bluuebunny/crossref_metadata_2025_split huggingface dataset:
National Center Biobank Network
Authors: Omae Yosuke , Goto Yu-ichi , Tokunaga Katsushi 
Published: November 2022

AbstractThere are six national centers (6NCs) for advanced and specialized medicine in Japan that conduct basic and clinical research on major diseases that have a substantial impact on national health. Disease-specific bioresources and information collected by each NC are stored in a separate biobank. The National Center Biobank Network (NCBN) was established in 2011 and coordinates the biobanks and researchers of the 6NCs via an open-access database (Catalogue Database: http://www2.ncbiobank.org/Index_en) as an efficient means of providing registered biological resources and data for use in research communities. The NCBN resources are characterized by their high-quality and rich medical information and are available for life science research and for the development of novel testing methodologies (biomarkers), new treatments, and drugs for future health care in the scope of personalized medicine through a deeper understanding of disease pathogenesis. Here, we explain the activities of the NCBN and the characteristics of the NCBN Catalogue Database.
Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer
Authors: Damrauer Jeffrey S. , Beckabir Wolfgang , Klomp Jeff , Zhou Mi , Plimack Elizabeth R. , Galsky Matthew D. , Grivas Petros , Hahn Noah M. , O’Donnell Peter H. , Iyer Gopa , Quinn David I. , Vincent Benjamin G. , Quale Diane Zipursky , Wobker Sara E. , Hoadley Katherine A. , Kim William Y. , Milowsky Matthew I. 
Published: November 2022

AbstractUrothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (NCT02643043), UC-GENOME, is a genomic analysis and biospecimen repository study in 218 patients with metastatic urothelial carcinoma. Here we report on the primary outcome of the UC-GENOME—the proportion of subjects who received next generation sequencing (NGS) with treatment options—and present the initial genomic analyses and clinical correlates. 69.3% of subjects had potential treatment options, however only 5.0% received therapy based on NGS. We found an increased frequency ofTP53E285Kmutations as compared to non-metastatic cohorts and identified features associated with benefit to chemotherapy and immune checkpoint inhibition, including: Ba/Sq and Stroma-rich subtypes, APOBEC mutational signature (SBS13), and inflamed tumor immune phenotype. Finally, we derive a computational model incorporating both genomic and clinical features predictive of immune checkpoint inhibitor response. Future work will utilize the biospecimens alongside these foundational analyses toward a better understanding of urothelial carcinoma biology.
High resolution ancient sedimentary DNA shows that alpine plant diversity is associated with human land use and climate change
Authors: Garcés-Pastor Sandra , Coissac Eric , Lavergne Sébastien , Schwörer Christoph , Theurillat Jean-Paul , Heintzman Peter D. , Wangensteen Owen S. , Tinner Willy , Rey Fabian , Heer Martina , Rutzer Astrid , Walsh Kevin , Lammers Youri , Brown Antony G. , Goslar Tomasz , Rijal Dilli P. , Karger Dirk N. , Pellissier Loïc ,   The PhyloAlps Consortium, Pouchon Charles , Roquet Cristina , Thuiller Wilfried , Zimmermann Niklaus E. , Alberti Adriana , Wincker Patrick , Boleda Martí , Boyer Frédéric , Hombiat Anthony , Perrier Christophe , Douzet Rolland , Valay Jean-Gabriel , Aubert Serge , Denoeud France , Bzeznick Bruno , Gielly Ludovic , Taberlet Pierre , Rioux Delphine , Orvain Céline , Rome Maxime , Wüest Rafael O. , Latzin Sonia , Spillmann John , Feichtinger Linda , Van Es Jérémie , Garraud Luc , Villaret Jean-Charles , Abdulhak Sylvain , Bonnet Véronique , Huc Stéphanie , Fort Noémie , Legland Thomas , Sanz Thomas , Pache Gilles , Mikolajczak Alexis , Noble Virgile , Michaud Henri , Offerhaus Benoît , Dentant Cédric , Salomez Pierre , Bonet Richard , Delahaye Thierry , Leccia Marie-France , Perfus Monique , Eggenberg Stefan , Möhl Adrian , Hurdu Bogdan-Iuliu , Szatmari Paul-Marian , Pușcaș Mihai , Smyčka Jan , Mráz Patrik , Šemberová Kristýna , Ronikier Michał , Slovák Marek , Heiri Oliver , Alsos Inger Greve 
Published: November 2022

AbstractThe European Alps are highly rich in species, but their future may be threatened by ongoing changes in human land use and climate. Here, we reconstructed vegetation, temperature, human impact and livestock over the past ~12,000 years from Lake Sulsseewli, based on sedimentary ancient plant and mammal DNA, pollen, spores, chironomids, and microcharcoal. We assembled a highly-complete local DNA reference library (PhyloAlps, 3923 plant taxa), and used this to obtain an exceptionally rich sedaDNA record of 366 plant taxa. Vegetation mainly responded to climate during the early Holocene, while human activity had an additional influence on vegetation from 6 ka onwards. Land-use shifted from episodic grazing during the Neolithic and Bronze Age to agropastoralism in the Middle Ages. Associated human deforestation allowed the coexistence of plant species typically found at different elevational belts, leading to levels of plant richness that characterise the current high diversity of this region. Our findings indicate a positive association between low intensity agropastoral activities and precipitation with the maintenance of the unique subalpine and alpine plant diversity of the European Alps.
CD8+ T cell differentiation status correlates with the feasibility of sustained unresponsiveness following oral immunotherapy
Authors: Kaushik Abhinav , Dunham Diane , Han Xiaorui , Do Evan , Andorf Sandra , Gupta Sheena , Fernandes Andrea , Kost Laurie Elizabeth , Sindher Sayantani B. , Yu Wong , Tsai Mindy , Tibshirani Robert , Boyd Scott D. , Desai Manisha , Maecker Holden T. , Galli Stephen J. , Chinthrajah R. Sharon , DeKruyff Rosemarie H. , Manohar Monali , Nadeau Kari C. 
Published: November 2022

AbstractWhile food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs. with allergic reactions upon food challenge after a withdrawal period; n = 21 vs. 30 respectively among total 120 intent-to-treat participants). Lower frequencies of naïve CD8+ T cells and terminally differentiated CD57+CD8+ T cell subsets at baseline (pre-OIT) are associated with SU. Frequency of naïve CD8+ T cells shows a significant positive correlation with peanut-specific and Ara h 2-specific IgE levels at baseline. Higher frequencies of IL-4+ and IFNγ+ CD4+ T cells post-OIT are negatively correlated with SU. Our findings provide evidence that an immune signature consisting of certain CD8+ T cell subset frequencies is potentially predictive of SU following OIT.
Long-term monitoring of intravital biological processes using fluorescent protein-assisted NIR-II imaging
Authors: Chen Muxiong , Feng Zhe , Fan Xiaoxiao , Sun Jun , Geng Weihang , Wu Tianxiang , Sheng Jinghao , Qian Jun , Xu Zhengping 
Published: November 2022

AbstractHigh spatial resolution, low background, and deep tissue penetration have made near-infrared II (NIR-II) fluorescence imaging one of the most critical tools for in vivo observation and measurement. However, the relatively short retention time and potential toxicity of synthetic NIR-II fluorophores limit their long-term application. Here, we report the use of infrared fluorescent proteins (iRFPs) as in vitro and in vivo NIR-II probes permitting prolonged continuous imaging (up to 15 months). As a representative example, iRFP713 is knocked into the mouse genome to generate a transgenic model to allow temporal and/or spatial expression control of the probe. To demonstrate its feasibility in a genuine diagnostic context, we adopt two liver regeneration models and successfully track the process for a week. The performance and monitoring efficacy are comparable to those of μCT and superior to those of indocyanine green dye. We are also able to effectively observe the pancreas, despite its deep location, under both physiological and pathological conditions. These results indicate that the iRFP-assisted NIR-II fluorescence system is suitable for monitoring various tissues and in vivo biological processes, providing a powerful noninvasive long-term imaging platform.
Osteocytes directly regulate osteolysis via MYD88 signaling in bacterial bone infection
Authors: Yoshimoto Tetsuya , Kittaka Mizuho , Doan Andrew Anh Phuong , Urata Rina , Prideaux Matthew , Rojas Roxana E. , Harding Clifford V. , Henry Boom W. , Bonewald Lynda F. , Greenfield Edward M. , Ueki Yasuyoshi 
Published: November 2022

AbstractThe impact of bone cell activation on bacterially-induced osteolysis remains elusive. Here, we show that matrix-embedded osteocytes stimulated with bacterial pathogen-associated molecular patterns (PAMPs) directly drive bone resorption through an MYD88-regulated signaling pathway. Mice lacking MYD88, primarily in osteocytes, protect against osteolysis caused by calvarial injections of bacterial PAMPs and resist alveolar bone resorption induced by oral Porphyromonas gingivalis (Pg) infection. In contrast, mice with targeted MYD88 restoration in osteocytes exhibit osteolysis with inflammatory cell infiltration. In vitro, bacterial PAMPs induce significantly higher expression of the cytokine RANKL in osteocytes than osteoblasts. Mechanistically, activation of the osteocyte MYD88 pathway up-regulates RANKL by increasing binding of the transcription factors CREB and STAT3 to Rankl enhancers and by suppressing K48-ubiquitination of CREB/CREB binding protein and STAT3. Systemic administration of an MYD88 inhibitor prevents jawbone loss in Pg-driven periodontitis. These findings reveal that osteocytes directly regulate inflammatory osteolysis in bone infection, suggesting that MYD88 and downstream RANKL regulators in osteocytes are therapeutic targets for osteolysis in periodontitis and osteomyelitis.
Parkin regulates adiposity by coordinating mitophagy with mitochondrial biogenesis in white adipocytes
Authors: Moore Timothy M. , Cheng Lijing , Wolf Dane M. , Ngo Jennifer , Segawa Mayuko , Zhu Xiaopeng , Strumwasser Alexander R. , Cao Yang , Clifford Bethan L. , Ma Alice , Scumpia Philip , Shirihai Orian S. , Vallim Thomas Q. de Aguiar , Laakso Markku , Lusis Aldons J. , Hevener Andrea L. , Zhou Zhenqi 
Published: November 2022

AbstractParkin, an E3 ubiquitin ligase, plays an essential role in mitochondrial quality control. However, the mechanisms by which Parkin connects mitochondrial homeostasis with cellular metabolism in adipose tissue remain unclear. Here, we demonstrate that Park2 gene (encodes Parkin) deletion specifically from adipose tissue protects mice against high-fat diet and aging-induced obesity. Despite a mild reduction in mitophagy, mitochondrial DNA content and mitochondrial function are increased in Park2 deficient white adipocytes. Moreover, Park2 gene deletion elevates mitochondrial biogenesis by increasing Pgc1α protein stability through mitochondrial superoxide-activated NAD(P)H quinone dehydrogenase 1 (Nqo1). Both in vitro and in vivo studies show that Nqo1 overexpression elevates Pgc1α protein level and mitochondrial DNA content and enhances mitochondrial activity in mouse and human adipocytes. Taken together, our findings indicate that Parkin regulates mitochondrial homeostasis by balancing mitophagy and Pgc1α-mediated mitochondrial biogenesis in white adipocytes, suggesting a potential therapeutic target in adipocytes to combat obesity and obesity-associated disorders.
Computational analysis of arrhythmogenesis in KCNH2 T618I mutation-associated short QT syndrome and the pharmacological effects of quinidine and sotalol
Authors: Zhang Shugang , Lu Weigang , Yang Fei , Li Zhen , Wang Shuang , Jiang Mingjian , Wang Xiaofeng , Wei Zhiqiang 
Published: November 2022

AbstractShort QT syndrome (SQTS) is a rare but dangerous genetic disease. In this research, we conducted a comprehensive in silico investigation into the arrhythmogenesis in KCNH2 T618I-associated SQTS using a multi-scale human ventricle model. A Markov chain model of IKr was developed firstly to reproduce the experimental observations. It was then incorporated into cell, tissue, and organ models to explore how the mutation provided substrates for ventricular arrhythmias. Using this T618I Markov model, we explicitly revealed the subcellular level functional alterations by T618I mutation, particularly the changes of ion channel states that are difficult to demonstrate in wet experiments. The following tissue and organ models also successfully reproduced the changed dynamics of reentrant spiral waves and impaired rate adaptions in hearts of T618I mutation. In terms of pharmacotherapy, we replicated the different effects of a drug under various conditions using identical mathematical descriptions for drugs. This study not only simulated the actions of an effective drug (quinidine) at various physiological levels, but also elucidated why the IKr inhibitor sotalol failed in SQT1 patients through profoundly analyzing its mutation-dependent actions.
DNA sequence and chromatin modifiers cooperate to confer epigenetic bistability at imprinting control regions
Authors: Butz Stefan , Schmolka Nina , Karemaker Ino D. , Villaseñor Rodrigo , Schwarz Isabel , Domcke Silvia , Uijttewaal Esther C. H. , Jude Julian , Lienert Florian , Krebs Arnaud R. , de Wagenaar Nathalie P. , Bao Xue , Zuber Johannes , Elling Ulrich , Schübeler Dirk , Baubec Tuncay 
Published: November 2022

AbstractGenomic imprinting is regulated by parental-specific DNA methylation of imprinting control regions (ICRs). Despite an identical DNA sequence, ICRs can exist in two distinct epigenetic states that are memorized throughout unlimited cell divisions and reset during germline formation. Here, we systematically study the genetic and epigenetic determinants of this epigenetic bistability. By iterative integration of ICRs and related DNA sequences to an ectopic location in the mouse genome, we first identify the DNA sequence features required for maintenance of epigenetic states in embryonic stem cells. The autonomous regulatory properties of ICRs further enabled us to create DNA-methylation-sensitive reporters and to screen for key components involved in regulating their epigenetic memory. Besides DNMT1, UHRF1 and ZFP57, we identify factors that prevent switching from methylated to unmethylated states and show that two of these candidates, ATF7IP and ZMYM2, are important for the stability of DNA and H3K9 methylation at ICRs in embryonic stem cells.
Impact of curcumin loading on the physicochemical, mechanical and antimicrobial properties of a methacrylate-based experimental dental resin
Authors: Comeau Patricia , Panariello Beatriz , Duarte Simone , Manso Adriana 
Published: November 2022

AbstractOral biofilms are directly linked to one of the most common chronic human diseases, dental caries. Resin-based dental materials have significant potential to replace amalgam, however they lack sufficient antimicrobial power. This innovative study investigates a curcumin-loaded dental resin which can be utilized in an antimicrobial photodynamic therapy (aPDT) approach. The study evaluated the effects of curcumin loading on resin physicochemical, mechanical, and adhesive properties, as well as the antimicrobial response associated with blue light activation. Preliminary tests involving degree of conversion (DC) and sample integrity determined the optimal loading of curcumin to be restricted to 0.05 and 0.10 wt%. These optimal loadings were tested for flexural strength (FS), water sorption (WS) and solubility (SL), shear bond strength to dentin (SBS), and viability of Streptococcus mutans under 14.6 J/cm2 blue light or dark conditions, in 6 h and 24 h biofilms. The results demonstrated that 0.10 wt% curcumin had minimal impact on either FS or SBS, but detectably increased WS and SL. A 2 log10 (CFU/mL) reduction in S. mutans after light application in both 6 h and 24 h biofilms were corroborated by CLSM imaging and highlighted the significant potential of this novel aPDT approach with resin-based dental materials.
Radiation dose and gene expression analysis of wild boar 10 years after the Fukushima Daiichi Nuclear Plant accident
Authors: Morimoto Motoko , Kobayashi Jin , Kino Yasushi 
Published: November 2022

AbstractThe Fukushima Daiichi Nuclear Power Plant accident led to contamination with radioactive cesium in an extensive environment in Japan in 2011. We evaluated the concentration of radioactive cesium in the skeletal muscles of 22 wild boars and the expression of IFN-γ, TLR3, and CyclinG1 in the small intestine and compared them with those of wild boar samples collected from Hyogo prefecture. The average 137Cs radioactivity concentration in wild boars in the ex-evacuation zone was 470 Bq/kg. Most of samples still showed radioactivity concentration that exceeded the regulatory limit for foods, but the dose remarkably decreased compared with samples just after the accident. IFN-γ expression was significantly higher in wild boars in the ex-evacuation zone than in samples from Hyogo prefecture. TLR3 expression was also upregulated. CyclinG1 expression also tended to be high. Hence, wild boars might have received some effects of low-dose radiation, and immune cells were activated to some extent. However, pathological examination revealed no inflammatory cell infiltration or pathological damage in the small intestine of wild boars in the ex-evacuation area. Long-term monitoring would be necessary, but we consider that the living body responds appropriately to a stimulus from a contaminated environment.
Epidemiology, risk profile, management, and outcome in geriatric patients with atrial fibrillation in two long-term care hospitals
Authors: Wagner Gernot , Smeikal Michael , Gisinger Christoph , Moertl Deddo , Nopp Stephan , Gartlehner Gerald , Pabinger Ingrid , Ohrenberger Gerald , Ay Cihan 
Published: November 2022

AbstractAim of this study was investigate the prevalence and incidence of atrial fibrillation (AF) and to describe the clinical characteristics, risk profiles, and types of anticoagulant therapy for stroke prevention and the clinical outcomes in persons admitted to a long-term care hospital. We conducted a retrospective cohort study using data from the electronic medical records of patients aged 65 years or older living in two long-term care hospitals between January 1, 2014 and October 31, 2017. Overall data from 1148 patients (mean age 84.1 ± 7.9 years, 74.2% women) were analyzed. At baseline, the median CHA2DS2-VASc score was 4 (IQR 3–5) and the HAS-BLED score 2 (IQR 2–3). We observed patients over a median period of 3.7 years. The point prevalence of AF was 29.6% (95% CI 25.8–33.7) on January 1, 2014. The 1-year cumulative incidence of de novo AF was 4.0% (2.8–5.6). Oral anticoagulants were prescribed in 48% of patients with AF. The cumulative incidence at 1 year for a composite outcome of TIA, stroke, or systemic arterial embolism was 0.6% (0.1–3.1) and 1.7% (0.5–4.6) and for bleeding 2.6% (0.9–6.2) and 1.8% (0.5–4.8) in patients with AF and oral anticoagulants or no oral anticoagulants, respectively. In long-term care hospital patients, we observed a high burden of AF. However, only about half of patients with AF received oral anticoagulation for stroke prevention.
Assessment of the biofilm-forming ability on solid surfaces of periprosthetic infection-associated pathogens
Authors: Cho Jung-Ah , Roh Yoo Jin , Son Hye Rim , Choi Hojung , Lee Jeong-Won , Kim Sung Jae , Lee Chang-Hun 
Published: November 2022

AbstractBiofilm formation is one of the leading causes of complications after surgery in clinical settings. In this study, we profiled the biofilm-forming ability of various periprosthetic infection-associated pathogens on medically relevant surfaces, polystyrene (PS) and titanium (Ti). We also explored how a specific environmental stressor, epigallocatechin gallate (EGCG), affected biofilm formation. First, Congo red tests revealed that all microorganisms formed biofilms within 72 h. Then, the amounts of biofilm formation on PS at 24, 48 and 72 h and also on a Ti plate for 72 h were determined. Some microbes preferred one surface over the other, whereas other microbes formed consistent levels of biofilm regardless of the surface material. Staphylococcus lugdunenensis was the most potent, while Enterococcus faecalis and Staphylococcus aureus were the weakest. Bacterial adhesion to hydrocarbon (BATH) tests indicated that the biofilm-forming abilities were not directly correlated with cell surface hydrophobicity (CSH). Finally, an external signal, EGCG, was applied to challenge the biofilm formation of each microorganism. EGCG regulated each microorganism’s ability differently, though the change was consistent across surfaces for most pathogens. This study can help a better understanding of a broad spectrum of periprosthetic infection-associated pathogens by relative comparison of their biofilm-forming abilities.
Unraveling the complexities of urban fluvial flood hydraulics through AI
Authors: Mehedi Md Abdullah Al , Smith Virginia , Hosseiny Hossein , Jiao Xun 
Published: November 2022

AbstractAs urbanization increases across the globe, urban flooding is an ever-pressing concern. Urban fluvial systems are highly complex, depending on a myriad of interacting variables. Numerous hydraulic models are available for analyzing urban flooding; however, meeting the demand of high spatial extension and finer discretization and solving the physics-based numerical equations are computationally expensive. Computational efforts increase drastically with an increase in model dimension and resolution, preventing current solutions from fully realizing the data revolution. In this research, we demonstrate the effectiveness of artificial intelligence (AI), in particular, machine learning (ML) methods including the emerging deep learning (DL) to quantify urban flooding considering the lower part of Darby Creek, PA, USA. Training datasets comprise multiple geographic and urban hydraulic features (e.g., coordinates, elevation, water depth, flooded locations, discharge, average slope, and the impervious area within the contributing region, downstream distance from stormwater outfalls and dams). ML Classifiers such as logistic regression (LR), decision tree (DT), support vector machine (SVM), and K-nearest neighbors (KNN) are used to identify the flooded locations. A Deep neural network (DNN)-based regression model is used to quantify the water depth. The values of the evaluation matrices indicate satisfactory performance both for the classifiers and DNN model (F-1 scores- 0.975, 0.991, 0.892, and 0.855 for binary classifiers; root mean squared error- 0.027 for DNN regression). In addition, the blocked K-folds Cross Validation (CV) of ML classifiers in detecting flooded locations showed satisfactory performance with the average accuracy of 0.899, which validates the models to generalize to the unseen area. This approach is a significant step towards resolving the complexities of urban fluvial flooding with a large multi-dimensional dataset in a highly computationally efficient manner.