bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Aetiological and Observational Cohort study of Interstitial Lung Abnormalities (ILAs) Including Progressive Fibrosing Phenotype Interstitial Lung Diseases in a Large General Medical Check-up Population (Kumamoto ILA study in Japan) (KILA-J)
Authors: Ichikado Kazuya , Ichiyasu Hidenori , Iyonaga Kazuhiro , Kawamura Kodai , Higashi Noritaka , Johkoh Takeshi , Fujimoto Kiminori , Morinaga Jun , Yoshida Minoru , Mitsuzaki Katsuhiko , Suga Moritaka , Tanabe Naoya , Handa Tomohiro , Hirai Toyohiro , Sakagami Takuro 
Published: January 2023

ABSTRACTIntroductionInterstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5 % of the lungs on CT scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment.Methods and analysisThis is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression.Ethics and disseminationThis study protocol and informed consent documents have been approved by the Institutional Review Boards of Kumamoto University Hospital (approval number: 2368), Saiseikai Kumamoto Hospital (approval number: 809), and each participating institution. Additionally, written informed consent will be obtained from all participants. Patient recruitment commenced on 20 June 2022. The results will be disseminated through peer-reviewed publications and international conferences.Trial registration numberUMIN000045149Strengths and limitations of this studyThis is the first prospective, multicentre, observational study to clarify the following points:the aetiological data of patients with ILA from a large general health check-up populationthe natural course of IPF or PPF from the asymptomatic stagethe effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA.The limitations of the study:participants missing the regular 6-monthly visits after consenting to participate in the study because of their asymptomatic or the pandemic viral infection.
OH-EpiCap: a semi-quantitative tool for the evaluation of One Health epidemiological surveillance capacities and capabilities
Authors: Tegegne Henok Ayalew , Bogaardt Carlijn , Collineau Lucie , Cazeau Géraldine , Lailler Renaud , Reinhardt Johana , Taylor Emma L. , Prada Joaquin , Hénaux Viviane 
Published: January 2023

AbstractAlthough international health agencies encourage the development of One Health (OH) surveillance, many systems remain mostly compartmentalized, with limited collaborations among sectors and disciplines. In the framework of the OH European Joint Programme “MATRIX” project, a generic evaluation tool called OH-EpiCap has been developed to enable individual institutes/governments to characterize, assess and monitor their own OH epidemiological surveillance capacities and capabilities. The tool is organized around three dimensions: organization, operational activities, and impact of the OH surveillance system; each dimension is then divided into four targets, each including four indicators. A semi-quantitative questionnaire enables the scoring of each indicator, with four levels according to the degree of satisfaction in the studied OH surveillance system. The evaluation is conducted by a panel of surveillance representatives (during a half-day workshop or with a back-and-forth process to reach a consensus). An R Shiny-based web application facilitates implementation of the evaluation and visualization of the results, and includes a benchmarking option. The tool was piloted on several foodborne hazards (i.e.Salmonella, Campylobacter, Listeria), emerging threats (e.g. antimicrobial resistance) and other zoonotic hazards (psittacosis) in multiple European countries in 2022. These case studies showed that the OH-EpiCap tool supports the tracing of strengths and weaknesses in epidemiological capacities and the identification of concrete and direct actions to improve collaborative activities at all steps of surveillance. It appears complementary to the existing EU-LabCap tool, designed to assess the capacity and capability of European microbiology laboratories. In addition, it provides opportunity to reinforce trust between surveillance stakeholders from across the system and to build a good foundation for a professional network for further collaboration.
Acceptability of decentralizing childhood tuberculosis diagnosis in low-income countries with high tuberculosis incidence: experiences and perceptions from health care workers in sub-Saharan Africa and South-East Asia
Authors: Joshi Basant , De Lima Yara Voss , Massom Douglas Mbang , Kaing Sanary , Banga Marie-France , Kamara Egerton Tamba , Sesay Sheriff , Borand Laurence , Taguebue Jean-Voisin , Moh Raoul , Khosa Celso , Breton Guillaume , Mwanga-Amumpaire Juliet , Bonnet Maryline , Wobudeya Eric , Marcy Olivier , Orne-Gliemann Joanna 
Published: January 2023

AbstractBackgroundDecentralizing childhood tuberculosis services, including diagnosis, is now recommended by the WHO and could contribute to increasing tuberculosis detection in high burden countries. However, implementing microbiological tests and clinical evaluation could be challenging for health care workers (HCWs) in Primary Health Centers (PHCs) and even District Hospitals (DHs). We sought to assess the acceptability of decentralizing a comprehensive childhood tuberculosis diagnosis package from HCWs’ perspective.Design/MethodsWe conducted implementation research nested within the TB-Speed Decentralization study. HCWs from two health districts of Cambodia, Cameroon, Côte d’Ivoire, Mozambique, Sierra Leone, and Uganda implemented systematic screening, nasopharyngeal aspirates (NPA) and stool sample collection with molecular testing, clinical evaluation and chest X-ray (CXR) interpretation. We investigated their experiences and perceptions in delivering the diagnostic package components in 2020-21 using individual semi-structured interviews. We conducted thematic analysis, supported by the Theoretical Framework of Acceptability.ResultsHCWs (n=130, 55% female, median age 36 years, 53% nurses, 72% PHC-based) perceived that systematic screening, although increasing workload, was beneficial as it improved childhood tuberculosis awareness. Most HCWs shared satisfaction and confidence in performing NPA, despite procedure duration, need to involve parents/colleagues and discomfort for children. HCWs shared positive attitudes towards stool sample-collection but were frustrated by delayed collection associated with cultural practices, transport and distance challenges. Molecular testing, conducted by nurses or laboratory technicians, was perceived as providing quality results, contributing to diagnosis. Clinical evaluation and diagnosis raised self-efficacy issues and need for continuous training and clinical mentoring. HCWs valued CXR, however complained that technical and logistical problems limited access to digital reports. Referral from PHC to DH was experienced as burdensome.ConclusionHCWs at DH and PHC-levels perceived and experienced decentralized childhood tuberculosis diagnosis as acceptable. Implementation however could be hampered by feasibility issues, and calls for innovative referral mechanisms for patients, samples and CXR.
Symptomatic malaria enhances protection from reinfection with homologousPlasmodium falciparumparasites
Authors: Markwalter Christine F. , Petersen Jens E. V. , Zeno Erica E. , Sumner Kelsey M. , Freedman Elizabeth , Mangeni Judith N. , Abel Lucy , Obala Andrew A. , Prudhomme-O’Meara Wendy , Taylor Steve M. 
Published: January 2023

ABSTRACTA signature remains elusive of naturally-acquired immunity againstPlasmodium falciparum. We identifiedP. falciparumin a 14-month cohort of 239 people in Kenya, genotyped at immunogenic parasite targets expressed in the pre-erythrocytic (circumsporozoite protein, CSP) and blood (apical membrane antigen 1, AMA-1) stages, and classified into epitope type based on variants in the DV10, Th2R, and Th3R epitopes in CSP and the c1L region of AMA-1. Compared to asymptomatic index infections, symptomatic malaria was associated with a reduced reinfection by parasites bearing homologous CSP-Th2R (adjusted hazard ratio [aHR]:0.63; 95% CI:0.45–0.89; p=0.008) CSP-Th3R (aHR:0.71; 95% CI:0.52–0.97; p=0.033), and AMA-1 c1L (aHR:0.63; 95% CI:0.43–0.94; p=0.022) epitope types. The association of symptomatic malaria with reduced risk of homologous reinfection was strongest for rare epitope types. Symptomatic malaria more effectively promotes functional immune responses. The phenotype represents a legible molecular epidemiologic signature of naturally-acquired immunity by which to identify new antigen targets.
Spatial molecular imaging of the human type 2 diabetic islet
Authors: Kolar Grant R. , Ross David , Killingbeck Emily E. , Samson Willis K. , Yosten Gina L. C. 
Published: January 2023

ABSTRACTThe islets of Langerhans are complex micro-organs comprised of multiple cell types essential for the maintenance of glucose homeostasis. The endocrine cell types of the islets engage in intimate, intercellular communication that is necessary for normal secretory activity. Disruption of this intercellular communication, which is at least partially dependent on the spatial organization of individual islets, leads to secretory dysfunction and exacerbation of the symptomology of disease states such as type 2 diabetes. However, the molecular determinants of the mechanisms underlying disrupted intercellular communication remain incompletely understood. Herein we describe the utilization of CosMx™ Spatial Molecular Imaging (SMI) to interrogate transcriptomic changes associated with the transition from the obese, prediabetic state to overt type 2 diabetes. Using SMI, we verified previously reported findings regarding islet composition in the obese and type 2 diabetic states, including loss of beta cells and expansion of alpha cell mass. In addition, we identified changes in the islet neighborhood that have implications for the function of islet endocrine cells. In particular, we identified a subset of alpha cells oriented in the periphery of the islets that appear to exhibit a transcriptomic profile suggestive of de-differentiation toward a beta cell-like transcriptome-type. To our knowledge, this is the first study utilizing spatial molecular imaging to investigate single-cell transcriptomes of individual islets. Further exploration of the intersection of islet architecture and gene expression using spatial technologies is expected to yield novel insights into the mechanisms underlying the development and progression of metabolic diseases like type 2 diabetes.
Machine Learning Reveals Lipidome Remodeling Dynamics in a Mouse Model of Ovarian Cancer
Authors: Bifarin Olatomiwa O. , Sah Samyukta , Gaul David A. , Moore Samuel G. , Chen Ruihong , Palaniappan Murugesan , Kim Jaeyeon , Matzuk Martin M. , Fernández Facundo M. 
Published: January 2023

AbstractOvarian cancer (OC) is one of the deadliest cancers affecting the female reproductive system. It may present little or no symptoms at the early stages, and typically unspecific symptoms at later stages. High-grade serous ovarian cancer (HGSC) is the subtype responsible for most ovarian cancer deaths. However, very little is known about the metabolic course of this disease, particularly in its early stages. In this longitudinal study, we examined the temporal course of serum lipidome changes using a robust HGSC mouse model and machine learning data analysis. Early progression of HGSC was marked by increased levels of phosphatidylcholines and phosphatidylethanolamines. In contrast, later stages featured more diverse lipids alterations, including fatty acids and their derivatives, triglycerides, ceramides, hexosylceramides, sphingomyelins, lysophosphatidylcholines, and phosphatidylinositols. These alterations underscored unique perturbations in cell membrane stability, proliferation, and survival during cancer development and progression, offering potential targets for early detection and prognosis of human ovarian cancer.TeaserTime-resolved lipidome remodeling in an ovarian cancer model is studied through lipidomics and machine learning.
Simultaneous proteome localization and turnover analysis reveals spatiotemporal features of protein homeostasis disruptions
Authors: Currie Jordan , Manda Vyshnavi , Robinson Sean K. , Lai Celine , Agnihotri Vertica , Hidalgo Veronica , Ludwig R. W. , Zhang Kai , Pavelka Jay , Wang Zhao V. , Rhee June-Wha , Lam Maggie P. Y. , Lau Edward 
Published: January 2023

AbstractThe functions of proteins depend on their spatial and temporal distributions, which are not directly measured by static protein abundance. Under endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) pathway remediates proteostasis in part by altering the turnover kinetics and spatial distribution of proteins. A global view of these spatiotemporal changes has yet to emerge and it is unknown how they affect different cellular compartments and pathways. Here we describe a mass spectrometry-based proteomics strategy and data analysis pipeline, termed Simultaneous Proteome Localization and Turnover (SPLAT), to measure concurrently the changes in protein turnover and subcellular distribution in the same experiment. Investigating two common UPR models of thapsigargin and tunicamycin challenge in human AC16 cells, we find that the changes in protein turnover kinetics during UPR varies across subcellular localizations, with overall slowdown but an acceleration in endoplasmic reticulum and Golgi proteins involved in stress response. In parallel, the spatial proteomics component of the experiment revealed an externalization of amino acid transporters and ion channels under UPR, as well as the migration of RNA-binding proteins toward an endosome co-sedimenting compartment. The SPLAT experimental design classifies heavy and light SILAC labeled proteins separately, allowing the observation of differential localization of new and old protein pools and capturing a partition of newly synthesized EGFR and ITGAV to the ER under stress that suggests protein trafficking disruptions. Finally, application of SPLAT toward human induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) exposed to the cancer drug carfilzomib, identified a selective disruption of proteostasis in sarcomeric proteins as a potential mechanism of carfilzomib-mediated cardiotoxicity. Taken together, this study provides a global view into the spatiotemporal dynamics of human cardiac cells and demonstrates a method for inferring the coordinations between spatial and temporal proteome regulations in stress and drug response.
Dimensional Reduction for Single Molecule Imaging of DNA and Nucleosome Condensation by Polyamines, HP1α and Ki-67
Authors: Benning Nils A. , Kæstel-Hansen Jacob , Rashid Fahad , Park Sangwoo , Urteaga Raquel Merino , Liao Ting-Wei , Hao Jingzhou , Berger James M. , Hatzakis Nikos S. , Ha Taekjip 
Published: January 2023

ABSTRACTMacromolecules organize themselves into discrete membrane-less compartments. Mounting evidence has suggested that nucleosomes as well as DNA itself can undergo clustering or condensation to regulate genomic activity. Current in vitro condensation studies provide insight into the physical properties of condensates, such as surface tension and diffusion. However, such studies lack the resolution needed for complex kinetic studies of multicomponent condensation. Here, we use a supported lipid bilayer platform in tandem with total internal reflection microscopy to observe the 2-dimensional movement of DNA and nucleosomes at the single-molecule resolution. This dimensional reduction from 3-dimensional studies allows us to observe the initial condensation events and dissolution of these early condensates in the presence of physiological condensing agents. Using polyamines, we observed that the initial condensation happens on a timescale of minutes while dissolution occurs within seconds upon charge inversion. Polyamine valency, DNA length and GC content affect threshold polyamine concentration for condensation. Protein-based nucleosome condensing agents, HP1α and Ki-67, have much lower threshold concentration for condensation than charge-based condensing agents, with Ki-67 being the most effective as low as 100 pM for nucleosome condensation. In addition, we did not observe condensate dissolution even at the highest concentrations of HP1α and Ki-67 tested. We also introduce a two-color imaging scheme where nucleosomes of high density labeled in one color is used to demarcate condensate boundaries and identical nucleosomes of another color at low density can be tracked relative to the boundaries after Ki-67 mediated condensation. Our platform should enable the ultimate resolution of single molecules in condensation dynamics studies of chromatin components under defined physicochemical conditions.Abstract Figure
Detection of tumor-derived extracellular vesicles interactions with immune cells is dependent on EV-labelling methods
Authors: Loconte Luisa , Arguedas Davinia , Chipont Anna , El Rojbin , Guyonnet Lea , Guerin Coralie , Piovesana Ester , Vázquez-Ibar José Luis , Joliot Alain , Théry Clotilde , Martín-Jaular Lorena 
Published: January 2023

ABSTRACTCell-cell communication within the complex tumor microenvironment is critical to cancer progression. Tumor-derived extracellular vesicles (TD-EVs) are key players in this process. They can interact with immune cells and modulate their activity, either suppressing or activating the immune system. Understanding the interactions between TD-EVs and immune cells is essential for understanding immune modulation by cancer cells. Fluorescent labelling of TD-EVs is a method of choice to study such interaction. This work aims to determine the impact of EV labelling methods on the detection of EV interaction and capture by the different immune cell types within human Peripheral Blood Mononuclear Cells (PBMCs), analyzed by imaging flow cytometry and multicolor spectral flow cytometry. EVs released by the triple-negative breast carcinoma cell line MDA-MB-231 were labeled either with the lipophilic dye MemGlow-488 (MG-488), with Carboxyfluorescein diacetate, succinimidyl ester (CFDA-SE), or through expression of a MyrPalm-superFolder GFP (sfGFP) that incorporates into EVs during their biogenesis using a genetically engineered cell line. Our results showed that these different labeling strategies, although analyzed with the same techniques, led to diverging results. While MG-488-labelled EVs incorporate in all cell types, CFSE-labelled EVs are restricted to a minor subset of cells and sfGFP-labelled EVs are mainly detected in CD14+ monocytes which are the main uptakers of EVs and other particles, regardless of the labeling method. Moreover, MG-488-labeled liposomes behaved similarly to MG-488 EVs, highlighting the predominant role of the labelling strategy on the visualization and analysis of TD-EVs uptake by immune cell types. Consequently, the use of different EV labeling methods has to be considered as they can provide complementary information on various types of EV-cell interaction and EV fate.
Drug-Mediated Control of Receptor Valency Enhances Immune Cell Potency
Authors: Finn Paul B. , Chavez Michael , Chen Xinyi , Wang Haifeng , Rane Draven A. , Gurjar Jitendra , Qi Lei S. 
Published: January 2023

ABSTRACTDesigner T cells offer a novel paradigm for treating diseases like cancer, yet they are often hindered by target recognition evasion and limited in vivo control. To overcome these challenges, we develop valency-controlled receptors (VCRs), a novel class of synthetic receptors engineered to enable precise modulation of immune cell activity. VCRs use custom-designed valency-control ligands (VCLs) to modulate T cell signaling via spatial molecular clustering. Using multivalent DNA origami as VCL, we first establish that valency is important for tuning the activity of CD3-mediated immune activation. We then generate multivalent formats of clinically relevant drugs as VCL and incorporate VCR into the architecture of chimeric antigen receptors (CARs). Our data demonstrate that VCL-mediated VCRs can significantly amplify CAR activities and improve suboptimal CARs. Finally, through medicinal chemistry, we synthesize programmable, bioavailable VCL drugs that potentiate targeted immune response against low-antigen tumors both in vitro and in vivo. Our findings establish receptor valency as a core mechanism for enhancing CAR functionality and offer a synthetic chemical biology platform for strengthening customizable, potent, and safer cell therapies.
The AFB1 auxin receptor controls the cytoplasmic auxin response pathway inArabidopsis thaliana
Authors: Dubey Shiv Mani , Han Soeun , Stutzman Nathan , Prigge Michael J , Medvecká Eva , Platre Matthieu Pierre , Busch Wolfgang , Fendrych Matyáš , Estelle Mark 
Published: January 2023

AbstractThe phytohormone auxin triggers root growth inhibition within seconds via a non-transcriptional pathway. Among members of the TIR1/AFBs auxin receptor family, AFB1 has a primary role in this rapid response. However, the unique features that confer this specific function have not been identified. Here we show that the N-terminal region of AFB1, including the F-box domain and residues that contribute to auxin binding, are essential and sufficient for its specific role in the rapid response. Substitution of the N-terminal region of AFB1 with that of TIR1 disrupts its distinct cytoplasm-enriched localization and activity in rapid root growth inhibition. Importantly, the N-terminal region of AFB1 is indispensable for auxin-triggered calcium influx which is a prerequisite for rapid root growth inhibition. Furthermore, AFB1 negatively regulates lateral root formation and transcription of auxin-induced genes, suggesting that it plays an inhibitory role in canonical auxin signaling. These results suggest that AFB1 may buffer the transcriptional auxin response while it regulates rapid changes in cell growth that contribute to root gravitropism.