bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver
Authors: Lin Heng , Huang Yen-Sung , Fustin Jean-Michel , Doi Masao , Chen Huatao , Lai Hui-Huang , Lin Shu-Hui , Lee Yen-Lurk , King Pei-Chih , Hou Hsien-San , Chen Hao-Wen , Young Pei-Yun , Chao Hsu-Wen 
Published: January 2021

AbstractHepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilobular (CL) region is demonstrated to be closely linked with the development of HCC cells after diethylnitrosamine treatment. We identify the CL region as a dominant lobule for accumulation of hyperpolyploid hepatocytes and preneoplastic tumor foci formation. We also demonstrate that upregulation of Aurkb plays a critical role in promoting hyperpolyploidization. Increase of AURKB phosphorylation is detected on the midbody during cytokinesis, causing abscission failure and hyperpolyploidization. Pharmacological inhibition of AURKB dramatically reduces nucleus size and tumor foci number surrounding the CL region in diethylnitrosamine-treated liver. Our work reveals an intimate molecular link between pathological hyperpolyploidy of CL hepatocytes and transformation into HCC cells.
Automated design of synthetic microbial communities
Authors: Karkaria Behzad D. , Fedorec Alex J. H. , Barnes Chris P. 
Published: January 2021

AbstractMicrobial species rarely exist in isolation. In naturally occurring microbial systems there is strong evidence for a positive relationship between species diversity and productivity of communities. The pervasiveness of these communities in nature highlights possible advantages for genetically engineered strains to exist in cocultures as well. Building synthetic microbial communities allows us to create distributed systems that mitigate issues often found in engineering a monoculture, especially as functional complexity increases. Here, we demonstrate a methodology for designing robust synthetic communities that include competition for nutrients, and use quorum sensing to control amensal bacteriocin interactions in a chemostat environment. We computationally explore all two- and three- strain systems, using Bayesian methods to perform model selection, and identify the most robust candidates for producing stable steady state communities. Our findings highlight important interaction motifs that provide stability, and identify requirements for selecting genetic parts and further tuning the community composition.
Direct allele introgression into pure chicken breeds using Sire Dam Surrogate (SDS) mating
Authors: Ballantyne Maeve , Woodcock Mark , Doddamani Dadakhalandar , Hu Tuanjun , Taylor Lorna , Hawken Rachel J. , McGrew Mike J. 
Published: January 2021

AbstractPoultry is the most abundant livestock species with over 60 billion chickens raised globally per year. The majority of chicken are produced from commercial flocks, however many indigenous chicken breeds play an important role in rural economies as they are well adapted to local environmental and scavenging conditions. The ability to make precise genetic changes in chicken will permit the validation of genetic variants responsible for climate adaptation and disease resilience, and the transfer of beneficial alleles between breeds. Here, we generate a novel inducibly sterile surrogate host chicken. Introducing donor genome edited primordial germ cells into the sterile male and female host embryos produces adult chicken carrying only exogenous germ cells. Subsequent direct mating of the surrogate hosts, Sire Dam Surrogate (SDS) mating, recreates the donor chicken breed carrying the edited allele in a single generation. We demonstrate the introgression and validation of two feather trait alleles, Dominant white and Frizzle into two pure chicken breeds using the SDS surrogate hosts.
A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy
Authors: Douguet Laetitia , Janho dit Hreich Serena , Benzaquen Jonathan , Seguin Laetitia , Juhel Thierry , Dezitter Xavier , Duranton Christophe , Ryffel Bernhard , Kanellopoulos Jean , Delarasse Cecile , Renault Nicolas , Furman Christophe , Homerin Germain , Féral Chloé , Cherfils-Vicini Julien , Millet Régis , Adriouch Sahil , Ghinet Alina , Hofman Paul , Vouret-Craviari Valérie 
Published: January 2021

AbstractOnly a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7-expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4+ T cells within tumors. Combined with immune checkpoint inhibitor, the molecule induces a complete tumor regression in 80% of LLC tumor-bearing mice. Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a strategy that may be active against NSCLC.
Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans
Authors: Case Laura K. , Liljencrantz Jaquette , Madian Nicholas , Necaise Aaron , Tubbs Justin , McCall Micaela , Bradson Megan L. , Szczot Marcin , Pitcher Mark H. , Ghitani Nima , Frangos Eleni , Cole Jonathan , Bharucha-Goebel Diana , Saade Dimah , Ogata Tracy , Donkervoort Sandra , Foley A. Reghan , Bönnemann Carsten G. , Olausson Håkan , Bushnell M. Catherine , Chesler Alexander T. 
Published: January 2021

AbstractThe sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure. We show that the ability to perceive innocuous pressures is lost when myelinated fiber function is experimentally blocked in healthy volunteers and that two patients lacking Aβ fibers are strikingly unable to feel innocuous pressures at all. We find that seven individuals with inherited mutations in the mechanoreceptor PIEZO2 gene, who have major deficits in touch and proprioception, are nearly as good at sensing pressure as healthy control subjects. Together, these data support a role for Aβ afferents in pressure sensation and suggest the existence of an unknown molecular pathway for its detection.
Transdermal electroosmotic flow generated by a porous microneedle array patch
Authors: Kusama Shinya , Sato Kaito , Matsui Yuuya , Kimura Natsumi , Abe Hiroya , Yoshida Shotaro , Nishizawa Matsuhiko 
Published: January 2021

AbstractA microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. Here, we report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The PMN modified with a charged hydrogel brings three innovative advantages in iontophoresis at once: (1) lowering the transdermal resistance by low-invasive puncture of the highly resistive stratum corneum, (2) transporting of larger molecules through the interconnected micropores, and (3) generating electroosmotic flow (EOF). In particular, the PMN-generated EOF greatly enhances the transdermal molecular penetration or extraction, similarly to the flow induced by external pressure. The enhanced efficiencies of the EOF-assisted delivery of a model drug (dextran) and of the extraction of glucose are demonstrated using a pig skin sample. Furthermore, the powering of the PMN-based transdermal EOF system by a built-in enzymatic biobattery (fructose / O2 battery) is also demonstrated as a possible totally organic iontophoresis patch.
In situ mechanical reinforcement of polymer hydrogels via metal-coordinated crosslink mineralization
Authors: Kim Sungjin , Regitsky Abigail U. , Song Jake , Ilavsky Jan , McKinley Gareth H. , Holten-Andersen Niels 
Published: January 2021

AbstractBiological organic-inorganic materials remain a popular source of inspiration for bioinspired materials design and engineering. Inspired by the self-assembling metal-reinforced mussel holdfast threads, we tested if metal-coordinate polymer networks can be utilized as simple composite scaffolds for direct in situ crosslink mineralization. Starting with aqueous solutions of polymers end-functionalized with metal-coordinating ligands of catechol or histidine, here we show that inter-molecular metal-ion coordination complexes can serve as mineral nucleation sites, whereby significant mechanical reinforcement is achieved upon nanoscale particle growth directly at the metal-coordinate network crosslink sites.
Learning from scaling up ultra-rapid genomic testing for critically ill children to a national level
Authors: Best Stephanie , Brown Helen , Lunke Sebastian , Patel Chirag , Pinner Jason , Barnett Christopher P. , Wilson Meredith , Sandaradura Sarah A. , McClaren Belinda , Brett Gemma R. , Braithwaite Jeffrey , Stark Zornitza 
Published: January 2021

AbstractIn scaling up an ultra-rapid genomics program, we used implementation science principles to design and investigate influences on implementation and identify strategies required for sustainable “real-world” services. Interviews with key professionals revealed the importance of networks and relationship building, leadership, culture, and the relative advantage afforded by ultra-rapid genomics in the care of critically ill children. Although clinical geneticists focused on intervention characteristics and the fit with patient-centered care, intensivists emphasized the importance of access to knowledge, in particular from clinical geneticists. The relative advantage of ultra-rapid genomics and trust in consistent and transparent delivery were significant in creating engagement at initial implementation, with appropriate resourcing highlighted as important for longer term sustainability of implementation. Our findings demonstrate where common approaches can be used and, significantly, where there is a need to tailor support by professional role and implementation phase, to maximize the potential of ultra-rapid genomic testing to improve patient care.
Lung cancer patients’ comorbidities and attendance of German ambulatory physicians in a 5-year cross-sectional study
Authors: Bossert Jasmin , Ludwig Marion , Wronski Pamela , Koetsenruijter Jan , Krug Katja , Villalobos Matthias , Jacob Josephine , Walker Jochen , Thomas Michael , Wensing Michel 
Published: January 2021

AbstractThe majority of lung cancer patients are diagnosed with an advanced stage IV, which has short survival time. Many lung cancer patients have comorbidities, which influence treatment and patients’ quality of life. The aim of the study is to describe comorbidities in incident lung cancer patients and explore their attendance of ambulatory care physicians in Germany. In the observed period, 13,111 persons were first diagnosed with lung cancer (1-year incidence of 36.4 per 100,000). The mean number of comorbidities over 4 quarters was 30.77 ± 13.18; mean Charlson Comorbidity Index was 6.66 ± 2.24. In Germany, ambulatory care physicians most attended were general practitioners (2.6 quarters with contact within 4 quarters). Lung cancer was diagnosed by a general practitioner in 38% of the 13,111 incident patients. The average number of ambulatory care physician contacts over 4 quarters was 35.82 ± 27.31. High numbers of comorbidities and contacts in ambulatory care are common in patients with lung cancer. Therefore, a cross-sectoral and interdisciplinary approach is required for effective, patient-centred care. This was a 5-year cross-sectoral study, based on the InGef research database, which covers anonymized health insurance data of 7.2 million individuals in Germany. Incident lung cancer patients in a 5-year period (2013–2017) were identified. Descriptive statistics were calculated for sociodemographic characteristics, comorbidities, and attendance of ambulatory care physicians.
A patient-centric dataset of images and metadata for identifying melanomas using clinical context
Authors: Rotemberg Veronica , Kurtansky Nicholas , Betz-Stablein Brigid , Caffery Liam , Chousakos Emmanouil , Codella Noel , Combalia Marc , Dusza Stephen , Guitera Pascale , Gutman David , Halpern Allan , Helba Brian , Kittler Harald , Kose Kivanc , Langer Steve , Lioprys Konstantinos , Malvehy Josep , Musthaq Shenara , Nanda Jabpani , Reiter Ofer , Shih George , Stratigos Alexander , Tschandl Philipp , Weber Jochen , Soyer H. Peter 
Published: January 2021

AbstractPrior skin image datasets have not addressed patient-level information obtained from multiple skin lesions from the same patient. Though artificial intelligence classification algorithms have achieved expert-level performance in controlled studies examining single images, in practice dermatologists base their judgment holistically from multiple lesions on the same patient. The 2020 SIIM-ISIC Melanoma Classification challenge dataset described herein was constructed to address this discrepancy between prior challenges and clinical practice, providing for each image in the dataset an identifier allowing lesions from the same patient to be mapped to one another. This patient-level contextual information is frequently used by clinicians to diagnose melanoma and is especially useful in ruling out false positives in patients with many atypical nevi. The dataset represents 2,056 patients (20.8% with at least one melanoma, 79.2% with zero melanomas) from three continents with an average of 16 lesions per patient, consisting of 33,126 dermoscopic images and 584 (1.8%) histopathologically confirmed melanomas compared with benign melanoma mimickers.
A global dataset for crop production under conventional tillage and no tillage systems
Authors: Su Yang , Gabrielle Benoit , Makowski David 
Published: January 2021

AbstractNo tillage (NT) is often presented as a means to grow crops with positive environmental externalities, such as enhanced carbon sequestration, improved soil quality, reduced soil erosion, and increased biodiversity. However, whether NT systems are as productive as those relying on conventional tillage (CT) is a controversial issue, fraught by a high variability over time and space. Here, we expand existing datasets to include the results of the most recent field experiments, and we produce a global dataset comparing the crop yields obtained under CT and NT systems. In addition to crop yield, our dataset also reports information on crop growing season, management practices, soil characteristics and key climate parameters throughout the experimental year. The final dataset contains 4403 paired yield observations between 1980 and 2017 for eight major staple crops in 50 countries. This dataset can help to gain insight into the main drivers explaining the variability of the productivity of NT and the consequence of its adoption on crop yields.
Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer
Authors: Elkholi Islam E. , Di Iorio Massimo , Fahiminiya Somayyeh , Arcand Suzanna L. , Han HyeRim , Nogué Clara , Behl Supriya , Hamel Nancy , Giroux Sylvie , de Ladurantaye Manon , Aleynikova Olga , Gotlieb Walter H. , Côté Jean-François , Rousseau François , Tonin Patricia N. , Provencher Diane , MesMasson Anne-Marie , Akbari Mohammad R. , Rivera Barbara , Foulkes William D. 
Published: January 2021

AbstractThe nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case–control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations.
An eight-camera fall detection system using human fall pattern recognition via machine learning by a low-cost android box
Authors: Shu Francy , Shu Jeff 
Published: January 2021

AbstractFalls are a leading cause of unintentional injuries and can result in devastating disabilities and fatalities when left undetected and not treated in time. Current detection methods have one or more of the following problems: frequent battery replacements, wearer discomfort, high costs, complicated setup, furniture occlusion, and intensive computation. In fact, all non-wearable methods fail to detect falls beyond ten meters. Here, we design a house-wide fall detection system capable of detecting stumbling, slipping, fainting, and various other types of falls at 60 m and beyond, including through transparent glasses, screens, and rain. By analyzing the fall pattern using machine learning and crafted rules via a local, low-cost single-board computer, true falls can be differentiated from daily activities and monitored through conventionally available surveillance systems. Either a multi-camera setup in one room or single cameras installed at high altitudes can avoid occlusion. This system’s flexibility enables a wide-coverage set-up, ensuring safety in senior homes, rehab centers, and nursing facilities. It can also be configured into high-precision and high-recall application to capture every single fall in high-risk zones.
Death is associated to the type of drug-eluting stent in patients with left ventricular dysfunction and elevated natriuretic peptide levels
Authors: Roth Christian , Gangl Clemens , Speidl Walter S. , Goliasch Georg , Schneider Matthias , Dalos Daniel , Berger Rudolf 
Published: January 2021

AbstractAs advanced heart failure (HF) with elevated NT-proBNP is characterized by an activated coagulation system, coronary events clinically noticed as sudden or HF death may be more common after treatment with first- compared to newer-generation DES. Our study evaluates (1) if patients with left ventricular dysfunction (LVSD) who underwent percutaneous coronary intervention have a better survival with first- or newer-generation DES, and (2) if the survival benefit is predicted by NT-proBNP. Our observational study evaluated patients with LVSD who were registered in the coronary catheter laboratory database of the Medical University of Vienna. Multivariate Cox regression analyses tested an interaction in the risk of death between those with lower or elevated NT-proBNP levels and the stent-generation. The relative risk of newer- compared to first-generation DES as reference was calculated for patients with low and elevated NT-proBNP levels. In 340 patients (178 newer- and 162 first-generation DES) stent-generation and NT-proBNP were independent predictors of death. When the stent-generation*NTproBNP interaction was forced into a Cox regression model, this term independently predicted death. The relative risk of first- compared to newer-generation DES was similar in patients with lower NT-proBNP (HR 1.02, 95% CI 0.95–1.10, p = 0.560), but was higher in patients with elevated NT-proBNP (HR 1.06, 95% CI 1.01–1.10, p = 0.020). Death is associated to stent-generation. NT-proBNP is a predictor for the stent generation used: elevated levels demonstrated a higher mortality risk when using first- compared to newer-generation DES, while lower levels showed a similar risk when using either DES-generation.
Spotted fever group rickettsiae (SFGR) detection in ticks following reported human case of Japanese spotted fever in Niigata Prefecture, Japan
Authors: Arai Reiko , Sato Megumi , Kato Miwako , Aoki Junko , Nishida Akiko , Watanabe Kaori , Hirokawa Chika , Ikeda Sumire , Watanabe Kozo , Regilme Maria Angenica F. , Sato Marcello Otake , Tamura Tsutomu 
Published: January 2021

AbstractJapanese spotted fever, a tick-borne disease caused byRickettsia japonica, was firstly described in southwestern Japan. There was a suspicion ofRickettsia japonicainfected ticks reaching the non-endemic Niigata Prefecture after a confirmed case of Japanese spotted fever in July 2014. Therefore, from 2015 to 2017, 38 sites were surveyed and rickettsial pathogens were investigated in ticks from north to south of Niigata Prefecture including Sado island. A total of 3336 ticks were collected and identified revealing ticks of three genera and ten species:Dermacentor taiwanensis,Haemaphysalis flava,Haemaphysalis hystricis,Haemaphysalis longicornis,Haemaphysalis megaspinosa,Ixodes columnae,Ixodes monospinosus,Ixodes nipponensis,Ixodes ovatus,andIxodes persulcatus. Investigation of rickettsial DNA showed no ticks infected byR. japonica. However, three species of spotted fever group rickettsiae (SFGR) were found in ticks,R. asiatica,R. helvetica,andR. monacensis, confirming Niigata Prefecture as a new endemic area to SFGR. These results highlight the need for public awareness of the occurrence of this tick-borne disease, which necessitates the establishment of public health initiatives to mitigate its spread.
Comparing detectability patterns of bird species using multi-method occupancy modelling
Authors: Zamora-Marín José M. , Zamora-López Antonio , Calvo José F. , Oliva-Paterna Francisco J. 
Published: January 2021

AbstractA robust knowledge of biodiversity distribution is essential for designing and developing effective conservation actions. The choice of a suitable sampling method is key to obtaining sufficiently accurate information of species distribution and consequently to improve biodiversity conservation. This study applies multi-method occupancy models to 36 common bird species associated with small ponds in the province of Murcia (south-eastern Spain), one of the most arid regions of Europe, in order to compare their effectiveness for detecting different bird species: direct observation, combined observation and video monitoring and mist netting captures. The results showed that the combined method and direct observation were similar and most effective than mist netting for detecting species occupancy, although detection rates ranged widely among bird groups, while some large species were poorly detected by all the methods used. Average detectability did not increase during the breeding period. The chosen approach is particularly applicable to both single- and multi-species bird monitoring programmes. However, we recommend evaluating the cost-effectiveness of all the available methods in order to reduce costs and improve the success of sampling designs.