bluuebunny/crossref_metadata_2025 huggingface dataset:
A tale of two centers: Is low-molecular-weight heparin really superior for prevention of posttraumatic venous thromboembolism?
Authors: Checchi Kyle D. , Costantini Todd W. , Badiee Jayraan , Berndtson Allison E. , Calvo Richard Y. , Rooney Alexandra S. , Wessels Lyndsey E. , Prieto James M. , Sise C. Beth , Sise Michael J. , Martin Matthew J. , Bansal Vishal
Published: April 2021

BACKGROUND

Low-molecular-weight heparin (LMWH) is widely used for venous thromboembolism chemoprophylaxis following injury. However, unfractionated heparin (UFH) is a less expensive option. We compared LMWH and UFH for prevention of posttraumatic deep venous thrombosis (DVT) and pulmonary embolism (PE).

METHODS

Trauma patients 15 years or older with at least one administration of venous thromboembolism chemoprophylaxis at two level I trauma centers with similar DVT-screening protocols were identified. Center 1 administered UFH every 8 hours for chemoprophylaxis, and center 2 used twice-daily antifactor Xa-adjusted LMWH. Clinical characteristics and primary chemoprophylaxis agent were evaluated in a two-level logistic regression model. Primary outcome was incidence of DVT and PE.

RESULTS

There were 3,654 patients: 1,155 at center 1 and 2,499 at center 2. The unadjusted DVT rate at center 1 was lower than at center 2 (3.5% vs. 5.0%; p = 0.04); PE rates did not significantly differ (0.4% vs. 0.6%; p = 0.64). Patients at center 2 were older (mean, 50.3 vs. 47.3 years; p < 0.001) and had higher Injury Severity Scores (median, 10 vs. 9; p < 0.001), longer stays in the hospital (mean, 9.4 vs. 7.0 days; p < 0.001) and intensive care unit (mean, 3.0 vs. 1.3 days; p < 0.001), and a higher mortality rate (1.6% vs. 0.6%, p = 0.02) than patients at center 1. Center 1’s patients received their first dose of chemoprophylaxis earlier than patients at center 2 (median, 1.0 vs. 1.7 days; p < 0.001). After risk adjustment and accounting for center effects, primary chemoprophylaxis agent was not associated with risk of DVT (odds ratio, 1.01; 95% confidence interval, 0.69–1.48; p = 0.949). Cost calculations showed that UFH was less expensive than LMWH.

CONCLUSION

Primary utilization of UFH is not inferior to LMWH for posttraumatic DVT chemoprophylaxis and rates of PE are similar. Given that UFH is lower in cost, the choice of this chemoprophylaxis agent may have major economic implications.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level II; Therapeutic, level III.
Designing a Liver Transplant Patient and Family Decision Support Tool for Organ Offer Decisions
Authors: Schaffhausen Cory R. , Bruin Marilyn J. , Chu Sauman , McKinney Warren T. , Lake Jack R. , Chinnakotla Srinath , Israni Ajay K.
Published: April 2021

Background.

For liver transplant candidates on the waiting list, deciding to accept a donor organ with known or potential risk factors can be stressful and can lead to declined offers. Current education for patients and family often takes place during transplant evaluations and can be overwhelming and result in low retention and poor understanding of donor quality.

Methods.

In the first phase, we sought to understand provider experiences when counseling patients about donor risks and donor offers. We conducted interviews and focus groups with liver transplant providers at 1 local center and at a national clinician conference. Twenty providers participated: 15 hepatologists and 5 surgeons. The provider feedback was used to create an initial outline of content that is consistent with decision support frameworks. In a second phase, graphic design collaborators created mockups of a patient-friendly tool. We reviewed mockups with 4 transplant coordinators and 9 liver transplant candidates for feedback on clarity and utility to prepare for an organ offer. Patient responses allowed a comparison of perceived readiness to receive an offer call before and after viewing mockups.

Results.

We identified themes relating to the offer process, repetition and timing of education, and standardization and tailoring of content. The results indicated a gap in available education after the evaluation session, and information specific to offer decisions is needed. Patient feedback emphasized the need to review the offer process before a real offer.

Conclusions.

Patients and providers responded favorably to a patient tool addressing existing gaps in education while waiting for a donor offer. Additional patient, family, and provider feedback will guide the development of an interactive tool to prepare patients and families for an offer decision.
Adapting Alzheimer Disease and Related Dementias Clinical Research Evaluations in the Age of COVID-19
Authors: Loizos Maria , Neugroschl Judith , Zhu Carolyn W. , Li Clara , Sewell Margaret , Kinsella Michael T. , Aloysi Amy , Grossman Hillel , Schimming Corbett , Martin Jane , Sano Mary
Published: April 2021

In March 2020, the novel coronavirus (COVID-19) became a global pandemic that would cause most in-person visits for clinical studies to be put on pause. Coupled with protective stay at home guidelines, clinical research at the Icahn School of Medicine at Mount Sinai Alzheimer’s Disease Research Center (ISMMS ADRC) needed to quickly adapt to remain operational and maintain our cohort of research participants. Data collected by the ISMMS ADRC as well as from other National Institute on Aging (NIA) Alzheimer Disease centers, follows the guidance of the National Alzheimer Coordinating Center (NACC). However, at the start of this pandemic, NACC had no alternative data collection mechanisms that could accommodate these safety guidelines. To stay in touch with our cohort and to ensure continued data collection under different stages of quarantine, the ISMMS ADRC redeployed their work force to continue their observational study via telehealth assessment. On the basis of this experience and that of other centers, NACC was able to create a data collection process to accommodate remote assessment in mid-August. Here we review our experience in filling the gap during this period of isolation and describe the adaptations for clinical research, which informed the national dialog for conducting dementia research in the age of COVID-19 and beyond.
Ornithological insights from Taylor White's birds
Authors: Javidi Vida , Montgomerie Robert
Published: April 2021

The Taylor White Collection of paintings from the 1700s, held at the McGill University Library, includes 661 paintings that illustrate 832 birds from around the world. With illustrations of 443 species in 30 avian orders, this collection represents a substantial proportion of the bird species known at the time and is one of the most comprehensive and
accurate collections of coloured bird illustrations made during the eighteenth century. Most of the paintings were made by Charles Collins and Peter Paillou from live birds or dead specimens in the cabinets and aviaries of White and his contemporaries. We compared a large sample of the paintings with the same birds depicted in modern bird guides to assess quantitatively the accuracy of the illustrations with respect to the colours and patterns of plumages and soft parts. We found that fewer than 3% of the paintings contained errors, and usually only in one of the 28 body regions that we assessed. Given this high level of accuracy, we identified a small red macaw from the West Indies as likely representing a previously unknown but now extinct subspecies of the Scarlet Macaw, and two other paintings of species that could not be convincingly matched to any known species.
Taylor White's ‘paper museum’ (1725–1772): understanding the scientific work of an unpublished naturalist
Authors: Stantina Céline M.
Published: April 2021

From approximately his election as a Fellow of the Royal Society in 1725 to his death in 1772, as the London barrister Taylor White (1701–1772) moved up the legal ladder, he commissioned, gathered, and organized a tremendous collection of zoological paintings now held in the Blacker Wood Collection of McGill University Rare Books and Archives. As White did not publish any major work during his lifetime, he has been substantially ignored in the historiography of science. By investigating the considerable painting compilation available in the collection, this article aims to understand White's scientific practice as a naturalist, working primarily from non-textual primary sources. The taxonomical work comprises the global arrangement of the plates, and the referencing practice, as well as the limited correspondence available on the English barrister, and these help to position the anonymous Taylor White within the world of naturalists at that time.
Lactobacillus nasalidis sp. nov., isolated from the forestomach of a captive proboscis monkey (Nasalis larvatus)
Authors: Suzuki-Hashido Nami , Tsuchida Sayaka , Hayakawa Takashi , Sakamoto Mitsuo , Azumano Akinori , Seino Satoru , Matsuda Ikki , Ohkuma Moriya , Ushida Kazunari
Published: April 2021

Three strains (YZ01T, YZ02 and YZ03) of Gram-stain-positive, facultatively anaerobic rods were isolated from the forestomach contents collected from a captive male proboscis monkey (Nasalis larvatus) at Yokohama Zoo in Japan. Phylogenetic analysis of the 16S rRNA gene sequences revealed that these strains belonged to the genus

Lactobacillus

. Based on the sequence similarity of the 16S rRNA gene,

Lactobacillus delbrueckii

subsp.

indicus

JCM 15610T was the closest phylogenetic neighbour to YZ01T. Sequence analyses of two partial concatenated housekeeping genes, the RNA polymerase alpha subunit (rpoA) and phenylalanyl-tRNA synthase alpha subunit (pheS) also indicated that the novel strains belonged to the genus

Lactobacillus

. The average nucleotide identity and digital DNA–DNA hybridization (dDDH) between

L. delbrueckii

subsp.

indicus

and YZ01T were 85.9 and 31.4 %, respectively. The phylogenetic tree based on the whole genomic data of strains YZ01T, YZ02 and YZ03 suggested that these three strains formed a single monophyletic cluster in the genus

Lactobacillus

, indicating that it belonged to a new species. The DNA G+C content of strain YZ01T was 51.6 mol%. The major fatty acids were C16 : 0 and C18 : 1 ω9c. Therefore, based on phylogenetic, phenotypic and physiological evidence, strains YZ01T, YZ02 and YZ03 represent a novel species of the genus

Lactobacillus

, for which the name Lactobacillus nasalidis sp. nov. is proposed with the type strain YZ01T (=JCM 33769T=DSM 110539T).
Effective vaccine allocation strategies, balancing economy with infection control against COVID-19 in Japan
Authors: Sunohara Satoshi , Asakura Toshiaki , Kimura Takashi , Ozawa Shun , Oshima Satoshi , Yamauchi Daigo , Tamakoshi Akiko
Published: April 2021

Due to COVID-19, many countries including Japan have implemented a suspension of economic activities for infection control. It has contributed to reduce the transmission of COVID-19 but caused severe economic losses. Today, several promising vaccines have been developed and are already being distributed in some countries. Therefore, we evaluated various vaccine and intensive countermeasure strategies with constraint of economic loss using SEIR model to obtain knowledge of how to balance economy with infection control in Japan. Our main result is that the vaccination strategy that prioritizes younger generation outperformed the other strategies in terms of deaths. On the other hand, when we focused on strategies that prioritize older generation, as Japan has decided to do, the optimal vaccination strategy was determined by the basic reproduction number and acceptable economic loss. The strategy vaccinating the young next to the old age group was the best when acceptable economic loss was high, or the basic reproduction number was low. Alternatively, the strategy vaccinating the middle next to the old age group was superior to the others with a moderate acceptable economic loss and the high basic reproduction number setting.
Have news reports on suicide and attempted suicide during the COVID-19 pandemic adhered to guidance on safer reporting? A UK-wide content analysis study
Authors: Marzano L. , Hawley M. , Fraser L. , Harris-Skillman E. , Lainez Y.X. , Hawton K.
Published: April 2021

Associations between sensational news coverage of suicide and subsequent increases in suicidal behaviour in the general population have been well documented. Amidst growing concern over the impact of the COVID-19 pandemic on suicide rates, it is especially important that news coverage of suicidal behaviour adheres to recommended standards for the responsible reporting of suicide. Using a set of dimensions based on international media guidelines, we analysed the quality and content of all UK news reports of possible COVID-19 related suicides and suicide attempts in the first four months of the pandemic (N=285 reports of 78 individual incidents published in print and online newspapers between 16th March and 12th July 2020). The majority of news reports made an explicit link between suicidal behaviour and the COVID-19 pandemic in the headline (187/285, 65.5%), and portrayed this association as strong and direct (n=196/272, 72.1%), mostly based on statements by family, friends or acquaintances of the deceased (171/285, 60%). The impact of the pandemic on suicidal behaviour was most often attributed to feelings of isolation (78/285, 27.4%), poor mental health (42, 14.7%) and sense of entrapment (41, 14.4%) as a result of government-imposed restrictions. Although rarely of poor overall quality, reporting was biased towards young people, frontline staff and relatively unusual suicides (including those involving a celebrity, murder-suicide and violent methods) Also, to varying degrees, reports failed to meet recommended standards; for example, 41.1% (117/285) did not signpost readers to sources of support, a quarter (69, 24.2%) included examples of sensational language and a third provided over-simplistic explanations for the suicidal behavior (93, 32.6%). While news reporting has improved compared to earlier coverage of suicide in the UK, it is essential that careful attention is paid to the quality and content of reports, especially as longer-term consequences of the COVID-19 pandemic develop.
When can we stop wearing masks? Agent-based modeling to identify when vaccine coverage makes nonpharmaceutical interventions for reducing SARS-CoV-2 infections redundant in indoor gatherings
Authors: Farthing Trevor S. , Lanzas Cristina
Published: April 2021

As vaccination efforts to combat the COVID-19 pandemic are ramping up worldwide, there are rising concerns that individuals will begin to eschew nonpharmaceutical interventions for preventing SARS-CoV-2 transmission and attempt to return to pre-pandemic normalcy before vaccine coverage levels effectively mitigate transmission risk. In the U.S.A., some governing bodies have already weakened or repealed guidelines for nonpharmaceutical intervention use, despite a recent spike in national COVID-19 cases and majority population of unvaccinated individuals. Recent modeling suggests that repealing nonpharmaceutical intervention guidelines too early into vaccine rollouts will lead to localized increases in COVID-19 cases, but the magnitude of nonpharmaceutical intervention effects on individual-level SARS-CoV-2 infection risk in fully- and partially-vaccinated populations is unclear. We use a previously-published agent-based model to simulate SARS-CoV-2 transmission in indoor gatherings of varying durations, population densities, and vaccination coverage levels. By simulating nonpharmaceutical interventions in some gatherings but not others, we were able to quantify the difference in SARS-CoV-2 infection risk when nonpharmaceutical interventions were used, relative to scenarios with no nonpharmaceutical interventions. We found that nonpharmaceutical interventions will often reduce secondary attack rates, especially during brief interactions, and therefore there is no definitive vaccination coverage level that makes nonpharmaceutical interventions completely redundant. However, the reduction effect on absolute SARS-CoV-2 infection risk conferred by nonpharmaceutical interventions is likely proportional to COVID-19 prevalence. Therefore, if COVID-19 prevalence decreases in the future, nonpharmaceutical interventions will likely still confer protective effects but potential benefits may be small enough to remain within “effectively negligible” risk thresholds.
One-Step Rapid Quantification of Serum Neutralizing Antibody after COVID-19 Vaccination by a High-Throughput Nanoplasmonic Sensor Platform
Authors: Huang Liping , Li Ying , Changyou Luo , Touil Nadia , Annaz Hicham el , Cheng Youqian , Zeng Shaoqi , Dang Tang , Liang Jiawei , Hu Wenjun , Xu Hao , Tu Jiasheng , Shen Yan , Liu Gang L.
Published: April 2021

The COVID-19 vaccination efficacy depends on serum production level of the neutralizing IgG antibody (NA) specific to the receptor binding domain of SARS-Cov-2 spike protein. Therefore, a high-throughput rapid assay to measure the total SARS-CoV-2 NA level is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, vaccine development, and assessment. Here, we developed a nanoplasmonic immunosorbent assay (NanoPISA) platform for one-step rapid quantification of SARS-CoV-2 NAs in clinical serum samples for high-throughput evaluation of COVID-19 vaccine effectiveness. The NanoPISA platform enhanced by the use of nanoporous hollow gold nanoparticle coupling was able to detect SARS-CoV-2 NAs with a limit of detection of 0.1 ng/mL within 15 min. The one-step NanoPISA for SARS-CoV-2 NA detection in clinical specimens yielded good results, comparable to those obtained in the gold standard seroneutralization test and the surrogate virus neutralizing ELISA. Collectively, our findings indicate that the one-step NanoPISA may offer a rapid and high-throughput NA quantification platform for evaluating the effectiveness of COVID-19 vaccines.
A Generalizable Data Assembly Algorithm for Infectious Disease Outbreaks
Authors: Majumder Maimuna S. , Rose Sherri
Published: April 2021

Background & Objective

During infectious disease outbreaks, health agencies often share text-based information about cases and deaths. This information is usually text-based and rarely machine-readable, thus creating challenges for outbreak researchers. Here, we introduce a generalizable data assembly algorithm that automatically curates text-based, outbreak-related information and demonstrate its performance across three outbreaks.

Methods

After developing an algorithm with regular expressions, we automatically curated data from health agencies via three information sources: formal reports, email newsletters, and Twitter. A validation data set was also curated manually for each outbreak.

Findings

When compared against the validation data sets, the overall cumulative missingness and misidentification of the algorithmically curated data were ≤2% and ≤1%, respectively, for all three outbreaks.

Conclusions

Within the context of outbreak research, our work successfully addresses the need for generalizable tools that can transform text-based information into machine-readable data across varied information sources and infectious diseases.
Evaluation of Different Types of Face Masks to Limit the Spread of SARS-CoV-2 – A Modeling Study
Authors: Gurbaxani Brian M. , Hill Andrew N. , Paul Prabasaj , Prasad Pragati V. , Slayton Rachel B.
Published: April 2021

We updated a published mathematical model of SARS-CoV-2 transmission with laboratory-derived source and wearer protection efficacy estimates for a variety of face masks to estimate their impact on COVID-19 incidence and related mortality in the United States. When used at already-observed population rates of 80% for those ≥65 years and 60% for those <65 years, face masks are associated with 69% (cloth) to 78% (medical procedure mask) reductions in cumulative COVID-19 infections and 82% (cloth) to 87% (medical procedure mask) reductions in related deaths over a 6-month timeline in the model, assuming a basic reproductive number of 2.5. If cloth or medical procedure masks’ source control and wearer protection efficacies are boosted about 30% each to 84% and 60% by cloth over medical procedure masking, fitters, or braces, the COVID-19 basic reproductive number of 2.5 could be reduced to an effective reproductive number ≤ 1.0, and from 6.0 to 2.3 for a variant of concern similar to delta (B.1.617.2).

Article Summary Line

Adapting a published SARS-CoV-2 transmission model together with updated, laboratory-derived source control and wearer protection efficacy estimates for a variety of face coverings as well as N95 respirators, we demonstrate that community masking as currently practiced has likely reduced cases and deaths and that this benefit can be increased with wider adoption of better performing masks.
Geographic clusters of objectively measured physical activity and the characteristics of their built environment in a Swiss urban area
Authors: Vallarta-Robledo Juan R , Joost Stéphane , André Vieira Ruas Marco , Gubelmann Cédric , Vollenweider Peter , Marques-Vidal Pedro , Guessous Idris
Published: April 2021

Introduction

Evidence suggests that the built environment can influence the intensity of physical activity. However, despite the importance of the geographic context, most of the studies do not consider the spatial framework of this association. We aimed to assess individual spatial dependence of objectively measured moderate and vigorous physical activity (MVPA) and describe the characteristics of the built environment among spatial clusters of MVPA.

Methods

Cross-sectional data from the second follow-up (2014-2017) of CoLaus|PsyCoLaus, a longitudinal population-based study of the Lausanne area (Switzerland), was used to objectively measure MVPA using accelerometers. Local Moran’s I was used to assess the spatial dependence of MVPA and detect geographic clusters of low and high MVPA. Additionally, the characteristics of the built environment observed in the clusters based on raw MVPA and MVPA adjusted for socioeconomic and demographic factors were described.

Results

Data from 1,889 participants (median age 63, 55% women) were used. The geographic distribution of MVPA and the characteristics of the built environment among clusters were similar for raw and adjusted MVPA. In the adjusted model, we found a low concentration of individuals within spatial clusters of high MVPA (median: 36.9 mins; 3% of the studied population) and low MVPA (median: 10.1 mins; 2% of the studied population). Yet, clear differences were found in both models between clusters regarding the built environment; high MVPA clusters were located in areas where specific compositions of the built environment favor physical activity.

Conclusions

Our results suggest the built environment may influence spatial patterns of MVPA independently of socioeconomic and demographic factors. Interventions in the built environment should be considered to promote physically active behaviors in urban areas.
Penetrance of breast cancer genes from the eMERGE III Network
Authors: Fan Xiao , Wynn Julia , Shang Ning , Liu Cong , Fedotov Alexander , Hallquist Miranda L.G. , Buchanan Adam H. , Williams Marc S. , Smith Maureen E. , Hoell Christin , Rasmussen-Torvik Laura J. , Peterson Josh F. , Wiesner Georgia L. , Murad Andrea M. , Jarvik Gail P. , Gordon Adam S. , Rosenthal Elisabeth A. , Stanaway Ian B. , Crosslin David R. , Larson Eric B. , Leppig Kathleen A. , Henrikson Nora B. , Williams Janet L. , Li Rongling , Hebbring Scott , Weng Chunhua , Shen Yufeng , Crew Katherine D. , Chung Wendy K.
Published: April 2021

We studied the penetrance and clinical outcomes of seven breast cancer susceptibility genes (BRCA1, BRCA2, TP53, CHEK2, ATM, PALB2 and PTEN) in almost 25,000 participants unselected for personal or family history of breast cancer. We identified 420 participants with pathogenic or likely pathogenic variants, and 147 were women who did not previously know their genetic results. Out of these 147 women, 32 women were diagnosed with breast cancer at an average age of 52.8 years. Estimated penetrance by age 60 years ranged from 18-44%, depending on the gene. Within the first twelve months after genetic results disclosure, 42% of women had taken actions related to their genetic results and two new breast cancer cases were identified. Our study provides population-based penetrance estimates for the understudied genes, CHEK2, ATM, and PALB2, and highlights the importance of using unselected populations for penetrance studies. It also demonstrates the potential clinical impact of genetic testing to improve healthcare through early diagnosis and preventative screening.
A Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men
Authors: Manikpurage Hasanga D. , Eslami Aida , Perrot Nicolas , Li Zhonglin , Couture Christian , Mathieu Patrick , Bossé Yohan , Arsenault Benoit J. , Thériault Sébastien
Published: April 2021

Background

Several risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established.

Methods

A PRSCAD including the weighted effects of >1.14 million SNPs associated with CAD was calculated in UK Biobank (n=408,422), using LDPred. Cox regressions were performed, stratified by age quartiles and sex, for incident MI and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRSCAD to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI0.02) and continuous NRI (NRI>0).

Results

From 7,746 incident MI cases and 393,725 controls, hazard ratio (HR) for MI reached 1.53 (95% CI [1.49-1.56], p=2.69e-296) per standard deviation (SD) increase of PRSCAD. PRSCAD was significantly associated with MI in both sexes, with a stronger association in men (interaction p=0.002), particularly in those aged between 40-51 years (HR=2.00, 95% CI [1.86-2.16], p=1.93e-72). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI0.02=0.199, 95% CI [0.157-0.248] and NRI>0=0.602, 95% CI [0.525-0.683]). From 23,982 deaths, HR for mortality was 1.08 (95% CI [1.06-1.09], p=5.46e-30) per SD increase of PRSCAD, with a stronger association in men (interaction p=1.60e-6).

Conclusion

Our PRSCAD predicts MI incidence and all-cause mortality, especially in men aged between 40-51 years. PRS could optimize the identification and management of individuals at risk for CAD.
The genome of New Zealand trevally (Carangidae: Pseudocaranx georgianus) uncovers a XY sex determination locus
Authors: Ruigrok Mike , Catanach Andrew , Bowatte Deepa , Davy Marcus , Storey Roy , Valenza-Troubat Noémie , López-Girona Elena , Hilario Elena , Wylie Matthew J. , Chagné David , Wellenreuther Maren
Published: April 2021

Background

The genetic control of sex determinism in teleost species is poorly understood. This is partly because of the diversity of sex determining mechanisms in this large group, including constitutive genes linked to sex chromosomes, polygenic constitutive mechanisms, environmental factors, hermaphroditism, and unisexuality. Here we use ade novogenome assembly of New Zealand silver trevally (Pseudocaranx georgianus) together with whole genome sequencing to detect sexually divergent regions, identify candidate genes and develop molecular makers.

Results

Thede novoassembly of an unsexed trevally (Trevally_v1) resulted in an assembly of 579.4 Mb in length, with a N50 of 25.2 Mb. Of the assembled scaffolds, 24 were of chromosome scale, ranging from 11 to 31 Mb. A total of 28416 genes were annotated after 12.8% of the assembly was masked with repetitive elements. Whole genome re-sequencing of 13 sexed trevally (7 males, 6 females) identified sexually divergent regions located on two scaffolds, including a 6 kb region at the proximal end of chromosome 21. Blast analyses revealed similarity between one region and the aromatase genescyp19 (a1a/b). Males contained higher numbers of heterozygous variants in both regions, while females showed regions of very low read-depth, indicative of deletions. Molecular markers tested on 96 histologically-sexed fish (42 males, 54 females). Three markers amplified in absolute correspondence with sex.

Conclusions

The higher number of heterozygous variants in males combined with deletions in females support a XY sex-determination model, indicating the trevally_v1 genome assembly was based on a male. This sex system contrasts with the ZW-type sex system documented in closely related species. Our results indicate a likely sex-determining function of thecyp19b-like gene, suggesting the molecular pathway of sex determination is somewhat conserved in this family. Our genomic resources will facilitate future comparative genomics works in teleost species, and enable improved insights into the varied sex determination pathways in this group of vertebrates. The sex marker will be a valuable resource for aquaculture breeding programmes, and for determining sex ratios and sex-specific impacts in wild fisheries stocks of this species.
The neuroinflammatory interleukin-12 signaling pathway drives Alzheimer’s disease-like pathology by perturbing oligodendrocyte survival and neuronal homeostasis
Authors: Schneeberger Shirin , Kim Seung Joon , Eede Pascale , Boltengagen Anastasiya , Braeuning Caroline , Andreadou Myrto , Becher Burkhard , Karaiskos Nikos , Kocks Christine , Rajewsky Nikolaus , Heppner Frank L.
Published: April 2021

Alzheimer’s disease (AD) is characterized by deposition of pathological amyloid-β (Aβ) and tau protein aggregates and involves chronic neuroinflammation, ultimately leading to neurodegeneration and cognitive decline. Central in AD-related neuroinflammation is the proinflammatory interleukin-12 (IL-12)/IL-23 signaling pathway whose inhibition has been shown to attenuate pathology and cognitive defects in AD-like mice. In order to explore which cell types are involved in this neuroinflammatory cascade, we used single-nuclei RNA sequencing in AD-like APPPS1 mice lacking or harboring IL-12/IL-23 signaling. We foundIl12btranscripts encoding the common p40 subunit of IL-12/IL-23 signaling to be expressed preferentially, but not exclusively, in microglia in an AD-specific manner. In contrast, transcripts for the other subunits of the IL-12 signaling pathway were expressed constitutively in neurons and oligodendrocytes irrespective of AD pathology, while transcripts for IL-23 were almost undetectable. Notably, genetic ablation of IL-12/IL-23 signaling did not affect the inflammatory gene expression profile of the AD-specific disease associated microglia (DAM), but reversed the loss of mature myelin-producing oligodendrocytes and alterations in neuronal homeostasis in APPPS1 mice. Taken together, our results reveal that IL-12, but not IL-23 is the main driver of AD-specific IL-12/IL-23 neuroinflammation, which alters neuronal and oligodendrocyte functions. Given that drugs targeting IL-12 already exist, our data may foster first clinical trials in AD subjects using this novel neuroimmune target.
Using Human Induced Pluripotent Stem Cell Derived Organoids to Identify New Pathologies in Patients with PDX1 Mutations
Authors: Krishnamurthy Mansa , Kechele Daniel O , Broda Taylor , Zhang Xinghao , Enriquez Jacob R , McCauley Heather A , Sanchez J Guillermo , Palermo Joseph , Collins Margaret , Thomas Inas H , Neef Haley C , Heider Amer , Dauber Andrew , Wells James M
Published: April 2021

Two patients with mutations inPDX1presented with pancreatic agenesis, chronic diarrhea and poor weight gain, the causes of which were not identified through routine clinical testing. We generated patient derived organoids as a novel diagnostic strategy and observed thatPDX1188delC/188delCantral organoids convert to an intestinal phenotype, while intestinal organoids undergo gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsies from bothPDX1188delC/188delCpatients, which recapitulated organoid phenotypes. Antral biopsies had increased parietal cells and lacked G-cells suggesting loss of antral identity. These patients will now be monitored for the progression of metaplasia. This study demonstrates the utility of organoids for patient diagnoses and treatment.
Conserved in 186 countries the RBD fraction of SARS CoV-2 S-protein with in-silicoT500S mutation strongly blocks ACE2 rejecting the viral spike; A Molecular-docking analysis
Authors: Banerjee Amrita , Kanwar Mehak , Santra Dipannita , Maiti Smarajit
Published: April 2021

SARS-CoV-2 developed global-pandemic with millions of infections/deaths. Blocker/inhibitor of ACE2 and viral-spikes Receptor-Binding-Domain RBD-blockers are helpful. Here, conserved RBD (CUTs) from 186-countries were compared with WUHAN-Hu-1 wild-type by CLUSTAL-X2 and Structural-alignment using Pymol. The RBD of ACE2-bound nCOV2 crystal-structure (2.68Å) 6VW1 was analyzed by Haddock-PatchDock. Extensive structural study/trial to introduce point/double/triple mutations in the following locations (Y489S/Y453S/T500S/T500Y)/(Y489S,Y453S/Y489S,T500S/Y489S,T500Y/Y453S,T500S/Y453S, T500Y)/ (Y489S,Y453S,T500S/Y489S,Y453S,T500Y) of CUT4 (most-effective) were tested with Swiss-Model-Expacy. Blind-docking of mutated-CUTs to ACE2 (6VW1) by Haddock-Hawkdock was performed and optimally complete-rejection of nCOV2 to ACE2 was noticed. Further, competitive-docking/binding-analyses were done by PRODIGY. Present results suggest that compared to the wild-spike, CUT4 showed extra LYS31-PHE490/GLN42-GLN498 bonding and lack of TYR41-THR500 interaction (in wild H-bond:2.639Å) with ACE2 RBD. Mutated-CUT4 strongly binds with the ACE2-RBD, promoting TYR41-T500S (H-bond: 2.0Å and 1.8Å)/T500Y (H-bond:2.6Å) interaction and complete inhibition of ACE2 RBD-nCOV2. Mutant combinations T500S,Y489S,T500S and Y489S,Y453S,T500Y mostly blocked ACE2. Conclusively, CUT4-mutant rejects whole glycosylated-nCoV2 pre-dock/post-dock/competitive-docking conditions.
Patterns of SARS-CoV-2 Aerosol Spread in Typical Classrooms
Authors: Rencken Gerhard K. , Rutherford Emma K. , Ghanta Nikhilesh , Kongoletos John , Glicksman Leon
Published: April 2021

Although current industry guidelines to control the spread of SARS-CoV-2 (COVID-19) have adopted a six-foot (∼1.8m) spacing between individuals indoors, recent evidence suggests that longer range spread is also responsible for infections in public spaces. The vehicle for long-range spread is smaller droplets or particles, termed bio-aerosols, or aerosols for short, which have a large surface area to volume ratio such that aerodynamic drag is much larger than gravity forces. The aerosols remain suspended in air for extended time periods and they essentially move with air currents. Prediction of the danger to occupants in a closed room when exposed to an infected individual requires knowledge of the period of exposure and the concentration level of aerosols in the breathing zone of an occupant. To obtain an estimate of the concentration level, a common assumption is well-mixed conditions within an interior space. This is obtained from a mass balance between the level of aerosol produced by an infected individual along with the airflow rate into and out of the entire space. In this work, we use computational fluid dynamics, verified by experimental results, to explore the aerosol concentration distribution in a typical classroom for several common conditions and compare these results to the well-mixed assumption. We use a tracer gas to simulate the flow and dispersion of the aerosol-air mixture. The two ventilation systems examined, ceiling diffusers and open windows, yield average concentrations at occupant breathing level 50% greater than the well mixed case, and some scenarios yield concentrations that are 150% greater than the well mixed concentration at specific breathing-level locations. Of particular concern are two conditions: horizontal air flow from an open window in line with a row of seating and, second, an infected individual seated near a sealed cold window. For the former, conditions are improved if a baffle is placed inside the open window to direct the air toward the floor, creating a condition similar to displacement ventilation. In the latter, the cold air flowing down along the cold window recirculates aerosols back into the breathing zone. Adding window covers or a portable heater below the window surface will moderate this condition.
Single-cell dissection of the human cerebrovasculature in health and disease
Authors: Garcia Francisco J. , Sun Na , Lee Hyeseung , Godlewski Brianna , Galani Kyriaki , Mantero Julio , Bennett David A. , Sahin Mustafa , Kellis Manolis , Heiman Myriam
Published: April 2021

Despite the importance of the blood-brain barrier in maintaining normal brain physiology and in understanding neurodegeneration and CNS drug delivery, human cerebrovascular cells remain poorly characterized due to their sparsity and dispersion. Here, we perform the first single-cell characterization of the human cerebrovasculature using bothex vivofresh-tissue experimental enrichment andpost mortem in silicosorting of human cortical tissue samples. We capture 31,812 cerebrovascular cells across 17 subtypes, including three distinct subtypes of perivascular fibroblasts as well as vasculature-coupled neurons and glia. We uncover human-specific expression patterns along the arteriovenous axis and determine previously uncharacterized cell type-specific markers. We use our newly discovered human-specific signatures to study changes in 3,945 cerebrovascular cells of Huntington’s disease patients, which reveal an activation of innate immune signaling in vascular and vasculature-coupled cell types and the concomitant reduction to proteins critical for maintenance of BBB integrity. Finally, our study provides a comprehensive resource molecular atlas of the human cerebrovasculature to guide future biological and therapeutic studies.
The encapsulin fromThermatoga maritimais a flavoprotein with a symmetry matched ferritin-like cargo protein
Authors: LaFrance Benjamin , Cassidy-Amstutz Caleb , Nichols Robert J , Oltrogge Luke M , Nogales Eva , Savage David F
Published: April 2021

Bacterial nanocompartments, also known as encapsulins, are an emerging class of protein-based ‘organelles’ found in bacteria and archaea. Encapsulins are virus-like icosahedral particles comprising a ∼25-50 nm shell surrounding a specific cargo enzyme. Compartmentalization is thought to create a unique chemical environment to facilitate catalysis and isolate toxic intermediates. Many questions regarding nanocompartment structure-function remain unanswered, including how shell symmetry dictates cargo loading and to what extent the shell facilitates enzymatic activity. Here, we explore these questions using the modelT. maritimananocompartment known to encapsulate a redox-active ferritin-like protein. Biochemical analysis revealed the encapsulin shell to possess a flavin binding site located at the interface between capsomere subunits, suggesting the shell may play a direct and active role in the function of the encapsulated cargo. Furthermore, we used cryoEM to show that cargo proteins use a form of symmetry-matching to facilitate encapsulation and define stoichiometry. In the case of theT. maritimaencapsulin, the decameric cargo protein with 5-fold symmetry preferentially binds to the pentameric-axis of the icosahedral shell. Taken together, these observations suggest the shell is not simply a passive barrier—it also plays a significant role in the structure and function of the cargo enzyme.
A human brain vascular atlas reveals diverse cell mediators of Alzheimer’s disease risk
Authors: Yang Andrew C. , Vest Ryan T. , Kern Fabian , Lee Davis P. , Maat Christina A. , Losada Patricia M. , Chen Michelle B. , Agam Maayan , Schaum Nicholas , Khoury Nathalie , Calcuttawala Kruti , Pálovics Róbert , Shin Andrew , Wang Elizabeth Y. , Luo Jian , Gate David , Siegenthaler Julie A. , McNerney M. Windy , Keller Andreas , Wyss-Coray Tony
Published: April 2021

The human brain vasculature is of vast medical importance: its dysfunction causes disability and death, and the specialized structure it forms—the blood-brain barrier—impedes treatment of nearly all brain disorders. Yet, no molecular atlas of the human brain vasculature exists. Here, we develop Vessel Isolation and Nuclei Extraction for Sequencing (VINE-seq) to profile the major human brain vascular and perivascular cell types through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 17 control and Alzheimer’s disease (AD) patients. We identify brain region-enriched pathways and genes divergent between humans and mice, including those involved in disease. We describe the principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum; but discover that many zonation and cell-type markers differ between species. We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization; and define perivascular versus meningeal fibroblast specialization. In AD, we observe a selective vulnerability of ECM-maintaining pericytes and gene expression patterns implicating dysregulated blood flow. With an expanded survey of brain cell types, we find that 30 of the top 45 AD GWAS genes are expressed in the human brain vasculature, confirmedin situ. Vascular GWAS genes map to endothelial protein transport, adaptive immune, and ECM pathways. Many are microglia-specific in mice, suggesting an evolutionary transfer of AD risk to human vascular cells. Our work unravels the molecular basis of the human brain vasculature, informing our understanding of overall brain health, disease, and therapy.
Woody species do not differ in dormancy progression: differences in time to budbreak due to forcing and cold hardiness
Authors: Kovaleski Al
Published: April 2021

Budbreak is one of the most observed and studied phenological phases in perennial plants. Two dimensions of exposure to temperature are generally used to model budbreak: accumulation of time spent at low temperatures (chilling); and accumulation of heat units (forcing). These two effects have a well-established negative correlation: the more chilling, the less forcing required for budbreak. Furthermore, temperate plant species are assumed to vary in amount of chilling required to complete endodormancy and begin the transition to breaking bud. Still, prediction of budbreak remains a challenge. The present work demonstrates across a wide range of species how bud cold hardiness must be accounted for to study dormancy and accurately predict time to budbreak. Cold hardiness defines the path length to budbreak, meaning the difference between the cold hardiness buds attain during the winter, and the cold hardiness at which deacclimated buds are predicted to open. This distance varies among species and throughout winter within a species. Increases in rate of cold hardiness loss (deacclimation) measured throughout winter show that chilling controls deacclimation potential – the proportion of the maximum rate response attained at high chill accumulation – which has a sigmoid relationship to chilling accumulation. For forcing, rates of deacclimation increase non-linearly in response to temperature. Comparisons of deacclimation potential show a dormancy progresses similarly for all species. This observation suggests that comparisons of physiologic and genetic control of dormancy requires an understanding of cold hardiness dynamics and the necessity for an update of the framework for studying dormancy and its effects on spring phenology.
The maize hexokinase geneZmHXK7confers salt resistance in transgenicArabidopsisplants
Authors: Liu Qianqian , Tian Zengyuan , Guo Yuqi
Published: April 2021

The hexokinase (HXK) gene family, whose members play vital roles in sugar induction signals and glycolysis in organisms, is widely found in plants. Although some hexokinase genes have been studied in maize, a systematic report of the gene family and its role in plant resistance is lacking. In this study, 10 hexokinase genes were systematically identified in maize based on the maize genome-wide database. Phylogenetic analysis divides the maize HXK protein family into four clusters. Prediction of cis-regulatory elements showed that a number of elements responding to abiotic stress exist in the promoter of hexokinase genes. The expression profile of these genes, originated from B73, showed that different members of hexokinase genes are highly expressed in roots and leaves of maize under salt or drought stress, which is similar to that of Mo17.The coding sequence ofZmHXK7gene, isolated from maize B73, was constructed into plant expression vector pMDC45 and then transformed intoathxk3(Salk_022188C). By hyg resistance detection, PCR analysis, and western blot confirmation, the homozygous progenies of transgenic Arabidopsis lines were identified. Subcellular localization analysis showed that theZmHXK7gene was located in cytosol. Seedling growth and salt stress inhibition in complementary mutant plants ofZmHXK7gene were significantly improved, and enhanced salt tolerance was displayed. Our study provides insights into the evolution and expression patterns of the hexokinase gene and show that maize ZmHXK7 proteins play an important role in resisting salt stress, which will be useful in plant breeding for abiotic stress resistance.
A general theory for temperature-dependence in biology
Authors: Arroyo José Ignacio , Díez Beatriz , Kempes Christopher P. , West Geoffrey B. , Marquet Pablo A.
Published: April 2021

At present, there is no simple, complete, and first principles-based model for quantitatively describing the full range of observed biological temperature responses. Here, we derive a theory exhibiting these features based on the Eyring-Evans-Polanyi theory governing chemical reaction rates, and which is applicable across all scales from the micro to the macro. Assuming only that the conformational entropy of molecules changes with temperature, we derive a theory for the temperature dependence which takes the form of an exponential function modified by a power-law. Our framework leads to six deductions applicable to any biological trait that depends on temperature, and elucidates novel aspects of universal temperature responses across the tree of life, from quantum to classical scales. All predictions are well supported by data for a wide variety of biological rates and steady states, from molecular to ecological scales and across multiple taxonomic groups. In addition, we provide novel explanations of several empirical relationships including optimal values in temperature response curves.

One-Sentence Summary

We derive a simple and universal formulae to characterize temperature responses of biological processes across the tree of life.
Spatial transcriptome sequencing revealed spatial trajectory in the Non-Small Cell Lung Carcinoma
Authors: Zhang Li , Mao Shengqiang , Yao Menglin , Chao Ningning , Yang Ying , Ni Yinyun , Song Tingting , Liu Zhiqiang , Yang Yongfeng , Li Weimin
Published: April 2021

Deepening understanding in the heterogeneity of tumors is critical for clinical treatment. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal lung cancer using the spatial transcriptomics (ST) technology. We identified gene expression gradients in stroma adjacent to tumor regions that allow for re-understanding of the tumor micro-environment. The establishment of these profiles was the first step towards an unbiased view of lung cancer and can serve as a dictionary for future studies. Tumor subclones were detected by ST technology in our research, while we contrast the EMT ability among in subclones which inferred the possible trajectory of tumor metastasis and invasion, which was confirmed by constructing the pseudo-time model of spatial transition within subclones. Together, these results uncovered lung cancer spatial heterogeneity, highlight potential tumor micro-environment differences and spatial evolution trajectory, and served as a resource for further investigation of tumor microenvironment.