tbuckley/cabot-search huggingface dataset:
The implications of single-cell RNA-seq analysis in prostate cancer: unraveling tumor heterogeneity, therapeutic implications and pathways towards personalized therapy
Authors: De-Chao Feng, Wei-Zhen Zhu, Jie Wang, Deng-Xiong Li, Xu Shi, Qiao Xiong, Jia You, Ping Han, Shi Qiu, Qiang Wei, Lu Yang
Journal: Military Medical Research (2024)

Abstract In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine.
Patient-Centered Adult Cardiovascular Care: A Scientific Statement From the American Heart Association
Authors: Michael J. Goldfarb, Martha Abshire Saylor, Biykem Bozkurt, Jillianne Code, Katherine E. Di Palo, Angela Durante, Kristin Flanary, Ruth Masterson Creber, Modele O. Ogunniyi, Fatima Rodriguez, Martha Gulati
Journal: Circulation (2024)

Patient-centered care is gaining widespread acceptance by the medical and lay communities and is increasingly recognized as a goal of high-quality health care delivery. Patient-centered care is based on ethical principles and aims at establishing a partnership between the health care team and patient, family member, or both in the care planning and decision-making process. Patient-centered care involves providing respectful care by tailoring management decisions to patients' beliefs, preferences, and values. A collaborative care approach can enhance patient engagement, foster shared decision-making that aligns with patient values and goals, promote more personalized and effective cardiovascular care, and potentially improve patient outcomes. The objective of this scientific statement is to inform health care professionals and stakeholders about the role and impact of patient-centered care in adult cardiovascular medicine. This scientific statement describes the background and rationale for patient-centered care in cardiovascular medicine, provides insight into patient-oriented medication management and patient-reported outcome measures, highlights opportunities and strategies to overcome challenges in patient-centered care, and outlines knowledge gaps and future directions.
Retraction Notice to: Corrigendum to “Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson’s Disease and Other Brain Disorders”
Authors: Hayate Javed, Sindhu A. Menon, Karima M. Al-Mansoori, Abdelmojib Al-Wandi, Nour K. Majbour, Mustafa T. Ardah, Shiji Varghese, Nishant N. Vaikath, M. Emdadul Haque, Mimoun Azzouz, Omar MA. El-Agnaf
Journal: Molecular Therapy (2024)
Retraction Notice to: Development of Nonviral Vectors Targeting the Brain as a Therapeutic Approach For Parkinson’s Disease and Other Brain Disorders
Authors: Hayate Javed, Sindhu A. Menon, Karima M. Al-Mansoori, Abdelmojib Al-Wandi, Nour K. Majbour, Mustafa T. Ardah, Shiji Varghese, Nishant N. Vaikath, M Emdadul Haque, Mimoun Azzouz, Omar MA. El-Agnaf
Journal: Molecular Therapy (2024)
Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment
Authors: Do Seon Song, Hee Yeon Kim, Young Kul Jung, Tae Hyung Kim, Hyung Joon Yim, Eileen L Yoon, Ki Tae Suk, Jeong-ju Yoo, Sang Gyune Kim, Moon Young Kim, Young Chang, Soung Won Jeong, Jae Young Jang, Sung-Eun Kim, Jung-Hee Kim, Jung Gil Park, Won Kim, Jin Mo Yang, Dong Joon Kim, Ashok Kumar Choudhury, Vinod Arora, Shiv Kumar Sarin
Journal: Clinical and Molecular Hepatology (2024)

Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF).
Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma
Authors: Chun-Ting Ho, Elise Chia-Hui Tan, Pei-Chang Lee, Chi-Jen Chu, Yi-Hsiang Huang, Teh-Ia Huo, Yu-Hui Su, Ming-Chih Hou, Jaw-Ching Wu, Chien-Wei Su
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups.Methods: The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort.Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores.Conclusions: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.
Ischemia-free liver transplantation improves the prognosis of recipients using functionally marginal liver grafts
Authors: Shuai Wang, Xiaohong Lin, Yunhua Tang, Yichen Liang, Min Zhang, Zhonghao Xie, Yiwen Guo, Yuqi Dong, Qiang Zhao, Zhiyong Guo, Dongping Wang, Xiaoshun He, Weiqiang Ju, Maogen Chen
Journal: Clinical and Molecular Hepatology (2024)

Background/Aims: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation.Methods: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles.Results: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012).Conclusions: FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.
Whole-heart electromechanical simulations using Latent Neural Ordinary Differential Equations
Authors: Matteo Salvador, Marina Strocchi, Francesco Regazzoni, Christoph M. Augustin, Luca Dede’, Steven A. Niederer, Alfio Quarteroni
Journal: npj Digital Medicine (2024)

Abstract Cardiac digital twins provide a physics and physiology informed framework to deliver personalized medicine. However, high-fidelity multi-scale cardiac models remain a barrier to adoption due to their extensive computational costs. Artificial Intelligence-based methods can make the creation of fast and accurate whole-heart digital twins feasible. We use Latent Neural Ordinary Differential Equations (LNODEs) to learn the pressure-volume dynamics of a heart failure patient. Our surrogate model is trained from 400 simulations while accounting for 43 parameters describing cell-to-organ cardiac electromechanics and cardiovascular hemodynamics. LNODEs provide a compact representation of the 3D-0D model in a latent space by means of an Artificial Neural Network that retains only 3 hidden layers with 13 neurons per layer and allows for numerical simulations of cardiac function on a single processor. We employ LNODEs to perform global sensitivity analysis and parameter estimation with uncertainty quantification in 3 hours of computations, still on a single processor.
Dynamic changes in lysosome‐related pathways in APP/PS1 mice with aging
Authors: Zhendong Xu, Jichang Hu, Zhen Wei, Yu Lei, Henok Kessete Afewerky, Yang Gao, Lu Wan, Longfei Li, Ling Lei, Yi Liu, Fang Huang, Tong Yu, Jian‐Zhi Wang, Hong‐Lian Li, Rong Liu, Xiaochuan Wang
Journal: MedComm (2024)

Abstract Senile plaque, composed of amyloid β protein (Aβ) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aβ aggregates exert age‐dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age‐gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of β‐amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age‐dependent Aβ deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age‐dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age‐dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age‐gradient changes in the autophagy–lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.
Lanosterol synthase deficiency promotes tumor progression by orchestrating PDL1‐dependent tumor immunosuppressive microenvironment
Authors: Yuan Gao, Kun Zhao, Yulan Huang, Dapeng Zhang, Na Luo, Xiaoqing Peng, Feng Yang, Weidong Xiao, Meng Wang, Rongchen Shi, Hongming Miao
Journal: MedComm (2024)

Abstract Lipid metabolic reprogramming is closely related to tumor progression with the mechanism not fully elucidated. Here, we report the immune‐regulated role of lanosterol synthase (LSS), an essential enzyme in cholesterol synthesis. Database analysis and clinical sample experiments suggest that LSS was lowly expressed in colon and breast cancer tissues, which indicates poor prognosis. The biological activity of tumor cell lines and tumor progression in NOD scid gamma (NSG) mice were not affected after LSS knockdown, whereas LSS deficiency obviously aggravated tumor burden in fully immunized mice. Flow cytometry analysis showed that LSS knockdown significantly promoted the formation of tumor immunosuppressive microenvironment, characterized by the increase in M2 macrophages and polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSCs), as well as the decrease in anti‐tumoral T lymphocytes. With the inhibition of myeloid infiltration or loss function of T lymphocytes, the propulsive effect of LSS knockdown on tumor progression disappeared. Mechanistically, LSS knockdown increased programmed death ligand 1 (PDL1) protein stability by 2,3‐oxidosqualene (OS) binding to PDL1 protein. Anti‐PDL1 therapy abolished LSS deficiency‐induced immunosuppressive microenvironment and cancer progression. In conclusion, our results show that LSS deficiency promotes tumor progression by establishing an OS–PDL1 axis‐dependent immunosuppressive microenvironment, indicative of LSS or OS as a potential hallmark of response to immune checkpoint blockade.
ATF3 and CH25H regulate effector trogocytosis and anti-tumor activities of endogenous and immunotherapeutic cytotoxic T lymphocytes
Authors: Zhen Lu, Noreen McBrearty, Jinyun Chen, Vivek S. Tomar, Hongru Zhang, Gianluca De Rosa, Aiwen Tan, Aalim M. Weljie, Daniel P. Beiting, Zhen Miao, Subin S. George, Allison Berger, Gurpanna Saggu, J. Alan Diehl, Constantinos Koumenis, Serge Y. Fuchs
Journal: Cell Metabolism (2024)
Development and validation of a point‐of‐care nursing mobile tool to guide the diagnosis of malnutrition in hospitalized adult patients: a multicenter, prospective cohort study
Authors: Nan Lin, Xueyan Zhou, Weichang Chen, Chengyuan He, Xiaoxuan Wang, Yuhao Wei, Zhiwen Long, Tao Shen, Lingyu Zhong, Chan Yang, Tingting Dai, Hao Zhang, Hubing Shi, Xuelei Ma
Journal: MedComm (2024)

Abstract Malnutrition is a prevalent and severe issue in hospitalized patients with chronic diseases. However, malnutrition screening is often overlooked or inaccurate due to lack of awareness and experience among health care providers. This study aimed to develop and validate a novel digital smartphone‐based self‐administered tool that uses facial features, especially the ocular area, as indicators of malnutrition in inpatient patients with chronic diseases. Facial photographs and malnutrition screening scales were collected from 619 patients in four different hospitals. A machine learning model based on back propagation neural network was trained, validated, and tested using these data. The model showed a significant correlation ( p &lt; 0.05) and a high accuracy (area under the curve 0.834–0.927) in different patient groups. The point‐of‐care mobile tool can be used to screen malnutrition with good accuracy and accessibility, showing its potential for screening malnutrition in patients with chronic diseases.
How to explain the beneficial effects of platelet‐rich plasma
Authors: Reinhard Gruber
Journal: Periodontology 2000 (2024)

Abstract Platelet‐rich plasma (PRP) is the platelet and leukocyte‐containing plasmatic fraction of anticoagulated autologous blood. While evidence supporting the clinical use of PRP in dentistry is low, PRP is widely used in sports medicine, orthopedics, and dermatology. Its beneficial activity is commonly attributed to the growth factors released from platelets accumulating in PRP; however, evidence is indirect and not comprehensive. There is thus a demand to revisit PRP with respect to basic and translational science. This review is to (i) recapitulate protocols and tools to prepare PRP; (ii) to discuss the cellular and molecular composition of PRP with a focus on platelets, leukocytes, and the fibrin‐rich extracellular matrix of coagulated plasma; and finally (iii) to discuss potential beneficial effects of PRP on a cellular and molecular level with an outlook on its current use in dentistry and other medical fields.
Evaluating and improving the representation of bacterial contents in long-read metagenome assemblies
Authors: Xiaowen Feng, Heng Li
Journal: Genome biology (2024)

Abstract Background In the metagenomic assembly of a microbial community, abundant species are often thought to assemble well given their deeper sequencing coverage. This conjuncture is rarely tested or evaluated in practice. We often do not know how many abundant species are missing and do not have an approach to recover them. Results Here, we propose k -mer based and 16S RNA based methods to measure the completeness of metagenome assembly. We show that even with PacBio high-fidelity (HiFi) reads, abundant species are often not assembled, as high strain diversity may lead to fragmented contigs. We develop a novel reference-free algorithm to recover abundant metagenome-assembled genomes (MAGs) by identifying circular assembly subgraphs. Complemented with a reference-free genome binning heuristics based on dimension reduction, the proposed method rescues many abundant species that would be missing with existing methods and produces competitive results compared to those state-of-the-art binners in terms of total number of near-complete genome bins. Conclusions Our work emphasizes the importance of metagenome completeness, which has often been overlooked. Our algorithm generates more circular MAGs and moves a step closer to the complete representation of microbial communities.
Nonbinary people living in a binary world: Minority stress in public and gendered places
Authors: Fau Rosati, Maric Martin Lorusso, Jessica Pistella, Annalisa Anzani, Bianca Di Giannantonio, Marta Mirabella, Roberto Baiocco
Journal: International Journal of Transgender Health (2024)

Introduction Nonbinary gender identities are widely erased and invalidated in Western societies, due to binary normativity. The segregation by binary gender of public spaces and sports categories may cause unique sources of stress for nonbinary people, manifesting at a structural and interpersonal level. Utilizing the nonbinary minority stress framework this study explores how the dichotomous gender division of public restrooms, store dressing rooms, locker rooms, and sports categories is associated with distal and proximal dimensions of minority stress.
Characteristic roadmap of linker governs the rational design of PROTACs
Authors: Yawen Dong, Tingting Ma, Ting Xu, Zhangyan Feng, Yonggui Li, Lingling Song, Xiaojun Yao, Charles R. Ashby, Ge-Fei Hao
Journal: Acta Pharmaceutica Sinica B (2024)

Proteolysis targeting chimera (PROTAC) technology represents a groundbreaking development in drug discovery, leveraging the ubiquitin‒proteasome system to specifically degrade proteins responsible for the disease. PROTAC is characterized by its unique heterobifunctional structure, which comprises two functional domains connected by a linker. The linker plays a pivotal role in determining PROTAC's biodegradative efficacy. Advanced and rationally designed functional linkers for PROTAC are under development. Nonetheless, the correlation between linker characteristics and PROTAC efficacy remains under-investigated. Consequently, this study will present a multidisciplinary analysis of PROTAC linkers and their impact on efficacy, thereby guiding the rational design of linkers. We will primarily discuss the structural types and characteristics of PROTAC linkers, and the optimization strategies used for their rational design. Furthermore, we will discuss how factors like linker length, group type, flexibility, and linkage site affect the biodegradation efficiency of PROTACs. We believe that this work will contribute towards the advancement of rational linker design in the PROTAC research area.
Feasibility of functional precision medicine for guiding treatment of relapsed or refractory pediatric cancers
Authors: Arlet M. Acanda De La Rocha, Noah E. Berlow, Maggie Fader, Ebony R. Coats, Cima Saghira, Paula S. Espinal, Jeanette Galano, Ziad Khatib, Haneen Abdella, Ossama M. Maher, Yana Vorontsova, Cristina M. Andrade-Feraud, Aimee Daccache, Alexa Jacome, Victoria Reis, Baylee Holcomb, Yasmin Ghurani, Lilliam Rimblas, Tomás R. Guilarte, Nan Hu, Daria Salyakina, Diana J. Azzam
Journal: Nature Medicine (2024)

Children with rare, relapsed or refractory cancers often face limited treatment options, and few predictive biomarkers are available that can enable personalized treatment recommendations. The implementation of functional precision medicine (FPM), which combines genomic profiling with drug sensitivity testing (DST) of patient-derived tumor cells, has potential to identify treatment options when standard-of-care is exhausted. The goal of this prospective observational study was to generate FPM data for pediatric patients with relapsed or refractory cancer. The primary objective was to determine the feasibility of returning FPM-based treatment recommendations in real time to the FPM tumor board (FPMTB) within a clinically actionable timeframe (<4 weeks). The secondary objective was to assess clinical outcomes from patients enrolled in the study. Twenty-five patients with relapsed or refractory solid and hematological cancers were enrolled; 21 patients underwent DST and 20 also completed genomic profiling. Median turnaround times for DST and genomics were within 10 days and 27 days, respectively. Treatment recommendations were made for 19 patients (76%), of whom 14 received therapeutic interventions. Six patients received subsequent FPM-guided treatments. Among these patients, five (83%) experienced a greater than 1.3-fold improvement in progression-free survival associated with their FPM-guided therapy relative to their previous therapy, and demonstrated a significant increase in progression-free survival and objective response rate compared to those of eight non-guided patients. The findings from our proof-of-principle study illustrate the potential for FPM to positively impact clinical care for pediatric and adolescent patients with relapsed or refractory cancers and warrant further validation in large prospective studies. ClinicalTrials.gov registration: NCT03860376 .
Longitudinal Cervical Length Measurements and Spontaneous Preterm Birth in Singleton and Twin Pregnancies
Authors: Tianchen Wu, Shuang Li, Xiaoli Gong, Jiaxin Li, Xuening Li, Yujia Zhai, Jiaqi Huang, Xiaona Li, Luyao Li, Jing Yang, Xueju Wang, Huifeng Shi, Pengbo Yuan, Yangyu Zhao, Yuan Wei
Journal: JAMA Network Open (2024)

Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear.