bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the COVID-19 Pandemic on Sexually Transmitted Infection Clinic Visits
Authors: Tao Jun , Napoleon Siena C. , Maynard Michaela A. , Almonte Alexi , Silva Elizabeth , Toma Emily , Chu Christina T. , Cormier Kevin , Strong Sabrina , Chan Philip A.
Published: November 2020

Coronavirus disease 2019 is responsible for a global pandemic and has impacted health care accessibility and delivery. Clinic data were reviewed for an STI clinic from September 2019 to May 2020. A significant decrease in rates of STI visits and treatments during the coronavirus disease 2019 pandemic was observed.
Distantly Metastatic Retinoblastoma to Soft Tissue and Bone
Authors: Meredith David M. , Charville Gregory W. , Fletcher Christopher D.M. , Hornick Jason L.
Published: November 2020

Distant metastasis of retinoblastoma to sites outside the central nervous system is rare; such cases may present years following primary treatment. Diagnosis may be difficult given the rarity of such events and considerable histologic mimics. We describe the clinicopathologic features of 6 cases of metastatic retinoblastoma to distant bone and soft tissue sites from 2 large academic centers. Patients were 3 female and 3 male children; median age was 9.5 years (range: 5 to 15 y) with a mean interval from primary disease diagnosis of 8.0 years (range: 0.75 to 14 y). Metastasis to bones of the lower extremities was most common, occurring in 4 of 6 cases. Tumors showed typical histologic features of retinoblastoma, with sheets of primitive round cells with minimal cytoplasm and indistinct nucleoli; however, characteristic Flexner-Wintersteiner rosettes were absent. A subset of cases demonstrated an alveolar growth pattern, and 2 cases showed higher grade cytology with nuclear anaplasia and prominent nucleoli. Immunohistochemistry for CRX and RB1 showed uniform positivity and loss of expression, respectively. Metastatic retinoblastoma outside the central nervous system may present following long disease-free intervals. Immunohistochemistry for CRX is helpful to confirm this challenging diagnosis.
Use of Honey Versus Standard Care for Hospital-Acquired Pressure Injury in Critically Ill Children: A Multicenter Randomized Controlled Trial
Authors: Sankar Jhuma , Lalitha AV , Rameshkumar Ramachandran , Mahadevan Subramanian , Kabra Sushil K. , Lodha Rakesh
Published: November 2020

OBJECTIVES:

To examine if the use of honey (medicated) for dressing is superior to standard care in terms of time to complete wound healing in stages 1–3 of pressure injuries in children admitted to the PICU.

DESIGN:

Multicenter, open-label, parallel-group, randomized trial.

SETTING:

Tertiary-care PICU from August 2017 to January 2019.

PATIENTS:

Critically ill children, 2 months to 17 years old, who developed pressure injury (stages 1–3) were included; those on more than two inotropes or with signs of acute wound infection or wounds with greater than 5 cm diameter or known allergy to honey were excluded.

INTERVENTIONS:

Children were randomized to receive either medicated honey dressing or standard (routine) wound care for the management of their pressure injury.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was the time to complete wound healing. Manuka or active Leptospermum honey dressing/gel was used in the intervention group. Enrolled children were followed up until death or discharge from the hospital. A total of 99 children were enrolled: 51 in the intervention group and 48 in the standard care group. Baseline characteristics, including the nutritional status, were comparable between the groups. The most common sites of injury were bony prominences at face mask contact points. The median time to complete healing was 7 days (95% CI, 6–7 d) versus 9 days (7–10 d) in the intervention and standard care groups, respectively (p = 0.002; log-rank test). At any random time, children in the intervention group were about 1.9-fold more likely to have their pressure injury completely healed than those in the standard care group (hazard ratio 1.86; 95% CI, 1.21–2.87). There were no allergic reactions or secondary wound infections in the intervention group.

CONCLUSIONS:

The use of medicated honey dressings decreased the time to wound healing in critically ill children with pressure injuries. There were no allergic reactions or secondary bacterial infections in any of these children.
Helmets Protect Pediatric Bicyclists From Head Injury and Do Not Increase Risk of Cervical Spine Injury
Authors: Hasjim Bima J. , Grigorian Areg , Schubl Sebastian D. , Lekawa Michael , Kim Dennis , Bernal Nicole , Nahmias Jeffry
Published: November 2020

Objectives

Only 21 states have mandatory helmet laws for pediatric bicyclists. This study sought to determine the incidence of helmeted riders among pediatric bicyclists involved in a collision and hypothesized the risk of a serious head and cervical spine injuries to be higher in nonhelmeted bicyclists (NHBs) compared with helmeted bicyclists (HBs).

Methods

The Pediatric Trauma Quality Improvement Program (2014–2016) was queried for pediatric (age <16 years) bicyclists involved in a collision. Helmeted bicyclists were compared with NHBs. A serious injury was defined by an abbreviated injury scale grade of greater than 2.

Results

From 3693 bicyclists, 3039 (82.3%) were NHBs. Compared with HBs, NHBs were more often Black (21.6% vs 3.8%,P< 0.001), Hispanic (17.5% vs 9.3%,P< 0.001), without insurance (4.6% vs 2.4%,P= 0.012), and had a higher rate of a serious head injury (24.6% vs 9.3%,P< 0.001). Both groups had similar rates of complications and mortality (P> 0.05). The associated risk of a serious head (odds ratio = 3.17,P< 0.001) and spine injury (odds ratio = 0.41,P= 0.012) were higher and lower respectively in NHBs. Associated risks for cervical spine fracture or cord injury were similar (P> 0.05).

Conclusions

Pediatric bicyclists involved in a collision infrequently wear helmets, and NHBs was associated with higher risks of serious head injury. However, the associated risk of serious spine injury among NHBs was lower. The associated risks for cervical spine fracture or cervical cord injuries were similar. Nonhelmeted bicyclists were more likely to lack insurance and to be Black or Hispanic. Targeted outreach programs may help decrease the risk of injury, especially in at-risk demographics.
Declines in HIV prevalence in female sex workers accessing an HIV treatment and prevention programme in Nairobi, Kenya over a 10-year period
Authors: Tago Achieng , McKinnon Lyle R. , Wanjiru Tabitha , Muriuki Festus , Munyao Julius , Gakii Gloria , Akolo Maureen , Kariri Anthony , Reed Neil , Shaw Souradet Y. , Gelmon Lawrence J. , Kimani Joshua
Published: November 2020

Objectives:

Empirical time trends in HIV prevalence in female sex workers (FSWs) are helpful to understand the evolving HIV epidemic, and to monitor the scale-up, coverage, and impact of ongoing HIV prevention and treatment programmes.

Design:

Serial HIV prevalence study.

Methods:

We analyzed time trends in HIV prevalence in FSWs accessing services at seven Sex Worker Outreach Programme (SWOP) clinics in Nairobi from 2008 to 2017 (N = 33 560). The Mantel--Haenszel test for trend and independent samples Kruskal--Wallis test were used to analyze categorical and continuous variables, respectively. Multivariable binomial regression was used to estimate prevalence ratios/year, adjusting for several covariates.

Results:

HIV prevalence decreased over time in all age groups. This was particularly evident among FSWs less than 25 years of age; HIV was 17.5% in 2008–2009, decreasing to 12.2% in 2010–2011, 8.3% in 2012–2013, 7.3% in 2014–2015, and 4.8% in 2016–2017 (P < 0.0001). Over time, FSWs reported increased condom use, particularly with regular partners, more frequent prior HIV testing, and were less likely to report a history of vaginal discharge (P < 0.0001). In adjusted analyses compared with 2008, HIV prevalence decreased in 2011 (aPR 0.64; 95% CI: 0.46–0.90), 2012 (aPR 0.58; 95% CI: 0.41–0.81), 2013 (aPR 0.53; 95% CI: 0.38–0.73), 2014 (aPR 0.48; 95% CI: 0.34–0.67), 2015 (aPR 0.50; 95% CI: 0.35–0.70), 2016 (aPR 0.40; 95% CI: 0.28–0.57), and 2017 (aPR 0.33; 95% CI: 0.22–0.50).

Conclusion:

HIV prevalence has decreased among FSW accessing SWOP in Nairobi, Kenya. This decline is consistent with the scale-up of HIV prevention and treatment efforts, both in FSWs and in the general population.
Aggressive Bone Metastatic Prostate Cancer With Periosteal Reaction in 18F-Choline PET/CT
Authors: De Leiris Nicolas , Ruggeri Valentin , Riou Laurent , Laramas Mathieu , Djaileb Loïc
Published: November 2020

Prostate cancer bone metastases usually appear as osteosclerotic lesions. However, atypical lesions have also been described. We report herein the case of a 65-year-old man treated since 2013 for prostate cancer with early bone metastases. This asymptomatic patient was referred for 18F-choline PET/CT due to a major elevation of prostate-specific antigen to >1500 ng/mL. The results indicated multiple bone lesions, disseminated on the axial skeleton, girdles, and upper extremities of femurs. Interestingly, we described the development of an intensely hypermetabolic spiculated periosteal reaction, evidencing a rapidly progressive disease.
Use of Islanded Supratrochlear Artery Component Paramedian Forehead Flap and Cranial Bone Graft for Composite Nasal Defect Reconstruction
Authors: Sharma Ramesh Kumar
Published: November 2020

The authors present a case series of patients with composite loss of nasal skin cover and lining following road accidents. The nasal skeletal framework in all these cases was also severely communited. The reconstruction of all the these was achieved in 1 operation. The authors have utilized islanded supratrochlear artery based paramedian forehead skin and pericranial flap for reconstruction of both skin and lining defects. The nasal skeletal framework was restored with the help of cantilevered split cranial bone graft. In all but 1 patient, the reconstruction was done in the emergency setting at the time of initial admission itself. One patient had infected wound that necessitated an initial debridement and split skin grafting. In this case, the definitive reconstruction was done after a gap of 3 months.

A long-term follow-up of these patients is presented.
Direct Airway Instillation of Neutrophils Overcomes Chemotactic Deficits Induced by Injury
Authors: Zhang Quanzhi , Kwon Woon Yong , Vlková Barbora , Riça Ingred , Kaczmarek Elzbieta , Park Jinbong , Kim Hyo In , Konecna Barbora , Jung Françoise , Douglas Garry , Otterbein Leo E. , Hauser Carl J. , Itagaki Kiyoshi
Published: November 2020

Background:

Trauma induces neutrophil migration toward injury sites, both initiating wound healing and protecting against local bacterial infection. We have previously shown that mitochondrial formyl peptides (mtFPs) released by injured tissues act as chemoattractants by ligating neutrophil (PMN) formyl peptide receptor 1 (FPR1). But this process can also internalize multiple neutrophil chemoattractant receptors and thus might limit neutrophil migration to the lung in response to bacteria. Our objective was to better understand susceptibility to pneumonia after injury and thus find ways to reverse it.

Methods and Results:

We modeled the alveolar chemotactic environment in pulmonary infections by incubating Staphylococcus aureus or Escherichia coli with peripheral blood mononuclear cells. Survey of the chemotactic mediators in the resultant conditioned media (CM) showed multiple potent chemoattractants. Pretreating PMN with mtFPs to mimic injury potently reduced net migration toward CM and this net effect was mostly reversed by an FPR1 antagonist. Using an established mouse model of injury-dependent lung infection, we then showed simple instillation of exogenous unstimulated human neutrophils into the airway resulted in bacterial clearance from the lung.

Conclusion:

Injury-derived mtFPs suppress global PMN localization into complex chemotactic environments like infected alveoli. Transplantation of naive exogenous human neutrophils into the airway circumvents that pathologic process and prevents development of post-traumatic pneumonia without injury noted to the recipients.
Complete microbial genomes for public health in Australia and the Southwest Pacific
Authors: Baines Sarah L. , da Silva Anders Gonçalves , Carter Glen P. , Jennison Amy , Rathnayake Irani , Graham Rikki M. , Sintchenko Vitali , Wang Qinning , Rockett Rebecca J. , Timms Verlaine J. , Martinez Elena , Ballard Susan , Tomita Takehiro , Isles Nicole , Horan Kristy A. , Pitchers William , Stinear Timothy P. , Williamson Deborah A. , Howden Benjamin P. , Seemann Torsten ,   Communicable Diseases Genomics Network (CDGN)
Published: November 2020

Complete genomes of microbial pathogens are essential for the phylogenomic analyses that increasingly underpin core public health laboratory activities. Here, we announce a BioProject (PRJNA556438) dedicated to sharing complete genomes chosen to represent a range of pathogenic bacteria with regional importance to Australia and the Southwest Pacific; enriching the catalogue of globally available complete genomes for public health while providing valuable strains to regional public health microbiology laboratories. In this first step, we present 26 complete high-quality bacterial genomes. Additionally, we describe here a framework for reconstructing complete microbial genomes and highlight some of the challenges and considerations for accurate and reproducible genome reconstruction.
Increased CHIP Prevalence Amongst People Living with HIV
Authors: Bick Alexander G. , Popadin Konstantin , Thorball Christian W. , Uddin Md Mesbah , Zanni Markella , Yu Bing , Cavassini Matthias , Rauch Andri , Tarr Philip , Schmid Patrick , Bernasconi Enos , Günthard Huldrych F. , Libby Peter , Boerwinkle Eric , McLaren Paul J. , Ballantyne Christie M. , Grinspoon Steven , Natarajan Pradeep , Fellay Jacques ,   the Swiss HIV Cohort Study
Published: November 2020

People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n=600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n=8,111) from blood DNA-derived exome sequences. We observed that HIV is associated with increased CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p=0.005). Additionally, unlike in ARIC, ASXL1 was the most commonly implicated mutated CHIP gene. We propose that CHIP may be one mechanism through which PLWH are at increased risk for CAD. Larger prospective studies should evaluate the hypothesis that CHIP contributes to the excess cardiovascular risk in PLWH.
Ready for a BASE jump? Do not neglect SARS-CoV-2 hospitalization and fatality risks in the middle-aged adult population
Authors: Lapidus Nathanael , Paireau Juliette , Levy-Bruhl Daniel , de Lamballerie Xavier , Severi Gianluca , Touvier Mathilde , Zins Marie , Cauchemez Simon , Carrat Fabrice ,   the SAPRIS-SERO study group
Published: November 2020

Seroprevalence results coupled with surveillance data were used to estimate the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France. IHR and IFR were dramatically high in the very elderly (80-90 years: IHR: 30%, IFR: 11%), but also substantial in middle-aged adults (40-50 years: IHR: 1.2%, IFR: 0.05%).
Non-Canonical Odor Coding in the Mosquito
Authors: Younger Meg A. , Herre Margaret , Goldman Olivia V. , Lu Tzu-Chiao , Caballero-Vidal Gabriela , Qi Yanyan , Gilbert Zachary N. , Gong Zhongyan , Morita Takeshi , Rahiel Saher , Ghaninia Majid , Ignell Rickard , Matthews Benjamin J. , Li Hongjie , Vosshall Leslie B.
Published: November 2020

FemaleAedes aegyptimosquitoes are a persistent human foe, transmitting arboviruses including dengue and yellow fever when they bite us to obtain a blood meal. Mosquitoes are intensely attracted to human-emitted body odor, heat, and carbon dioxide, which they detect using three different large multi-gene families encoding odor-gated ion channels. Genetic mutations that cause profound disruptions to the olfactory system have modest effects on human attraction, suggesting significant redundancy in odor coding. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. Using immunostaining, RNAin situhybridization, and single nucleus RNA sequencing, we discovered thatAedes aegyptiuses an entirely different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes.In vivoelectrophysiology demonstrates that the broad ligand-sensitivity of mosquito olfactory neurons is due to this non-canonical co-expression. The redundancy afforded by an olfactory system in which many neurons co-express multiple receptors with different chemical sensitivity may greatly increase the robustness of the mosquito olfactory system and explain our longstanding inability to engineer new compounds that disrupt the detection of human body odor by mosquitoes.
EGRET: Edge Aggregated Graph Attention Networks and Transfer Learning Improve Protein-Protein Interaction Site Prediction
Authors: Mahbub Sazan , Bayzid Md Shamsuzzoha
Published: November 2020

Motivation

Protein-protein interactions are central to most biological processes. However, reliable identification of protein-protein interaction (PPI) sites using conventional experimental methods is slow and expensive. Therefore, great efforts are being put into computational methods to identify PPI sites.

Results

We present EGRET, a highly accurate deep learning based method for PPI site prediction, where we have used an edge aggregated graph attention network to effectively leverage the structural information. We, for the first time, have used transfer learning in PPI site prediction. Our proposed edge aggregated network, together with transfer learning, has achieved notable improvement over the best alternate methods. Furthermore, we systematically investigated EGRET’s network behavior to provide insights about the causes of its decisions.

Availability

EGRET is freely available as an open source project athttps://github.com/Sazan-Mahbub/EGRET.

Contact

shams_bayzid@cse.buet.ac.bd

Key Points

We present a comprehensive assessment of a compendium of computational protocols to solve an important problem in computational proteomics.

We present a highly accurate deep learning method, EGRET, for Protein-Protein Interaction (PPI) site prediction for isolated proteins.

We have used an edge aggregated graph attention network to effectively capture the structural information for PPI site prediction.

We, for the first time, present a successful utilization of transfer-learning from pretrained transformer-like models in PPI site prediction.
Intraoperative enrichment of bone autograft with autologous bone marrow-derived mononuclear cells isolated simultaneously: moving towards tissue engineeringin situ
Authors: Baranovskii D.S. , Akhmedov B.G. , Krasilnikova O.A. , Demchenko A.G. , Krasheninnikov M.E. , Balyasin M.V. , Pavlova O.Yu. , Serova N.S. , Klabukov I.D.
Published: November 2020

Background

The use of tissue-engineered bone autografts is a promising approach for bone defects restoration. The isolation of cells and their seeding on bone autograft is usually carried out in a laboratory, requiring significant time and two separate surgical interventions. Intraoperative creation of tissue-engineered bone autograft can represent a perspective solution. The aim of this study is to investigate the possibility of creation of tissue-engineered bone autograft by intraoperative enrichment of bone tissue with bone marrow-derived mononuclear cells (BM-MNCs) isolated simultaneously.

Methods

Red bone marrow and autologous bone tissue (bone fragments and bone chips) of the donor were harvested intraoperatively. BM-MNCs were isolated, and bone fragments were enriched with BM-MNCs intraoperatively. Assessment of the adhesion and proliferation of BM-MNCs on bone fragments was carried out by fluorescence microscopy and histological examination. MTT assay was used to compare metabolic activity of BM-MNCs and wBMA cells seeded on bone chips.

Results

Autologous bone fragments were colonized with autologous BM-MNCs isolated simultaneously in the O.R. with further adhesion and active growth of cells. When seeded on bone chips, metabolic activity of BM-MNCs was statistically significantly higher compared to wBMA cells (p-value=0.0272) on day 14. There was no difference in metabolic activity of BM-MNCs and wBMA cells cultured in nutrient medium without bone chips.

Conclusion

Technically simple method of intraoperative enrichment of autologous bone fragments with BM-MNCs isolated simultaneously allowed to create tissue-engineered bone autograft in the O.R. The safety and effectiveness of intraoperatively enriched autografts should be investigated further.
Predicting Drug Interactions to Unassociated Biomedical Implants Using Machine Learning Techniques and Model Polymers
Authors: Kerner Jacob , Recum Horst von
Published: November 2020

Affinity based drug delivery mechanisms increase efficacy and minimalize off target effects when compared to non-specific methods due to the localization of drugs within target areas. While this is beneficial for targeted delivery, introduction of foreign polymeric medical devices into the body provide a potential area of localization due to high affinity between administered drugs and polymers. Previous attempts at creating models to predict affinity between small molecule drugs and polymers require a specific model be trained for each individual polymer failing to incorporate input features of both the polymer (host) and small molecule drug (guest). Within, we propose a universal model built using a neural network and quantitative structure activity relationships to predict the binding energy between guest and host molecules using input features. The trained model returned a correlation value, R2, of 0.9806 and 0.9958 between predicted and experimental binding affinity for the training and validation sets, respectively. This correlates to a mean absolute error of 0.951 kJ/mol and 0.771 kJ/mol for the training and validation sets, respectively. While limited to the current polymers used to train the model, the dataset can be expanded, and models retrained for further applications.
Building blocks of protein structures – Physics meets Biology
Authors: Škrbić Tatjana , Maritan Amos , Giacometti Achille , Rose George D. , Banavar Jayanth R.
Published: November 2020

The native state structures of globular proteins are stable and well-packed indicating that self-interactions are favored over protein-solvent interactions under folding conditions. We use this as a guiding principle to derive the geometry of the building blocks of protein structures – α-helices and strands assembled into β-sheets – with no adjustable parameters, no amino acid sequence information, and no chemistry. There is an almost perfect fit between the dictates of mathematics and physics and the rules of quantum chemistry. Our theory establishes an energy landscape that channels protein evolution by providing sequence-independent platforms for elaborating sequence-dependent functional diversity. Our work highlights the vital role of discreteness in life and has implications for the creation of artificial life and on the nature of life elsewhere in the cosmos.
RVAgene: Generative modeling of gene expression time series data
Authors: Mitra Raktim , MacLean Adam L.
Published: November 2020

Methods to model dynamic changes in gene expression at a genome-wide level are not currently sufficient for large (temporally rich or single-cell) datasets. Variational autoencoders offer means to characterize large datasets and have been used effectively to characterize features of single-cell datasets. Here we extend these methods for use with gene expression time series data. We present RVAgene: a recurrent variational autoencoder to model gene expression dynamics. RVAgene learns to accurately and efficiently reconstruct temporal gene profiles. It also learns a low dimensional representation of the data via a recurrent encoder network that can be used for biological feature discovery, and can generate new gene expression data by sampling from the latent space. We test RVAgene on simulated and real biological datasets, including embryonic stem cell differentiation and kidney injury response dynamics. In all cases, RVAgene accurately reconstructed complex gene expression temporal profiles. Via cross validation, we show that a low-error latent space representation can be learnt using only a fraction of the data. Through clustering and gene ontology term enrichment analysis on the latent space, we demonstrate the potential of RVAgene for unsupervised discovery. In particular, RVAgene identifies new programs of shared gene regulation ofLoxfamily genes in response to kidney injury.
A reduced level of consciousness affects non-conscious processes
Authors: Fontan A. , Lindgren L. , Pedale T. , Brorsson C. , Bergström F. , Eriksson J.
Published: November 2020

Being conscious is a profound aspect of human existence, and understanding its function and its inception is considered one of the truly grand scientific challenges. However, the nature of consciousness remains enigmatic, to a large part because “being conscious” can refer to both the content (phenomenology) and the level (arousal) of consciousness, and how these different aspects are related remains unclear. To empirically assess the relation between level and content of consciousness, we manipulated these two aspects by presenting stimuli consciously or non-consciously and by using Propofol sedation, while brain activity was measured using fMRI. We observed that sedation greatly affected non-conscious processes, which starkly contrasts the notion that anesthetics selectively reduce consciousness. Our findings reveal that level and content of consciousness are separate phenomena, and imply that one may need to reconsider what “being conscious” means.
Hippocampal-cortical encoding activity predicts the precision of episodic memory
Authors: Korkki Saana M. , Richter Franziska R. , Simons Jon S.
Published: November 2020

Our recollections of past experiences can vary both in the number of specific event details accessible from memory and the precision with which such details are reconstructed. Prior neuroimaging evidence suggests the success and precision of episodic recollection to rely on distinct neural substrates during memoryretrieval. In contrast, the specificencodingmechanisms supporting later memory precision, and whether they differ from those underlying successful memory formation in general, are currently unknown. Here, we combined continuous measures of memory retrieval with model-based analyses of behavioural and neuroimaging data to tease apart the encoding correlates of successful memory formation and mnemonic precision. In the MRI scanner, participants encoded object-scene displays, and later reconstructed features of studied objects using a continuous scale. We observed overlapping encoding activity in inferior prefrontal and posterior perceptual regions to predict both which object features were later remembered versus forgotten, and the precision with which they were reconstructed from memory. In contrast, hippocampal encoding activity significantly predicted the precision, but not overall success, of subsequent memory retrieval. The current results identify a hippocampal-cortical encoding basis for episodic memory precision, and suggest a contribution of shared cortical encoding mechanisms to the formation of both accessible and precise memory representations.
Quantifying the contribution of dominance effects to complex trait variation in biobank-scale data
Authors: Pazokitoroudi Ali , Chiu Alec M. , Burch Kathryn S. , Pasaniuc Bogdan , Sankararaman Sriram
Published: November 2020

The proportion of variation in complex traits that can be attributed to non-additive genetic effects has been a topic of intense debate. The availability of Biobank-scale datasets of genotype and trait data from unrelated individuals opens up the possibility of obtaining precise estimates of the contribution of non-additive genetic effects. We present an efficient method that can partition the variation in complex traits into variance that can be attributed to additive (additive heritability) and dominance (dominance heritability) effects across all genotyped SNPs in a large collection of unrelated individuals. Over a wide range of genetic architectures, our method yields unbiased estimates of heritability. We applied our method, in turn, to array genotypes as well as imputed genotypes (at common SNPs with minor allele frequency, MAF > 1%) and 50 quantitative traits measured in 291, 273 unrelated white British individuals in the UK Biobank. Averaged across these 50 traits, we find that additive heritability on array SNPs is 21.86% while dominance heritability is 0.13% (about 0.48% of the additive heritability) with qualitatively similar results for imputed genotypes. We find no evidence for dominance heritability (accounting for the number of traits tested) and estimate that dominance heritability is unlikely to exceed 1% for the traits analyzed. Our analyses indicate a limited contribution of dominance heritability to complex trait variation.
Root system influence on high dimensional leaf phenotypes over the grapevine growing season
Authors: Harris Zachary N. , Klein Laura L. , Awale Mani , Swift Joel F. , Migicovsky Zoë , Bhakta Niyati , Frawley Emma , Chitwood Daniel H. , Fennell Anne , Kovacs Laszlo G. , Kwasniewski Misha , Londo Jason P. , Ma Qin , Miller Allison J.
Published: November 2020

In many perennial crops, grafting the root system of one individual to the shoot system of another individual has become an integral part of propagation performed at industrial scales to enhance pest, disease, and stress tolerance and to regulate yield and vigor. Grafted plants offer important experimental systems for understanding the extent and seasonality of root system effects on shoot system biology.

Using an experimental vineyard where a common scion ‘Chambourcin’ is growing ungrafted and grafted to three different rootstocks, we explore associations between root system genotype and leaf phenotypes in grafted grapevines across a growing season. We quantified five high-dimensional leaf phenotyping modalities: ionomics, metabolomics, transcriptomics, morphometrics, and physiology and show that rootstock influence is subtle but ubiquitous across modalities.

We find strong signatures of rootstock influence on the leaf ionome, with unique signatures detected at each phenological stage. Moreover, all phenotypes and patterns of phenotypic covariation were highly dynamic across the season.

These findings expand upon previously identified patterns to suggest that the influence of root system on shoot system phenotypes is complex and broad understanding necessitates volumes of high-dimensional, multi-scale data previously unmet.
Optimising a Simple Fully Convolutional Network (SFCN) for accurate brain age prediction in the PAC 2019 challenge
Authors: Gong Weikang , Beckmann Christian F. , Vedaldi Andrea , Smith Stephen M. , Peng Han
Published: November 2020

Brain age prediction from brain MRI scans not only helps improve brain ageing modelling generally, but also provides benchmarks for predictive analysis methods. Brain-age delta, which is the difference between a subject’s predicted age and true age, has become a meaningful biomarker for the health of the brain. Here, we report the details of our brain age prediction models and results in the Predictive Analysis Challenge 2019. The aim of the challenge was to use T1-weighted brain MRIs to predict a subject’s age in multicentre datasets. We apply a lightweight deep convolutional neural network architecture, Simple Fully Convolutional Neural Network (SFCN), and combined several techniques including data augmentation, transfer learning, model ensemble, and bias correction for brain age prediction. The model achieved first places in both of the two objectives in the PAC 2019 brain age prediction challenge: Mean absolute error (MAE) = 2.90 years without bias removal, and MAE = 2.95 years with bias removal.
Prediction of the 4D Chromosome Structure From Time-Series Hi-C Data
Authors: Highsmith Max , Cheng Jianlin
Published: November 2020

Chromatin conformation plays an important role in a variety of genomic processes. Hi-C Data is frequently used to analyse structural features of chromatin such as AB compartments, topologically associated domains, and 3D structural models. Recently the genomics community has displayed growing interest in chromatin dynamics over time. Here we present 4DMax, a novel method which uses time-series Hi-C data to predict dynamic chromosome conformation. Using both synthetic data and real time-series Hi-C data from processes such as induced pluripotent stem cell reprogramming and cardiomyocyte differentiation, we construct fluid four dimensional models of individual chromosomes. These predicted 4D models effectively interpolate chromatin position across time, permitting prediction of unknown Hi-C contact maps at intermittent time points. Our results demonstrate that 4DMax correctly recovers higher order features of chromatin such as AB compartments and topologically associated domains, even at time points where Hi-C data is not made available to the algorithm. Use of 4DMax may alleviate the cost of expensive Hi-C experiments by interpolating intermediary timepoints while also providing valuable visualization of dynamic chromatin changes.
Phenotypic and environmental predictors of reproductive success in painted turtles
Authors: Judson Jessica M. , Hoekstra Luke A. , Holden Kaitlyn G. , Janzen Fredric J.
Published: November 2020

Sexual selection is often assumed to elicit sexually dimorphic traits. However, most work on this assumption in tetrapod vertebrates has focused on birds. In this field experiment, we assessed relationships between both sexually dimorphic (body size, claw length) and non-dimorphic traits (forelimb stripe color, baseline corticosterone concentrations) and reproductive success in adult painted turtles to explicate the roles of these phenotypes in mate choice and the evolution of sexual dimorphism. We also modified adult sex ratios in experimental ponds to elucidate the role of biased sex ratios on reproductive success, which is a timely test of the potential threat of biased sex ratios on population persistence in a species with temperature-dependent sex determination. We found no strong influence of male phenotypes on male siring success, but female body size and baseline corticosterone concentrations predicted female clutch sizes. We find weak evidence that adult sex ratio influences male siring success, with a male-biased sex ratio producing lower male siring success than a female-biased sex ratio. This study offers evidence that female mate choice may not be an important selective force on male phenotypes, but that instead selection occurs on female phenotypes, particularly body size and corticosterone concentrations. Further, biased adult sex ratios can influence reproductive success of both sexes. Finally, the use of Kompetitive Allele Specific PCR (KASP) was highly successful in parentage analysis, which adds reptiles to the growing list of taxa successfully genotyped with this new technology.

Lay Summary

Female painted turtles aren’t choosy about traits of their mates. In a field experiment, we find that male traits do not predict male fitness, but key female traits (body size and stress levels) do predict female reproductive success. Further, we find weak evidence that adult sex ratio influences individual fitness in this species with environmental sex determination. Ultimately, we reject the long-assumed importance of female mate choice in this freshwater turtle.
Centriole and PCM cooperatively recruit CEP192 to spindle poles to promote bipolar spindle assembly
Authors: Chinen Takumi , Yamazaki Kaho , Hashimoto Kaho , Fujii Ken , Watanabe Koki , Takeda Yutaka , Yamamoto Shohei , Nozaki Yuka , Tsuchiya Yuki , Takao Daisuke , Kitagawa Daiju
Published: November 2020

The pericentriolar material (PCM) that accumulates around the centriole expands during mitosis and nucleates microtubules. While centrosomes facilitate bipolar spindle formation, the individual functions of the centriole and PCM in mitosis remain elusive. Herein, we show the redundant roles of the centriole and PCM in bipolar spindle formation in human cells. Upon depletion of the PCM scaffold components, pericentrin and CDK5RAP2, centrioles remained able to recruit CEP192 onto their walls, which was sufficient for bipolar spindle formation. In contrast, through centriole removal, we found that pericentrin and CDK5RAP2 recruited CEP192 at the acentriolar spindle pole and facilitated bipolar spindle formation in mitotic cells with one centrosome. Furthermore, the chemical perturbation of polo-like kinase 1, a critical kinase for PCM assembly, efficiently suppressed the proliferation of various cancer cell lines from which centrioles were removed. Overall, these data suggest that the centriole and PCM cooperatively recruit CEP192 to spindle poles and facilitate bipolar spindle formation in human cells.
Precise Estimation of In Vivo Protein Turnover Rates
Authors: O’Brien Jonathon J. , Narayan Vikram , Wong Yao , Seitzer Phillip , Sandoval Celeste M. , Haste Nicole , Smith Megan , Rad Ramin , Gaun Aleksandr , Baker Adam , Kukurugya Matthew , Martin-McNulty Baby , Zhang Chunlian , Kolumam Ganesh , Sidrauski Carmela , Jojic Vladimir , McAllister Fiona , Bennett Bryson , Buffenstein Rochelle
Published: November 2020

Isotopic labeling with deuterium oxide (D2O) is a common technique for estimatingin vivoprotein turnover, but its use has been limited by two long-standing problems: (1) identifying non-monoisotopic peptides; and (2) estimating protein turnover rates in the presence of dynamic amino acid enrichment. In this paper, we present a novel experimental and analytical framework for solving these two problems. Peptides with high probabilities of labeling in many amino acids present fragmentation spectra that frequently do not match the theoretical spectra used in standard identification algorithms. We resolve this difficulty using a modified search algorithm we call Conditional Ion Distribution Search (CIDS). Increased identifications from CIDS along with direct measurement of amino acid enrichment and statistical modeling that accounts for heterogeneous information across peptides, dramatically improves the accuracy and precision of half-life estimates. We benchmark the approach in cells, where near-complete labeling is possible, and conduct an in vivo experiment revealing, for the first time, differences in protein turnover between mice and naked mole-rats commensurate with their disparate longevity.
Conflict over fertilization underlies the transient evolution of reinforcement
Authors: Rushworth Catherine A. , Wardlaw Alison M. , Ross-Ibarra Jeffrey , Brandvain Yaniv
Published: November 2020

When two species meet in secondary contact, the production of low fitness hybrids may be prevented by the adaptive evolution of increased prezygotic isolation, a process known as reinforcement. Theoretical challenges to the evolution of reinforcement are generally cast as a coordination problem, i.e. “how can LD between trait and preference be maintained in the face of recombination?” However, the evolution of reinforcement also poses a potential conflict between mates. For example, the opportunity costs to hybridization may differ between the sexes or species. This is particularly likely for reinforcement based on postmating prezygotic (PMPZ) incompatibilities, as the ability to fertilize both conspecific and heterospecific eggs is beneficial to male gametes, but heterospecific mating may incur a cost for female gametes. We develop a population genetic model of interspecific conflict over reinforcement inspired by “gametophytic factors”, which act as PMPZ barriers amongZea mayssubspecies. We demonstrate that this conflict results in the transient evolution of reinforcement—after females adaptively evolve to reject gametes lacking a signal common in conspecific gametes, this gamete signal adaptively introgresses into the other population. Ultimately the male gamete signal fixes in both species, and isolation returns to pre-reinforcement levels. We interpret geographic patterns of isolation amongZ. mayssubspecies in light of these findings, and suggest when and how this conflict can be resolved. Our results suggest that sexual conflict over fertilization may pose an understudied obstacle to the evolution of reinforcement.
Analysis of Hippocampal Subfields in Sickle Cell Disease Using Ultrahigh Field MRI
Authors: Santini Tales , Koo Minseok , Farhat Nadim , Campos Vinicius P. , Alkhateeb Salem , Vieira Marcelo A. C. , Butters Meryl A. , Rosano Caterina , Aizenstein Howard J. , Mettenburg Joseph , Novelli Enrico M. , Ibrahim Tamer S
Published: November 2020

Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes organ dysfunction, including cerebral vasculopathy and neurological complications. Hippocampal segmentation with newer and advanced 7 Tesla (7T) MRI protocols has revealed atrophy in specific subregions in other neurodegenerative and neuroinflammatory diseases, however, there is limited evidence of hippocampal involvement in SCD. Thus, we explored whether SCD may be also associated with abnormalities in hippocampal subregions. We conducted 7T MRI imaging in individuals with SCD, including the HbSS, HbSC and HbS/beta thalassemia genotypes (n=37), and healthy race and age-matched controls (n=40), using a customized head coil. Both T1 and T2 weighted images were used for automatic segmentation of the hippocampus subfields. Individuals with SCD had significantly smaller volume of the Dentate Gyrus and Cornu Ammonis (CA) 2 and 3 as compared to the control group. Other hippocampal subregions also showed a trend towards smaller volumes in the SCD group. These findings support previous reports of reduced volume in the temporal lobe in SCD patients. Further studies are necessary to investigate the mechanisms that lead to structural changes in the hippocampus subfields and their relationship with cognitive performance in SCD patients.
The SpliZ generalizes “Percent Spliced In” to reveal regulated splicing at single-cell resolution
Authors: Olivieri Julia Eve , Dehghannasiri Roozbeh , Salzman Julia
Published: November 2020

To date, detecting robust single-cell-regulated splicing is viewed as out of reach from droplet based technologies such as 10x Chromium. This prevents the discovery of single-cell-regulated splicing in rare cell types or those that are difficult or impossible to sequence deeply. Here, we introduce a novel, robust, and computationally efficient set of statistics, the Splicing Z Score (SpliZ) and SpliZVD, to detect regulated splicing in single cell RNA-seq including 10x Chromium. The SpliZ(VD) provides annotation-free detection of differentially regulated, complex alternative splicing events. The SpliZ generalizes and increases statistical power compared to the Percent Spliced In (PSI) and mathematically reduces to PSI for simple exon-skipping. We applied the SpliZ to primary human lung cells to discover hundreds of genes with new regulated cell-type-specific splicing. The SpliZ has wide application to enable biological discovery of genes predicted to have functionally significant splicing programs including those regulated in development.
Comparative genomic analyses provide clues to capsule switch inStreptococcus suis
Authors: Zhu Yinchu , Dong Wenyang , Ma Jiale , Zhang Yue , Zhong Xiaojun , Pan Zihao , Liu Guangjin , Wu Zongfu , Yao Huochun
Published: November 2020

Streptococcus suis(S. suis) is a major bacterial pathogen in swine industry and also an emerging zoonotic agent.S. suisproduces an important extracellular component, capsular polysaccharides (CPS). Based on which, dozens of serotypes have been identified. Through virulence genotyping, we uncovered the relatedness between proportions of SS2, SS3 and SS7 strains despite their differences in serotypes. Multi-locus sequence typing (MLST) was used to characterize wholeS. suispopulation, revealing that there is capsule switch betweenS. suisstrains. Importantly, capsule switch occurred in SS2, 3 and 7 strains belonging to CC28 and CC29, which is phylogenetically distinct from the main CC1 SS2 lineage. To further explore capsule switch inS. suis, comparative genomic analyses were performed using availableS. suiscomplete genomes. Phylogenetic analyses suggested that SS2 strains can be divided into two clades (1 and 2), and those classified into clade 2 are colocalized with SS3 and SS7 strains, which is in accordance with above virulence genotyping and MLST analyses. Clade 2 SS2 strains presented high genetic similarity with SS3 and SS7 and shared common competence and defensive elements, but are significantly different from Clade 1 SS2 strains. Notably, although thecpslocus shared by Clade 1 and 2 SS2 strains is almost the same, a specific region incpslocus of strain NSUI002 (Clade 2 SS2) can be found in SS3cpslocus, but not in Clade 1 SS2 strain. These data indicated that SS2 strains appeared in CC28 and CC29 might acquirecpslocus through capsule switch, which could well explain the distinction of genetic lineages within SS2 population.
On the necessity of recurrent processing during object recognition: it depends on the need for scene segmentation
Authors: Seijdel Noor , Loke Jessica , van de Klundert Ron , van der Meer Matthew , Quispel Eva , van Gaal Simon , de Haan Edward H.F. , Scholte H. Steven
Published: November 2020

While feed-forward activity may suffice for recognizing objects in isolation, additional visual operations that aid object recognition might be needed for real-world scenes. One such additional operation is figure-ground segmentation; extracting the relevant features and locations of the target object while ignoring irrelevant features. In this study of 60 participants, we show objects on backgrounds of increasing complexity to investigate whether recurrent computations are increasingly important for segmenting objects from more complex backgrounds. Three lines of evidence show that recurrent processing is critical for recognition of objects embedded in complex scenes. First, behavioral results indicated a greater reduction in performance after masking objects presented on more complex backgrounds; with the degree of impairment increasing with increasing background complexity. Second, electroencephalography (EEG) measurements showed clear differences in the evoked response potentials (ERPs) between conditions around 200ms - a time point beyond feed-forward activity and object decoding based on the EEG signal indicated later decoding onsets for objects embedded in more complex backgrounds. Third, Deep Convolutional Neural Network performance confirmed this interpretation; feed-forward and less deep networks showed a higher degree of impairment in recognition for objects in complex backgrounds compared to recurrent and deeper networks. Together, these results support the notion that recurrent computations drive figure-ground segmentation of objects in complex scenes.