bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term income mobility in Latin America in the 2000s: intensity and characteristics
Authors: Beccaria Luis , Maurizio Roxana , Trombetta Martin , Vázquez Gustavo
Published: September 2020

The aim of this article is to compare the intensity and characteristics of short-term income mobility during the 2000s in Argentina, Brazil, Costa Rica, Ecuador, Mexico, Paraguay and Peru, countries with very dissimilar labor market structures and social protection coverage. This period is particularly relevant since Latin America experienced sustained economic growth together with improvements in labor and social conditions. Results show that the degree of mobility is higher in the region than in certain developed countries. The presence of a large number of income rises in all seven cases is another main finding of the analysis. However, at the same time, a great proportion of households suffered a reduction in their income. Finally, differences in mobility between countries are more closely linked to those in labor market structures than to those derived from disparities in overall economic performance during the period under analysis.
Desirable Bodies and Eugen Sandow’s Curative Institute in Edwardian England
Authors: Heffernan Conor
Published: September 2020

In 1907, Eugen Sandow, a famous strength performer, opened an ambitious business adventure centred on the eradication of disease without ‘harmful’ medicines. Sandow’s ‘Curative Institute’ was located in London, employed registered physicians to act as advisers and claimed to enjoy the patronage of thousands. Purporting to heal a variety of diseases through exercise and diet alone, Sandow’s Curative Institute, and his relationship with the medical community in England, has not previously enjoyed sustained study. Surveying Sandow’s Institute, the article highlights the manner in which Sandow co-opted, and was in turn co-opted by, the Medical community. For Sandow, associating with trained physicians gave a respectability and kudos to his endeavours. Among physicians, Sandow marked a point of knowledge, celebrity and, in the case of his Institute’s physicians, a living. Initially harmonious, for the most part, Sandow’s relationship with the medical community deteriorated in 1910 following the publication of a series of grandiose advertisements. Such advertisements were used by the General Medical Council (GMC) as a means of disbarring Sandow’s physicians and delineating public and private knowledge. Done at a time when the medical marketplace in England was teeming with competition, Sandow’s Institute, and his actions, represented a unique, and commercialised, medical enterprise. Studying Sandow’s Institute, and his conflict with the GMC in 1912, this article examines the limits of commercial medicine during this time, as well as the nexus between trained and untrained practitioners.
Effects of Bacillus subtilis PB6 and/or chromium propionate supplementation on clinical health, growth performance, and carcass traits of high-risk cattle during the feedlot receiving and finishing periods1
Authors: Smock Taylor M , Samuelson Kendall L , Hergenreder Jerilyn E , Rounds P Whitney , Richeson John T
Published: September 2020

The study objective was to determine the effects of Bacillus subtilis PB6 and/or chromium propionate supplementation on health, growth performance, and carcass characteristics of high-risk beef cattle during a 56-d feedlot receiving period and the subsequent finishing period. Four truckload blocks of crossbred beef bulls (n = 300) and steers [n = 84; body weight (BW) = 220 ± 16.2 kg] were sourced from regional auction markets and assigned randomly to treatments arranged in a 2 × 2 factorial. The generalized complete block design consisted of 12 pen replications per treatment with pen as the experimental unit. Treatments were: 1) placebo control (CON); 2) 13 g per animal daily of B. subtilis PB6 (CST); 3) 450 ppb dry matter (DM) chromium propionate (CHR); and 4) 13 g per animal daily of B. subtilis PB6 and 450 ppb DM chromium propionate (CST + CHR). Treatments were top dressed in feed bunks daily using 0.45 kg per animal ground corn carrier immediately following feed delivery. Data were analyzed using mixed models. During the receiving period, dry matter intake (DMI) increased (P ≤ 0.03) for CST during each interim period. Overall receiving period daily DMI was 0.35 kg per animal greater for CST (P = 0.01). Cattle fed CST had greater (P ≤ 0.06) BW on days 14, 28, and 56. Likewise, average daily gain (ADG) was improved for CST from day 0 to 14 (P = 0.04) and for the overall receiving period (days 0–56; P = 0.04). From days 0 to 14, CST tended (P = 0.08) to increase gain:feed. During the finishing period, CHR reduced (P = 0.02) final BW and ADG (day 56 to final; P = 0.01) and ADG was less for CHR over the entire feeding period (day 0 to final; P = 0.03). The main effect of both CST (P = 0.02) and CHR (P = 0.03) decreased the overall treatment rate for bovine respiratory disease (BRD), and CST reduced overall antimicrobial treatment cost by $3.50 per animal compared to CON (P = 0.03). Hot carcass weight (HCW) decreased (P = 0.01) in cattle fed CHR. The percentage of edible livers tended to increase (CST × CHR; P = 0.08) in the CST treatment. Feed intake and growth performance outcomes during the receiving period were improved by CST but not CHR supplementation. However, both CST and CHR supplementation decreased the BRD morbidity rate. During the finishing period, performance and HCW were reduced in cattle supplemented with CHR.
Pandemic Ponderings on the Limited Lens of Our Age Stereotyping Research: Considering Privilege and Racism
Authors: Finkelstein Lisa M
Published: September 2020

In this commentary, I observe the assumption of privilege of many of the age stereotypes that emerged to characterize both older and younger age groups at the start of the COVID-19 pandemic. This leads to a reflection of how much extant age stereotype research may be limited by the typical centering of a white and a middle- or upper-class perspective. I make acknowledgment of strides toward intersectional research and suggest some further research questions to move this work forward.
Plan-Do-Study-Act Methodology: Refining an Inpatient Pediatric Sepsis Screening Process
Authors: Nuss Kathryn E. , Kunar Jillian S. , Ahrens Erin A.
Published: September 2020

Introduction:

Pediatric sepsis remains a leading cause of death of children in the United States. Timely recognition and treatment are critical to prevent the onset of severe sepsis and septic shock. Electronic screening tools aid providers in identifying patients at risk for sepsis. Our overall project goal was to decrease the number of sepsis-related emergent transfers to the pediatric intensive care unit by optimizing sepsis screening tools, interruptive alerts, and a new paper tool and huddle process using Plan-Do-Study-Act (PDSA) methodology.

Methods:

Our team utilized historical data to develop inpatient electronic sepsis screening tools to identify pediatric patients at risk for sepsis. Using PDSA iterative cycles over 3 months, we tested the design of an interruptive alert, paper tool, and a new sepsis huddle process.

Results:

During the PDSA, the clinical teams conducted huddles on all patients who received an interruptive alert (n = 35). Eighty percent of huddles had a 5.7 minute average response time and an average duration of 5.3 minutes. Completion of the huddle outcome notes occurred 83% of the time, and 70% had feedback related to the alert, paper form, and huddle process. The number of days between sepsis-related emergent transfers to the pediatric intensive care unit increased from a median of 17.5 to 57.5 days, with a single point as high as 195 days between events.

Conclusions:

The inpatient sepsis team learned valuable lessons using PDSA methodology. The results of the iterative cycles allowed the team to optimize and refine the tests of change. System-wide implementation benefited from the application of this quality improvement tool.
Internalized stigma among people living with HIV: assessing the Internalized AIDS-Related Stigma Scale in four countries
Authors: Geibel Scott , Gottert Ann , Friedland Barbara A. , Jeremiah Kidola , McClair Tracy L. , Mallouris Christoforos , Kentutsi Stella , Hows Julian , Sprague Laurel , Pulerwitz Julie
Published: September 2020

Objective:

Measuring internalized stigma is critical to understanding its impact on the health and quality of life of people living with HIV (PLHIV). The aim of this study was to assess the performance of the Internalized AIDS-Related Stigma Scale (IA-RSS).

Design:

Secondary analysis of the six-item IA-RSS was conducted using data from four cross-sectional surveys implemented in Cambodia (n = 1207), the Dominican Republic (n = 891), Uganda (n = 391) and Tanzania (n = 529) between 2018 and 2019.

Methods:

IA-RSS scale item distribution was described. Multivariate regression models measured correlations between the IA-RSS and depression, antiretroviral therapy (ART) use and viral suppression. Confirmatory factor analysis assessed IA-RSS reliability and performance through analysis of standardized factor loadings and conditional probabilities of scale items. Analysis of qualitative interviews with PLHIV explored acceptability of IA-RSS item content.

Results:

Mean IA-RSS scores (possible 0–6) ranged from 2.06 (Uganda) to 3.84 (Cambodia), and internal consistency was more than 0.70 in each country (Kuder-Richardson 20), ranging from 0.71 to 0.83. Higher IA-RSS scores were strongly correlated with depression in (P < 0.001 in all countries), and inversely associated with current ART use (Dominican Republic and Tanzania) and self-reported viral suppression (Uganda and Tanzania). Confirmatory factor analysis showed good model fit (all CFI ≥ 0.950), but also that the IA-RSS may summarize two domains related to HIV status disclosure (two items) and PLHIV feelings about themselves (four items).

Conclusion:

Strong performance across countries supports continued use of the IA-RSS. Further study is needed to explore potential item refinements and to better understand the relationship between internalized stigma and HIV treatment outcomes.
Assessing the Risk/Benefit at Status Epilepticus Onset: The Prognostic Scores
Authors: Alvarez Vincent , Rossetti Andrea O.
Published: September 2020

Status epilepticus is a medical emergency with a wide range of etiology, severity, and outcome. Different scores that can help in the stratification of a patient's risk of mortality have been published. This study describes and compares the three available scores (Status Epilepticus Severity Score, Epidemiology-Based Mortality Score in Status Epilepticus and Encephalitis, Nonconvulsive, Diazepam resistance, Imaging, Tracheal intubation).
Use of fosfomycin combination therapy to treat multidrug-resistant urinary tract infection among paediatric surgical patients – a tertiary care centre experience
Authors: K.S. Shiju , Pallam Gopichand , Mandal Jharna , Jindal Bibekanand , S. Kumaravel
Published: September 2020

With increasing resistance to currently used antibiotics, antibiotic combinations are being resorted to. The present study deals with five children with complicated urinary tract infection (UTI) whose urine cultures grew multidrug-resistant (MDR) organisms. In all of these five cases, MDR organisms were the causative agents for UTI and the currently available antibiotics, including colistin, were ineffective, although the organisms were sensitive in vitro. In all of these cases, the isolates reverted to being susceptible to the quinolones and cephalosporins tested, namely ceftriaxone and ceftazidime. All were treated using a combination of fosfomycin with other antibiotics, since it has no interference with other classes of antibiotics. Our observations suggest that the use of a combination of fosfomycin with either a carbapenem or an aminoglycoside in a clinical setting would be a reasonable choice to treat UTIs caused by MDR organisms, especially in complicated cases that require chronic therapy.
Face-masking, an acceptable protective measure against COVID-19 - Findings of Ugandan high-risk groups
Authors: Mboowa Gerald , Musoke David , Bulafu Douglas , Aruhomukama Dickson
Published: September 2020

Face-masking could reduce the risk of COVID-19 transmission. We assessed: knowledge, attitudes, perceptions, and practices towards COVID-19 and face-mask use among 644 high risk-individuals in Kampala, Uganda. In data analysis, descriptive, bivariate and multivariate logistic regression analyses, with a 95% confidence interval were considered. Adjusted-odds ratios were used to determine the magnitude of associations. P-values < 0.05 were considered statistically-significant. Majority: 99.7% and 87.3% of the participants respectively had heard and believed that face-masks were protective against COVID-19, while 67.9% reported having received information on face-mask use. Males, food market vendors, those with no formal education, and those aged 24-33, 44-53 and 54-63 years were 0.58, 0.47, 0.25, 1.9, 2.12, and 3.39 times less likely to have received information about face-mask use respectively. Majority, 67.8% owned locally-made, non-medical face-masks, while 77.0% of face-mask owners believed that they knew the right procedure of wearing them. Those who had received information on face-mask use were 2.85 and 1.83 times more likely to own face-masks and to perceive them as protective. Food market vendors were 3.92 times more likely to re-use their face-masks. Our findings suggest that Ugandan high-risk groups have good knowledge, optimistic attitudes and perceptions, and relatively appropriate practices towards COVID-19.
Weighted RSA: an improved framework on the perception of audio-visual affective speech in left insula and superior temporal gyrus
Authors: Xu Junhai , Dong Haibin , Guo Fei , Wang Zeyu , Wei Jianguo , Dang Jianwu
Published: September 2020

Being able to accurately perceive the emotion expressed by the facial or verbal expression from others is critical to successful social interaction. However, only few studies examined the multimodal interactions on speech emotion, and there is no consistence in studies on the speech emotion perception. It remains unclear, how the speech emotion of different valence is perceived on the multimodal stimuli by our human brain. In this paper, we conducted a functional magnetic resonance imaging (fMRI) study with an event-related design, using dynamic facial expressions and emotional speech stimuli to express different emotions, in order to explore the perception mechanism of speech emotion in audio-visual modality. The representational similarity analysis (RSA), whole-brain searchlight analysis, and conjunction analysis of emotion were used to interpret the representation of speech emotion in different aspects. Significantly, a weighted RSA approach was creatively proposed to evaluate the contribution of each candidate model to the best fitted model. The results of weighted RSA indicated that the fitted models were superior to all candidate models and the weights could be used to explain the representation of ROIs. The bilateral amygdala has been shown to be associated with the processing of both positive and negative emotions except neutral emotion. It is indicated that the left posterior insula and the left anterior superior temporal gyrus (STG) play important roles in the perception of multimodal speech emotion.
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

Translocations 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

Cancer-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

Neurons 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

Menopause 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

Crop 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.

Highlight

An 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

The 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

Introduction

We 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 analysis

Participants 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 Dissemination

Ethical 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 study

Strengths 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

Background

New 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.

Methods

Tissue 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.

Results

Among 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.

Conclusion

The 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

The 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

The 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

The 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 statement

In 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.
High segregation and diminished global integration in large-scale brain functional networks enhances the perceptual binding of cross-modal stimuli
Authors: Singh Soibam Shyamchand , Mukherjee Abhishek , Raghunathan Partha , Ray Dipanjan , Banerjee Arpan
Published: September 2020

Speech perception requires the binding of spatiotemporally disjoint auditory--visual cues. The corresponding brain network-level information processing can be characterized by two complementary mechanisms: functional segregation which refers to the localization of processing in either isolated or distributed modules across the brain, and integration which pertains to cooperation among relevant functional modules. Here, we demonstrate using fMRI recordings that subjective perceptual experience of multisensory speech stimuli, real and illusory, are represented in differential states of segregation--integration. We controlled the inter-subject variability of illusory/cross-modal perception parametrically, by introducing temporal lags in the incongruent auditory--visual articulations of speech sounds within the McGurk paradigm. The states of segregation--integration balance were captured using two alternative computational approaches. First, the module responsible for cross-modal binding of sensory signals defined as the perceptual binding network (PBN) was identified using standardized parametric statistical approaches and their temporal correlations with all other brain areas were computed. With increasing illusory perception, the majority of the nodes of PBN showed decreased cooperation with the rest of the brain, reflecting states of high segregation but reduced global integration. Second, using graph theoretic measures, the altered patterns of segregation--integration were cross-validated.
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

The 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

Stimulation 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.
Oscillatory entrainment of the Frequency Following Response in auditory cortical and subcortical structures
Authors: Coffey Emily B.J. , Arseneau-Bruneau Isabelle , Zhang Xiaochen , Baillet Sylvain , Zatorre Robert J.
Published: September 2020

There is much debate about the existence and function of neural oscillatory entrainment mechanisms in the auditory system. The frequency-following response (FFR) is an index of neural periodicity encoding that can provide a vehicle to study entrainment in frequency ranges relevant to speech and music processing. Criteria for entrainment include the presence of post-stimulus oscillations and phase alignment between stimulus and endogenous activity. To test the hypothesis of entrainment, in experiment 1 we collected FFR data to a repeated syllable using magneto- (MEG) and electroencephalography in 20 healthy adults. We observed significant oscillatory activity after stimulus offset in auditory cortex and subcortical auditory nuclei, consistent with entrainment. In these structures the FFR fundamental frequency converged from a lower value over 100 ms to the stimulus frequency, consistent with phase alignment, and diverged to a lower value after offset, consistent with relaxation to a preferred frequency. In experiment 2, we tested how transitions between stimulus frequencies affected the MEG-FFR to a train of pure-tone pairs in 30 adults. We found that the FFR was affected by the frequency of the preceding tone for up to 40 ms at subcortical levels, and even longer durations at cortical levels. Our results suggest that oscillatory entrainment may be an integral part of periodic sound representation throughout the auditory neuraxis. The functional role of this mechanism is unknown, but it could serve as a fine-scale temporal predictor for frequency information, enhancing stability and reducing susceptibility to degradation that could be useful in real-life noisy environments.
Elucidating Human Milk Oligosaccharide biosynthetic genes through network-based multiomics integration
Authors: Kellman Benjamin P. , Richelle Anne , Yang Jeong-Yeh , Chapla Digantkumar , Chiang Austin W. T. , Najera Julia , Bao Bokan , Koga Natalia , Mohammad Mahmoud A. , Bruntse Anders Bech , Haymond Morey W. , Moremen Kelley W. , Bode Lars , Lewis Nathan E.
Published: September 2020

Abstract

Human Milk Oligosaccharides (HMOs) are abundant carbohydrates fundamental to infant health and development. Although these oligosaccharides were discovered more than half a century ago, their biosynthesis in the mammary gland remains largely uncharacterized. Here, we used a systems biology framework that integrated glycan and RNA expression data to construct an HMO biosynthetic network and predict glycosyltransferases involved. To accomplish this, we constructed models describing the most likely pathways for the synthesis of the oligosaccharides accounting for >95% of the HMO content in human milk. Through our models, we propose candidate genes for elongation, branching, fucosylation, and sialylation of HMOs. We further explored selected enzyme activities through kinetic assay and their co-regulation through transcription factor analysis. These results provide the molecular basis of HMO biosynthesis necessary to guide progress in HMO research and application with the ultimate goal of understanding and improving infant health and development.

Significance statement

With the HMO biosynthesis network resolved, we can begin to connect genotypes with milk types and thereby connect clinical infant, child and even adult outcomes to specific HMOs and HMO modifications. Knowledge of these pathways can simplify the work of synthetic reproduction of these HMOs providing a roadmap for improving infant, child, and overall human health with the specific application of a newly limitless source of nutraceuticals for infants and people of all ages.
Accurate spliced alignment of long RNA sequencing reads
Authors: Sahlin Kristoffer , Mäkinen Veli
Published: September 2020

Long-read RNA sequencing techniques are establishing themselves as the primary sequencing technique to study the transcriptome landscape. Many such analyses are dependent on read alignments. However, the error rate and sequencing length of long-read technologies create new challenges for accurately aligning these reads. We present an alignment method uLTRA based on a novel two-pass collinear chaining algorithm. Furthermore, uLTRA can be used both as a stand-alone aligner and as a wrapper around minimap2 for improved alignments in gene regions. We show that uLTRA produces higher accuracy over state-of-the-art aligners with substantially higher accuracy for small exons on simulated and synthetic data. On biological data where true read location is unknown, we show several examples where uLTRA aligns to known and novel isoforms with exon structures that are not detected with other aligners. uLTRA is available athttps://github.com/ksahlin/ultra.
Comment on “Rapid and efficientin vivoastrocyte-to-neuron conversion with regional identity and connectivity?”
Authors: Chen Gong , Li Wen , Xiang Zongqin , Xu Liang , Liu Minhui , Wang Qingsong , Lei Wenliang
Published: September 2020

Regenerating functional new neurons in the adult mammalian central nervous system (CNS) has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss. In contrast, glial cells in the CNS can divide and repopulate themselves under injury or disease conditions. Therefore, many groups around the world have been able to utilize internal glial cells to directly convert them into neurons for neural repair. We have previously demonstrated that ectopic expression of NeuroD1 in dividing glial cells can directly convert reactive glial cells into neurons. However, Wang et al. recently posted an article in bioRxiv challenging the entire field ofin vivoglia-to-neuron conversion after using one single highly toxic dose of AAV (2×1013gc/ml, 1 μl) in the mouse cortex, producing artifacts that are very difficult to interpret. We present data here that reducing AAV dosage to safe level will avoid artifacts caused by toxic dosage. We also demonstrate with Aldh1l1-CreERT2and Ai14 reporter mice that lineage-traced astrocytes can be successfully converted into NeuN+neurons after infected by AAV5 GFAP::NeuroD1. Retroviral expression of NeuroD1 further confirms our previous findings that dividing glial cells can be converted into neurons. Together, the incidence of Wang et al. sends an alarming signal to the entirein vivoreprogramming field that the dosage of viral vectors is a critical factor to consider when designing proper experiments. For AAV, we recommend a relatively safe dose of 1×1010- 1×1012gc/ml (~1 μl) in the rodent brain for cell conversion experiments addressing basic science questions. For therapeutic purpose under injury or diseased conditions, AAV dosage needs to be adjusted through a series of dose finding experiments. Moreover, we recommend that the AAV results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.