tbuckley/cabot-search huggingface dataset:
Highlighted research articles
Journal: Cancer Discovery (2023)

In This Issue| December 12 2023 Highlighted research articles Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2023 American Association for Cancer Research2023American Association for Cancer Research Cancer Discov (2023) 13 (12): 2489–2490. https://doi.org/10.1158/2159-8290.CD-13-12-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record December 12 2023 Citation Highlighted research articles. Cancer Discov 1 December 2023; 13 (12): 2489–2490. https://doi.org/10.1158/2159-8290.CD-13-12-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search LINE-1 ORF1p is a human transposon protein expressed at negligible levels in normal tissue but is pervasive in carcinomas and high-risk precursors, making it a potentially useful pan-cancer biomarker. Because ORF1p blood levels are very low, Taylor, Wu, and colleagues engineered and iteratively improved ultrasensitive assays that detect single ORF1p molecules in plasma. These plasma ORF1p assays were found to be highly specific, rapid, and inexpensive. Additionally, plasma ORF1p demonstrated potential utility in multiple clinical scenarios, with preliminary promise in early detection of ovarian cancer, early therapeutic response monitoring in gastric and esophageal cancers, and prognostic value in colorectal and gastroesophageal cancers. See article, p. 2532. PML nuclear bodies (NB) are disrupted by the PML-RARA oncogenic fusion protein in acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) and retinoic acid treatments are curative in APL by driving PML-RARA degradation and PML NB reassembly, but the mechanisms behind ATO-enforced NB assembly... You do not currently have access to this content.
Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer: results from the NeoSTAR trial
Authors: L.M. Spring, S.M. Tolaney, G. Fell, V. Bossuyt, R.O. Abelman, B. Wu, S. Maheswaran, L. Trippa, A. Comander, T. Mulvey, S. McLaughlin, P. Ryan, L. Ryan, E. Abraham, A. Rosenstock, A.C. Garrido-Castro, F. Lynce, B. Moy, S.J. Isakoff, N. Tung, E.A. Mittendorf, L.W. Ellisen, A. Bardia
Journal: Annals of Oncology (2023)

Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results.
Correction: Determinants of fluid use and the association between volume of fluid used and effect of balanced solutions on mortality in critically ill patients: a secondary analysis of the BaSICS trial
Authors: Fernando G. Zampieri, Flavia R. Machado, Viviane C. Veiga, Luciano C. P. Azevedo, Sean M. Bagshaw, Lucas P. Damiani, Alexandre B. Cavalcanti
Journal: Intensive Care Medicine (2023)
Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest Trial (GOT ICE): A Randomized Clinical Trial Comparing Outcomes After Aortic Arch Surgery
Authors: G. Chad Hughes, Edward P. Chen, Jeffrey N. Browndyke, Wilson Y. Szeto, J. Michael DiMaio, William T. Brinkman, Jeffrey G. Gaca, James A. Blumenthal, Jorn A. Karhausen, Tiffany Bisanar, Michael L. James, David Yanez, Yi-Ju Li, Joseph P. Mathew
Journal: Circulation (2023)

Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA.
Dynamics of Endothelial Cell Generation and Turnover in Arteries During Homeostasis and Diseases
Authors: Yi Li, Zixin Liu, Ximeng Han, Feng Liang, Qianyu Zhang, Xiuzhen Huang, Xin Shi, Huanhuan Huo, Maoying Han, Xiuxiu Liu, Huan Zhu, Lingjuan He, Linghong Shen, Xinyang Hu, Jian’an Wang, Qing-Dong Wang, Nicola Smart, Bin Zhou, Ben He
Journal: Circulation (2023)

Endothelial cell (EC) generation and turnover by self-proliferation contributes to vascular repair and regeneration. The ability to accurately measure the dynamics of EC generation would advance our understanding of cellular mechanisms of vascular homeostasis and diseases. However, it is currently challenging to evaluate the dynamics of EC generation in large vessels such as arteries because of their infrequent proliferation.
Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV
Authors: Michaela T. Hall, Kate T. Simms, John M. Murray, Adam Keane, Diep T. N. Nguyen, Michael Caruana, Gigi Lui, Helen Kelly, Linda O. Eckert, Nancy Santesso, Silvia de Sanjose, Edwin E. Swai, Ajay Rangaraj, Morkor Newman Owiredu, Cindy Gauvreau, Owen Demke, Partha Basu, Marc Arbyn, Shona Dalal, Nathalie Broutet, Karen Canfell
Journal: Nature Medicine (2023)

Abstract To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform (‘Policy1-Cervix-HIV’) to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7–33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3–5 years.
Evaluating the use of paralogous protein domains to increase data availability for missense variant classification
Authors: Adam Colin Gunning, Caroline Fiona Wright
Journal: Genome Medicine (2023)

Classification of rare missense variants remains an ongoing challenge in genomic medicine. Evidence of pathogenicity is often sparse, and decisions about how to weigh different evidence classes may be subjective. We used a Bayesian variant classification framework to investigate the performance of variant co-localisation, missense constraint, and aggregating data across paralogous protein domains ("meta-domains"). We constructed a database of all possible coding single nucleotide variants in the human genome and used PFam predictions to annotate structurally-equivalent positions across protein domains. We counted the number of pathogenic and benign missense variants at these equivalent positions in the ClinVar database, calculated a regional constraint score for each meta-domain, and assessed this approach versus existing missense constraint metrics for classifying variant pathogenicity and benignity. Alternative pathogenic missense variants at the same amino acid position in the same protein provide strong evidence of pathogenicity (positive likelihood ratio, LR+ = 85). Additionally, clinically annotated pathogenic or benign missense variants at equivalent positions in different proteins can provide moderate evidence of pathogenicity (LR+ = 7) or benignity (LR+ = 5), respectively. Applying these approaches sequentially (through PM5) increases sensitivity for classifying pathogenic missense variants from 27 to 41%. Missense constraint can also provide strong evidence of pathogenicity for some variants, but its absence provides no evidence of benignity. We propose using structurally equivalent positions across related protein domains from different genes to augment evidence for variant co-localisation when classifying novel missense variants. Additionally, we advocate adopting a numerical evidence-based approach to integrating diverse data in variant interpretation.
Camera–Radar Fusion with Modality Interaction and Radar Gaussian Expansion for 3D Object Detection
Authors: Xiang Liu, Zhenglin Li, Yang Zhou, Yan Peng, Jun Luo
Journal: Cyborg and Bionic Systems (2023)

The fusion of millimeter-wave radar and camera modalities is crucial for improving the accuracy and completeness of 3-dimensional (3D) object detection. Most existing methods extract features from each modality separately and conduct fusion with specifically designed modules, potentially resulting in information loss during modality transformation. To address this issue, we propose a novel framework for 3D object detection that iteratively updates radar and camera features through an interaction module. This module serves a dual purpose by facilitating the fusion of multi-modal data while preserving the original features. Specifically, radar and image features are sampled and aggregated with a set of sparse 3D object queries, while retaining the integrity of the original radar features to prevent information loss. Additionally, an innovative radar augmentation technique named Radar Gaussian Expansion is proposed. This module allocates radar measurements within each voxel to neighboring ones as a Gaussian distribution, reducing association errors during projection and enhancing detection accuracy. Our proposed framework offers a comprehensive solution to the fusion of radar and camera data, ultimately leading to heightened accuracy and completeness in 3D object detection processes. On the nuScenes test benchmark, our camera–radar fusion method achieves state-of-the-art 3D object detection results with a 41.6% mean average precision and 52.5% nuScenes detection score.
A Novel Electromagnetic Driving System for 5-DOF Manipulation in Intraocular Microsurgery
Authors: Yangyu Liu, Dezhi Song, Guanghao Zhang, Qingyu Bu, Yuanqing Dong, Chengzhi Hu, Chaoyang Shi
Journal: Cyborg and Bionic Systems (2023)

This work presents a novel electromagnetic driving system that consists of eight optimized electromagnets arranged in an optimal configuration and employs a control framework based on an active disturbance rejection controller (ADRC) and virtual boundary. The optimal system configuration enhances the system’s compatibility with other ophthalmic surgical instruments, while also improving its capacity to generate magnetic force in the vertical direction. Besides, the optimal electromagnet parameters provide a superior comprehensive performance on magnetic field generation capacity and thermal power. Hence, the presented design achieves a stronger capacity for sustained work. Furthermore, the ADRC controller effectively monitors and further compensates the total disturbance as well as gravity to enhance the system’s robustness. Meanwhile, the implementation of virtual boundaries substantially enhances interactive security via collision avoidance. The magnetic and thermal performance tests have been performed on the electromagnet to verify the design optimization. The proposed electromagnet can generate a superior magnetic field of 2.071 mT at a distance of 65 mm with an applied current of 1 A. Moreover, it demonstrates minimal temperature elevation from room temperature (25 °C) to 46 °C through natural heat dissipation in 3 h, thereby effectively supporting prolonged magnetic manipulation of intraocular microsurgery. Furthermore, trajectory tracking experiments with disturbances have been performed in a liquid environment similar to the practical ophthalmic surgery scenarios, to verify the robustness and security of the presented control framework. The maximum root mean square (RMS) error of performance tests in different operation modes remains 35.8 μm, providing stable support for intraocular microsurgery.
Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned
Authors: Alfonso López de Sá, Cristina Díaz-Tejeiro, Elisa Poyatos-Racionero, Cristina Nieto-Jiménez, Lucía Paniagua-Herranz, Adrián Sanvicente, Emiliano Calvo, Pedro Pérez-Segura, Víctor Moreno, Francisco Moris, Alberto Ocana
Journal: Journal of Hematology & Oncology (2023)

Antibody-drug conjugates (ADCs) have emerged as a novel therapeutic strategy that has successfully reached patient treatment in different clinical scenarios. ADCs are formed by an antibody against a specific tumor-associated antigen (TAA), a cytotoxic payload, and a chemical linker that binds both. To this regard, most efforts have been focused on target identification, antibody design and linker optimization, but other relevant aspects for clinical development have not received the necessary attention. In this article using data from approved ADCs, we evaluated all characteristics of these agents, including payload physicochemical properties, in vitro potency, drug antibody ratio (DAR), exposure-response relationships, and clinical development strategies. We suggest that compounds with best options for clinical development include those with optimal payload physicochemical properties and cleavable linkers that would lead to a bystander effect. These modalities can facilitate the development of ADCs in indications with low expression of the TAA. Early clinical development strategies including changes in the schedule of administration with more frequent doses are also discussed in the context of an efficient strategy. In conclusion, we highlight relevant aspects that are needed for the optimal development of ADCs in cancer, proposing options for improvement.
Bifidobacterium longum promotes postoperative liver function recovery in patients with hepatocellular carcinoma
Authors: Jingjing Yu, Peng Zhu, Linlin Shi, Na Gao, Yani Li, Chang Shu, Ying Xu, Ying Yu, Junqing He, Dingming Guo, Xiaoman Zhang, Xiangfeng Wang, Sirui Shao, Wei Dong, Yuwei Wang, Wei Zhang, Wanguang Zhang, Wei-Hua Chen, Xiaoping Chen, Zhi Liu, Xiangliang Yang, Bixiang Zhang
Journal: Cell Host & Microbe (2023)

Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B. longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients.
The landscape of immune dysregulation in Crohn’s disease revealed through single-cell transcriptomic profiling in the ileum and colon
Authors: Lingjia Kong, Vladislav Pokatayev, Ariel Lefkovith, Grace T. Carter, Elizabeth A. Creasey, Chirag Krishna, Sathish Subramanian, Bharati Kochar, Orr Ashenberg, Helena Lau, Ashwin N. Ananthakrishnan, Daniel B. Graham, Jacques Deguine, Ramnik J. Xavier
Journal: Immunity (2023)

(Immunity 56, 444–458.e1–e5; February 14, 2023) We recently became aware of an error in the clinical metadata provided in Table S1. During the aggregation of the records at the patient level, some of the columns were mistakenly sorted by age and mismatched from the patient IDs. We have now corrected this error in the article online. The datasets corresponding to sample-level and channel-level information, which were used as model covariates, are not affected, and therefore, this does not affect any of the analyses and conclusions presented in this work. We apologize for this issue. The landscape of immune dysregulation in Crohn’s disease revealed through single-cell transcriptomic profiling in the ileum and colonKong et al.ImmunityJanuary 30, 2023In BriefCrohn’s disease (CD) is a heterogeneous condition impacting the ileum and colon in unique ways. Here, Kong et al. define the unique epithelial, stromal, and immune characteristics of CD by generating a single-cell transcriptomic atlas of the ileum and colon and uncover novel regulators of collagen production in disease-associated fibroblasts. Full-Text PDF
TCR signaling promotes formation of an STS1-Cbl-b complex with pH-sensitive phosphatase activity that suppresses T cell function in acidic environments
Authors: Yuan-Li Tsai, Marcel Arias-Badia, Theresa A. Kadlecek, Yee May Lwin, Aahir Srinath, Neel H. Shah, Zhi-En Wang, Diane Barber, John Kuriyan, Lawrence Fong, Arthur Weiss
Journal: Immunity (2023)
Stat5 opposes the transcription factor Tox and rewires exhausted CD8+ T cells toward durable effector-like states during chronic antigen exposure
Authors: Jean-Christophe Beltra, Mohamed S. Abdel-Hakeem, Sasikanth Manne, Zhen Zhang, Hua Huang, Makoto Kurachi, Leon Su, Lora Picton, Shin Foong Ngiow, Yuki Muroyama, Valentina Casella, Yinghui J. Huang, Josephine R. Giles, Divij Mathew, Jonathan Belman, Max Klapholz, Hélène Decaluwe, Alexander C. Huang, Shelley L. Berger, K. Christopher Garcia, E. John Wherry
Journal: Immunity (2023)
Opportunistic Screening With Low-Dose Computed Tomography and Lung Cancer Mortality in China
Authors: Lijie Wang, Yue Qi, Ailing Liu, Xiaolei Guo, Shanshan Sun, Lanfang Zhang, Huaijun Ji, Guiyuan Liu, Huan Zhao, Yinan Jiang, Jingyi Li, Chengcun Song, Xin Yu, Liu Yang, Jinchao Yu, Hu Feng, Fujun Yang, Fuzhong Xue
Journal: JAMA Network Open (2023)

Importance Despite the recommendations of lung cancer screening guidelines and the evidence supporting the effectiveness of population-based lung screening, a common barrier to effective lung cancer screening is that the participation rates of low-dose computed tomography (LDCT) screening among individuals with the highest risk are not large. There are limited data from clinical practice regarding whether opportunistic LDCT screening is associated with reduced lung-cancer mortality. Objective To evaluate whether opportunistic LDCT screening is associated with improved prognosis among adults with lung cancer in mainland China. Design, Setting, and Participants This cohort study included patients diagnosed with lung cancer at Weihai Municipal Hospital Healthcare Group, Weihai City, China, from 2016 to 2021. Data were analyzed from January 2022 to February 2023. Exposures Data collected included demographic indicators, tumor characteristics, comorbidities, blood indexes, and treatment information. Patients were classified into screened and nonscreened groups on the basis of whether or not their lung cancer diagnosis occurred through opportunistic screening. Main Outcomes and Measures Follow-up outcome indicators included lung cancer–specific mortality and all-cause mortality. Propensity score matching (PSM) was adopted to account for potential imbalanced factors between groups. The associations between LDCT screening and outcomes were analyzed using Cox regression models based on the matched data with correction for lead time and length biases. Propensity score regression adjustment and inverse probability treatment weighting were used for sensitivity analysis. Results A total of 5234 patients (mean [SD] baseline age, 61.8 [9.8] years; 2518 [48.1%] female) with complete opportunistic screening information were included in the analytical sample, with 2251 patients (42.91%) receiving their lung cancer diagnosis through opportunistic screening. After 1:1 PSM, 2788 patients (1394 in each group) were finally included. The baseline characteristics of the matched patients were balanced between groups. Opportunistic screening with LDCT was associated with a 34% lower risk of lung cancer death (HR, 0.66; 95% CI, 0.54-0.80) and 28% lower risk of all-cause death (HR, 0.72; 95% CI, 0.60-0.86) after correction for lead time and length biases. Conclusions and Relevance In this cohort study of patients with lung cancer, opportunistic lung cancer screening with LDCT was associated with lower lung cancer mortality and all-cause mortality. These findings suggest that opportunistic screening is an important supplement to population screening to improve prognosis of adults with lung cancer.
Novel variants in <i>ABCA12</i> cause erythrokeratodermia variabilis
Authors: Yihe Liu, Ran Mo, Zhiming Chen, Yong Yang
Journal: British Journal of Dermatology (2023)

We present a patient clinically diagnosed with erythrokeratodermia variabilis harbored compound heterozygous variants in the ABCA12 gene, including an unreported c.3653A&amp;gt;G variant and c.7247C&amp;gt;T, both of which were predicted to be pathogenic. This finding provide evidence that ABCA12 pathogenic variants were associated with recessive erythrokeratodermia variabilis, an otherwise dominant disorder. This case highlighted the clinical diversity of ABCA12 variants and the genetic heterogeneity underlying the erythrokeratodermia variabilis, which is significant for genetic counseling and prenatal diagnosis.
Clinician Adherence to Hypertension Screening and Care Guidelines
Authors: Nikkil Sudharsanan, Vasanthi Subramonia Pillai, Caterina Favaretti, Jithin Jose, Sandra Jose, Margaret McConnell, Mohammed K. Ali
Journal: JAMA Network Open (2023)

This quality improvement study assesses opportunistic blood pressure measurement, communication of blood pressure reading to adult patients, and recommendation for a follow-up visit at health care facilities in 2 major cities in India.