bluuebunny/crossref_metadata_2025_split huggingface dataset:
Best practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease
Authors: Marshall Christian R. , Chowdhury Shimul , Taft Ryan J. , Lebo Mathew S. , Buchan Jillian G. , Harrison Steven M. , Rowsey Ross , Klee Eric W. , Liu Pengfei , Worthey Elizabeth A. , Jobanputra Vaidehi , Dimmock David , Kearney Hutton M. , Bick David , Kulkarni Shashikant , Taylor Stacie L. , Belmont John W. , Stavropoulos Dimitri J. , Lennon Niall J. ,   Medical Genome Initiative
Published: October 2020

AbstractWhole-genome sequencing (WGS) has shown promise in becoming a first-tier diagnostic test for patients with rare genetic disorders; however, standards addressing the definition and deployment practice of a best-in-class test are lacking. To address these gaps, the Medical Genome Initiative, a consortium of leading healthcare and research organizations in the US and Canada, was formed to expand access to high-quality clinical WGS by publishing best practices. Here, we present consensus recommendations on clinical WGS analytical validation for the diagnosis of individuals with suspected germline disease with a focus on test development, upfront considerations for test design, test validation practices, and metrics to monitor test performance. This work also provides insight into the current state of WGS testing at each member institution, including the utilization of reference and other standards across sites. Importantly, members of this initiative strongly believe that clinical WGS is an appropriate first-tier test for patients with rare genetic disorders, and at minimum is ready to replace chromosomal microarray analysis and whole-exome sequencing. The recommendations presented here should reduce the burden on laboratories introducing WGS into clinical practice, and support safe and effective WGS testing for diagnosis of germline disease.
CRY-dependent plasticity of tetrad presynaptic sites in the visual system of Drosophila at the morning peak of activity and sleep
Authors: Damulewicz Milena , Woźnicka Olga , Jasińska Małgorzata , Pyza Elżbieta 
Published: October 2020

AbstractTetrad synapses are formed between the retina photoreceptor terminals and postsynaptic cells in the first optic neuropil (lamina) of Drosophila. They are remodelled in the course of the day and show distinct functional changes during activity and sleep. These changes result from fast degradation of the presynaptic scaffolding protein Bruchpilot (BRP) by Cryptochrome (CRY) in the morning and depend on BRP-170, one of two BRP isoforms. This process also affects the number of synaptic vesicles, both clear and dense-core, delivered to the presynaptic elements. In cry01 mutants lacking CRY and in brpΔ170, the number of synaptic vesicles is lower in the morning peak of activity than during night-sleep while in wild-type flies the number of synaptic vesicles is similar at these two time points. CRY may also set phase of the circadian rhythm in plasticity of synapses. The process of synapse remodelling stimulates the formation of clear synaptic vesicles in the morning. They carry histamine, a neurotransmitter in tetrad synapses and seem to be formed from glial capitate projections inside the photoreceptor terminals. In turn dense-core vesicles probably carry synaptic proteins building the tetrad presynaptic element.
Reduced striatal vesicular monoamine transporter 2 in REM sleep behavior disorder: imaging prodromal parkinsonism
Authors: Beauchamp Leah C. , Villemagne Victor L. , Finkelstein David I. , Doré Vincent , Bush Ashley I. , Barnham Kevin J. , Rowe Christopher C. 
Published: October 2020

AbstractMotor deficits in parkinsonism are caused by degeneration of dopaminergic nigral neurons. The success of disease-modifying therapies relies on early detection of the underlying pathological process, leading to early interventions in the disease phenotype. Healthy (n = 16), REM sleep behavior disorder (RBD) (n = 14), dementia with Lewy bodies (n = 10), and Parkinson’s disease (PD) (n = 20) participants underwent 18F-AV133 vesicular monoamine transporter type-2 (VMAT2) PET to determine the integrity of the nigrostriatal pathway. Clinical, neurophysiological and neuropsychological testing was conducted to assess parkinsonian symptoms. There was reduced VMAT2 levels in RBD participants in the caudate and putamen, indicating nigrostriatal degeneration. RBD patients also presented with hyposmia and anxiety, non-motor symptoms associated with parkinsonism. 18F-AV133 VMAT2 PET allows identification of underlying nigrostriatal degeneration in RBD patients. These findings align with observations of concurrent non-motor symptoms in PD and RBD participants of the Parkinson’s Progression Markers Initiative. Together, these findings suggest that RBD subjects have prodromal parkinsonism supporting the concept of conducting neuroprotective therapeutic trials in RBD-enriched cohorts. Ongoing longitudinal follow-up of these subjects will allow us to determine the time-window of clinical progression.
Mesoscale structures in amorphous silks from a spider’s orb-web
Authors: Riekel Christian , Burghammer Manfred , Rosenthal Martin 
Published: October 2020

AbstractOf the 7–8 silk fibers making up an orb-web only the hierarchical structural organization of semicrystalline radial fibers -composed of major ampullate silk- has been studied in detail, given its fascinating mechanical features. While major ampullate silk’s nanofibrillar morphology is well established, knowhow on mesoscale (> 50–100 nm) assembly and its contribution to mechanical performance is limited. Much less is known on the hierarchical structural organization of other, generally less crystalline fibers contributing to an orb-webs’ function. Here we show by scanning X-ray micro&nanodiffraction that two fully amorphous, fine silk fibers from the center of an orb-web have different mesoscale features. One of the fibers has a fibrillar composite structure resembling stiff egg case silk. The other fiber has a skin–core structure based on a nanofibrillar ribbon wound around a disordered core. A fraction of nanofibrils appears to have assembled into mesoscale fibrils. This fiber becomes readily attached to the coat of major ampullate silk fibers. We observe that a detached fiber has ripped out the glycoprotein skin-layer containing polyglycine II nanocrystallites. The anchoring of the fiber in the coat suggests that it could serve for strengthening the tension and cohesion of major ampullate silk fibers.
Nature-based activities improve the well-being of older adults
Authors: Sia Angelia , Tam Wilson W. S. , Fogel Anna , Kua Ee Heok , Khoo Kenneth , Ho Roger C. M. 
Published: October 2020

AbstractCurrent literature shows that interaction with urban greenery can have a wide range of positive health outcomes. Targeted nature-based programs, such as therapeutic horticulture, have been shown to result in multiple health benefits for older adults residing in temperate environments, but much less research has been carried out on populations with different phenotypes, such as older Asian adults in the tropics. The current study investigated the effects of a 24-session therapeutic horticulture program on 47 older participants in Singapore, with an experimental pretest posttest design. We found that participants maintained healthy sleep patterns and psychological health, as well as showed reduced anxiety and improved cognitive functioning (p < 0.05). In addition, they reported an increase in mean happiness score after each session. This study provides new evidence using a comprehensive set of indicators across the affective, cognitive, functional, psychosocial and physical domains, supporting current literature on the benefits of nature programs, with a novel focus on tropical environments. It provides evidence that the nature-based intervention has the potential to be translated to programs to benefit older adults in the tropics.
Genomic analysis of European bovine Staphylococcus aureus from clinical versus subclinical mastitis
Authors: Hoekstra Jurriaan , Zomer Aldert L. , Rutten Victor P. M. G. , Benedictus Lindert , Stegeman Arjan , Spaninks Mirlin P. , Bennedsgaard Torben W. , Biggs Andrew , De Vliegher Sarne , Mateo Demetrio Herrera , Huber-Schlenstedt Reglindis , Katholm Jørgen , Kovács Péter , Krömker Volker , Lequeux Guillaume , Moroni Paolo , Pinho Luís , Smulski Sebastian , Supré Karlien , Swinkels Jantijn M. , Holmes Mark A. , Lam Theo J. G. M. , Koop Gerrit 
Published: October 2020

AbstractIntramammary infections (IMI) with Staphylococcus aureus are a common cause of bovine mastitis and can result in both clinical (CM) or subclinical mastitis (SCM). Although bacterial isolates of S. aureus differ in their virulence potential it is largely unclear which bacterial virulence factors are responsible for increased clinical severity. We performed a genome wide association study and used a generalized linear mixed model to investigate the correlation between gene carriage, lineage and clinical outcome of IMI in a collection of S. aureus isolates from cattle with CM (n = 125) and SCM (n = 151) from 11 European countries. An additional aim was to describe the genetic variation of bovine S. aureus in Europa. The dominant lineages in our collection were clonal complex (CC) 151 (81/276, 29.3%), CC97 (54/276, 19.6%), CC479 (32/276, 11.6%) and CC398 (19/276, 6.9%). Virulence and antimicrobial resistance (AMR) gene carriage was highly associated with CC. Among a selection of nine virulence and AMR genes, CC151, CC479 and CC133 carried more virulence genes than other CCs, and CC398 was associated with AMR gene carriage. Whereas CC151, CC97 were widespread in Europe, CC479, CC398 and CC8 were only found in specific countries. Compared to CC151, CC479 was associated with CM rather than SCM (OR 3.62; 95% CI 1.38–9.50) and the other CCs were not. Multiple genes were associated with CM, but due to the clustering within CC of carriage of these genes, it was not possible to differentiate between the effect of gene carriage and CC on clinical outcome of IMI. Nevertheless, this study demonstrates that characterization of S. aureus CC and virulence genes helps to predict the likelihood of the occurrence of CM following S. aureus IMI and highlights the potential benefit of diagnostics tools to identify S. aureus CC during bovine mastitis.
Inflammatory indexes as predictive factors for platinum sensitivity and as prognostic factors in recurrent epithelial ovarian cancer patients: a MITO24 retrospective study
Authors: Farolfi Alberto , Scarpi Emanuela , Greco Filippo , Bergamini Alice , Longo Lucia , Pignata Sandro , Casanova Claudia , Cormio Gennaro , Bologna Alessandra , Orditura Michele , Zavallone Laura , Attademo Laura , Gallà Valentina , Franzese Elisena , Pigozzi Eva , Loizzi Vera , Giorda Giorgio , Giardina Donatella , Cioffi Raffaella , De Giorgi Ugo 
Published: October 2020

AbstractNeutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory index (SII) are prognostic factors in epithelial ovarian cancer (EOC). Their predictive value for platinum-sensitivity and their role in recurrent EOC are unknown. A total of 375 EOC patients were retrospectively analyzed. The correlation between baseline NLR and SII, and platinum-free interval (PFI) according to first line bevacizumab treatment were analyzed using logistic regression analyses adjusted for baseline patient characteristics. Subsequently NLR and SII calculated before second line treatment initiation were evaluated to identify a potential correlation with progression-free survival (PFS) and overall survival (OS) in platinum-sensitive and in platinum-resistant population. In multivariate analysis, NLR ≥ 3 is an independent predictive factor for PFI at 6 months in the chemotherapy group (OR = 2.77, 95% CI 1.38–5.56, p = 0.004), not in bevacizumab treated patients. After having adjusted for ECOG performance status, histology, ascites, bevacizumab treatment at second line and BRCA status, NLR ≥ 3 and SII ≥ 730 are significantly associated with worse OS in platinum-sensitive (HR = 2.69, 95% CI 1.60–4.53, p = 0.002; HR = 2.11, 95% CI 1.29–3.43, p = 0.003, respectively), not in platinum-resistant EOC patients. Low NLR is an independent predictive factor for platinum-sensitivity in patients treated without bevacizumab. NLR and SII are prognostic factors in recurrent platinum-sensitive EOC patients.
Limited usefulness of serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels for gastrointestinal and whole-body cancer screening
Authors: Sekiguchi Masau , Matsuda Takahisa 
Published: October 2020

AbstractThe diagnostic performance of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels for multiple-organ cancer screening has not been fully elucidated. However, they are widely used for real-world opportunistic screening of multiple-organ cancers. This study aimed to examine the diagnostic performance of these serum markers in multiple-organ cancer screening. Data from asymptomatic individuals subjected to opportunistic cancer screening were analyzed. The diagnostic performance of CEA and CA 19-9 was assessed for (A) upper/lower gastrointestinal cancers and (B) whole-body cancers (including both gastrointestinal and other organ cancers) using the results of upper/lower gastrointestinal endoscopy and whole-body imaging as reference. Data from 12,349 and 7616 screened individuals were used to assess the diagnostic performance of CEA and CA 19-9 for (A) and (B), respectively. For (A), the sensitivity and positive predictive value (PPV) of CEA (cut-off: 5 ng/mL) were 7.8% and 3.7%, respectively; those of CA19-9 (cut-off: 37 U/mL) were 7.4% and 2.7%, respectively. For (B), the sensitivity and PPV of CEA were 6.6% and 4.1%, respectively, and those of CA19-9 were 10.8% and 5.8%, respectively. Considering even multiple cancers, the sensitivity and PPV of CEA and CA 19-9 were low, thus confirming their limited usefulness in multiple-organ cancer screening.
From whole-mount to single-cell spatial assessment of gene expression in 3D
Authors: Waylen Lisa N. , Nim Hieu T. , Martelotto Luciano G. , Ramialison Mirana 
Published: October 2020

AbstractUnravelling spatio-temporal patterns of gene expression is crucial to understanding core biological principles from embryogenesis to disease. Here we review emerging technologies, providing automated, high-throughput, spatially resolved quantitative gene expression data. Novel techniques expand on current benchmark protocols, expediting their incorporation into ongoing research. These approaches digitally reconstruct patterns of embryonic expression in three dimensions, and have successfully identified novel domains of expression, cell types, and tissue features. Such technologies pave the way for unbiased and exhaustive recapitulation of gene expression levels in spatial and quantitative terms, promoting understanding of the molecular origin of developmental defects, and improving medical diagnostics.
Comparing rates of introgression in parasitic feather lice with differing dispersal capabilities
Authors: Doña Jorge , Sweet Andrew D. , Johnson Kevin P. 
Published: October 2020

AbstractOrganisms vary in their dispersal abilities, and these differences can have important biological consequences, such as impacting the likelihood of hybridization events. However, there is still much to learn about the factors influencing hybridization, and specifically how dispersal ability affects the opportunities for hybridization. Here, using the ecological replicate system of dove wing and body lice (Insecta: Phthiraptera), we show that species with higher dispersal abilities exhibited increased genomic signatures of introgression. Specifically, we found a higher proportion of introgressed genomic reads and more reticulated phylogenetic networks in wing lice, the louse group with higher dispersal abilities. Our results are consistent with the hypothesis that differences in dispersal ability might drive the extent of introgression through hybridization.
Myostatin regulates fatty acid desaturation and fat deposition through MEF2C/miR222/SCD5 cascade in pigs
Authors: Ren Hongyan , Xiao Wei , Qin Xingliang , Cai Gangzhi , Chen Hao , Hua Zaidong , Cheng Cheng , Li Xinglei , Hua Wenjun , Xiao Hongwei , Zhang Liping , Dai Jiali , Zheng Xinmin , Zhu Zhe , Qian Chong , Yao Jie , Bi Yanzhen 
Published: October 2020

AbstractMyostatin (MSTN), associated with the “double muscling” phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.
Spin–orbit torque nano-oscillator with giant magnetoresistance readout
Authors: Chen Jen-Ru , Smith Andrew , Montoya Eric A. , Lu Jia G. , Krivorotov Ilya N. 
Published: October 2020

AbstractSpin-orbit torque nano-oscillators based on bilayers of ferromagnetic and nonmagnetic metals are ultra-compact current-controlled microwave signal sources. They are attractive for practical applications such as microwave assisted magnetic recording, neuromorphic computing, and chip-to-chip wireless communications. However, a major drawback of these devices is low output microwave power arising from the relatively small anisotropic magnetoresistance of the ferromagnetic layer. Here we experimentally show that the output power of a spin-orbit torque nano-oscillator can be significantly enhanced without compromising its structural simplicity. Addition of a ferromagnetic reference layer to the oscillator allows us to employ current-in-plane giant magnetoresistance to boost the output power of the device. This enhancement of the output power is a result of both large magnitude of giant magnetoresistance compared to that of anisotropic magnetoresistance and their different angular dependencies. Our results hold promise for practical applications of spin-orbit torque nano-oscillators.
CircSERPINE2 weakens IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis
Authors: Zhang Qingpu , Qiao Xiaomiao , Xia Wenwei 
Published: October 2020

Abstract
The dysregulated circular RNAs (circRNAs) are relevant to the development of osteoarthritis (OA). The circRNA serpin family E member 2 (circSERPINE2) is dysregulated in OA, while the role and mechanism of circSERPINE2 in OA are largely unknown. The aim of our research is to explore how and whether circSERPINE2 regulates interleukin-1β (IL-1β)-caused chondrocyte damage in OA. In the present study, the chondrocytes (CHON-001 cells) were exposed to IL-1β to mimic the injury in OA. CircSERPINE2, microRNA-495 (miR-495) and transforming growth factor-β receptor 2 (TGFBR2) abundances were detected via quantitative reverse-transcription polymerase chain reaction (qRT-PCR) or Western blot. Cell apoptosis was assessed via viability, apoptotic rate and caspase-3 activity. Extracellular matrix was investigated by levels of Sry-type high-mobility-group box 9 (SOX9), collagen type II α 1 (COL2A1) and Aggrecan using Western blot. The interaction among circSERPINE2, miR-495 and TGFBR2 was assessed via dual-luciferase reporter analysis and RNA immunoprecipitation (RIP). The results showed that circSERPINE2 expression was reduced in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 overexpression mitigated IL-1β-caused apoptosis and extracellular matrix degradation. miR-495 was targeted by circSERPINE2 and up-regulated in OA patients and IL-1β-treated chondrocytes. miR-495 up-regulation reversed overexpression of circSERPINE2-mediated inhibition of apoptosis and extracellular matrix degradation. TGFBR2 was targeted by miR-495 and lowly expressed in OA patients and IL-1β-treated chondrocytes. CircSERPINE2 could mediate TGFBR2 expression by binding with miR-495. As a conclusion, circSERPINE2 attenuated IL-1β-caused apoptosis and extracellular matrix degradation of chondrocytes by regulating miR-495/TGFBR2 axis, indicating a new target for OA treatment.
Eicosanoid blood vessel regulation in physiological and pathological states
Authors: Imig John D. 
Published: October 2020

AbstractArachidonic acid can be metabolized in blood vessels by three primary enzymatic pathways; cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 (CYP). These eicosanoid metabolites can influence endothelial and vascular smooth muscle cell function. COX metabolites can cause endothelium-dependent dilation or constriction. Prostaglandin I2 (PGI2) and thromboxane (TXA2) act on their respective receptors exerting opposing actions with regard to vascular tone and platelet aggregation. LO metabolites also influence vascular tone. The 12-LO metabolite 12S-hydroxyeicosatrienoic acid (12S-HETE) is a vasoconstrictor whereas the 15-LO metabolite 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA) is an endothelial-dependent hyperpolarizing factor (EDHF). CYP enzymes produce two types of eicosanoid products: EDHF vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-HETE. The less-studied cross-metabolites generated from arachidonic acid metabolism by multiple pathways can also impact vascular function. Likewise, COX, LO, and CYP vascular eicosanoids interact with paracrine and hormonal factors such as the renin–angiotensin system and endothelin-1 (ET-1) to maintain vascular homeostasis. Imbalances in endothelial and vascular smooth muscle cell COX, LO, and CYP metabolites in metabolic and cardiovascular diseases result in vascular dysfunction. Restoring the vascular balance of eicosanoids by genetic or pharmacological means can improve vascular function in metabolic and cardiovascular diseases. Nevertheless, future research is necessary to achieve a more complete understanding of how COX, LO, CYP, and cross-metabolites regulate vascular function in physiological and pathological states.