in women with and without a family history, while endometriosis and menopausal hormone therapy were associated with increased risk. Multiparity and OC use presented protective effects across all histologic subtypes except mucinous ovarian cancer, which was not associated with OC use. Menopausal hormone treatment increased the risk of serous ovarian cancer but decreased the risk of the mucinous and clear cell cancers. Endometriosis was especially related to an increased risk of endometrioid and clear cell ovarian cancer. Conclusion Factors associated with a decreased ovarian cancer risk were similar between women with and without a family history of breast and/or ovarian cancer. Given the higher baseline risk for women with a family history, special attention should be paid to risk factors like endometriosis and nulliparity in this high-risk population.
Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance
Authors: Siqi Zhang, Xiaohui Ma, Jiang Wu, Jieting Shen, Yuntao Shi, Xingkai Wang, Lin Xie, Xiaona Sun, Yuxuan Wu, Hao Tian, Xin Gao, Xueyao Chen, Hongyi Huang, Lu Chen, Xuekai Song, Qichen Hu, Hailong Zhang, Feng Wang, Zhao-Hui Jin, Ming-Rong Zhang, Rui Wang, Kuan Hu
Journal: Acta Pharmaceutica Sinica B (2024)

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
Spatial metabolomics highlights metabolic reprogramming in acute myeloid leukemia mice through creatine pathway
Authors: Yucheng Bao, Jing Qiao, Wenjie Gong, Ruihong Zhang, Yanting Zhou, Yinyin Xie, Yuan Xie, Jiuming He, Tong Yin
Journal: Acta Pharmaceutica Sinica B (2024)

Acute myeloid leukemia (AML) is recognized as an aggressive cancer that is characterized by significant metabolic reprogramming. Here, we applied spatial metabolomics to achieve high-throughput, in situ identification of metabolites within the liver metastases of AML mice. Alterations at metabolite and protein levels were further mapped out and validated by integrating untargeted metabolomics and proteomics. This study showed a downregulation in arginine's contribution to polyamine biosynthesis and urea cycle, coupled with an upregulation of the creatine metabolism. The upregulation of creatine synthetases Gatm and Gamt, as well as the creatine transporter Slc6a8, resulted in a marked accumulation of creatine within tumor foci. This process further enhances oxidative phosphorylation and glycolysis of leukemia cells, thereby boosting ATP production to foster proliferation and infiltration. Importantly, we discovered that inhibiting Slc6a8 can counter these detrimental effects, offering a new strategy for treating AML by targeting metabolic pathways.
Acute cough in outpatients: what causes it, how long does it last, and how severe is it for different viruses and bacteria?
Authors: Mark H. Ebell, Dan J. Merenstein, Bruce Barrett, Michelle Bentivegna, Cassie Hulme, Caroline Hamer, Sarah Walters, Alea Sabry, Shari Barlow
Journal: Clinical Microbiology and Infection (2024)
How to verify and validate a clinical microbiology test before it can be used in routine diagnostics: a practical guide
Authors: Erlangga Yusuf, Maarten J. Schijffelen, Mariska Leeflang
Journal: Clinical Microbiology and Infection (2024)

BackgroundBefore a new test can be routinely used in your laboratory, its reliability must be established in the laboratory where it will be used. International standards demand validation and verification procedures for new tests. The International Organization for Standardization (ISO) 15189 was recently updated, and the European Commission's In Vitro Diagnostic Regulation (IVDR) came into effect. These events will likely increase the need for validation and verification procedures.ObjectivesThis paper aims to provide practical guidance in validating or verifying microbiology tests, including antimicrobial susceptibility tests in a clinical microbiology laboratory.SourcesIt summarizes and interprets certain parts of standards such as ISO 15189:2022, and regulations, such as IVDR 2017/746 regarding validation or verification of a new test in a routine clinical microbiology laboratory.ContentThe reasons for choosing a new test and the outline of the validation and verification plan are discussed. Furthermore, the following topics are touched upon: the choice of reference standard, number of samples, testing procedures, how to solve the discrepancies between results from new test and reference standard, and acceptance criteria. Arguments for selecting certain parameters (such as reference standard and sample size) and examples are given.ImplicationsWith the expected increase in validation and verification procedures because of the implementation of IVDR, this paper may aid in planning and executing these procedures.
A strategy of “adding fuel to the flames” enables a self-accelerating cycle of ferroptosis-cuproptosis for potent antitumor therapy
Authors: Lin Huang, Jiaoyang Zhu, Guochao Wu, Wei Xiong, Jie Feng, Chenggong Yan, Jing Yang, Zongheng Li, Qingdeng Fan, Bin Ren, Yan Li, Chaomin Chen, Xiangrong Yu, Zheyu Shen
Journal: Biomaterials (2024)