tbuckley/cabot-search huggingface dataset:
Clinical outcomes of hypomethylating agents plus Venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: Real‐world data from eight <scp>US</scp> academic centers
Authors: Yasmin Abaza, Eric S. Winer, Guru Subramanian Guru Murthy, Rory M. Shallis, Andrew H. Matthews, Talha Badar, Emily M. Geramita, Vamsi K. Kota, Alok Swaroop, Peter Doukas, Danielle Bradshaw, Irene B. Helenowski, Yingzhe Liu, Hui Zhang, Annie Im, Mark R. Litzow, Alexander E. Perl, Ehab Atallah, Jessica K. Altman
Journal: American Journal of Hematology (2024)

Abstract Venetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real‐world data published on HMAs plus VEN have been either single‐center studies or using community‐based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real‐world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85–13.5), with OS significantly worse among patients with TP53 ‐mutated AML (2.5 months) and improved in patients harboring NPM1 , IDH1 , and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30‐day and 60‐day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE‐A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need.
Digital health technologies and machine learning augment patient reported outcomes to remotely characterise rheumatoid arthritis
Authors: Andrew P. Creagh, Valentin Hamy, Hang Yuan, Gert Mertes, Ryan Tomlinson, Wen-Hung Chen, Rachel Williams, Christopher Llop, Christopher Yee, Mei Sheng Duh, Aiden Doherty, Luis Garcia-Gancedo, David A. Clifton
Journal: npj Digital Medicine (2024)

Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient reported outcomes (PRO) to determine RA status and severity in a study of 30 moderate-to-severe RA patients, compared to 30 matched healthy controls (HC). Sensor-based measures of health status, mobility, dexterity, fatigue, and other RA specific symptoms were extracted from daily iPhone guided tests (GT), as well as actigraphy and heart rate sensor data, which was passively recorded from patients' Apple smartwatch continuously over the study duration. We subsequently developed a machine learning (ML) framework to distinguish RA status and to estimate RA severity. It was found that daily wearable sensor-outcomes robustly distinguished RA from HC participants (F1, 0.807). Furthermore, by day 7 of the study (half-way), a sufficient volume of data had been collected to reliably capture the characteristics of RA participants. In addition, we observed that the detection of RA severity levels could be improved by augmenting standard patient reported outcomes with sensor-based features (F1, 0.833) in comparison to using PRO assessments alone (F1, 0.759), and that the combination of modalities could reliability measure continuous RA severity, as determined by the clinician-assessed RAPID-3 score at baseline (r
Translating color fundus photography to indocyanine green angiography using deep-learning for age-related macular degeneration screening
Authors: Ruoyu Chen, Weiyi Zhang, Fan Song, Honghua Yu, Dan Cao, Yingfeng Zheng, Mingguang He, Danli Shi
Journal: npj Digital Medicine (2024)

Abstract Age-related macular degeneration (AMD) is the leading cause of central vision impairment among the elderly. Effective and accurate AMD screening tools are urgently needed. Indocyanine green angiography (ICGA) is a well-established technique for detecting chorioretinal diseases, but its invasive nature and potential risks impede its routine clinical application. Here, we innovatively developed a deep-learning model capable of generating realistic ICGA images from color fundus photography (CF) using generative adversarial networks (GANs) and evaluated its performance in AMD classification. The model was developed with 99,002 CF-ICGA pairs from a tertiary center. The quality of the generated ICGA images underwent objective evaluation using mean absolute error (MAE), peak signal-to-noise ratio (PSNR), structural similarity measures (SSIM), etc., and subjective evaluation by two experienced ophthalmologists. The model generated realistic early, mid and late-phase ICGA images, with SSIM spanned from 0.57 to 0.65. The subjective quality scores ranged from 1.46 to 2.74 on the five-point scale (1 refers to the real ICGA image quality, Kappa 0.79–0.84). Moreover, we assessed the application of translated ICGA images in AMD screening on an external dataset ( n = 13887) by calculating area under the ROC curve (AUC) in classifying AMD. Combining generated ICGA with real CF images improved the accuracy of AMD classification with AUC increased from 0.93 to 0.97 ( P &lt; 0.001). These results suggested that CF-to-ICGA translation can serve as a cross-modal data augmentation method to address the data hunger often encountered in deep-learning research, and as a promising add-on for population-based AMD screening. Real-world validation is warranted before clinical usage.
Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis
Authors: Peng Wu, Chaoqi Zhang, Xiaoya Tang, Dongyu Li, Guochao Zhang, Xiaohui Zi, Jingjing Liu, Enzhi Yin, Jiapeng Zhao, Pan Wang, Le Wang, Ruirui Li, Yue Wu, Nan Sun, Jie He
Journal: Molecular Cancer (2024)

Abstract Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method. Five machine learning algorithms were adopted to construct cf-IRmiRNAs signature, and the diagnostic classifies based on XGBoost algorithm showed the excellent performance for cancer detection in the validation set (AUC: 0.984, CI: 0.980–0.989), determined through 5-fold cross-validation and grid search. Further evaluation in the test and external test sets confirmed the reliability and efficacy of the classifier (AUC: 0.980 to 1.000). The classifier successfully detected early-stage cancers, particularly lung, prostate, and gastric cancers. It also distinguished between benign and malignant tumors. This study represents the largest and most comprehensive pan-cancer analysis on cf-IRmiRNAs, offering a promising non-invasive diagnostic biomarker for early cancer detection and potential impact on clinical practice.
<scp>DNA</scp> Damage and Cellular Senescence in Osteoarthritis: An Unexpected Role for Interferon Regulatory Factor 1 in Chondrocyte <scp>DNA</scp> Repair
Authors: Brian O. Diekman, Richard F. Loeser
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Integrated multiomic profiling of breast cancer in the Chinese population reveals patient stratification and therapeutic vulnerabilities
Authors: Yi-Zhou Jiang, Ding Ma, Xi Jin, Yi Xiao, Ying Yu, Jinxiu Shi, Yi-Fan Zhou, Tong Fu, Cai-Jin Lin, Lei-Jie Dai, Cheng-Lin Liu, Shen Zhao, Guan-Hua Su, Wanwan Hou, Yaqing Liu, Qingwang Chen, Jingcheng Yang, Naixin Zhang, Wen-Juan Zhang, Wei Liu, Weigang Ge, Wen-Tao Yang, Chao You, Yajia Gu, Virginia Kaklamani, François Bertucci, Claire Verschraegen, Anneleen Daemen, Nakul M. Shah, Ting Wang, Tiannan Guo, Leming Shi, Charles M. Perou, Yuanting Zheng, Wei Huang, Zhi-Ming Shao
Journal: Nature Cancer (2024)
Met and unmet need for medical gender affirmation in the Australian non-binary community
Authors: Sav Zwickl, Tomi Ruggles, Stephanie Sheahan, Joel Murray, Julian Grace, Ariel Ginger, Alex Fang Qi Wong, Ada S. Cheung
Journal: International Journal of Transgender Health (2024)

Background: There is a widely held assumption that non-binary people do not, or rarely, pursue gender-affirming hormone therapy (GAHT) or gender-affirming surgery (GAS), however, little is known about the medical gender affirmation needs of non-binary people in Australia.
Basal ganglia–spinal cord pathway that commands locomotor gait asymmetries in mice
Authors: Jared M. Cregg, Simrandeep K. Sidhu, Roberto Leiras, Ole Kiehn
Journal: Nature Neuroscience (2024)

Abstract The basal ganglia are essential for executing motor actions. How the basal ganglia engage spinal motor networks has remained elusive. Medullary Chx10 gigantocellular (Gi) neurons are required for turning gait programs, suggesting that turning gaits organized by the basal ganglia are executed via this descending pathway. Performing deep brainstem recordings of Chx10 Gi Ca 2+ activity in adult mice, we show that striatal projection neurons initiate turning gaits via a dominant crossed pathway to Chx10 Gi neurons on the contralateral side. Using intersectional viral tracing and cell-type-specific modulation, we uncover the principal basal ganglia–spinal cord pathway for locomotor asymmetries in mice: basal ganglia → pontine reticular nucleus, oral part (PnO) → Chx10 Gi → spinal cord. Modulating the restricted PnO → Chx10 Gi pathway restores turning competence upon striatal damage, suggesting that dysfunction of this pathway may contribute to debilitating turning deficits observed in Parkinson’s disease. Our results reveal the stratified circuit architecture underlying a critical motor program.
Modulating Lipid Nanoparticles with Histidinamide‐Conjugated Cholesterol for Improved Intracellular Delivery of mRNA
Authors: Onesun Jung, Hye‐youn Jung, Le Thi Thuy, Minyoung Choi, Seongyeon Kim, Hae‐Geun Jeon, Jihyun Yang, Seok‐Min Kim, Tae‐Don Kim, Eunjung Lee, Yoonkyung Kim, Joon Sig Choi
Journal: Advanced Healthcare Materials (2024)

Abstract Recently, mRNA‐based therapeutics, including vaccines, have gained significant attention in the field of gene therapy for treating various diseases. Among the various mRNA delivery vehicles, lipid nanoparticles (LNPs) have emerged as promising vehicles for packaging and delivering mRNA with low immunogenicity. However, while mRNA delivery has several advantages, the delivery efficiency and stability of LNPs remain challenging for mRNA therapy. In this study, an ionizable helper cholesterol analog, 3β[L‐histidinamide‐carbamoyl] cholesterol (Hchol) lipid is developed and incorporated into LNPs instead of cholesterol to enhance the LNP potency. The p K a values of the Hchol‐LNPs are ≈6.03 and 6.61 in MC3‐ and SM102‐based lipid formulations. Notably, the Hchol‐LNPs significantly improve the delivery efficiency by enhancing the endosomal escape of mRNA. Additionally, the Hchol‐LNPs are more effective in a red blood cell hemolysis at pH 5.5, indicating a synergistic effect of the protonated imidazole groups of Hchol and cholesterol on endosomal membrane destabilization. Furthermore, mRNA delivery is substantially enhanced in mice treated with Hchol‐LNPs. Importantly, LNP‐encapsulated SARS‐CoV‐2 spike mRNA vaccinations induce potent antigen‐specific antibodies against SARS‐CoV‐2. Overall, incorporating Hchol into LNP formulations enables efficient endosomal escape and stability, leading to an mRNA delivery vehicle with a higher delivery efficiency.
A molecularly defined amygdala-independent tetra-synaptic forebrain-to-hindbrain pathway for odor-driven innate fear and anxiety
Authors: Hao Wang, Qin Wang, Liuzhe Cui, Xiaoyang Feng, Ping Dong, Liheng Tan, Lin Lin, Hong Lian, Shuxia Cao, Huiqian Huang, Peng Cao, Xiao-Ming Li
Journal: Nature Neuroscience (2024)
Histamine- and pruritogen-induced itch is inhibited by a TRPM8 agonist: a randomized vehicle-controlled human trial
Authors: Soyeon Lee, Edward T Wei, Tudor Selescu, Alexandru Babes, Jinseo Park, Jincheol Kim, Boyoung Chung, Chunwook Park, Hye One Kim
Journal: British Journal of Dermatology (2024)

Lay Summary Managing itching and the effects of histamine can be difficult for people with allergies. Cooling the skin or applying menthol provides some relief from itch, but the way they work is not fully understood. Cooling agents interact with a protein called TRPM8 (also known as the ‘cold and menthol receptor’) and have shown potential for the management of itch. However, much of the research has been done on animals and has limitations when compared with human studies. Antihistamine medications can help with histamine-induced itching, but they may not work for other causes of itch. This study investigated the effects of a specific TRPM8 agonist (a chemical that activates a receptor to produce a biologic response) gel called cryosim-1 on itch in human skin. To do this, we conducted tests on 30 healthy people using five different substances that cause itching. Participants rated the itch intensity and pain using a scale and we measured various aspects of their skin. The results showed that all substances caused significant itching compared to a control substance, but itchiness gradually decreased over time. Histamine and compound 48/80 also caused pain. However, when participants applied the TRPM8 activator gel before exposure, they experienced less itching and lower itch intensity versus the gel without the activator. There were no significant differences in pain between the TRPM8 activator and the gel without it. In summary, our findings showed that activating TRPM8 receptors with a specific substance effectively relieved itching caused by various irritants on human skin. This suggests its potential as a treatment for itch-related conditions. Further research is needed to understand its mechanisms better and evaluate its effectiveness in real-life situations.
Near-gapless and haplotype-resolved apple genomes provide insights into the genetic basis of rootstock-induced dwarfing
Authors: Wei Li, Chong Chu, Hui Li, Hengtao Zhang, Haochen Sun, Shiyao Wang, Zijun Wang, Yuqi Li, Toshi M. Foster, Elena López-Girona, Jiaxin Yu, Yi Li, Yue Ma, Ke Zhang, Yongming Han, Bowen Zhou, Xingqiang Fan, Yao Xiong, Cecilia H. Deng, Yi Wang, Xuefeng Xu, Zhenhai Han
Journal: Nature Genetics (2024)
Molecular-guided therapy for the treatment of patients with relapsed and refractory childhood cancers: a Beat Childhood Cancer Research Consortium trial
Authors: Giselle L. Saulnier Sholler, Genevieve Bergendahl, Elizabeth C. Lewis, Jacqueline Kraveka, William Ferguson, Abhinav B. Nagulapally, Karl Dykema, Valerie I. Brown, Michael S. Isakoff, Joseph Junewick, Deanna Mitchell, Jawhar Rawwas, William Roberts, Don Eslin, Javier Oesterheld, Randal K. Wada, Devang Pastakia, Virginia Harrod, Kevin Ginn, Raya Saab, Kevin Bielamowicz, Jason Glover, Eugenia Chang, Gina K. Hanna, Daniel Enriquez, Tyler Izatt, Rebecca F. Halperin, Abigail Moore, Sara A. Byron, William P. D. Hendricks, Jeffrey M. Trent
Journal: Genome Medicine (2024)

Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make real‑time treatment decisions for children with relapsed/refractory solid tumors. Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors. Tumor samples were sent for tumor/normal whole-exome (WES) and tumor whole-transcriptome (WTS) sequencing, and the genomic data were used in a multi-institutional MTB to make real‑time treatment decisions. The MTB recommended plan allowed for a combination of up to 4 agents. Feasibility was measured by time to completion of genomic sequencing, MTB review and initiation of treatment. Response was assessed after every two cycles using Response Evaluation Criteria in Solid Tumors (RECIST). Patient clinical benefit was calculated by the sum of the CR, PR, SD, and NED subjects divided by the sum of complete response (CR), partial response (PR), stable disease (SD), no evidence of disease (NED), and progressive disease (PD) subjects. Grade 3 and higher related and unexpected adverse events (AEs) were tabulated for safety evaluation. A total of 186 eligible patients were enrolled with 144 evaluable for safety and 124 evaluable for response. The average number of days from biopsy to initiation of the MTB-recommended combination therapy was 38 days. Patient benefit was exhibited in 65% of all subjects, 67% of neuroblastoma subjects, 73% of CNS tumor subjects, and 60% of rare tumor subjects. There was little associated toxicity above that expected for the MGT drugs used during this trial, suggestive of the safety of utilizing this method of selecting combination targeted therapy. This trial demonstrated the feasibility, safety, and efficacy of a comprehensive sequencing model to guide personalized therapy for patients with any relapsed/refractory solid malignancy. Personalized therapy was well tolerated, and the clinical benefit rate of 65% in these heavily pretreated populations suggests that this treatment strategy could be an effective option for relapsed and refractory pediatric cancers. ClinicalTrials.gov, NCT02162732. Prospectively registered on June 11, 2014.
Merge-and-Split Graph Convolutional Network for Skeleton-Based Interaction Recognition
Authors: Haoqiang Wang, Yong Wang, Sheng Yan, Xin Du, Yuan Gao, Hong Liu
Journal: Cyborg and Bionic Systems (2024)

We introduce an innovative approach to address a significant challenge in interaction recognition, specifically the capture of correlation features between different interaction body parts. These features are often overlooked by traditional graph convolution networks commonly used in interaction recognition tasks. Our solution, the Merge-and-Split Graph Convolutional Network, takes a unique perspective, treating interaction recognition as a global problem. It leverages a Merge-and-Split Graph structure to effectively capture dependencies between interaction body parts. To extract the essential interaction features, we introduce the Merge-and-Split Graph Convolution module, which seamlessly combines the Merge-and-Split Graph with Graph Convolutional Networks. This fusion enables the extraction of rich semantic information between adjacent joint points. In addition, we introduce a Short-term Dependence module designed to extract joint and motion characteristics specific to each type of interaction. Furthermore, to extract correlation features between different hierarchical sets, we present the Hierarchical Guided Attention Module. This module plays a crucial role in highlighting the relevant hierarchical sets that contain essential interaction information. The effectiveness of our proposed model is demonstrated by achieving state-of-the-art performance on 2 widely recognized datasets, namely, the NTU60 and NTU120 interaction datasets. Our model’s efficacy is rigorously validated through extensive experiments, and we have made the code available for the research community at https://github.com/wanghq05/MS-GCN/ .
Proliferation of HIV-1 reservoir cells: The delusion of infinite growth
Authors: Melanie Lancien, Mathias Lichterfeld
Journal: The Journal of Experimental Medicine (2024)

Proliferation of HIV-1-infected cells contributes to viral persistence despite antiretroviral therapy. A new study by Kufera et al. (https://doi.org/10.1084/jem.20231511) demonstrates that proliferative growth of cells infected with genome-intact HIV-1 is not limitless; rather, these cells seem to be at least partially refractory to TCR stimulation, restricting their ability to proliferate in response to antigenic challenge.
<b>Recent Advances in Electrospinning Techniques for Precise Medicine</b>
Authors: Wei Li, Yue Yin, Huaijuan Zhou, Yingwei Fan, Yingting Yang, Qiqi Gao, Pei Li, Ge Gao, Jinhua Li
Journal: Cyborg and Bionic Systems (2024)

In the realm of precise medicine, the advancement of manufacturing technologies is vital for enhancing the capabilities of medical devices such as nano/microrobots, wearable/implantable biosensors, and organ-on-chip systems, which serve to accurately acquire and analyze patients’ physiopathological information and to perform patient-specific therapy. Electrospinning holds great promise in engineering materials and components for advanced medical devices, due to the demonstrated ability to advance the development of nanomaterial science. Nevertheless, challenges such as limited composition variety, uncontrollable fiber orientation, difficulties in incorporating fragile molecules and cells, and low production effectiveness hindered its further application. To overcome these challenges, advanced electrospinning techniques have been explored to manufacture functional composites, orchestrated structures, living constructs, and scale-up fabrication. This review delves into the recent advances of electrospinning techniques and underscores their potential in revolutionizing the field of precise medicine, upon introducing the fundamental information of conventional electrospinning techniques, as well as discussing the current challenges and future perspectives.