tbuckley/cabot-search huggingface dataset:
Colorectal Cancer Recurrence Prediction Using a Tissue-Free Epigenomic Minimal Residual Disease Assay
Authors: Yoshiaki Nakamura, Yuichiro Tsukada, Nobuhisa Matsuhashi, Tatsuro Murano, Manabu Shiozawa, Yusuke Takahashi, Eiji Oki, Masahiro Goto, Yoshinori Kagawa, Akiyoshi Kanazawa, Takashi Ohta, Akira Ouchi, Hideaki Bando, Hiroshi Uchigata, Chiemi Notake, Hiroaki Ikematsu, Takayuki Yoshino
Journal: Clinical Cancer Research (2024)

Posttreatment detection of ctDNA is strongly predictive of recurrence. Most minimal/molecular residual disease assays require prior tissue testing to guide ctDNA analysis, resulting in lengthy time to initial results and unevaluable patients.
Phosphate Ion‐Responsive and Calcium Peroxide‐Based Nanomedicine for Bone‐Targeted Treatment of Breast Cancer Bone Metastasis
Authors: Dehui Fan, Jing Li, Luwei Li, Ming An, Hua Yang, Guoqiang Zhou, Shutao Gao, Massimo Bottini, Jinchao Zhang, Kun Ge
Journal: Advanced Healthcare Materials (2024)

Abstract The treatment of breast cancer bone metastasis is an unresolved clinical challenge, mostly because currently therapeutic approaches cannot simultaneously block the tumor growth and repair the osteolytic bone injuries at the metastatic site. Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion‐responsive and calcium peroxide‐based nanoparticles carrying the bone‐targeting agent zoledronic acid on the surface and loaded with the photosensitizer indocyanine green. Following intravenous administration to a mouse model of breast cancer bone metastasis, the nanoparticles efficiently accumulate at the bone metastasis site, react with free phosphate ions, and form hydroxyapatite nanoaggregates and O 2 , while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor‐bearing legs with an 808 nm laser source, the O 2 and free photosensitizer produced 1 O 2 by the reaction of the nanoparticles with phosphate ions, further boosting the anti‐tumor effect. Tumor killing hampers the vicious cycle at the site of bone metastasis, translating to osteolysis blockade and further encouraging the remineralization of bone matrix. This work sheds light on the development of a novel, safe, and efficient approach for the treatment of breast cancer bone metastasis.
Disparate Pathways for Extrachromosomal DNA Biogenesis and Genomic DNA Repair
Authors: John C. Rose, Julia A. Belk, Ivy Tsz-Lo Wong, Jens Luebeck, Hudson T. Horn, Bence Daniel, Matthew G. Jones, Kathryn E. Yost, King L. Hung, Kevin S. Kolahi, Ellis J. Curtis, Calvin J. Kuo, Vineet Bafna, Paul S. Mischel, Howard Y. Chang
Journal: Cancer Discovery (2024)

Abstract Oncogene amplification on extrachromosomal DNA (ecDNA) is a pervasive driver event in cancer, yet our understanding of how ecDNA forms is limited. In this study, we couple a CRISPR-based method for ecDNA induction with extensive characterization of newly formed ecDNAs to examine their biogenesis. We find that DNA circularization is efficient, irrespective of 3D genome context, with the formation of 800 kb, 1 Mb, and 1.8 Mb ecDNAs reaching or exceeding 15%. We show nonhomologous end joining and microhomology-mediated end joining both contribute to ecDNA formation, whereas inhibition of DNA-PK catalytic subunit and ATM have opposing impacts on ecDNA formation. ecDNA and the corresponding chromosomal excision scar can form at significantly different rates and respond differently to DNA-PK catalytic subunit and ATM inhibition. Taken together, our results support a model of ecDNA formation in which double-strand break ends dissociate from their legitimate ligation partners prior to joining of illegitimate ends to form the ecDNA and excision scar. Significance: Our study harnesses a CRISPR-based method to examine ecDNA biogenesis, uncovering efficient circularization between double-strand breaks. ecDNAs and their corresponding chromosomal scars can form via nonhomologous end joining or microhomology-mediated end joining, but the ecDNA and scar formation processes are distinct. Based on our findings, we establish a mechanistic model of excisional ecDNA formation.
Wirelessly Actuated Microfluidic Pump and Valve for Controlled Liquid Delivery in Dental Implants
Authors: Yilan Xu, Honglu Lin, Boyang Xiao, Hutomo Tanoto, Joel Berinstein, Alend Khoshnaw, Simon Young, Yuxiao Zhou, Xiaoguang Dong
Journal: Advanced Healthcare Materials (2024)

Enabling minimally invasive and precise control of liquid release in dental implants is crucial for therapeutic functions such as delivering antibiotics to prevent biofilm formation, infusing stem cells to promote osseointegration, and administering other biomedicines. However, achieving controllable liquid cargo release in dental implants remains challenging due to the lack of wireless and miniaturized fluidic control mechanisms. Here wireless miniature pumps and valves that allow remote activation of liquid cargo delivery in dental implants, actuated and controlled by external magnetic fields (<65 mT), are reported. A magnet-screw mechanism in a fluidic channel to function as a piston pump, alongside a flexible magnetic valve designed to open and close the fluidic channel, is proposed. The mechanisms are showcased by storing and releasing of liquid up to 52 µL in a dental implant. The liquid cargos are delivered directly to the implant-bone interface, a region traditionally difficult to access. On-demand liquid delivery is further showed by a metal implant inside both dental phantoms and porcine jawbones. The mechanisms are promising for controllable liquid release after implant placement with minimal invasion, paving the way for implantable devices that enable long-term and targeted delivery of therapeutic agents in various bioengineering applications.
A deep learning system for myopia onset prediction and intervention effectiveness evaluation in children
Authors: Ziyi Qi, Tingyao Li, Jun Chen, Jason C. Yam, Yang Wen, Gengyou Huang, Hua Zhong, Mingguang He, Dan Zhu, Rongping Dai, Bo Qian, Jingjing Wang, Chaoxu Qian, Wei Wang, Yanfei Zheng, Jian Zhang, Xianglong Yi, Zheyuan Wang, Bo Zhang, Chunyu Liu, Tianyu Cheng, Xiaokang Yang, Jun Li, Yan-Ting Pan, Xiaohu Ding, Ruilin Xiong, Yan Wang, Yan Zhou, Dagan Feng, Sichen Liu, Linlin Du, Jinliuxing Yang, Zhuoting Zhu, Lei Bi, Jinman Kim, Fangyao Tang, Yuzhou Zhang, Xiujuan Zhang, Haidong Zou, Marcus Ang, Clement C. Tham, Carol Y. Cheung, Chi Pui Pang, Bin Sheng, Xiangui He, Xun Xu
Journal: npj Digital Medicine (2024)

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of −17.8%, 95% CI: −29.4%, −6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children.
Flow cytometric analysis of erythroid precursors and mutational signatures of lower risk myelodysplastic syndromes identify responders to erythroid stimulating agents
Authors: Marco G. Raddi, Sara Bencini, Benedetta Peruzzi, Giorgio Mattiuz, Sven De Pourcq, Michele Tanturli, Nicolas Chapuis, Angela Consagra, Luca Rigodanza, Cristina Amato, Alessandro Sanna, Elena Tofacchi, Enrico Attardi, Sophie Park, Olivier Kosmider, Francesco Annunziato, Michaela Fontenay, Valeria Santini
Journal: Blood Cancer Journal (2024)

Flow cytometric analysis of erythroid precursors
Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence
Authors: J Martinez-Lopez, N Lopez-Muñoz, A Chari, S Dorado, S Barrio, S Arora, A Kumar, A Chung, T Martin, J Wolf
Journal: Blood Cancer Journal (2024)

Minimal residual disease (MRD) assessment is a known surrogate marker for survival in multiple myeloma (MM). Here, we present a single institution's experience assessing MRD by NGS of Ig genes and the long-term impact of depth of response as well as clonal diversity on the clinical outcome of a large population of MM patients; 482 MM patients at the University of California, San Francisco (UCSF) diagnosed from 2008 to 2020 were analyzed retrospectively. MRD assessment was performed by NGS. PFS curves were plotted by the Kaplan-Meier method. In the newly diagnosed group, 119 of 304, achieved MRD negativity at the level of 10
Serum levels of B-cell activating factor are associated with a reduced risk of chronic lymphocytic leukemia
Authors: Eleanor Frost, Jonathan N. Hofmann, Wen-Yi Huang, Ashley A. Frazer-Abel, Kevin D. Deane, Sonja I. Berndt
Journal: Blood Cancer Journal (2024)

Immune dysregulation is thought to contribute to chronic lymphocytic leukemia (CLL) risk, but biological mechanisms are unclear. We discovered that increased serum levels of B-cell activating factor (BAFF), an important regulator of B-cell maturation, were associated with a decreased risk of CLL, even >10 years after blood draw. Our findings suggest that BAFF could be a useful biomarker to assess risk among individuals at high risk, such as those with monoclonal b-cell lymphocytosis.
Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial
Authors: Lixin Wang, Chuling Fang, Qingzheng Kang, Wenfa Huang, Ziren Chen, Weiqiang Zhao, Lei Wang, Yiran Wang, Kun Tan, Xiao Guo, Yuanyuan Xu, Shuhong Wang, Lijun Wang, Jingqiao Qiao, Zhixiong Tang, Chuan Yu, Yang Xu, Yisheng Li, Li Yu
Journal: Blood Cancer Journal (2024)

Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.
Liver elastography for risk-assessment of liver toxicity and risk factors for Sinusoidal obstruction syndrome in patients with acute lymphoblastic leukemia receiving inotuzumab ozogamicin
Authors: Jayastu Senapati, Elias Jabbour, Nicholas J. Short, Nitin Jain, Fadi Haddad, Tharakeswara Bathala, Iuliia Kovalenko, Aram Bidikian, Farhad Ravandi, Issa Khouri, Tapan M. Kadia, Rebecca Garris, Guillermo Montalban Bravo, Kelly Chien, Elizabeth Shpall, Partow Kebriaei, Hagop M. Kantarjian
Journal: Blood Cancer Journal (2024)

Liver elastography for risk-assessment of liver toxicity and
Prenatal cell-free DNA testing of women with pregnancy-associated cancer: a retrospective cross-sectional study
Authors: Catharina J Heesterbeek, Vivianne C G Tjan-Heijnen, Joosje H Heimovaara, Liesbeth Lenaerts, Christianne Lok, Ingeborg J H Vriens, Diane Van Opstal, Elles M J Boon, Daoud Sie, Christine E M de Die-Smulders, Frédéric Amant, Merryn V E Macville
Journal: The Lancet Regional Health - Europe (2024)

Incidentally, the non-invasive prenatal test (NIPT) shows chromosomal aberrations suspicious of a maternal malignancy, especially after genome-wide testing. The aim of this study is to determine how many cases of cancer in pregnancy are diagnosed or missed with NIPT and whether in retrospect subtle changes in NIPT results could have detected cancer.
“I got given all these keys”: a photovoice study examining master and alternative narratives and nonbinary identity formation in London’s queer communities
Authors: Anna Peter Magyarlaki, Alastair Pipkin
Journal: International Journal of Transgender Health (2024)

Background Nonbinary people may rely on queer communities to resist cisnormative erasure and shape their sense of identity. However, transnormativity within queer communities may repudiate nonbinary identities. The Master Narrative Framework informs our understanding of how cis- and transnormative narratives are negotiated within queer communities, but no study has yet applied this framework to specifically study nonbinary identity formation. Better understanding of nonbinary identity formation is a key task for clinicians and researchers to offer appropriate care to these populations.
The impact of tucking on fertility among transgender women: A systematic review
Authors: Ethan Manafi, André R. Belarmino, Jesse N. Mills, Sriram V. Eleswarapu, Gladys Y. Ng
Journal: International Journal of Transgender Health (2024)

Introduction Tucking involves maneuvering the testicles into the inguinal canal and compressing one's penis and scrotum posteriorly for a smoother pelvic area. A study based in Baltimore reports that 74.7% of transgender women engage in this practice.
Essential gene screening identifies the bromodomain-containing protein BRPF1 as a new actionable target for endocrine therapy-resistant breast cancers
Authors: Annamaria Salvati, Giorgio Giurato, Jessica Lamberti, Ilaria Terenzi, Laura Crescenzo, Viola Melone, Luigi Palo, Alessandro Giordano, Francesco Sabbatino, Giuseppina Roscigno, Cristina Quintavalle, Gerolama Condorelli, Francesca Rizzo, Roberta Tarallo, Giovanni Nassa, Alessandro Weisz
Journal: Molecular Cancer (2024)

Identifying master epigenetic factors controlling proliferation and survival of cancer cells allows to discover new molecular targets exploitable to overcome resistance to current pharmacological regimens. In breast cancer (BC), resistance to endocrine therapy (ET) arises from aberrant Estrogen Receptor alpha (ERα) signaling caused by genetic and epigenetic events still mainly unknown. Targeting key upstream components of the ERα pathway provides a way to interfere with estrogen signaling in cancer cells independently from any other downstream event. By combining computational analysis of genome-wide 'drop-out' screenings with siRNA-mediated gene knock-down (kd), we identified a set of essential genes in luminal-like, ERα + BC that includes BRPF1, encoding a bromodomain-containing protein belonging to a family of epigenetic readers that act as chromatin remodelers to control gene transcription. To gather mechanistic insights into the role of BRPF1 in BC and ERα signaling, we applied chromatin and transcriptome profiling, gene ablation and targeted pharmacological inhibition coupled to cellular and functional assays. Results indicate that BRPF1 associates with ERα onto BC cell chromatin and its blockade inhibits cell cycle progression, reduces cell proliferation and mediates transcriptome changes through the modulation of chromatin accessibility. This effect is elicited by a widespread inhibition of estrogen signaling, consequent to ERα gene silencing, in antiestrogen (AE) -sensitive and -resistant BC cells and pre-clinical patient-derived models (PDOs). Characterization of the functional interplay of BRPF1 with ERα reveals a new regulator of estrogen-responsive BC cell survival and suggests that this epigenetic factor is a potential new target for treatment of these tumors.
Distinct basal forebrain-originated neural circuits promote homoeostatic feeding and suppress hedonic feeding in male mice
Authors: Hailan Liu, Jonathan C. Bean, Yongxiang Li, Meng Yu, Olivia Z. Ginnard, Kristine M. Conde, Mengjie Wang, Xing Fang, Hesong Liu, Longlong Tu, Na Yin, Junying Han, Yongjie Yang, Qingchun Tong, Benjamin R. Arenkiel, Chunmei Wang, Yang He, Yong Xu
Journal: Nature Metabolism (2024)
Overcome the challenge for intratumoral injection of STING agonist for pancreatic cancer by systemic administration
Authors: Keyu Li, Junke Wang, Rui Zhang, Jiawei Zhou, Birginia Espinoza, Nan Niu, Jianxin Wang, Noelle Jurcak, Noah Rozich, Arsen Osipov, MacKenzie Henderson, Vanessa Funes, Melissa Lyman, Alex B. Blair, Brian Herbst, Mengni He, Jialong Yuan, Diego Trafton, Chunhui Yuan, Michael Wichroski, Xubao Liu, Juan Fu, Lei Zheng
Journal: Journal of Hematology & Oncology (2024)

Due to the challenge for intratumoral administration, innate agonists have not made it beyond preclinical studies for efficacy testing in most tumor types. Pancreatic ductal adenocarcinoma (PDAC) has a hostile tumor microenvironment that renders T cells dysfunctional. Innate agonist treatments may serve as a T cell priming mechanism to sensitize PDACs to anti-PD-1 antibody (a-PD-1) treatment. Using a transplant mouse model with spontaneously formed liver metastasis, a genetically engineered KPC mouse model that spontaneously develops PDAC, and a human patient-derived xenograft model, we compared the antitumor efficacy between intrahepatic/intratumoral and intramuscular systemic administration of BMS-986301, a next-generation STING agonist. Flow cytometry, Nanostring, and cytokine assays were used to evaluate local and systemic immune responses. This study demonstrated that administration of STING agonist systemically via intramuscular injection is equivalent to its intratumoral injection in inducing both effector T cell response and antitumor efficacy. Compared to intratumoral administration, T cell exhaustion and immunosuppressive signals induced by systemic administration were attenuated. Nonetheless, either intratumoral or systemic treatment of STING agonist was associated with increased expression of CTLA-4 on tumor-infiltrating T cells. However, the combination of a-PD-1 and anti-CTLA-4 antibody with systemic STING agonist demonstrated the antitumor efficacy in the KPC mouse spontaneous PDAC model. The mouse pancreatic and liver orthotopic model of human patient-derived xenograft reconstituted with PBMC also showed that antitumor and abscopal effects of both intratumoral and intramuscular STING agonist are equivalent. Taken together, this study supports the clinical development of innate agonists via systemic administration for treating PDAC.
A generalist vision–language foundation model for diverse biomedical tasks
Authors: Kai Zhang, Rong Zhou, Eashan Adhikarla, Zhiling Yan, Yixin Liu, Jun Yu, Zhengliang Liu, Xun Chen, Brian D. Davison, Hui Ren, Jing Huang, Chen Chen, Yuyin Zhou, Sunyang Fu, Wei Liu, Tianming Liu, Xiang Li, Yong Chen, Lifang He, James Zou, Quanzheng Li, Hongfang Liu, Lichao Sun
Journal: Nature Medicine (2024)
Prevalence of fungal DNAemia mediated by putatively non-pathogenic fungi in immunocompromised patients with febrile neutropenia: a prospective cohort study
Authors: Chantal Lucini, Klára Obrová, Isabella Krickl, Filomena Nogueira, Iva Kocmanová, Susanne Herndlhofer, Karoline V. Gleixner, Wolfgang R. Sperr, Tijana Frank, Nuno Andrade, Christina Peters, Gernot Engstler, Michael Dworzak, Andishe Attarbaschi, Martine van Grotel, Marry M. van den Heuvel-Eibrink, Ivan S Moiseev, Yuliya Rogacheva, Ludmilla Zubarovskaya, Natalia Zubarovskaya, Herbert Pichler, Anita Lawitschka, Elisabeth Koller, Felix Keil, Jiří Mayer, Barbora Weinbergerová, Peter Valent, Thomas Lion
Journal: Journal of Hematology & Oncology (2024)

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies.