bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell Phenotypic and Molecular Characterization of Circulating Tumor Cells Isolated from Cryopreserved Peripheral Blood Mononuclear Cells of Patients with Lung Cancer and Sarcoma
Authors: Vismara Marta , Reduzzi Carolina , Silvestri Marco , Murianni Fabio , Lo Russo Giuseppe , Fortunato Orazio , Motta Rosita , Lanzoni Davide , Giovinazzo Francesca , Miodini Patrizia , Pasquali Sandro , Suatoni Paola , Pastorino Ugo , Roz Luca , Sozzi Gabriella , Cappelletti Vera , Bertolini Giulia 
Published: February 2022

Abstract

Background
The isolation of circulating tumor cells (CTCs) requires rapid processing of the collected blood due to their inherent fragility. The ability to recover CTCs from peripheral blood mononuclear cells (PBMCs) preserved from cancer patients could allow for retrospective analyses or multicenter CTC studies.

Methods
We compared the efficacy of CTC recovery and characterization using cryopreserved PMBCs vs fresh whole blood from patients with non-small cell lung cancer (NSCLC; n = 8) and sarcoma (n = 6). Two epithelial cellular adhesion molecule (EpCAM)-independent strategies for CTC enrichment, based on Parsortix® technology or immunomagnetic depletion of blood cells (AutoMACS®) were tested, followed by DEPArray™ single-cell isolation. Phenotype and genotype, assessed by copy number alterations analysis, were evaluated at a single-cell level. Detection of target mutations in CTC-enriched samples from frozen NSCLC PBMCs was also evaluated by digital PCR (dPCR).

Results
The use of cryopreserved PBMCs from cancer patients allowed for the retrospective enumeration of CTCs and their molecular characterization, using both EpCAM-independent strategies that performed equally in capturing CTC. Cells isolated from frozen PBMCs were representative of whole blood-derived CTCs in terms of number, phenotype, and copy number aberration profile/target mutations. Long-term storage (≥3 years) did not affect the efficacy of CTC recovery. Detection of target mutations was also feasible by dPCR in CTC-enriched samples derived from stored PBMCs.

Conclusions
Isolating CTCs from longitudinally collected PBMCs using an unbiased selection strategy can offer a wider range of retrospective genomic/phenotypic analyses to guide patients’ personalized therapy, paving the way for sample sharing in multicenter studies.
Highly Specific Droplet-Digital PCR Detection of Universally Methylated Circulating Tumor DNA in Endometrial Carcinoma
Authors: Beinse Guillaume , Borghese Bruno , Métairie Marie , Just Pierre-Alexandre , Poulet Geoffroy , Garinet Simon , Parfait Beatrice , Didelot Audrey , Bourreau Camille , Agueeff Natacha , Lavollé Alexandre , Terris Benoit , Chapron Charles , Goldwasser François , Leroy Karen , Blons Helene , Laurent-Puig Pierre , Taly Valérie , Alexandre Jérôme 
Published: February 2022

Abstract

Background
No circulating biomarker is available for endometrial carcinoma (EC). We aimed to identify DNA positions universally hypermethylated in EC, and to develop a digital droplet PCR (ddPCR) assay for detection of hypermethylated circulating tumor DNA (meth-ctDNA) in plasma from patients with EC.

Methods
DNA positions hypermethylated in EC, and without unspecific hypermethylation in tissue/cell types releasing circulating cell-free DNA in plasma, were identified in silico from TCGA/Gene Expression Omnibus (GEO) data. A methylation-specific ddPCR (meth-ddPCR) assay following bisulfite conversion of DNA extracted from plasma was optimized for detection of meth-ctDNA according to dMIQE guidelines. Performances were validated on a retrospective cohort (n = 78 tumors, n = 30 tumor-adjacent tissues), a prospective pilot cohort (n = 33 stage I–IV patients), and 55 patients/donors without cancer.

Results
Hypermethylation of zinc finger and SCAN domain containing 12 (ZSCAN12) and/or oxytocin (OXT) classified EC samples from multiple noncancer samples with high diagnostic specificity/sensitivity [&gt;97%; area under the curve (AUC) = 0.99; TCGA/GEO tissues/blood samples]. These results were confirmed in the independent retrospective cohort (AUC = 0.99). Meth-ddPCR showed a high analytical specificity (limit of blank = 2) and sensitivity (absolute lower threshold of detection = 50 pgmethDNA/mLplasma). In the pilot cohort, meth-ctDNA was detected in pretreatment plasma samples from 9/11 and 5/20 patients with advanced and non-advanced EC, respectively. 2 of 9 patients had ctDNA detected after macroscopic complete surgery and experienced progression within 6 months. No healthy donors had any copy of hypermethylated DNA detected in plasma.

Conclusions
Meth-ddPCR of ZSCAN12/OXT allows a highly specific and sensitive detection of ctDNA in plasma from patients with EC and appears promising for personalized approaches for these patients.
The genome of the Paleogene relic treeBretschneidera sinensis: insights into trade-offs in gene family evolution, demographic history, and adaptive SNPs
Authors: Liu Hai-Lin , Harris A J , Wang Zheng-Feng , Chen Hong-Feng , Li Zhi-An , Wei Xiao 
Published: February 2022

AbstractAmong relic species, genomic information may provide the key to inferring their long-term survival. Therefore, in this study, we investigated the genome of the Paleogene relic tree species, Bretschneidera sinensis, which is a rare endemic species within southeastern Asia. Specifically, we assembled a high-quality genome for B. sinensis using PacBio high-fidelity and high-throughput chromosome conformation capture reads and annotated it with long and short RNA sequencing reads. Using the genome, we then detected a trade-off between active and passive disease defences among the gene families. Gene families involved in salicylic acid and MAPK signalling pathways expanded as active defence mechanisms against disease, but families involved in terpene synthase activity as passive defences contracted. When inferring the long evolutionary history of B. sinensis, we detected population declines corresponding to historical climate change around the Eocene–Oligocene transition and to climatic fluctuations in the Quaternary. Additionally, based on this genome, we identified 388 single nucleotide polymorphisms (SNPs) that were likely under selection, and showed diverse functions in growth and stress responses. Among them, we further found 41 climate-associated SNPs. The genome of B. sinensis and the SNP dataset will be important resources for understanding extinction/diversification processes using comparative genomics in different lineages.
Spatialized ecological network analysis for ecosystem-based management: effects of climate change, marine renewable energy, and fishing on ecosystem functioning in the Bay of Seine
Authors: Nogues Quentin , Araignous Emma , Bourdaud Pierre , Halouani Ghassen , Raoux Aurore , Foucher Éric , Loc'h François Le , Loew-Turbout Frédérique , Ben Rais Lasram Frida , Dauvin Jean-Claude , Niquil Nathalie 
Published: February 2022

Abstract
Integrative and spatialized tools for studying the effects of a wide variety of ecosystem drivers are needed to implement ecosystem-based management and marine spatial planning. We developed a tool for analyzing the direct and indirect effects of anthropic activities on the structure and functioning of coastal and marine ecosystems. Using innovative modelling techniques, we ran a spatially explicit model to carry out an ecological network analysis (ENA) of the effects of climate change (CC), of an offshore wind farm (OWF) and of multiple fishing scenarios on the Bay of Seine (eastern part of the English Channel) ecosystem. ENA indices described the effects of those different drivers in a holistic and spatial way. The spatial analysis of ecosystem properties revealed local and global patterns of modifications attributed to CC, while the OWF resulted in localized changes in the ecosystem. This ability of ENA indicators to detect human-induced changes in ecosystem functioning at various spatial scales allows for a more integrative view of the effects of human activities on ecosystems. ENA indices could be used to link both local and global ecosystem changes, for a more cross-scale approach to ecosystem management.
Increased Breadth of Group A Streptococcus Antibody Responses in Children With Acute Rheumatic Fever Compared to Precursor Pharyngitis and Skin Infections
Authors: Whitcombe Alana L , McGregor Reuben , Bennett Julie , Gurney Jason K , Williamson Deborah A , Baker Michael G , Moreland Nicole J 
Published: February 2022

Abstract

Background
Group A Streptococcus (GAS) causes superficial pharyngitis and skin infections as well as serious autoimmune sequelae such as acute rheumatic fever (ARF) and subsequent rheumatic heart disease. ARF pathogenesis remains poorly understood. Immune priming by repeated GAS infections is thought to trigger ARF, and there is growing evidence for the role of skin infections in this process.

Methods
We utilized our recently developed 8-plex immunoassay, comprising antigens used in clinical serology for diagnosis of ARF (SLO, DNase B, SpnA), and 5 conserved putative GAS vaccine antigens (Spy0843, SCPA, SpyCEP, SpyAD, Group A carbohydrate), to characterize antibody responses in sera from New Zealand children with a range of clinically diagnosed GAS disease: ARF (n = 79), GAS-positive pharyngitis (n = 94), GAS-positive skin infection (n = 51), and matched healthy controls (n = 90).

Results
The magnitude and breadth of antibodies in ARF was very high, giving rise to a distinct serological profile. An average of 6.5 antigen-specific reactivities per individual was observed in ARF, compared to 4.2 in skin infections and 3.3 in pharyngitis.

Conclusions
ARF patients have a unique serological profile, which may be the result of repeated precursor pharyngitis and skin infections that progressively boost antibody breadth and magnitude.
A Biomass Pyrolysis Oil as a Novel Insect Growth Regulator Mimic for a Variety of Stored Product Beetles
Authors: Bruce Alexander , Wilson A Nolan , Ranabhat Sabita , Montgomery Jaden , Nicholson Scott , Harris Kylee , Morrison William R 
Published: February 2022

AbstractAs fumigants face increasing regulatory restrictions, resistance, and consumer pushback, it is vital to expand the integrated pest management (IPM) chemical toolkit for stored products. The production of biomass derived insecticides (e.g., bio-oil fraction) from byproducts of biofuel production may be a promising alternative source of chemistries for controlling stored product insects. These potential insecticidal bio-oils were fractionated based on boiling points (ranging from 115 to 230°C in one series and 245–250°C in another). Fractions were analyzed using GC-MS, and were found to be unique in composition. The lethality of these fractions was tested on Tribolium castaneum, Tribolium confusum, and Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae). Fractions were tested at concentrations ranging from 5–260 mg/ml to screen for efficacy against adults for durations of 2–8 hr sprayed on concrete arenas. In addition, a separate assay evaluated adult emergence of larvae after 6 wk with supplemental food in arenas, while repellency was evaluated against four stored product insect species in a laminar wind tunnel. A greenhouse gas (GHG) emissions life cycle assessment was also performed, which found the use of the bio-oil fraction could reduce GHG emissions associated with the insecticide supply chain by 25–61% relative to a fossil-fuel based insecticide or pyrethroid. While adults were largely unaffected, we found that larval emergence was significantly suppressed compared to controls by roughly half or more. We also determined that there was minimal repellency to most fractions by most species. We conclude that the use of bio-oil fractions is a climate-friendly choice that may support IPM programs.
Powerful Identification of Large Quantitative Trait Loci Using Genome-Wide R/glmnet-Based Regression
Authors: Yang Li’ang , Qu Qiannan , Hao Zhiyu , Sha Ke , Li Ziyu , Li Shuling 
Published: February 2022

AbstractR/glmnet has been successfully applied to jointly mapped multiple quantitative trait loci for linkage analysis, along with statistical inference for quantitative trait loci candidates with nonzero genetic effects using R/lm for normally distributed traits, R/glm for discrete traits, and R/coxph for survival times. In this study, we extended R/glmnet to a genome-wide association study by means of parallel computation. A multi-locus genome-wide association study for high-throughput single-nucleotide polymorphisms was implemented in the “Multi-Runking” software written within the R workspace. This software can better detect common and large quantitative trait nucleotides and more accurately estimate than genome-wide mixed model analysis for one single-nucleotide polymorphism at a time and linear mixed models-least absolute shrinkage and selection operator. Its applicability and utility were demonstrated by multi-locus genome-wide association studies for the simulated and real traits distributed normally, binary traits, and survival times.
In a Storm of Lies and Half-truths
Authors: Anderson Janet , Duerr Benjamin 
Published: February 2022

Abstract
Media professionals are increasingly confronted with misinformation and disinformation, which impedes their professional responsibility to communicate the truth. Institutions such as the International Criminal Court are critically dependent on public legitimacy and state support to achieve their function, and yet, may be vulnerable to harmful narratives which erode these vital pillars. Using the example of the Kenya situation, this comment describes how such narratives may be constructed and employed and identifies lessons for the ICC in working better with media professionals to ensure that these false information storms can be weathered.
Sustainable Seafood Consumption in Action: Reinvigorating Consumers’ Right to Information in a Borderless Digital World
Authors: He Juan 
Published: February 2022

ABSTRACT
Sustainable consumption is a core pillar to give effect to Goal 12 of the 2030 Agenda for Sustainable Development adopted by the United Nations in 2015. This article identifies consumers’ right to information as a legal conduit to integrate consumer interests with those of industry and regulatory stakeholders through globalized and digitized supply chains. Drawing on the momentum for integration in global fisheries management, the article studies the rise and proliferation of transnational governance models for information to secure legal and sustainable seafood supplies. It critically evaluates the reasons for and consequences of less-than-full engagement and legal protection of consumers in major seafood retail markets, including the European Union and the USA. Their existing seafood traceability systems fail to make sufficient information available to consumers, despite the ability to trace imported seafood to the origin of catch. As the goal of sustainable consumption hinges on consumer choice in an increasingly borderless market, the unavoidable challenge is to enhance consumer-facing traceability and transparency.
Population sizes and activity patterns of little brown myotis in Yellowstone National Park
Authors: Waag Austin G , Treanor John J , Kropczynski Jess N , Johnson Joseph S 
Published: February 2022

AbstractThe spread of white-nose syndrome into western North America has caused concerns that bat species inhabiting the region will soon experience population declines like those seen to the east. However, much of the region lacks baseline estimates of abundance for bats believed to be susceptible to WNS due to a scarcity of known hibernacula, where populations are traditionally monitored. The goal of this study was to determine the abundance, roost fidelity, and activity patterns of summer colonies of female little brown myotis (Myotis lucifugus) in an area with no known hibernacula. To accomplish this, we subcutaneously implanted passive integrated transponder (PIT) tags into 297 female little brown myotis from 2015 to 2018 and installed radio-frequency identification (RFID) readers and antennas inside three maternity roosts in Yellowstone National Park. Bats occupied RFID-monitored roosts on 32% of days and were never detected at maternity roosts located &gt; 16 km from where they were tagged. Roost fidelity varied throughout summer and was greatest during late gestation and early lactation. This allowed us to combine nightly scans of RFID-tagged bats with visual emergence counts to estimate the population of bats using two roosts located &gt;16 km apart during 2017–2018. Population estimates of both colonies were markedly higher (N* = 208 ± 6 bats and N* = 836 ± 67 bats during 2018) than the number of bats seen during evening emergence (high counts of 127 and 222, respectively). Nocturnal visits of tagged bats to these roosts increased around the time of parturition, indicative of bats returning to nurse young. These data show that emergence count and PIT tag data can be combined to monitor bat population abundance and activity patterns in areas where hibernacula are absent or where their locations are unknown.
The relationship of centralized pain in fibromyalgia syndrome with sleep, fatigue and quality of life
Authors: Unal-Ulutatar Cagri , Ozsoy-Unubol Tugba 
Published: February 2022

Abstract

Objectives
The aim of this study was to examine the central role of pain in patients’ lives by evaluating the relationship between the centralization of pain and clinical and functional parameters.

Methods
Adult patients aged 18–70 diagnosed with FM were included in the study. The Fibromyalgia Impact Questionnaire (FIQ) was used to assess the severity of FM, and the Centrality of Pain Scale (COPS) was used to assess pain centralization. The European Quality of Life Scale 5 Dimension (EQ-5D) assessed quality of life, the Jenkins Sleep Scale (JSS-TR) sleep, and the Beck Depression Inventory (BDI) depression.Spearman correlation coefficient (rho) was used to examine the relationship between COPS scores and other parameters, and p &lt; .05 was considered significant.

Results
One hundred and sixty-five FM patients (143 female) were included in the study. The mean age of the patients was 43.7 ± 10.1 years, and the mean disease duration was 4.8 ± 7.8 years. Centrality of pain was found to be related to FIQ (rho = 0.59, p = .0005), EQ-5D (rho = −0.53, p = .0005), JSS-TR (rho = 0.43, p = .0005), and BDI (rho = 0.41, p = .0005).

Conclusion
Centralization of pain in FM was more common in patients with high disease severity, poor quality of life, and sleep and depression problems.
The prevalence of locomotive syndrome and its associated factors in patients with Type 2 diabetes mellitus
Authors: Handa Makoto , Kato Satoshi , Sakurai Goro , Yabe Takuya , Demura Satoru , Takeshita Yumie , Kanamori Takehiro , Nakano Yujiro , Shinmura Kazuya , Yokogawa Noriaki , Kashihara Naoko , Yahata Tetsutaro , Takamura Toshinari , Tsuchiya Hiroyuki 
Published: February 2022

ABSTRACTObjectivesWe investigated the prevalence of locomotive syndrome (LS) and related musculoskeletal diseases [osteoarthritis (OA), lumbar spondylosis, and spinal alignment] in Type 2 diabetes mellitus (DM) patients.MethodsClinical data were collected from 101 patients (55 males; 46 females) admitted to our hospital for diabetes education from October 2018 to April 2021. Patients underwent full-spine and whole-legs standing radiography and physical measurements (10-m walking and grip strength tests and three LS risk tests).ResultsThe estimated prevalence of LS was 86.1% (Stage 1: 44.5%, Stage 2: 41.6%), lumbar spondylosis was 11.9%, and hip, knee, and ankle OA were 16.9%, 51.5%, and 12.9%, respectively. Multiple logistic regression analysis identified grip strength [odds ratio (OR) = 0.89, confidence interval (CI) = 0.83–0.94], diabetic retinopathy (OR = 5.85, CI = 1.64–20.78), knee OA (OR = 3.34, CI = 1.11–10.02), and a sagittal vertical axis &gt;40 mm (OR = 3.42, CI = 1.13–10.39) as significantly associated risk factors for worsening LS in Type 2 DM patients.ConclusionsThis study clarified the epidemiological indicators of LS and associated factors in DM patients. Exercise therapy and DM management are effective strategies to reduce the occurrence and progression of LS.
Clinical efficacy of alternative TNF inhibitor and secukinumab between primary non-responder and secondary non-responder of prior TNF inhibitor in ankylosing spondylitis
Authors: Min Hong Ki , Kim Hae-Rim , Lee Sang-Heon , Hong Yeon Sik , Kim Moon-Young , Park Sung-Hwan , Kang Kwi Young 
Published: February 2022

ABSTRACT

Objectives
To compare the drug retention times and clinical efficacy of alternative tumour necrosis factor inhibitors (TNFi) and secukinumab in primary and secondary non-responders with ankylosing spondylitis (AS).

Methods
AS patients treated with biologics and enrolled in the Korean College of Rheumatology Biologics registry were examined. Patients who did not respond to previous TNFi treatment were defined as primary and secondary non-responders. Data regarding drug discontinuation and clinical efficacy were collected after 1 year. Kaplan–Meier and Cox regression analyses were performed to compare drug survival and associated factors. Logistic regression analyses were conducted to compare the clinical efficacy secukinumab with that of alternative TNFi.

Results
In total, 124 patients (83 receiving alternative TNFi and 41 receiving secukinumab) had biologic changes due to clinical inefficacy. Drug retention rates in the alternative TNFi and secukinumab groups were similar (P = 0.096). However, subgroup analyses including only secondary non-responders revealed that secukinumab users showed a higher hazard ratio (HR) for drug discontinuation (HR = 3.77, P = 0.045). In addition, secukinumab was negatively associated with achieving BASDAI50 or a major improvement in the ASDAS.

Conclusion
Alternative TNFi showed better drug retention and clinical efficacy in AS patients experiencing previous TNFi failure, in secondary non-responders. Therefore, alternative TNFi may be a more suitable treatment for secondary non-responders.
DNA methylation cues in nucleosome geometry, stability and unwrapping
Authors: Li Shuxiang , Peng Yunhui , Landsman David , Panchenko Anna R 
Published: February 2022

Abstract
Cytosine methylation at the 5-carbon position is an essential DNA epigenetic mark in many eukaryotic organisms. Although countless structural and functional studies of cytosine methylation have been reported, our understanding of how it influences the nucleosome assembly, structure, and dynamics remains obscure. Here, we investigate the effects of cytosine methylation at CpG sites on nucleosome dynamics and stability. By applying long molecular dynamics simulations on several microsecond time scale, we generate extensive atomistic conformational ensembles of full nucleosomes. Our results reveal that methylation induces pronounced changes in geometry for both linker and nucleosomal DNA, leading to a more curved, under-twisted DNA, narrowing the adjacent minor grooves, and shifting the population equilibrium of sugar-phosphate backbone geometry. These DNA conformational changes are associated with a considerable enhancement of interactions between methylated DNA and the histone octamer, doubling the number of contacts at some key arginines. H2A and H3 tails play important roles in these interactions, especially for DNA methylated nucleosomes. This, in turn, prevents a spontaneous DNA unwrapping of 3–4 helical turns for the methylated nucleosome with truncated histone tails, otherwise observed in the unmethylated system on several microseconds time scale.