bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including MERTK, TEK, FGFR2, and FGFR1: a molecular and clinicopathologic analysis
Authors: Liu Yajuan J. , Wang Wenjing , Yeh Jeffrey , Wu Yu , Mantilla Jose G. , Fletcher Christopher D.M. , Ricciotti Robert W. , Chen Eleanor Y. 
Published: September 2020

ABSTRACTTranslocations involving FN1 have been described in a variety of neoplasms, which share the presence of cartilage matrix and a variable extent of calcification. Fusions of FN1 to FGFR1 or FGFR2 have been reported in nine soft tissue chondromas, mostly demonstrated indirectly by FISH analysis. Delineation of FN1 fusions with various partner genes will facilitate our understanding of the pathogenesis and diagnostic classification of these neoplasms. In this study, we present molecular, clinical and pathologic features of 9 cartilaginous soft tissue neoplasms showing a predilection for the TMJ region and the extremities. We analyzed for gene fusions with precise breakpoints using targeted RNA-seq with a 115-gene panel, including FN1, FGFR1 and FGFR2. All 9 cases were positive for a gene fusion, including two novel fusions, FN1-MERTK and FN1-TEK, each in one case, recurrent FN1-FGFR2 in 5 cases, FN1-FGFR1 without the Ig3 domain in one case, and FGFR1-PLAG1 in one case. The breakpoints in the 5’ partner gene FN1 ranged from exons 11-48, retaining the domains of signal peptide, FN1, FN2, and/or FN3, while the 3’partner genes retained the trans-membrane domain, tyrosine kinase domains and /or Ig domain. The tumors with FN1-FGFR1, FN1-FGFR2 and FN1-MERTK fusions are generally characterized by nodular/lobular growth of polygonal to stellate cells within a chondroid matrix, often accompanied by various patterns of calcification. These features resemble those as described for the chondroblastoma-like variant of soft tissue chondroma. Additional histologic findings include calcium pyrophosphate dehydrate deposition and features resembling tenosynovial giant cell tumor. Overall, while the tumors from our series show significant morphologic overlap with chondroblastoma-like soft tissue chondroma, we describe novel findings that expand the morphologic spectrum of these neoplasms and have therefore labeled them as “calcified chondroid mesenchymal neoplasms.” These neoplasms represent a distinct pathologic entity given the presence of recurrent FN1-receptor tyrosine kinase fusions.
Sensitization of cutaneous primary afferents in bone cancer revealed byin vivocalcium imaging
Authors: de Clauser Larissa , Luiz Ana P. , Santana-Varela Sonia , Wood John N. , Sikandar Shafaq 
Published: September 2020

AbstractCancer-induced bone pain (CIBP) is a complex condition comprising components of inflammatory and neuropathic processes, but changes in the physiological response profiles of bone-innervating afferents remain poorly understood. We used a combination of retrograde labelling andin vivocalcium imaging of bone marrow-innervating DRG neurons to determine the contribution of these cells in the establishment and maintenance of CIBP. We found a majority of femoral bone afferent cell bodies in L3 DRG that also express the sodium channel subtype Nav1.8 - a marker of nociceptive neurons- and lack expression of parvalbumin - a marker for proprioceptive primary afferents. Surprisingly, the response properties of bone marrow afferents to both increased intraosseous pressure and acid were unchanged by the presence of cancer. On the other hand, we found increased excitability and polymodality of cutaneous afferents innervating the ipsilateral paw in cancer bearing animals, as well as a behavioral phenotype that suggests changes at the level of the DRG contribute to secondary hypersensitivity.
Feature-based encoding of face identity by single neurons in the human amygdala and hippocampus
Authors: Cao Runnan , Wang Jinge , Lin Chujun , De Falco Emanuela , Peter Alina , Rey Hernan G. , DiCarlo James , Todorov Alexander , Rutishauser Ueli , Li Xin , Brandmeir Nicholas J. , Wang Shuo 
Published: September 2020

AbstractNeurons in the human amygdala and hippocampus that are selective for the identity of specific people are classically thought to encode a person’s identity invariant to visual features (e.g., skin tone, eye shape). However, it remains largely unknown how visual information from higher visual cortical areas is translated into such a semantic representation of an individual person. Here, we show that some amygdala and hippocampal neurons are selective to multiple different unrelated face identities based on shared visual features. The encoded identities form clusters in the representation of a deep neural network trained to recognize faces. Contrary to prevailing views, these neurons thus represent an individual’s face with a visual feature-based code rather than one based on association with known concepts. Feature neurons encoded faces regardless of their identity, race, gender, familiarity, or pixel-level visual features; and the region of feature space to which feature neurons are tuned predicted their response to new face stimuli. Our results reveal a new class of neurons that bridge the perception-driven representation of facial features in the higher visual cortex with mnemonic semantic representations in the MTL, which may form the basis for declarative memory.
Blockade of Kinin B1receptor counteracts the depressive-like behavior and mechanical allodynia in ovariectomized mice
Authors: de Souza Maciel Izaque , Azevedo Vanessa Machado , Oliboni Patricia , Campos Maria Martha 
Published: September 2020

AbstractMenopause is related to a decline in ovarian estrogen production, affecting the perception of the somatosensory stimulus, changing the immune-inflammatory systems, and triggering depressive symptoms. Inhibition of kinin B1and B2receptors (B1R and B2R) inhibits the depressive-like behavior and mechanical allodynia induced by immune-inflammatory mediators in mice. However, there is no evidence on the role of kinin receptors in depressive-like and nociceptive behavior in female mice submitted to bilateral ovariectomy. This study shows that ovariectomized mice (OVX) developed time-related mechanical allodynia and increased immobility time in the tail suspension test (TST). The genetic deletion of B1R, or the pharmacological blockade by selective kinin B1R antagonist R-715 (acute, i.p), reduced the increase of immobility time and mechanical allodynia induced by ovariectomy. Neither genetic deletion nor pharmacological inhibition of B2R (HOE 140, i.p) prevented the behavioral changes elicited by OVX. Our data suggested a particular modulation of kinin B1R in the nociceptive and depressive-like behavior in ovariectomized mice. Selective inhibition of the B1R receptor may be a new pharmacological target for treating pain and depression symptoms in women on the perimenopause/menopause period.
Early metabolic priming under differing carbon sufficiency conditions influences peach fruit quality development
Authors: Anthony Brendon M. , Chaparro Jacqueline M. , Prenni Jessica E. , Minas Ioannis S. 
Published: September 2020

AbstractCrop load management is an important preharvest factor to balance yield, quality, and maturation in peach. However, few studies have addressed how preharvest factors impact metabolism on fruit of equal maturity. An experiment was conducted to understand how carbon competition impacts fruit internal quality and metabolism in ‘Cresthaven’ peach trees by imposing distinct thinning severities. Fruit quality was evaluated at three developmental stages (S2, S3, S4), while controlling for equal maturity using non-destructive near-infrared spectroscopy. Non-targeted metabolite profiling was used to characterize fruit at each developmental stage from trees that were unthinned (carbon starvation) or thinned (carbon sufficiency). Carbon sufficiency resulted in significantly higher fruit dry matter content and soluble solids concentration at harvest when compared to the carbon starved, underscoring the true impact of carbon manipulation on fruit quality. Significant differences in the fruit metabolome between treatments were observed at S2 when phenotypes were similar, while less differences were observed at S4 when the carbon sufficient fruit exhibited a superior phenotype. This suggests a potential metabolic priming effect on fruit quality when carbon is sufficiently supplied during early fruit growth and development. In particular, elevated levels of catechin may suggest a link between secondary/primary metabolism and fruit quality development.HighlightAn investigation of variable carbon supply conditions in peach fruit reveals that early metabolic priming is associated with quality development
Structural Variants in SARS-CoV-2 Occur at Template-Switching Hotspots
Authors: Chrisman Brianna , Paskov Kelley , Stockham Nate , Tabatabaei Kevin , Jung Jae-Yoon , Washington Peter , Varma Maya , Sun Min Woo , Maleki Sepideh , Wall Dennis P. 
Published: September 2020

ABSTRACTThe evolutionary dynamics of SARS-CoV-2 have been carefully monitored since the COVID-19 pandemic began in December 2019, however, analysis has focused primarily on single nucleotide polymorphisms and largely ignored the role of structural variants (SVs) as well as recombination in SARS-CoV-2 evolution. Using sequences from the GISAID database, we catalogue over 100 insertions and deletions in the SARS-CoV-2 consensus sequences. We hypothesize that these indels are artifacts of imperfect homologous recombination between SARS-CoV-2 replicates, and provide four independent pieces of evidence. (1) The SVs from the GISAID consensus sequences are clustered at specific regions of the genome. (2) These regions are also enriched for 5’ and 3’ breakpoints in the transcription regulatory site (TRS) independent transcriptome, presumably sites of RNA-dependent RNA polymerase (RdRp) template-switching. (3) Within raw reads, these structural variant hotspots have cases of both high intra-host heterogeneity and intra-host homogeneity, suggesting that these structural variants are both consequences ofde novorecombination events within a host and artifacts of previous recombination. (4) Within the RNA secondary structure, the indels occur in “arms” of the predicted folded RNA, suggesting that secondary structure may be a mechanism for TRS-independent template-switching in SARS-CoV-2 or other coronaviruses. These insights into the relationship between structural variation and recombination in SARS-CoV-2 can improve our reconstructions of the SARS-CoV-2 evolutionary history as well as our understanding of the process of RdRp template-switching in RNA viruses.
COVID-19: Impact on the health and wellbeing of ex-serving personnel (Veterans-CHECK) protocol paper
Authors: Sharp Marie-Louise , Serfioti Danai , Jones Margaret , Burdett Howard , Pernet David , Hull Lisa , Murphy Dominic , Stevelink Sharon , Wessely Simon , Fear Nicola T 
Published: September 2020

AbstractIntroductionWe will use a sub-sample of a current longitudinal study to investigate the impact of COVID-19 on the health and wellbeing of ex-service personnel in the UK. The study will provide evidence for the UK Office of Veterans’ Affairs (OVA), UK stakeholders supporting the ex-service community, and evidence to inform our international counterparts working with ex-service communities in allied countries regarding the impact of COVID-19 on the health and wellbeing of ex-service personnel.Methods and analysisParticipants were eligible to participate if they lived in the UK, had Regular service history from the UK Armed Forces and had previously completed the King’s Centre for Military Health Research (KCMHR) Health and Wellbeing survey between 2014–2016. Participants who met these criteria were recruited through email to take part in an online questionnaire. The study provides additional quantitative longitudinal data on this sub-sample. Data are being collected June 2020-September 2020. Specific measures are used to capture participants’ COVID-19 experiences, health and wellbeing status and lifestyle behaviours. Other key topics will include questions regarding the impact of COVID-19 pandemic on employment, finances, volunteering, charitable giving, accommodation and living arrangements, help-seeking behaviours, as well as any potential positive changes during this period.Ethics and DisseminationEthical approval has been gained from King’s College London Research Ethics Committee (Ref: HR-19/20–18626). Participants were provided with information and agreed to a series of consent statements before enrolment. Data are kept on secure servers with access to personally identifiable information limited. Findings will be disseminated to the OVA, UK ex-service stakeholders and international research institutions through stakeholder meetings, project reports and scientific publications.Strengths and limitations of this studyStrengths include recruitment from a population where underlying characteristics are known, and longitudinal data is held on their health and wellbeing.There has been rapid roll-out of the survey to ensure relevance for participants’ COVID-19 experiences and use of validated measures for mental health and wellbeing outcomes.Study limitations include recruitment from a specific cohort; hence the study cannot comment on the impact of COVID-19 in other veteran populations.
Deep Learning Image Analysis of Benign Breast Disease to Identify Subsequent Risk of Breast Cancer
Authors: Vellal Adithya D , Sirinukunwattana Korsuk , Kensler Kevin H , Baker Gabrielle M , Stancu Andreea L , Pyle Michael E , Collins Laura C , Schnitt Stuart J , Connolly James L , Veta Mitko , Eliassen A Heather , Tamimi Rulla M , Heng Yujing J 
Published: September 2020

AbstractBackgroundNew biomarkers of risk may improve breast cancer risk prediction. We developed a computational pathology method to segment benign breast disease (BBD) whole slide images (WSIs) into epithelium, fibrous stroma, and fat. We applied our method to the BBD breast cancer nested case-control study within the Nurses’ Health Studies to assess whether computer-derived tissue composition or a morphometric signature was associated with subsequent risk of breast cancer.MethodsTissue segmentation and nuclei detection deep-learning networks were established and applied to 3795 WSIs from 293 cases who developed breast cancer and 1132 controls who did not. Percentages of each tissue region were calculated and 615 morphometric features were extracted. Elastic net regression was used to create a breast cancer morphometric signature. Associations between breast cancer risk factors and age-adjusted tissue composition among controls were assessed using analysis of covariance. Unconditional logistic regression, adjusting for the matching factors, BBD histological subtypes, parity, menopausal status, and BMI evaluated the relationship between tissue composition and breast cancer risk.ResultsAmong controls, BBD subtypes, parity, and number of births were differentially associated with all three tissue regions (p< 0.05); select regions were associated with childhood body size, BMI, age of menarche, and menopausal status (p< 0.05). Higher proportion of epithelial tissue was associated with increased breast cancer risk (OR = 1.39, 95% CI 0.91–2.14 comparing highest and lowest quartiles; p-trend< 0.05). No morphometric signature was associated with breast cancer.ConclusionThe amount of epithelial tissue may be incorporated into risk assessment models to improve breast cancer risk prediction.
Correction in Active Cases Data of COVID-19 for the US States by Analytical study
Authors: Solanki Ravi , Varshney Anubhav , Gourishetty Raveesh , Minase Saniya , Sivadas Namitha , Mahajan Ashutosh 
Published: September 2020

AbstractThe reported recovered cases for many US states are low which could be due to difficulties in keeping track of recoveries and resulted in higher numbers for the reported active cases than the actual numbers on the ground. These incorrect numbers can lead to misleading inferences. In this work, based on the typical range of recovery rate of COVID-19, we estimate the active data from the total cases and death cases and bring out a correction for the data for all the US states reported on worldometer.
Multiplexed Detection and Quantification of Human Antibody Response to COVID-19 Infection Using a Plasmon Enhanced Biosensor Platform
Authors: Cady Nathaniel C. , Tokranova Natalya , Minor Armond , Nikvand Nima , Strle Klemen , Lee William T. , Page William , Guignon Ernest , Pilar Arturo , Gibson George N. 
Published: September 2020

ABSTRACTThe 2019 SARS CoV-2 (COVID-19) pandemic has highlighted the need for rapid and accurate tests to diagnose acute infection and determine immune response to infection. In this work, a multiplexed grating-coupled fluorescent plasmonics (GC-FP) biosensing approach was shown to have 100% selectivity and sensitivity (n = 23) when measuring serum IgG levels against three COVID-19 antigens (spike S1, spike S1S2, and the nucleocapsid protein). The entire biosensing procedure takes less than 30 min, making it highly competitive with well-established ELISA and immunofluorescence assays. GC-FP is quantitative over a large dynamic range, providing a linear response for serum titers ranging from 1:25 to 1:1,600, and shows high correlation with both ELISA and a Luminex-based microsphere immunoassay (MIA) (Pearson r > 0.9). Compatibility testing with dried blood spot samples (n = 63) demonstrated 100% selectivity and 86.7% sensitivity. A machine learning (ML) model was trained to classify dried blood spot samples for prior COVID-19 infection status, based on the combined antibody response to S1, S1S2, and Nuc antigens. The ML model yielded 100% selectivity and 80% sensitivity and demonstrated a higher stringency than a single antibody-antigen response. The biosensor platform is flexible and will readily accommodate detection of multiple immunoglobulin isotypes. Further, it uses sub-nanogram quantities of capture ligand and is thus readily modified to include additional antigens, which is shown by the addition of RBD in later iterations of the test. The combination of rapid, multiplexed, and quantitative detection for both blood serum and dried blood spot samples makes GC-FP an attractive biosensor platform for COVID-19 antibody testing.
Striatal Direct Pathway Targets Npas1+Pallidal Neurons
Authors: Cui Qiaoling , Du Xixun , Chang Isaac Y. M. , Pamukcu Arin , Lilascharoen Varoth , Berceau Brianna L. , García Daniela , Hong Darius , Chon Uree , Narayanan Ahana , Kim Yongsoo , Lim Byung Kook , Chan C. Savio 
Published: September 2020

AbstractThe classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway striatal projection neurons (iSPNs), direct-pathway striatal projection neurons (dSPNs) innervate the external globus pallidus (GPe). However, the functions of the latter were not known. In this study, we interrogated the organization principles of striatopallidal projections and their roles in full-body movement in mice (both males and females). In contrast to the canonical motor-promoting response of dSPNs in the dorsomedial striatum (DMSdSPNs), optogenetic stimulation of dSPNs in the dorsolateral striatum (DLSdSPNs) suppressed locomotion. Circuit analyses revealed that dSPNs selectively target Npas1+neurons in the GPe. In a chronic 6-hydroxydopamine lesion model of Parkinson’s disease, the dSPN-Npas1+projection was dramatically strengthened. AsDLSdSPN-Npas1+projection suppresses movement, the enhancement of this projection represents a circuit mechanism for the hypokinetic symptoms of Parkinson’s disease that has not been previously considered. In sum, our results suggest that dSPN input to the GPe is a critical circuit component that is involved in the regulation of movement in both healthy and parkinsonian states.Significance statementIn the classic basal ganglia model, the striatum is described as a divergent structure—it controls motor and adaptive functions through two segregated, opposing output streams. However, the experimental results that show the projection from direct-pathway neurons to the external pallidum have been largely ignored. Here, we showed that this striatopallidal sub-pathway targets a select subset of neurons in the external pallidum and is motor-suppressing. We found that this sub-pathway undergoes changes in a Parkinson’s disease model. In particular, our results suggest that the increase in strength of this sub-pathway contributes to the slowness or reduced movements observed in Parkinson’s disease.
Spatial distribution of Arctic bacterioplankton abundance is linked to distinct water masses and summertime phytoplankton bloom dynamics (Fram Strait, 79°N)
Authors: Cardozo-Mino Magda G. , Fadeev Eduard , Salman-Carvalho Verena , Boetius Antje 
Published: September 2020

AbstractThe Arctic is impacted by climate warming faster than any other oceanic region on Earth. Assessing the baseline of microbial communities in this rapidly changing ecosystem is vital for understanding the implications of ocean warming and sea ice retreat on ecosystem functioning. Using CARD-FISH and semi-automated counting, we quantified 14 ecologically relevant taxonomic groups of bacterioplankton (BacteriaandArchaea) from surface (0-30 m) down to deep waters (2500 m) in summerly ice-covered and ice-free regions of the Fram Strait, the main gateway for Atlantic inflow into the Arctic Ocean. Cell abundances of the bacterioplankton communities in surface waters varied from 105cells mL-1in ice-covered regions to 106cells mL-1in the ice-free regions, and were overall driven by variations in phytoplankton bloom conditions across the Strait. The bacterial classesBacteroidiaandGammaproteobacteriashowed several-fold higher cell abundances under late phytoplankton bloom conditions of the ice-free regions. Other taxonomic groups, such as theRhodobacteraceae,revealed a distinct association of cell abundances with the surface Atlantic waters. With increasing depth (>500 m), the total cell abundances of the bacterioplankton communities decreased by up to two orders of magnitude, while largely unknown taxonomic groups (e.g., SAR324 and SAR202 clades) maintained constant cell abundances throughout the entire water column (ca. 103cells mL-1). This suggests that these enigmatic groups may occupy a specific ecological niche in the entire water column. Our results provide the first quantitative spatial variations assessment of bacterioplankton in the summerly ice-covered and ice-free Arctic water column, and suggest that further shift towards ice-free Arctic summers with longer phytoplankton blooms can lead to major changes in the associated standing stock of the bacterioplankton communities.
Stimulation of zona incerta selectively modulates pain in humans
Authors: Lu Charles W , Harper Daniel E , Askari Asra , Willsey Matthew S , Vu Philip P , Schrepf Andrew D , Harte Steven E , Patil Parag G 
Published: September 2020

ABSTRACTStimulation of zona incerta in rodent models has been shown to modulate behavioral reactions to noxious stimuli. Sensory changes observed in Parkinsonian patients with subthalamic deep brain stimulation suggest that this effect is translatable to humans. Here, we utilized the serendipitous placement of subthalamic deep brain stimulation leads to directly investigate the effects of zona incerta stimulation on human pain perception. We found that stimulation at 20 Hz, the physiological firing frequency of zona incerta, reduces experimental heat pain by a modest but significant amount, achieving a 30% reduction in one fifth of implants. Stimulation at higher frequencies did not modulate heat pain. Modulation was selective for heat pain and was not observed for warmth perception or pressure pain. These findings provide a mechanistic explanation of sensory changes seen in subthalamic deep brain stimulation patients and identify zona incerta as a potential target for neuromodulation of pain.