tbuckley/cabot-search huggingface dataset:
Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study
Authors: AnnaLynn M. Williams, Angie Mae Rodday, Qinglin Pei, Tara O. Henderson, Frank G. Keller, Angela Punnett, Kara M. Kelly, Sharon M. Castellino, Susan K. Parsons
Journal: Journal of Clinical Oncology (2024)

PURPOSEThere have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown.PATIENTS AND METHODSAfter treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm.RESULTSParticipant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever (
Vebreltinib for Advanced Non–Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study
Authors: Jin-Ji Yang, Yan Zhang, Lin Wu, Jie Hu, Zhe-Hai Wang, Jing-Hua Chen, Yun Fan, Gen Lin, Qi-Ming Wang, Yu Yao, Jun Zhao, Yuan Chen, Jian Fang, Yong Song, Wei Zhang, Ying Cheng, Ren-Hua Guo, Xing-Ya Li, He-Peng Shi, Wei-Zhe Xue, Di Han, Pei-Long Zhang, Yi-Long Wu
Journal: Journal of Clinical Oncology (2024)

The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations. This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1. As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%). Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.
Prospective Study of Supplemental Screening With Contrast-Enhanced Mammography in Women With Elevated Risk of Breast Cancer: Results of the Prevalence Round
Authors: Bhavika K. Patel, Molly B. Carnahan, Donald Northfelt, Karen Anderson, Gina L. Mazza, Victor J. Pizzitola, Marina E. Giurescu, Roxanne Lorans, William G. Eversman, Richard E. Sharpe, Laura K. Harper, Heidi Apsey, Patricia Cronin, Juliana Kling, Brenda Ernst, Jennifer Palmieri, Jessica Fraker, Lida Mina, Felipe Batalini, Barbara Pockaj
Journal: Journal of Clinical Oncology (2024)

PURPOSE Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients. MATERIALS AND METHODS A prospective, single-institution, institutional review board–approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months. RESULTS Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2–, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM. CONCLUSION A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.
Biocompatible and nondegradable microcapsules using an ethylamine-bridged EGCG dimer for successful therapeutic cell transplantation
Authors: Seonmi Jang, Jae Bin Lee, Chaerim Yoo, Hyung Shik Kim, Kimyung Choi, Joonseok Lee, Dong Yun Lee
Journal: Journal of Controlled Release (2024)
The economic burden of cancer, coronary heart disease, dementia, and stroke in England in 2018, with projection to 2050: an evaluation of two cohort studies
Authors: Filipa Landeiro, Callum Harris, David Groves, Samuel O'Neill, Kuljinder Singh Jandu, Eliana M C Tacconi, Samantha Field, Nileema Patel, Anya Göpfert, Hannes Hagson, José Leal, Ramón Luengo-Fernández
Journal: The Lancet Healthy Longevity (2024)
Effect of weekly fever-screening and treatment and monthly RDT testing and treatment on the infectious reservoir of malaria parasites in Burkina Faso: a cluster-randomised trial
Authors: Katharine A Collins, Alphonse Ouedraogo, Wamdaogo Moussa Guelbeogo, Issiaka Soulama, Maurice S Ouattara, Salif Sombie, Nicolas Ouedraogo, Aboubacar S Coulibaly, Apollinaire Nombre, Kjerstin Lanke, Jordache Ramjith, Shehu S Awandu, Samuel S Serme, Noelie Henry, Will Stone, Issa N Ouedraogo, Amidou Diarra, Tobias M Holden, Sodiomon B Sirima, John Bradley, Seyi Soremekun, Prashanth Selvaraj, Jaline Gerardin, Chris Drakeley, Teun Bousema, Alfred B Tiono
Journal: The Lancet Microbe (2024)

The majority of Plasmodium spp infections in endemic countries are asymptomatic and a source of onward transmission to mosquitoes. We aimed to examine whether Plasmodium falciparum transmission and malaria burden could be reduced by improving early detection and treatment of infections with active screening approaches.
An infusible biologically active adhesive for chemotherapy-related heart failure in elderly rats
Authors: Jialu Yao, Junlang Li, Dashuai Zhu, Yuan Li, Panagiotis Tasoudis, Shuo Liu, Xuan Mei, Kristen Popowski, Thomas G. Caranasos, Haipeng Wang, Mingzhu Xu, Tingbo Jiang, Kan Shen, Hongxia Li, Ke Huang
Journal: Bioactive Materials (2024)

Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections. In vitro, we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability, but also inhibited their apoptosis. In vivo, we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation, angiogenesis, and mitochondrial respiration. Additionally, we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system. In general, our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.
Fabrication and performance of Zinc-based biodegradable metals: From conventional processes to laser powder bed fusion
Authors: Aobo Liu, Yu Qin, Jiabao Dai, Fei Song, Yun Tian, Yufeng Zheng, Peng Wen
Journal: Bioactive Materials (2024)

Zinc (Zn)-based biodegradable metals (BMs) fabricated through conventional manufacturing methods exhibit adequate mechanical strength, moderate degradation behavior, acceptable biocompatibility, and bioactive functions. Consequently, they are recognized as a new generation of bioactive metals and show promise in several applications. However, conventional manufacturing processes face formidable limitations for the fabrication of customized implants, such as porous scaffolds for tissue engineering, which are future direction towards precise medicine. As a metal additive manufacturing technology, laser powder bed fusion (L-PBF) has the advantages of design freedom and formation precision by using fine powder particles to reliably fabricate metallic implants with customized structures according to patient-specific needs. The combination of Zn-based BMs and L-PBF has become a prominent research focus in the fields of biomaterials as well as biofabrication. Substantial progresses have been made in this interdisciplinary field recently. This work reviewed the current research status of Zn-based BMs manufactured by L-PBF, covering critical issues including powder particles, structure design, processing optimization, chemical compositions, surface modification, microstructure, mechanical properties, degradation behaviors, biocompatibility, and bioactive functions, and meanwhile clarified the influence mechanism of powder particle composition, structure design, and surface modification on the biodegradable performance of L-PBF Zn-based BM implants. Eventually, it was closed with the future perspectives of L-PBF of Zn-based BMs, putting forward based on state-of-the-art development and practical clinical needs.
A two-pronged approach to inhibit ferroptosis of MSCs caused by the iron overload in postmenopausal osteoporosis and promote osseointegration of titanium implant
Authors: Yulu Yang, Xianhui Zhang, Yao Yang, Pengfei Gao, Wuzhe Fan, Tao Zheng, Weihu Yang, Yu Tang, Kaiyong Cai
Journal: Bioactive Materials (2024)

Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.
Autism-associated neuroligin-3 deficiency in medial septum causes social deficits and sleep loss in mice
Authors: Haiyan Sun, Yu Shen, Pengtao Ni, Xin Liu, Yan Li, Zhentong Qiu, Jiawen Su, Yihan Wang, Miao Wu, Xiangxi Kong, Jun-Li Cao, Wei Xie, Shuming An
Journal: Journal of Clinical Investigation (2024)

Patients with autism spectrum disorder (ASD) frequently experience sleep disturbance. Genetic mutations in Neuroligin-3 (NLG3) genes are highly correlative with ASD and sleep disturbance. However, the cellular and neural circuit bases of this correlation remain elusive. Here, we find the conditional knockout of NLG3 (NLG3-CKO) in the medial septum (MS) impairs social memory and reduces sleep. NLG3 knockout in MS causes hyperactivity of MS-GABA neurons during social avoidance and wakefulness. Activation of MSGABA neurons induces social memory deficits and sleep loss in C57BL/6 mice. In contrast, inactivation of these neurons ameliorates social memory deficits and sleep loss in NLG3-CKO mice. Sleep deprivation leads to social memory deficits, while social isolation causes sleep loss, both resulting in a reduction of NLG3 expression and an increase in activity of GABAergic neurons in MS from C57BL/6 mice. Furthermore, MS-GABA-innervated CA2 neurons specifically regulate social memory without impacting sleep, whereas MSGABA-innervating neurons in the preoptic area selectively control sleep without affecting social behavior. Together, these findings demonstrate that the hyperactive MS-GABA neurons impair social memory and disrupt sleep resulting from NLG3 knockout in MS, and achieve the modality specificity through their divergent downstream targets.
Sterile production of interferons in the thymus affects T cell repertoire selection
Authors: K. Maude Ashby, Matouš Vobořil, Oscar C. Salgado, S. Thera Lee, Ryan J. Martinez, Christine H. O’Connor, Elise R. Breed, Shuya Xuan, Charles R. Roll, Saumith Bachigari, Hattie Heiland, Daniel B. Stetson, Sergei V. Kotenko, Kristin A. Hogquist
Journal: Science Immunology (2024)

Type I and III interferons (IFNs) are robustly induced during infections and protect cells against viral infection. Both type I and III IFNs are also produced at low levels in the thymus at steady state; however, their role in T cell development and immune tolerance is unclear. Here, we found that both type I and III IFNs were constitutively produced by a very small number of AIRE + murine thymic epithelial cells, independent of microbial stimulation. Antigen-presenting cells were highly responsive to thymic IFNs, and IFNs were required for the activation and maturation of thymic type 1 conventional dendritic cells, macrophages, and B cells. Loss of IFN sensing led to reduced regulatory T cell selection, reduced T cell receptor (TCR) repertoire diversity, and enhanced autoreactive T cell responses to self-antigens expressed during peripheral IFN signaling. Thus, constitutive exposure to IFNs in the thymus is required for generating a tolerant and diverse TCR repertoire.
Timing and location dictate monocyte fate and their transition to tumor-associated macrophages
Authors: Garett Dunsmore, Wei Guo, Ziyi Li, David Alejandro Bejarano, Rhea Pai, Katharine Yang, Immanuel Kwok, Leonard Tan, Melissa Ng, Carlos De La Calle Fabregat, Aline Yatim, Antoine Bougouin, Kevin Mulder, Jake Thomas, Javiera Villar, Mathilde Bied, Benoit Kloeckner, Charles-Antoine Dutertre, Grégoire Gessain, Svetoslav Chakarov, Zhaoyuan Liu, Jean-Yves Scoazec, Ana-Maria Lennon-Dumenil, Thomas Marichal, Catherine Sautès-Fridman, Wolf Herman Fridman, Ankur Sharma, Bing Su, Andreas Schlitzer, Lai Guan Ng, Camille Blériot, Florent Ginhoux
Journal: Science Immunology (2024)

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells whose phenotypes and functions are shaped by factors that are incompletely understood. Herein, we asked when and where TAMs arise from blood monocytes and how they evolve during tumor development. We initiated pancreatic ductal adenocarcinoma (PDAC) in inducible monocyte fate-mapping mice and combined single-cell transcriptomics and high-dimensional flow cytometry to profile the monocyte-to-TAM transition. We revealed that monocytes differentiate first into a transient intermediate population of TAMs that generates two longer-lived lineages of terminally differentiated TAMs with distinct gene expression profiles, phenotypes, and intratumoral localization. Transcriptome datasets and tumor samples from patients with PDAC evidenced parallel TAM populations in humans and their prognostic associations. These insights will support the design of new therapeutic strategies targeting TAMs in PDAC.
Keystone individuals – linking predator traits to community ecology
Authors: Laura R. LaBarge, Miha Krofel, Maximilian L. Allen, Russell A. Hill, Andreanna J. Welch, Andrew T.L. Allan
Journal: Trends in Ecology & Evolution (2024)

Individual behavioral plasticity enables animals to adjust to different scenarios. Yet, personality traits limit this flexibility, leading to consistent interindividual differences in behavior. These individual behavioral traits have the potential to govern community interactions, although testing this is difficult in complex natural systems. For large predators who often exert strong effects on ecosystem functioning, this behavioral diversity may be especially important and lead to individualized ecosystem roles. We present a framework for quantifying individual behavioral plasticity and personality traits of large wild predators, revealing the extent to which certain natural behaviors are governed by these latent traits. The outcomes will reveal how the innate characteristics of wildlife can scale up to affect community interactions.
Oncology-respirology: a discipline in dire need
Authors: Chengzhi Zhou, Tao Luan, Weijie Guan, Wenhua Jian, Shuaiying Wang, Shiyue Li, Nanshan Zhong
Journal: Trends in cancer (2024)

Despite the success of various cancer therapies on patient survival, these treatments can have negative side effects, particularly severe damage to the respiratory system. Given the rise in respiratory-associated illnesses in response to cancer treatment, we urge the field to consider a new discipline referred to as 'oncology–respirology' (or onco-respirology).
It’s about time to exercise: development of the exercise participation explained in relation to time model
Authors: Sean Healy, Freda Patterson, Stuart Biddle, Dorothea Dumuid, Ignace Glorieux, Tim Olds, Catherine Woods, Adrian E Bauman, Aleš Gába, Matthew P Herring, Kaja Kastelic, Ugo Lachapelle, Stella L Volpe, Saška Benedičić Tomat, Zeljko Pedisic
Journal: British Journal of Sports Medicine (2024)

A perceived 'lack of time' is consistently the most commonly reported barrier to exercise. However, the term fails to capture the multifaceted nature of time-related factors. Recognising the need for a more comprehensive analysis of 'lack of time' as a barrier to exercise, the aim of this study was to develop the exercise participation explained in relation to time (EXPERT) model. The model was developed through a sequential process including (1) an umbrella literature review of time as a barrier, determinant, and correlate of physical activity; (2) a targeted review of existing temporal models; (3) drafting the model and refining it via discussions between eight authors; (4) a three-round Delphi process with eight panel members; and (5) consultations with seven experts and potential end-users. The final EXPERT model includes 31 factors within four categories: (1) temporal needs and preferences for exercise (ie, when and how long does an individual need/want to exercise), (2) temporal autonomy for exercise (ie, autonomy in scheduling free time for exercise), (3) temporal conditions for exercise (ie, available time for exercise) and (4) temporal dimensions of exercise (ie, use of time for exercise). Definitions, examples and possible survey questions are presented for each factor. The EXPERT model provides a comprehensive framework for understanding the multi-dimensional nature of 'time' as it relates to exercise participation. It moves beyond the simplistic notion of 'lack of time' and delves into the complexity of time allocation in the context of exercise. Empirical and cross-cultural validations of the model are warranted.
Exome-wide association analysis identifies novel risk loci for alcohol-associated hepatitis
Authors: Qiaoping Yuan, Colin Hodgkinson, Xiaochen Liu, Bruce Barton, Nancy Diazgranados, Melanie Schwandt, Timothy Morgan, Ramon Bataller, Suthat Liangpunsakul, Laura E. Nagy, David Goldman
Journal: Hepatology (2024)

Background and Aims: Alcohol-associated hepatitis (AH) is a clinically severe, acute disease that afflicts only a fraction of patients with alcohol use disorder. Genomic studies of alcohol-associated cirrhosis (AC) have identified several genes of large effect, but the genetic and environmental factors that lead to AH and AC, and their degree of genetic overlap, remain largely unknown. This study aims to identify genes and genetic variations that contribute to the development of AH. Approach and Results: Exome-sequencing of patients with AH (N=784) and heavy drinking controls (N=951) identified an exome-wide significant association for AH at patalin-like phospholipase domain containing 3, as previously observed for AC in genome-wide association study, although with a much lower effect size. Single nucleotide polymorphisms (SNPs) of large effect size at inducible T cell costimulatory ligand ( ICOSLG ) (Chr 21) and TOX4/RAB2B (Chr 14) were also exome-wide significant. ICOSLG encodes a co-stimulatory signal for T-cell proliferation and cytokine secretion and induces B-cell proliferation and differentiation. TOX high mobility group box family member 4 ( TOX4 ) was previously implicated in diabetes and immune system function. Other genes previously implicated in AC did not strongly contribute to AH, and the only prominently implicated (but not exome-wide significant) gene overlapping with alcohol use disorder was alcohol dehydrogenase 1B ( ADH1B ). Polygenic signals for AH were observed in both common and rare variant analysis and identified genes with roles associated with inflammation. Conclusions: This study has identified 2 new genes of high effect size with a previously unknown contribution to alcohol-associated liver disease and highlights both the overlap in etiology between liver diseases and the unique origins of AH.