bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective, Multicenter Registry Study to Evaluate the Clinical Feasibility of Targeted Axillary Dissection (TAD) in Node-positive Breast Cancer Patients
Authors: Kuemmel Sherko , Heil Joerg , Rueland Anna , Seiberling Christine , Harrach Hakima , Schindowski Dorothea , Lubitz Juliane , Hellerhoff Karin , Ankel Christine , Graßhoff Sven-Thomas , Deuschle Petra , Hanf Volker , Belke Kerstin , Dall Peter , Dorn Julia , Kaltenecker Gabriele , Kuehn Thorsten , Beckmann Ulrike , Potenberg Jochem , Blohmer Jens-Uwe , Kostara Athina , Breit Elisabeth , Holtschmidt Johannes , Traut Eugen , Reinisch Mattea 
Published: November 2020

Objective:
This study aimed to investigate the feasibility and accuracy of non-radioactive TLN biopsy and TAD in routine clinical practice.

Background Data:
TAD involves TLN biopsy (TLNB) and sentinel lymph node biopsy and was recently introduced as a new standard for less invasive axillary staging in BC patients undergoing neoadjuvant systemic therapy (NST); however, clinical evidence is limited.

Methods:
The SenTa study is a prospective registry study conducted at 50 centers. Patients with invasive BC who nderwent clip insertion into the most suspicious axillary lymph node were eligible. Axillary surgery was performed with or without sentinel lymph node biopsy, TLNB, and/or axillary lymph node dissection (ALND). Main endpoints were the detection rate and FNR of TLNB and TAD after NST.

Results:
Between 2017 and 2018, 548 consecutive BC patients underwent clip placement into biopsy-confirmed positive lymph nodes. After NST (n = 473), the clipped TLN was intraoperatively resected in 329 of 423 patients [77.8%, 95% confidence interval (CI): 74.0–82.0]. TAD was successful in 199 of 229 patients (detection rate: 86.9%, 95% CI: 81.8–91.0), the SLN and TLN were identical in 129 patient (64.8%). FNRs were 7.2% (8 of 111, 95% CI: 3.1–13.6) for TLNB followed by ALND (n = 203) and 4.3% (2 of 46, 95% CI: 0.5–14.8) for TAD followed by ALND (n = 77).

Conclusions:
The SenTa study demonstrates the feasibility of TAD in a real-world cohort of BC patients. Our findings are of great importance for de-escalation of surgical strategies.
The Value of Source Localization for Clinical Magnetoencephalography: Beyond the Equivalent Current Dipole
Authors: Tenney Jeffrey R. , Fujiwara Hisako , Rose Douglas F. 
Published: November 2020

Summary:
Source localization for clinical magnetoencephalography recordings is challenging, and many methods have been developed to solve this inverse problem. The most well-studied and validated tool for localization of the epileptogenic zone is the equivalent current dipole. However, it is often difficult to summarize the richness of the magnetoencephalography data with one or a few point sources. A variety of source localization algorithms have been developed to more fully explain the complexity of clinical magnetoencephalography data used to define the epileptogenic network. In this review, various clinically available source localization methods are described and their individual strengths and limitations are discussed.
The condition of coral reefs in Timor-Leste before and after the 2016–2017 marine heatwave
Authors: Kim Catherine JS , Roelfsema Chris , Dove Sophie , Hoegh-Guldberg Ove 
Published: November 2020

AbstractEl Niño Southern Oscillation global coral bleaching events are increasing in frequency; however, the severity of bleaching is not geographically uniform. There were two major objectives of the present project: 1) assess the state of reefs and coral health at several sites and 2) explore water quality and climate change impacts on Timorese reefs. The impacts of climate change (principally by following coral mortality) were surveyed on coral reefs before and after the 2016–2017 underwater heatwave, using temperature loggers deployed between surveys which were compared to Coral Reef Watch (CRW) experimental virtual station sea surface temperature (SST). CRW is an important and widely used tool; however, we found the SST was significantly warmer (> 1°C) thanin situtemperature during the austral summer accruing 5.79 degree heating weeks.In situtemperature showed no accumulation. Change in coral cover between surveys was attributed to reef heterogeneity. There were significant differences in coral cover, coral diversity, and nutrient concentrations between site and depth and a low prevalence of disease recorded in both years. The comparison of temperature and SST indicate that bleaching stress in Timor-Leste is potentially mitigated by seasonal and oceanographic dynamics. This is corroborated by Timor-Leste’s location within the Indonesian ThroughFlow. Timor-Leste is a climate refugium and the immediate conservation work lies in the management of localized anthropogenic impacts on coral reefs such as sedimentation and fishing.
Novel imprints in mouse blastocysts are predominantly DNA methylation independent
Authors: Santini Laura , Halbritter Florian , Titz-Teixeira Fabian , Suzuki Toru , Asami Maki , Ramesmayer Julia , Ma Xiaoyan , Lackner Andreas , Warr Nick , Pauler Florian , Hippenmeyer Simon , Laue Ernest , Farlik Matthias , Bock Christoph , Beyer Andreas , Perry Anthony C. F. , Leeb Martin 
Published: November 2020

ABSTRACTIn mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation.
MiniFAST: A sensitive and fast miniaturized microscope forin vivoneural recording
Authors: Juneau Jill , Duret Guillaume , Chu Joshua P. , Rodriguez Alexander V. , Morozov Savva , Aharoni Daniel , Robinson Jacob T. , St-Pierre François , Kemere Caleb 
Published: November 2020

AbstractObserving the activity of large populations of neuronsin vivois critical for understanding brain function and dysfunction. The use of fluorescent genetically-encoded calcium indicators (GECIs) in conjunction with miniaturized microscopes is an exciting emerging toolset for recording neural activity in unrestrained animals. Despite their potential, current miniaturized microscope designs are limited by using image sensors with low frame rates, sensitivity, and resolution. Beyond GECIs, there are many neuroscience applications which would benefit from the use of other emerging neural indicators, such as fluorescent genetically-encoded voltage indicators (GEVIs) that have faster temporal resolution to match neuron spiking, yet, require imaging at high speeds to properly sample the activity-dependent signals. We integrated an advanced CMOS image sensor into a popular open-source miniaturized microscope platform. MiniFAST is a fast and sensitive miniaturized microscope capable of 1080p video, 1.5 µm resolution, frame rates up to 500 Hz and high gain ability (up to 70 dB) to image in extremely low light conditions. We report results of high speed 500 Hzin vitroimaging of a GEVI and ∼300 Hzin vivoimaging of transgenic Thy1-GCaMP6f mice. Finally, we show the potential for a reduction in photobleaching by using high gain imaging with ultra-low excitation light power (0.05 mW) at 60 Hz frame rates while still resolving Ca2+spiking activity. Our results extend miniaturized microscope capabilities in high-speed imaging, high sensitivity and increased resolution opening the door for the open-source community to use fast and dim neural indicators.
CT-based Rapid Triage of COVID-19 Patients: Risk Prediction and Progression Estimation of ICU Admission, Mechanical Ventilation, and Death of Hospitalized Patients
Authors: Xu Qinmei , Zhan Xianghao , Zhou Zhen , Li Yiheng , Xie Peiyi , Zhang Shu , Li Xiuli , Yu Yizhou , Zhou Changsheng , Zhang Longjiang , Gevaert Olivier , Lu Guangming 
Published: November 2020

SummaryThe wave of COVID-19 continues to overwhelm the medical resources, especially the stressed intensive care unit (ICU) capacity and the shortage of mechanical ventilation (MV). Here we performed CT-based analysis combined with electronic health records and clinical laboratory results on Cohort 1 (n = 1662 from 17 hospitals) with prognostic estimation for the rapid stratification of PCR confirmed COVID-19 patients. These models, validated on Cohort 2 (n = 700) and Cohort 3 (n = 662) constructed from 9 external hospitals, achieved satisfying performance for predicting ICU, MV and death of COVID-19 patients (AUROC 0.916, 0.919 and 0.853), even on events happened two days later after admission (AUROC 0.919, 0.943 and 0.856). Both clinical and image features showed complementary roles in events prediction and provided accurate estimates to the time of progression (p<.001). Our findings are valuable for delivering timely treatment and optimizing the use of medical resources in the pandemic of COVID-19.
Development of an automated chemiluminescence assay system for quantitative measurement of multiple anti-SARS-CoV-2 antibodies
Authors: Kubo Sousuke , Ohtake Norihisa , Miyakawa Kei , Jeremiah Sundararaj Stanleyraj , Yamaoka Yutaro , Murohashi Kota , Hagiwara Eri , Mihara Takahiro , Goto Atsushi , Yamazaki Etsuko , Ogura Takashi , Kaneko Takeshi , Yamanaka Takeharu , Ryo Akihide 
Published: November 2020

AbstractObjectiveSerological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against two of the most immunologically relevant SARS-CoV-2 antigens, nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples.MethodsWe designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP (ΔN-NP) or receptor-binding domain (RBD) antigen) on the advanced chemiluminescence enzyme immunoassay system TOSOH AIA-CL. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera. Subsequently, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors.ResultsAll of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63-100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63-100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested.ConclusionOur newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.
Platelet Activating Immune Complexes Identified in COVID-19 Associated Coagulopathy
Authors: Nazy Ishac , Jevtic Stefan D , Moore Jane C , Huynh Angela , Smith James W , Kelton John G , Arnold Donald M 
Published: November 2020

AbstractThrombosis is a prominent feature of coronavirus disease 2019 (COVID-19) and often occurs in patients who are critically ill; however, the mechanism is unclear. This COVID-19 associated coagulopathy (CAC) shares features with heparin-induced thrombocytopenia (HIT), including mild thrombocytopenia and thrombosis. We thus tested 10 CAC patients for anti-PF4/heparin antibodies and functional platelet activation. HIT was excluded in all samples based on anti-PF4/heparin antibody and serotonin release assay results. Of note, 6 CAC patients demonstrated platelet activation by the serotonin release assay that was inhibited by FcγRIIA receptor blockade, confirming an IgG-specific immune complex (IC)-mediated reaction. Platelet activation was independent of heparin, but inhibitable by both therapeutic and high dose heparin. All 6 samples were positive for IgG-specific antibodies targeting the receptor binding domain (RBD) or the spike protein of the SARS-CoV-2 virus. These samples were additionally characterized by significant endothelial activation, shown by increased von Willebrand factor antigen and activity. ADAMTS13 activity was not severely reduced, and ADAMTS13 inhibitors were not present, ruling out thrombotic thrombocytopenic purpura. Our study thus identifies platelet-activating ICs as a mechanism that contributes to CAC thrombosis.Scientific CategoryThrombosis and HemostasisKey PointsPatients with COVID-19 thrombosis have immune complexes that activate platelets through FcγRIIA signallingPatients with COVID-19 thrombosis demonstrate increased VWF antigen and activity that is not related to severe ADAMTS13 reduction
Comparison of Radiomic Feature Aggregation Methods for Patients with Multiple Tumors
Authors: Chang Enoch , Joel Marina , Chang Hannah Y. , Du Justin , Khanna Omaditya , Omuro Antonio , Chiang Veronica , Aneja Sanjay 
Published: November 2020

AbstractBackgroundRadiomic feature analysis has been shown to be effective at modeling cancer outcomes. It has not yet been established how to best combine these radiomic features in patients with multifocal disease. As the number of patients with multifocal metastatic cancer continues to rise, there is a need for improving personalized patient-level prognostication to better inform treatment.MethodsWe compared six mathematical methods of combining radiomic features of 3596 tumors in 831 patients with multiple brain metastases and evaluated the performance of these aggregation methods using three survival models: a standard Cox proportional hazards model, a Cox proportional hazards model with LASSO regression, and a random survival forest.ResultsAcross all three survival models, the weighted average of the largest three metastases had the highest concordance index (95% confidence interval) of 0.627 (0.595-0.661) for the Cox proportional hazards model, 0.628 (0.591-0.666) for the Cox proportional hazards model with LASSO regression, and 0.652 (0.565-0.727) for the random survival forest model.ConclusionsRadiomic features can be effectively combined to establish patient-level outcomes in patients with multifocal brain metastases. Future studies are needed to confirm that the volume-weighted average of the largest three tumors is an effective method for combining radiomic features across other imaging modalities and disease sites.
Mepolizumab effectiveness in patients with severe eosinophilic asthma and co-presence of bronchiectasis: a real-world retrospective pilot study
Authors: Crimi Claudia , Campisi Raffaele , Nolasco Santi , Cacopardo Giulia , Intravaia Rossella , Porto Morena , Impellizzeri Pietro , Pelaia Corrado , Crimi Nunzio 
Published: November 2020

AbstractBackgroundThe association of bronchiectasis (BE) in patients with severe eosinophilic asthma (SEA) is quite frequent. Mepolizumab is a well-recognized treatment for SEA; we aim to evaluate its effectiveness in SEA patients with and without BE in real-life.MethodsWe performed a single-center retrospective pilot study, including patients with SEA treated with mepolizumab for one year. Asthma control test (ACT), lung function, annual exacerbations rate, oral corticosteroid dosage, FeNO, chronic mucous secretions, blood and sputum eosinophils were recorded at baseline and after 6 and 12 months.Resultswe included 32 patients (mean age: 52.3±10, 59% female). 50% showed co-presence of bronchiectasis, (SEA+BE). Significant improvements were found in ACT [(13.8±4.6 to 20.7±4.1, p=0.0009) and (13±4.8 to 20.7±4.6, p=0.0003)], annual exacerbations rate [from 7 (4-12) to 0 (0.00-0.75) and from 8 (4-12) to 0 (0-1), p<0.0001], and blood eosinophils count [748 cells/μL (400-1250) vs. 84 cells/μL (52.5-100), and from 691 cells/μL (405-798) vs. 60 cells/μL (41-105), p<0.0001] in SEA and SEA+BE group respectively, already after 6 months of treatment. A reduction in daily oral corticosteroids intake at 12 months was shown [from 15 mg (0-25) to 0 mg (0-0), p=0.003 and from 8.8 mg (0-25) to 0 mg (0-0) (p=0.01)] in both SEA and SEA+BE, respectively. Similar results were found, comparing SEA+BE patients based on the severity of bronchiectasis.ConclusionsMepolizumab effectively improves asthma symptoms control, reducing annual exacerbations and corticosteroid intake in all patients with SEA, even in the subgroup with coexisting bronchiectasis, independently of their severity.HighlightsMepolizumab is effective in the treatment of severe eosinophilic asthma (SEA) in clinical trials and real-life studies.Bronchiectasis is a frequent comorbidity in patients with severe eosinophilic asthma.Mepolizumab proved to be effective in improving asthma symptoms control, mucus hypersecretion, lung function, and reducing sputum and blood eosinophils, corticosteroids dependency and annual exacerbations both in severe eosinophilic asthma patients with or without co-presence of bronchiectasis.Mepolizumab showed to be effective in patients with asthma and co-presence of bronchiectasis, regardless of BE severity.Assessing the co-presence and severity of bronchiectasis may help clinicians select the right biologic for a prompt treatment-specific effect.
A random-walk-based epidemiological model
Authors: Chu Andrew , Huber Greg , McGeever Aaron , Veytsman Boris , Yllanes David 
Published: November 2020

ABSTRACTRandom walkers on a two-dimensional square lattice are used to explore the spatio-temporal growth of an epidemic. We have found that a simple random-walk system generates non-trivial dynamics compared with traditional well-mixed models. Phase diagrams characterizing the long-term behaviors of the epidemics are calculated numerically. The functional dependence of the basic reproductive number R0 on the model’s defining parameters reveals the role of spatial fluctuations and leads to a novel expression for R0. Special attention is given to simulations of inter-regional transmission of the contagion. The scaling of the epidemic with respect to space and time scales is studied in detail in the critical region, which is shown to be compatible with the directed-percolation universality class.
Scaling up biodiversity ecosystem functioning relationships: the role of environmental heterogeneity in space and time
Authors: Thompson Patrick L. , Kéfi Sonia , Zelnik Yuval R. , Dee Laura E. , Wang Shaopeng , de Mazancourt Claire , Loreau Michel , Gonzalez Andrew 
Published: November 2020

AbstractThe biodiversity and ecosystem functioning (BEF) relationship is expected to be scale-dependent. The autocorrelation of environmental heterogeneity is hypothesized to explain this scale dependence because it influences how quickly biodiversity accumulates over space or time. However, this link has yet to be demonstrated in a formal model. Here we use a Lotka-Volterra competition model to simulate community dynamics when environmental conditions vary across either space or time. Species differ in their optimal environmental conditions, which results in turnover in community composition. We vary biodiversity by modelling communities with different sized regional species pools and ask how the amount of biomass per unit area depends on the number of species present, and the spatial or temporal scale at which it is measured. We find that more biodiversity is required to maintain functioning at larger temporal and spatial scales. The number of species required increases quickly when environmental autocorrelation is low, and slowly when autocorrelation is high. Both spatial and temporal environmental heterogeneity led to scale dependence in BEF, but autocorrelation had larger impacts when environmental change was temporal. These findings show how the biodiversity required to maintain functioning is expected to increase over space and time.
Prevalence of sustainable and unsustainable use of wild species inferred from the IUCN Red List
Authors: Marsh Sophie M.E. , Hoffmann Michael , Burgess Neil D. , Brooks Thomas M. , Challender Daniel W.S. , Cremona Patricia J. , Hilton-Taylor Craig , de Micheaux Flore Lafaye , Lichtenstein Gabriela , Roe Dilys , Böhm Monika 
Published: November 2020

AbstractUnsustainable exploitation of wild species represents a serious threat to biodiversity and to the livelihoods of local communities and indigenous peoples. However, managed, sustainable use has the potential to forestall extinctions, aid recovery, and meet human needs. Research to date has focused on unsustainable biological resource use with little consideration of sustainable use; we infer the current prevalence of both. We analyzed species-level data for 30,923 species from 13 taxonomic groups on the IUCN Red List. Our results demonstrate the broad taxonomic prevalence of use, with 40% of species (10,098 of 25,009 species from 10 data-sufficient taxonomic groups) documented as being used. The main purposes of use are pets, display animals and horticulture, and human consumption. Use often has an adverse impact on species extinction risk (we define this as biologically unsustainable): intentional use is currently contributing to elevated extinction risk for over a quarter of all threatened or Near Threatened (NT) species (2,752 – 2,848 of 9,753 species). Intentional use also threatens 16% of all species used (1,597 – 1,631 of 10,098). However, 72% of species that are used (7,291 of 10,098) are Least Concern (LC), of which nearly half (3,469) also have stable or improving population trends. The remainder of used species are not documented as threatened by biological resource use, including 172 threatened or NT species with stable or improving populations. Around a third of species that have use documented as a threat do not currently receive targeted species management actions to directly address this threat. We offer suggestions for improving use-related Red List data. Our findings on the prevalence of sustainable and unsustainable use, and variation across taxa, can inform international policymaking, including the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, the Convention on Biological Diversity, and the Convention on International Trade in Endangered Species.