tbuckley/cabot-search huggingface dataset:
Foundation Model for Advancing Healthcare: Challenges, Opportunities and Future Directions
Authors: Yuting He, Fuxiang Huang, Xinrui Jiang, Yuxiang Nie, Minghao Wang, Jiguang Wang, Hao Chen
Journal: IEEE Reviews in Biomedical Engineering (2024)

Foundation model, trained on a diverse range of data and adaptable to a myriad of tasks, is advancing healthcare. It fosters the development of healthcare artificial intelligence (AI) models tailored to the intricacies of the medical field, bridging the gap between limited AI models and the varied nature of healthcare practices. The advancement of a healthcare foundation model (HFM) brings forth tremendous potential to augment intelligent healthcare services across a broad spectrum of scenarios. However, despite the imminent widespread deployment of HFMs, there is currently a lack of clear understanding regarding their operation in the healthcare field, their existing challenges, and their future trajectory. To answer these critical inquiries, we present a comprehensive and in-depth examination that delves into the landscape of HFMs. It begins with a comprehensive overview of HFMs, encompassing their methods, data, and applications, to provide a quick understanding of the current progress. Subsequently, it delves into a thorough exploration of the challenges associated with data, algorithms, and computing infrastructures in constructing and widely applying foundation models in healthcare. Furthermore, this survey identifies promising directions for future development in this field. We believe that this survey will enhance the community's understanding of the current progress of HFMs and serve as a valuable source of guidance for future advancements in this domain. For the latest HFM papers and related resources, please refer to our website.
Is hip adductor or abductor strength in healthy athletes associated with future groin pain? A systematic review and meta-analysis
Authors: Marcos Quintana-Cepedal, Germán Vicente-Rodríguez, Irene Crespo, Hugo Olmedillas
Journal: British Journal of Sports Medicine (2024)

To systematically review the association between hip adduction and abduction strength, and adduction-to-abduction strength ratio in healthy athletes with the occurrence of future groin pain and time-loss groin injuries.
Life Course Associations Between Ambient Fine Particulate Matter and the Prevalence of Prediabetes and Diabetes: A Longitudinal Cohort Study in Taiwan and Hong Kong
Authors: Yuanyuan Yi, Cui Guo, Yiling Zheng, Siyi Chen, Changqing Lin, Alexis K. H. Lau, Martin C. S. Wong, David M. Bishai
Journal: Diabetes Care (2024)

OBJECTIVE Both air pollution and diabetes are key urban challenges. The association between particulate matter with a diameter of &amp;lt;2.5 μm (PM2.5) exposure and prediabetes/diabetes in adults is well documented, but the health effects of life course exposure remain unclear. This study evaluated the impact of PM2.5 exposure throughout various life stages on the prevalence of prediabetes/diabetes in adulthood. RESEARCH DESIGN AND METHODS We included 4,551 individuals with 19,593 medical visits from two open cohorts in Taiwan and Hong Kong between 2000 and 2018. Ambient PM2.5 exposure was assessed using a satellite-based model, delivering a 2-year average exposure at a resolution of 1 km2. Logistic mixed-effects models were used to investigate longitudinal associations between PM2.5 exposure and the prevalence of prediabetes/diabetes. Life course models were used to examine the impact of PM2.5 exposure at different life stages on prediabetes/diabetes in adulthood. RESULTS Over an average follow-up period of 9.93 years, 1,660 individuals with prediabetes/diabetes were observed. For the longitudinal association, every 10 μg/m3 increase in PM2.5 was associated with an increased odds of having prediabetes/diabetes (odds ratio 1.32, 95% CI 1.13, 1.54). The odds of adulthood prediabetes/diabetes increased by 15%, 18%, and 29% for each 10 μg/m3 increase in PM2.5 exposure during school age, adolescence, and adulthood, respectively. CONCLUSIONS Our findings suggest a link between PM2.5 exposure during each life stage and the prevalence of prediabetes/diabetes in adulthood, with the health impacts of exposure during adulthood being slightly greater. This study underscores the need for life course air pollution control strategies to mitigate the substantial disease burden of diabetes.
Enhancing Chemoimmunotherapy for Colorectal Cancer with Paclitaxel and Alantolactone via CD44-Targeted Nanoparticles: A STAT3 Signaling Pathway Modulation Approach
Authors: Fugen Wu, Xingsi An, Shize Li, Chenyu Qiu, Yixuan Zhu, Zhanzheng Ye, Shengnan Song, Yunzhi Wang, Dingchao Shen, Xinyu Di, Yinsha Yao, Wanling Zhu, Xinyu Jiang, Xianbao Shi, Ruijie Chen, Longfa Kou
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Chemoimmunotherapy has the potential to enhance chemotherapy and modulate the immunosuppressive tumor microenvironment by activating immunogenic cell death (ICD), making it a promising strategy for clinical application. Alantolactone (A) was found to augment the anticancer efficacy of paclitaxel (P) at a molar ratio of 1:0.5 (P:A) through induction of more potent ICD via modulation of STAT3 signaling pathways. Nano drug delivery systems can synergistically combine natural drugs with conventional chemotherapeutic agents, thereby enhancing multi-drug chemoimmunotherapy. To improve tumor targeting ability and bioavailability of hydrophobic drugs, an amphiphilic prodrug conjugate (HA-PTX) was chemically modified with paclitaxel (PTX) and hyaluronic acid (HA) as a backbone. Based on this concept, CD44-targeted nanodrugs (A@HAP NPs) were developed for co-delivery of A and P in colorectal cancer treatment, aiming to achieve synergistic toxicity-based chemo-immunotherapy. The uniform size and high drug loading capacity of A@HAP NPs facilitated their accumulation within tumors through enhanced permeability and retention effect as well as HA-mediated targeting, providing a solid foundation for subsequent synergistic therapy and immunoregulation. In vitro and in vivo studies demonstrated that A@HAP NPs exhibited potent cytotoxicity against tumor cells while also remodeling the immune-suppressive tumor microenvironment by promoting antigen presentation and inducing dendritic cell maturation, thus offering a novel approach for colorectal cancer chemoimmunotherapy.
Recent advances in clinical practice: mastering the challenge—managing IBS symptoms in IBD
Authors: Judith Wellens, João Sabino, Tim Vanuytsel, Jan Tack, Séverine Vermeire
Journal: Gut (2024)

Many patients with IBD report persisting symptoms, despite resolution of the inflammatory process. Although by definition, a diagnosis of IBS cannot be made, the prevalence of 'IBS in IBD' surpasses the rate of IBS in the global population by fivefold. Because IBS-like symptoms are associated with a decreased quality of life and increased healthcare utilisation in IBD, diagnosis and treatment are necessary. In this review, we summarise the current knowledge on IBS-like symptoms in IBD. A pathophysiological common ground is present, which includes genetic susceptibility, environmental triggers, gut microbial dysbiosis, increased intestinal permeability, visceral hypersensitivity and involvement of brain-gut interaction. When symptoms persist after resolution of inflammation, other GI diseases should be excluded based on the chief complaint, considering any possible psychological co-morbidity early in the diagnostic work-up. Subsequent treatment should be initiated that is evidence-based and often multimodal, including classical and non-classical pharmacological agents as well as lifestyle and microbiota-based approaches, spanning the breadth of the gut, brain and its interaction. Treatment goals in this substantial part of the IBD population should be adapted to not only focus on treating the inflammation but taking care of the patient.
Impact of knowledge of HPV positivity on cervical cytology performance in latin america
Authors: Arianis Tatiana Ramírez, David Mesher, Armando Baena, Yuli Salgado, Elena Kasamatsu, Carmen Cristaldo, Rodrigo Álvarez, Freddy David Rojas, Katherine Ramírez, Julieta Guyot, Odessa Henríquez, Hans González Palma, Bettsy Flores, Jhaquelin Peñaranda, María José Vero, Isabel Robinson, Mary Luz Rol, Guillermo Rodríguez, Carolina Terán, Annabelle Ferrera, María Alejandra Picconi, Alejandro Calderon, Laura Mendoza, Carolina Wiesner, Maribel Almonte, Rolando Herrero
Journal: JNCI Journal of the National Cancer Institute (2024)

Cervical cytology is recommended by WHO as a triage option in HPV-based cervical cancer screening programmes. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity.
Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study
Authors: Maya Aboumrad, Corinne Joshu, Kala Visvanathan
Journal: JNCI Journal of the National Cancer Institute (2024)

Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality.
Supporting Evidence in Phase 2 Cancer Trial Protocols: A Content Analysis
Authors: Selin Bicer, Angela Nelson, Katerina Carayannis, Jonathan Kimmelman
Journal: JNCI Journal of the National Cancer Institute (2024)

Phase 2 trials are instrumental for designing definitive efficacy trials or attaining accelerated approval. However, high attrition of drug candidates in phase 2 raises questions about their supporting evidence.
Clonal outbreak of Candida vulturna in a paediatric oncology ward in Maranhão, Brazil
Authors: Alessandra Teixeira de Macedo, Daniel Wagner de Castro Lima Santos, Bram Spruijtenburg, Dayse Azevedo Coelho de Souza, Leila Ferreira Moreira Dos Santos Barbosa, Sirlei Garcia Marques, Julliana Ribeiro Alves Dos Santos, Eelco F J Meijer, Theun de Groot, Conceição de Maria Pedrozo E Silva de Azevedo, Jacques F Meis
Journal: Journal of Infection (2024)

To describe an outbreak due to Candida vulturna, a newly emerging Candida species belonging to the Candida haemulonii species complex in the Metschnikowiaceae family. In this retrospective cohort study we genotyped 14 C. vulturna bloodstream isolates, occurring in a 4-month-period in paediatric cancer patients in a Brazilian hospital. To prove an outbreak, ITS sequence analysis and whole genome sequencing (WGS) was done. Antifungal susceptibility was performed with the reference CLSI method and the commercial Sensititre YeastOne (SYO) YO10 plates. A control C. vulturna isolate from another region in Brazil was included in all analyses. MALDI-TOF-MS identified isolates as C. pseudohaemulonii and C. duobushaemulonii albeit with low scores and therefore molecular methods were required for accurate identification. ITS sequence analyses clearly differentiated C. vulturna from other species in the C. haemulonii species complex. WGS proved the presence of a clonal outbreak with C. vulturna involving 14 paediatric patients. Antifungal susceptibility testing (AFST) with two methods showed the isolates had low MICs of commonly available antifungals. This study describes an outbreak due to the rare yeast C. vulturna, related to C. auris, during a four-month period in patients admitted to a paediatric oncology ward in a Brazilian hospital. In contrast to previous studies the yeast was susceptible to all antifungals and patient outcome was good.
Overcoming Tumor Hypoxic Bismuth-based Ternary Heterojunctions Enable Defect Modulation-augmented Tumor Sonocatalytic Immunotherapy
Authors: Zongyan He, Qian Wang, Jun Du, Sijia Wu, Qing Miao, Yuhao Li, Yuqing Miao, Jingxiang Wu
Journal: Biomaterials (2024)
A p38 MAPK-ROS axis fuels proliferation stress and DNA damage during CRISPR-Cas9 gene editing in hematopoietic stem and progenitor cells
Authors: Lucrezia Della Volpe, Federico Midena, Roberta Vacca, Teresa Tavella, Laura Alessandrini, Giacomo Farina, Chiara Brandas, Elena Lo Furno, Kety Giannetti, Edoardo Carsana, Matteo M Naldini, Matteo Barcella, Samuele Ferrari, Stefano Beretta, Antonella Santoro, Simona Porcellini, Angelica Varesi, Diego Gilioli, Anastasia Conti, Ivan Merelli, Bernhard Gentner, Anna Villa, Luigi Naldini, Raffaella Di Micco
Journal: Cell Reports Medicine (2024)

Ex vivo activation is a prerequisite to reaching adequate levels of gene editing by homology-directed repair (HDR) for hematopoietic stem and progenitor cell (HSPC)-based clinical applications. Here, we show that shortening culture time mitigates the p53-mediated DNA damage response to CRISPR-Cas9-induced DNA double-strand breaks, enhancing the reconstitution capacity of edited HSPCs. However, this results in lower HDR efficiency, rendering ex vivo culture necessary yet detrimental. Mechanistically, ex vivo activation triggers a multi-step process initiated by p38 mitogen-activated protein kinase (MAPK) phosphorylation, which generates mitogenic reactive oxygen species (ROS), promoting fast cell-cycle progression and subsequent proliferation-induced DNA damage. Thus, p38 inhibition before gene editing delays G1/S transition and expands transcriptionally defined HSCs, ultimately endowing edited cells with superior multi-lineage differentiation, persistence throughout serial transplantation, enhanced polyclonal repertoire, and better-preserved genome integrity. Our data identify proliferative stress as a driver of HSPC dysfunction with fundamental implications for designing more effective and safer gene correction strategies for clinical applications.
IL-21/IL-21R signaling renders acute myeloid leukemia stem cells more susceptible to cytarabine treatment and CAR T cell therapy
Authors: Viviana Rubino, Michelle Hüppi, Sabine Höpner, Luigi Tortola, Noah Schnüriger, Hugo Legenne, Lea Taylor, Svenja Voggensperger, Irene Keller, Remy Bruggman, Marie-Noëlle Kronig, Ulrike Bacher, Manfred Kopf, Adrian F Ochsenbein, Carsten Riether
Journal: Cell Reports Medicine (2024)

Self-renewal programs in leukemia stem cells (LSCs) predict poor prognosis in patients with acute myeloid leukemia (AML). We identify CD4
Probiotics and their metabolite spermidine enhance IFN-γ+CD4+ T cell immunity to inhibit hepatitis B virus
Authors: Tixiao Wang, Yuchen Fan, Siyu Tan, Zehua Wang, Mengzhen Li, Xiaowei Guo, Xiangguo Yu, Qinghai Lin, Xiaojia Song, Leiqi Xu, Lixiang Li, Shiyang Li, Lifen Gao, Xiaohong Liang, Chunyang Li, Chunhong Ma
Journal: Cell Reports Medicine (2024)

The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γ
PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers
Authors: Yiqian Gu, Ann Ly, Sara Rodriguez, Hanwei Zhang, Jiyoon Kim, Zhiyuan Mao, Ankush Sachdeva, Nazy Zomorodian, Matteo Pellegrini, Gang Li, Sandy Liu, Alexandra Drakaki, Matthew B Rettig, Arnold I Chin
Journal: Cell Reports Medicine (2024)

Small cell neuroendocrine cancers share biologic similarities across tissue types, including transient response to platinum-based chemotherapy with rapid progression of disease. We report a phase 1b study of pembrolizumab in combination with platinum-based chemotherapy in 15 patients with stage III-IV small cell bladder (cohort 1) or small cell/neuroendocrine prostate cancers (cohort 2). Overall response rate (ORR) is 43% with two-year overall survival (OS) rate of 86% (95% confidence interval [CI]: 0.63, 1.00) for cohort 1 and 57% (95% CI: 0.30, 1.00) for cohort 2. Treatment is tolerated well with grade 3 or higher adverse events occurring in 40% of patients with no deaths or treatment cessation secondary to toxicity. Single-cell and T cell receptor sequencing of serial peripheral blood samples reveals clonal expansion of diverse T cell repertoire correlating with progression-free survival. Our results demonstrate promising efficacy and safety of this treatment combination and support future investigation of this biomarker. This study was registered at ClinicalTrials.gov (NCT03582475).
Discovery of biophysical rate laws from the electronic health record enables real-time liver injury estimation from transaminase dynamics
Authors: Marc S Sherman, Wolfram Goessling
Journal: Cell Reports Medicine (2024)

Alanine (ALT) and aspartate (AST) aminotransferases are standard-of-care biomarkers for liver injury though their temporal dynamics during injury and resolution remain incompletely characterized. Here, we analyze aminotransferase kinetics to determine whether rate laws can be ascertained during acute liver injury agnostic to etiology. From 6.5 million AST and ALT measurements in 91,086 patients, we identify a single rate-limiting step in transaminase decline enabling the discovery of plasma clearance rates of AST (1.13 days
Stability in fecal metabolites amid a diverse gut microbiome composition: a one-month longitudinal study of variability in healthy individuals
Authors: Matteo Sangermani, Indri Desiati, Solveig M. Jørgensen, Jia V. Li, Trygve Andreassen, Tone F. Bathen, Guro F. Giskeødegård
Journal: Gut Microbes (2024)

An extensive network of microbial-host interactions exists in the gut, making the gut microbiome a complex ecosystem to untangle. The microbial composition and the fecal metabolites are important readouts to investigate intricate microbiota-diet-host interplay. However, this ecosystem is dynamic, and it is of interest to understand the degree and timescale of changes occurring in the gut microbiota, during disease as well as in healthy individuals. Cross-sectional study design is often used to investigate the microbiome, but this design provides a static snapshot and cannot provide evidence on the dynamic nature of the gut microbiome. Longitudinal studies are better suited to extrapolate causation in a study or assess changes over time. This study investigates longitudinal change in the gut microbiome and fecal metabolites in 14 healthy individuals with weekly sampling over a period of one-month (four time points), to elucidate the temporal changes occurring in the gut microbiome composition and fecal metabolites. Utilizing 16S rRNA amplicon sequencing for microbiome analysis and NMR spectroscopy for fecal metabolite characterization, we assessed the stability of these two types of measurable parameters in fecal samples during the period of one month. Our results show that the gut microbiome display large variations between healthy individuals, but relatively lower within-individual variations, which makes it possible to uniquely identify individuals. The fecal metabolites showed higher stability over time compared to the microbiome and exhibited consistently smaller variations both within and between individuals. This relative higher stability of the fecal metabolites suggests a balanced, consistent output even amid individual's differences in microbial composition and they can provide a viable complementary readout to better understand the microbiome activity.
Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway
Authors: Yunzhu Chen, Baiwen Chen, Jingyu Li, Haixin Li, Gaoyang Wang, Xuemin Cai, Qianqian Zhang, Xiaoxu Liu, Chen Kan, Lei Wang, Zhengting Wang, Hua-Bing Li
Journal: Cellular and Molecular Immunology (2024)

Abstract Macrophage hyperactivation is a hallmark of inflammatory diseases, yet the role of alternative polyadenylation (APA) of mRNAs in regulating innate immunity remains unclear. In this study, we focused on 3’UTR-APA and demonstrated that Nudt21, a crucial RNA-binding component of the 3’UTR-APA machinery, is significantly upregulated in various inflammatory conditions. By utilizing myeloid-specific Nudt21-deficient mice, we revealed a protective effect of Nudt21 depletion against colitis and severe hyperinflammation, primarily through diminished production of proinflammatory cytokines. Notably, Nudt21 regulates the mRNA stability of key autophagy-related genes, Map1lc3b and Ulk2 , by mediating selective 3’UTR polyadenylation in activated macrophages. As a result, Nudt21-deficient macrophages display increased autophagic activity, which leads to reduced cytokine secretion. Our findings highlight an unexplored role of Nudt21-mediated 3’UTR-APA in modulating macrophage autophagy and offer new insights into the modulation of inflammation and disease progression.
Abstract 4137243: Dynamic changes of pericoronary fat attenuation index predicting changes of coronary plaque burden
Authors: Tianhao Zhang, Xuelian Gao, Xiaoming Zhang, Yu Du, Yujie Zhou
Journal: Circulation (2024)

Background: Percent atheroma volume (PAV) is a validated index of coronary plaque burden, linking to adverse cardiac events. Meanwhile, pericoronary fat attenuation index (FAI) on coronary computed tomography angiography (CCTA) image is a novel prognostic marker of coronary inflammation. Research Questions: It is unknown the impact of coronary inflammation (i.e., FAI) on the progression of coronary PAV in patients at an increased risk of adverse cardiac events. Methods: Patients with type 2 diabetes mellitus (T2DM) who underwent at least two clinically indicated CCTA examinations (time interval &gt; 1 year) at our center were potentially eligible for enrollment. Eligible patients presented with more than one study plaque, defined as non-obstructive stenosis at baseline and not being intervened during serial CCTA. Longitudinal CCTA images were assessed for FAI and compositional plaque characteristics (e.g., PAV) using dedicated post-processing softwares. The relationships between changes in FAI and progression of compositional PAV were examined using the logistic and linear regression analysis. Results: A total of 204 T2DM patients (mean age, 61.2 ± 9.3 years; male, 68.1%) with 366 study plaques were enrolled. All patients were treated with statins, and their time interval between longitudinal CCTAs was 14.1 (12.9, 17.6) months. Compared with patients with improved coronary inflammation (ΔFAI ≤ 0), those with deteriorated coronary inflammation (ΔFAI &gt; 0) had lower high density lipoprotein cholesterol and baseline FAI, whereas higher blood pressure (all p &lt; 0.05). Meanwhile, compared to patients with ΔFAI ≤ 0, those with ΔFAI &gt; 0 had more Δoverall and Δnon-calcified PAV (all p &lt; 0.05). Importantly, these findings were consistent in a dedicated propensity score matching analysis. In logistic regression analysis, ΔFAI &gt; 0 was associated with annual progression of overall PAV and non-calcified PAV, whereas ΔFAI ≤ 0 associated with annual regression of overall PAV and non-calcified PAV after adjusting for cardiac risk factors, baseline PAV and medications (all p &lt; 0.05). Similarly, in linear regression analysis, changes of FAI were independently positively associated with annual changes of overall PAV (β=0.545, p&lt; 0.001) and non-calcified PAV (β=0.461, p&lt; 0.001) (Figure 1). Conclusion: In this longitudinal CCTA study, changes of coronary inflammation are closely correlated with changes of overall and non-calcified PAV among T2DM patients treated with statins.