tbuckley/cabot-search huggingface dataset:
Combination Assay of Methylated &lt;i&gt;HOXA1&lt;/i&gt; with Tumor Markers Shows High Sensitivity for Detection of Early-Stage Hepatocellular Carcinoma
Authors: Yuki Kunimune, Yutaka Suehiro, Issei Saeki, Yurika Yamauchi, Norikazu Tanabe, Toshihiko Matsumoto, Shingo Higaki, Ikuei Fujii, Chieko Suzuki, Naoko Okayama, Mitsuaki Nishioka, Kiyoshi Ichihara, Hiroaki Nagano, Isao Sakaida, Taro Takami, Takahiro Yamasaki
Journal: Liver Cancer (2024)

Introduction: Patients with hepatitis virus-related hepatocellular carcinoma (viral HCC) are decreasing as hepatitis control improves, but those with non-viral-related HCC (non-viral HCC) are increasing in Japan. No established surveillance system exists for patients with non-viral HCC, so they are often diagnosed at an advanced stage. To address this, we performed this study. Methods: We collected serum samples from 516 participants (154 healthy subjects, 93 chronic liver disease [CLD] patients without HCC, and 269 HCC patients). Participants were divided into a control group comprising healthy subjects and patients with CLD and an HCC group. We evaluated serum methylated HOXA1 (m-HOXA1) copy numbers using modified combined restriction digital PCR (CORD) assay (1-step CORD assay). We assessed diagnostic performance of m-HOXA1 compared to HCC tumor markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) and created a novel index to improve HCC prediction. Results: Serum m-HOXA1 level was significantly higher in each HCC stage group versus the control group. Its sensitivity was 69.1% and specificity was 78.5% for diagnosing HCC. The area under the curve (AUC) of m-HOXA1 was superior to that of AFP and equal to that of DCP. Multivariate logistic regression analysis revealed independent contributions of m-HOXA1, DCP, and AFP, in that order of strength, to diagnose HCC after adjustment for age and sex. We designated the predictive probability of HCC based on the regression model as the ASDAm-H1 (&lt;underline&gt;A&lt;/underline&gt;ge, &lt;underline&gt;S&lt;/underline&gt;ex, &lt;underline&gt;D&lt;/underline&gt;CP, &lt;underline&gt;A&lt;/underline&gt;FP, and &lt;underline&gt;m&lt;/underline&gt;&lt;underline&gt;-&lt;/underline&gt;&lt;underline&gt;H&lt;/underline&gt;OXA&lt;underline&gt;1&lt;/underline&gt;) index. Its diagnostic accuracy was 0.96 by AUC with a sensitivity of 86.2% and specificity of 93.9%. Sensitivity was identical for viral and non-viral HCCs. When limited to early-stage HCC, sensitivity of the ASDAm-H1 index was 76.3%. Conclusions: We showed distinguished performance of the ASDAm-H1 index to detect viral and non-viral HCC, even at an early stage. This index might have potential as a non-viral HCC surveillance system.
Author Correction: Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial
Authors: Christine E. Brown, Jonathan C. Hibbard, Darya Alizadeh, M. Suzette Blanchard, Heini M. Natri, Dongrui Wang, Julie R. Ostberg, Brenda Aguilar, Jamie R. Wagner, Jinny A. Paul, Renate Starr, Robyn A. Wong, Wuyang Chen, Noah Shulkin, Maryam Aftabizadeh, Aleksandr Filippov, Ammar Chaudhry, Julie A. Ressler, Julie Kilpatrick, Paige Myers-McNamara, Mike Chen, Leo D. Wang, Russell C. Rockne, Joseph Georges, Jana Portnow, Michael E. Barish, Massimo D’Apuzzo, Nicholas E. Banovich, Stephen J. Forman, Behnam Badie
Journal: Nature Medicine (2024)
One Stone Three Birds: Silver Sulfadiazine Modulates the Stability and Dynamics of Hydrogels for Infected Wound Healing
Authors: Ye Huang, Haifei Kang, Yue Wang, Kun Liu, Wenying Wei, Honglian Dai
Journal: Advanced Healthcare Materials (2024)

Abstract Dynamic covalent bond hydrogels have demonstrated significant application potential in biomedical fields for their dynamic reversibility. However, the contradiction between the stability and dynamics of the hydrogel restricts its application. Here, utilizing silver sulfadiazine (AgSD) as a catalyst, hyaluronic acid‐based hydrogels are constructed through imine bond crosslinking and incorporated disulfide bonds within the same crosslinking chain. It is found that AgSD can accelerate the formation of imine crosslinking bonds to improve the stability of hydrogels, thereby shortening the gelation time by ≈36.9 times, enhancing compression strength and adhesion strength by ≈2.4 times and 1.7 times, respectively, while inhibiting swelling and degradation rates to ≈2.1 times and 3.7 times. Besides, AgSD can coordinate with disulfide bonds to enhance the dynamics of hydrogel, enhancing the hydrogel self‐healing efficiency by ≈2.3 times while reducing the relaxation time by ≈25.1 times. Significantly, AgSD imparts remarkable antibacterial properties to the hydrogel, thereby effectively facilitating the healing of bacterial infected wounds. Consequently, introducing AgSD enables hydrogels to possess concurrent stability, dynamics, and antibacterial properties. This strategy of regulating hydrogels by introducing AgSD provides a valuable reference for the application of dynamic covalent bonds.
Cancer Treatment Disparities in People With HIV in the United States, 2001-2019
Authors: Jennifer K. McGee-Avila, Gita Suneja, Eric A. Engels, Anne F. Rositch, Marie-Josephe Horner, Qianlai Luo, Meredith S. Shiels, Jessica Y. Islam
Journal: Journal of Clinical Oncology (2024)

PURPOSE People with HIV (PWH) have worse cancer outcomes, partially because of inequities in cancer treatment. We evaluated cancer treatment disparities among PWH, including an assessment of changes in disparities over time. METHODS We used data from the HIV/AIDS Cancer Match Study, a population-based HIV and cancer registry linkage to examine diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and cancers of the cervix, lung, anus, prostate, colon, and female breast. Outcomes included receipt of (1) any cancer treatment and (2) standard therapy among patients with local-stage cancer. We assessed associations between HIV and each outcome by estimating adjusted prevalence odds ratios (aORs) with 95% CI and trends over time. We identified predictors of nonreceipt of cancer treatment in PWH. RESULTS From 2001 to 2019, compared with people with cancer without HIV (n = 2,880,955), PWH (n = 16,334) were more likely to not receive cancer treatment for cervical cancer (aOR, 2.03 [95% CI, 1.52 to 2.70]), DLBCL (aOR, 1.53 [95% CI, 1.38 to 1.70]), HL (aOR, 1.39 [95% CI, 1.19 to 1.63]), lung cancer (aOR, 1.79 [95% CI, 1.65 to 1.93]), prostate cancer (aOR, 1.32 [95% CI, 1.21 to 1.44]), colon cancer (aOR, 1.73 [95% CI, 1.43 to 2.08]), and breast cancer (aOR, 1.38 [95% CI, 1.07 to 1.77]). Similar associations were observed in PWH with local-stage cancers although no difference was observed for anal cancers. The association between HIV and nonreceipt of cancer treatment significantly decreased over time for breast, colon, and prostate cancers (all P trend &lt;.0001), but PWH remained less likely to receive treatment in 2014-2019 for DLBCL, cervix, and lung cancers. Among PWH, Black individuals, people who inject drugs, and those 65 years and older were less likely to receive cancer treatment. CONCLUSION Disparities in receipt of cancer treatment persist for PWH in the United States in contemporary time periods. Solutions to address inequitable receipt of cancer treatment among PWH are urgently needed.
PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer
Authors: Erica L. Mayer, Yue Ren, Nikhil Wagle, Reshma Mahtani, Cynthia Ma, Angela DeMichele, Massimo Cristofanilli, Jane Meisel, Kathy D. Miller, Yara Abdou, Elizabeth C. Riley, Rubina Qamar, Priyanka Sharma, Sonya Reid, Natalie Sinclair, Meredith Faggen, Caroline C. Block, Naomi Ko, Ann H. Partridge, Wendy Y. Chen, Michelle DeMeo, Victoria Attaya, Amanda Okpoebo, Jillian Alberti, Yuan Liu, Eric Gauthier, Harold J. Burstein, Meredith M. Regan, Sara M. Tolaney
Journal: Journal of Clinical Oncology (2024)

Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting.
BV2 Membrane‐Coated PEGylated‐Liposomes Delivered hFGF21 to Cortical and Hippocampal Microglia for Alzheimer's Disease Therapy
Authors: Heng‐Cai Wang, Wei Yang, Ling Xu, Yong‐Hui Han, Yi Lin, Cui‐Tao Lu, Kwonseop Kim, Ying‐Zheng Zhao, Xi‐Chong Yu
Journal: Advanced Healthcare Materials (2024)

Microglia-mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood-brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane-coated PEGylated liposomes (hFGF21@BCM-LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM-LIP specifically targets Aβ
Transthoracic and transoesophageal echocardiography for tricuspid transcatheter edge-to-edge repair: a step-by-step protocol
Authors: Matteo Mazzola, Cristina Giannini, Alessandro Sticchi, Paolo Spontoni, Nicola Riccardo Pugliese, Luna Gargani, Marco De Carlo
Journal:  (2024)

Abstract Tricuspid regurgitation (TR) carries an unfavourable prognosis and often leads to progressive right ventricular (RV) failure. Secondary TR accounts for over 90% of cases and is caused by RV and/or tricuspid annulus dilation, in the setting of left heart disease or pulmonary hypertension. Surgical treatment for isolated TR entails a high operative risk and is seldom performed. Recently, transcatheter edge-to-edge repair (TEER) has emerged as a low-risk alternative treatment in selected patients. Although the experience gained from mitral TEER has paved the way for the technique’s adaptation to the tricuspid valve (TV), its anatomical complexity necessitates precise imaging. To this end, a comprehensive protocol integrating 2D and 3D imaging from both transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) plays a crucial role. TTE allows for an initial morphological assessment of the TV, quantification of TR severity, evaluation of biventricular function, and non-invasive haemodynamic evaluation of pulmonary circulation. TOE, conversely, provides a detailed evaluation of TV morphology, enabling precise assessment of TR mechanism and severity, and represents the primary method for determining eligibility for TEER. Once a patient is considered eligible for TEER, TOE, alongside fluoroscopy, will guide the procedure in the catheterization lab. High-quality TOE imaging is crucial for patient selection and to achieve procedural success. The present review examines the roles of TTE and TOE in managing patients with severe TR eligible for TEER, proposing the step-by-step protocol successfully adopted in our centre.
Clonal hematopoiesis and its impact on the aging osteo-hematopoietic niche
Authors: Susann Winter, Katharina S. Götze, Judith S. Hecker, Klaus H. Metzeler, Borhane Guezguez, Kevin Woods, Hind Medyouf, Alexander Schäffer, Marc Schmitz, Rebekka Wehner, Ingmar Glauche, Ingo Roeder, Martina Rauner, Lorenz C. Hofbauer, Uwe Platzbecker
Journal: Leukemia (2024)

Clonal hematopoiesis (CH) defines a premalignant state predominantly found in older persons that increases the risk of developing hematologic malignancies and age-related inflammatory diseases. However, the risk for malignant transformation or non-malignant disorders is variable and difficult to predict, and defining the clinical relevance of specific candidate driver mutations in individual carriers has proved to be challenging. In addition to the cell-intrinsic mechanisms, mutant cells rely on and alter cell-extrinsic factors from the bone marrow (BM) niche, which complicates the prediction of a mutant cell's fate in a shifting pre-malignant microenvironment. Therefore, identifying the insidious and potentially broad impact of driver mutations on supportive niches and immune function in CH aims to understand the subtle differences that enable driver mutations to yield different clinical outcomes. Here, we review the changes in the aging BM niche and the emerging evidence supporting the concept that CH can progressively alter components of the local BM microenvironment. These alterations may have profound implications for the functionality of the osteo-hematopoietic niche and overall bone health, consequently fostering a conducive environment for the continued development and progression of CH. We also provide an overview of the latest technology developments to study the spatiotemporal dependencies in the CH BM niche, ideally in the context of longitudinal studies following CH over time. Finally, we discuss aspects of CH carrier management in clinical practice, based on work from our group and others.
Improved pulmonary function and exercise tolerance despite persistent pulmonary fibrosis over 1 year after severe COVID-19 infection
Authors: Claire F McGroder, Mary M Salvatore, Belinda M D'Souza, Eric A Hoffman, Matthew R Baldwin, Christine Kim Garcia
Journal: Thorax (2024)

We conducted a prospective single-centre cohort study of 104 multi-ethnic severe COVID-19 survivors from the first wave of the pandemic 15 months after hospitalisation. Of those who were assessed at 4 and 15 months, improvement of ground glass opacities correlated with worsened fibrotic reticulations. Despite a high prevalence of fibrotic patterns (64%), pulmonary function, grip strength, 6 min walk distance and frailty normalised. Overall, dyspnoea, cough and exhaustion did not improve and were not correlated with pulmonary function or radiographic fibrosis at 15 months, suggesting non-respiratory aetiologies. Monitoring persistent, and often subclinical, fibrotic interstitial abnormalities will be needed to determine their potential for future progression.
Clinical implications of airway obstruction with normal or low FEV<sub>1</sub>in childhood and adolescence
Authors: Hans Jacob Lohne Koefoed, Gang Wang, Ulrike Gehring, Sandra Ekstrom, Inger Kull, Roel Vermeulen, Jolanda M A Boer, Anna Bergstrom, Gerard H Koppelman, Erik Melén, Judith M Vonk, Jenny Hallberg
Journal: Thorax (2024)

Background Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV 1 ) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV 1 (classic) or a normal FEV 1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear. Aims To investigate the association between airway obstruction with a low or normal FEV 1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR). Methods In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV 1 :FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV 1 &lt;LLN) or dysanaptic (FEV 1 ≥LLN) obstruction. Cross-sectional and longitudinal associations between these two types of obstruction and respiratory health outcomes were estimated by cohort-adjusted logistic regression on pooled data. Results The prevalence of classic obstruction at ages 8, 12 and 16 in the two cohorts was 1.5%, 1.1% and 1.5%, respectively. Dysanaptic obstruction was slightly more prevalent: 3.9%, 2.5% and 4.6%, respectively. Obstruction, regardless of FEV 1 , was consistently associated with higher odds of asthma (dysanaptic obstruction: OR 2.29, 95% CI 1.40 to 3.74), wheezing, asthma medication use and BHR compared with the normal lung function group. Approximately one-third of the subjects with dysanaptic obstruction in childhood remained dysanaptic during adolescence. Clinical implications Children and adolescents with airway obstruction had, regardless of their FEV 1 level, a higher prevalence of asthma and wheezing. Follow-up and treatment at these ages should be guided by the presence of airway obstruction.
Genomic Diversity in the Endosymbiotic Bacteria of Human Head Lice
Authors: Bret M Boyd, Niyomi House, Christopher W Carduck, David L Reed
Journal: Molecular Biology and Evolution (2024)

Abstract Insects have repeatedly forged symbioses with heritable microbes, gaining novel traits. For the microbe, the transition to symbioses can lead to the degeneration of the symbiont's genome through transmission bottlenecks, isolation, and the loss of DNA repair enzymes. However, some insect-microbial symbioses have persisted for millions of years, suggesting that natural selection slows genetic drift and maintains functional consistency between symbiont populations. By sampling in multiple countries, we examine genomic diversity within a symbiont species, a heritable symbiotic bacterium found only in human head lice. We find that human head louse symbionts contain genetic diversity that appears to have arisen contemporaneously with the appearance of anatomically modern humans within Africa and/or during the colonization of Eurasia by humans. We predict that the observed genetic diversity underlies functional differences in extant symbiont lineages, through the inactivation of genes involved in symbiont membrane construction. Furthermore, we find evidence of additional gene losses prior to the appearance of modern humans, also impacting the symbiont membrane. From this, we conclude that symbiont genome degeneration is proceeding, via gene inactivation and subsequent loss, in human head louse symbionts, while genomic diversity is maintained. Collectively, our results provide a look into the genomic diversity within a single symbiont species and highlight the shared evolutionary history of humans, lice, and bacteria.
Sexual dimorphism in the antitumor immune responses elicited by the combination of fasting and chemotherapy
Authors: Andrés Pastor‐Fernández, Manuel Montero Gómez de las Heras, Jose Ignacio Escrig‐Larena, Marta Barradas, Cristina Pantoja, Adrian Plaza, Jose Luis Lopez‐Aceituno, Esther Durán, Alejo Efeyan, Maria Mittelbrunn, Lola Martinez, Pablo Jose Fernandez‐Marcos
Journal: Cancer Communications (2024)
Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD)
Authors: Raquel Benedé-Ubieto, Francisco Javier Cubero, Yulia A. Nevzorova
Journal: Gut Microbes (2024)

Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), a growing health concern. The complex progression of MASLD extends beyond the liver, driven by "gut-liver axis," where diet, genetics, and gut-liver interactions influence disease development. The pathophysiology of MASLD involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, and fibrosis, with subsequent risk of hepatocellular carcinoma (HCC). The gut, a tripartite barrier, with mechanical, immune, and microbial components, engages in a constant communication with the liver. Recent evidence links dysbiosis and disrupted barriers to systemic inflammation and disease progression. Toll-like receptors (TLRs) mediate immunological crosstalk between the gut and liver, recognizing microbial structures and triggering immune responses. The "multiple hit model" of MASLD development involves factors like fat accumulation, insulin resistance, gut dysbiosis, and genetics/environmental elements disrupting the gut-liver axis, leading to impaired intestinal barrier function and increased gut permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, and microbiome modulation approaches through prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). This review underscores the complex interactions between diet, metabolism, microbiome, and their impact on MASLD pathophysiology and therapeutic prospects.
Impact of obesity progression or regression on the longitudinal assessment of fibrosing interstitial lung disease
Authors: Hadeel Alqurashi, Mathieu Marillier, Igor Neder-Serafini, Anne-Catherine Bernard, Onofre Moran-Mendoza, J. Alberto Neder
Journal: European Respiratory Journal (2024)

Abnormalities in lung mechanics (restriction) and pulmonary gas exchange (hypoxemia) may jointly conspire to elicit exertional dyspnea and decrease exercise tolerance in patients with fibrosing interstitial lung diseases ( f -ILD) [1]. Obesity (body mass index (BMI)≥30 kg·m−2), a prevalent co-morbidity of f -ILD [2], may negatively impact on "static" ( e.g. , total lung capacity (TLC)) and dynamic (forced vital capacity (FVC)) lung volumes relevant to dyspnea genesis [3]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of Interest: All authors have nothing to disclose.
Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis
Authors: Rong-Guang Luo, Yi-Fan Wu, Hai-Wen Lu, Dong Weng, Jia-Yan Xu, Le-Le Wang, Li-Sha Zhang, Cai-Qi Zhao, Jian-Xiong Li, Yong Yu, Xin-Ming Jia, Jin-Fu Xu
Journal: European Respiratory Journal (2024)

Introduction Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. Methods We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21 + CD4 + T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4 + T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured. Results ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5 + IL-13 + IL-21 + CD4 + T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5 + IL-13 + IL-21 + CD4 + T-cells were mainly peripheral T-helper (Tph) cells (PD-1 + CXCR5 − ), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5 + IL-13 + IL-21 + Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro , Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. Conclusion We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.