bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of essential genes in Caenorhabditis elegans through whole-genome sequencing of legacy mutant collections
Authors: Li-Leger Erica , Feichtinger Richard , Flibotte Stephane , Holzkamp Heinke , Schnabel Ralf , Moerman Donald G
Published: September 2021

It has been estimated that 15%–30% of the ∼20,000 genes in C. elegans are essential, yet many of these genes remain to be identified or characterized. With the goal of identifying unknown essential genes, we performed whole-genome sequencing on complementation pairs from legacy collections of maternal-effect lethal and sterile mutants. This approach uncovered maternal genes required for embryonic development and genes with apparent sperm-specific functions. In total, 58 putative essential genes were identified on chromosomes III–V, of which 52 genes are represented by novel alleles in this collection. Of these 52 genes, 19 (40 alleles) were selected for further functional characterization. The terminal phenotypes of embryos were examined, revealing defects in cell division, morphogenesis, and osmotic integrity of the eggshell. Mating assays with wild-type males revealed previously unknown male-expressed genes required for fertilization and embryonic development. The result of this study is a catalog of mutant alleles in essential genes that will serve as a resource to guide further study toward a more complete understanding of this important model organism. As many genes and developmental pathways in C. elegans are conserved and essential genes are often linked to human disease, uncovering the function of these genes may also provide insight to further our understanding of human biology.
MIND Diet and Cognitive Function in Puerto Rican Older Adults
Authors: Boumenna Tahani , Scott Tammy M , Lee Jong-Soo , Zhang Xiyuan , Kriebel David , Tucker Katherine L , Palacios Natalia
Published: September 2021

Background

Healthy diets have been associated with better cognitive function. Socioeconomic factors including education, poverty, and job complexity may modify the relationship between diet and cognition.

Methods

We used adjusted linear mixed models to examine the association between long-term adherence to the Mediterranean-Dietary Approaches to Stop Hypertension - Intervention for Neurodegenerative Delay (MIND) diet and cognitive function over 8 years of follow-up in Puerto Rican adults residing in the Boston, MA area (aged 45–75 years at baseline). We also examined whether the MIND diet—cognition association was confounded or modified by socioeconomic measures.

Results

In both cross-sectional and longitudinal analyses the highest, versus lowest, MIND quintile was associated with better cognition function (β = 0.093; 95% CI: 0.035, 0.152; p trend = .0019), but not with cognitive trajectory over 8 years. Education <=8th grade (β = −0.339; 95% CI: 0.394, −0.286; p < .0001) and income-to-poverty ratio <120% (β = −0.049; 95% CI: −0.092, −0.007; p = .024) were significantly associated with lower cognitive function, while higher job complexity (β = 0.008; 95% CI: 0.006, 0.011; p < .0001) was associated with better cognition function. These variables acted as confounders, but not effect modifiers of the MIND-diet—cognitive function relationship.

Conclusion

Adherence to the MIND diet was associated with better cognitive function at baseline and over 8 years of follow-up; however, MIND diet was not associated with 8-year cognitive trajectory. More studies are needed to better understand whether the MIND diet is protective against long-term cognitive decline.
α-synuclein inhibits Snx3-retromer retrograde trafficking of the conserved membrane-bound proprotein convertase Kex2 in the secretory pathway of Saccharomyces cerevisiae
Authors: Rajasekaran Santhanasabapathy , Peterson Patricia P , Liu Zhengchang , Robinson Lucy C , Witt Stephan N
Published: September 2021

We tested the ability of alpha-synuclein (α-syn) to inhibit Snx3-retromer-mediated retrograde trafficking of Kex2 and Ste13 between late endosomes and the trans-Golgi network (TGN) using a Saccharomyces cerevisiae model of Parkinson’s disease. Kex2 and Ste13 are a conserved, membrane-bound proprotein convertase and dipeptidyl aminopeptidase, respectively, that process pro-α-factor and pro-killer toxin. Each of these proteins contains a cytosolic tail that binds to sorting nexin Snx3. Using a combination of techniques, including fluorescence microscopy, western blotting and a yeast mating assay, we found that α-syn disrupts Snx3-retromer trafficking of Kex2-GFP and GFP-Ste13 from the late endosome to the TGN, resulting in these two proteins transiting to the vacuole by default. Using three α-syn variants (A53T, A30P, and α-synΔC, which lacks residues 101–140), we further found that A53T and α-synΔC, but not A30P, reduce Snx3-retromer trafficking of Kex2-GFP, which is likely to be due to weaker binding of A30P to membranes. Degradation of Kex2 and Ste13 in the vacuole should result in the secretion of unprocessed, inactive forms of α-factor, which will reduce mating efficiency between MATa and MATα cells. We found that wild-type α-syn but not A30P significantly inhibited the secretion of α-factor. Collectively, our results support a model in which the membrane-binding ability of α-syn is necessary to disrupt Snx3-retromer retrograde recycling of these two conserved endopeptidases.
The utility of Conversation Analysis versus Roter’s Interaction Analysis System for studying communication in pharmacy settings: a scoping review
Authors: Alsubaie Sarah , Grant Daniel , Donyai Parastou
Published: September 2021

Objectives

To compare the usefulness of the Roter Interaction Analysis System with Conversation Analysis (CA) for studying dynamic patient–pharmacist interactions within pharmacy practice. A scoping review was undertaken to identify all studies using Roter’s method or CA to investigate patient–pharmacist interactions. The studies were then compared and contrasted for their methodological advantages and disadvantages.

Key findings

In total, 31 studies met the inclusion criteria. Roter’s method is effective in briefly describing patient–pharmacist interactions and can be used to measure the effect of training courses without consuming too much time. CA, although a time-consuming undertaking, looks at very specific features and the sequence of conversations including the dynamics of two-way interactions and can therefore be used to identify the source of conflict or misunderstandings. A flowchart showing the usefulness of both methods is suggested to help other researchers select the appropriate method(s) for their own research.

Although both methods are effective for investigating patient–pharmacist interactions independently, using them sequentially could enable researchers to firstly identify how to make improvements (via CA), design relevant training and then investigate the impact of such training (via Roter’s method) to enrich communications research.
Competition policy’s role in the economic recovery process from the Covid-19 pandemic crisis—insight from UNCTAD
Authors: Moreira Teresa
Published: September 2021

The COVID-19 pandemic outbreak disrupted markets and had a serious negative impact in economies across the world. Competition Authorities were at the forefront of initial public response measures through strong law enforcement and active market monitoring actions, temporary exemptions from competition provisions, merger control procedural adjustments and advocacy, an increasingly important function vis-à-vis Governments and all relevant stakeholders. Competition law and policy have therefore remained highly relevant during this period in both developed and developing countries. Current common challenges faced are raised by the increased digitalization of the economy and the dominance of digital platforms, especially considering the number and market share of micro and Small and Medium Sized enterprises (SMEs), the most seriously affected by the pandemic lockdown measures. Several jurisdictions and international organizations are equipping themselves with new legislation and instruments to address these challenges, namely supporting SMEs fair access to digital markets and promoting competitive public procurement, but less experienced and resource-constrained authorities of developing countries must prioritize otherwise. Competition advocacy is now more than ever a priority for them so that the economic recovery packages preserver open, fair, and equitable markets. International cooperation, bringing together developed and developing countries authorities, provides a crucial framework of support especially at this time. UNCTAD is particularly well placed to support developing countries’ Competition Authorities contributions to “building back better” in times of crisis.
Epigenetic Profiling and Response to CD19 Chimeric Antigen Receptor T-Cell Therapy in B-Cell Malignancies
Authors: Garcia-Prieto Carlos A , Villanueva Lorea , Bueno-Costa Alberto , Davalos Veronica , González-Navarro Europa Azucena , Juan Manel , Urbano-Ispizua Álvaro , Delgado Julio , Ortiz-Maldonado Valentín , del Bufalo Francesca , Locatelli Franco , Quintarelli Concetta , Sinibaldi Matilde , Soler Marta , Castro de Moura Manuel , Ferrer Gerardo , Urdinguio Rocio G , Fernandez Agustin F , Fraga Mario F , Bar Diana , Meir Amilia , Itzhaki Orit , Besser Michal J , Avigdor Abraham , Jacoby Elad , Esteller Manel
Published: September 2021

Background

Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance of epigenetic changes in cancer immunology prompted us to determine the impact of the DNA methylation profiles of CART19 cells on the clinical course.

Methods

We recruited 114 patients with B-cell malignancies, comprising 77 patients with acute lymphoblastic leukemia and 37 patients with non-Hodgkin lymphoma who were treated with CART19 cells. Using a comprehensive DNA methylation microarray, we determined the epigenomic changes that occur in the patient T cells upon transduction of the CAR vector. The effects of the identified DNA methylation sites on clinical response, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, event-free survival, and overall survival were assessed. All statistical tests were 2-sided.

Results

We identified 984 genomic sites with differential DNA methylation between CAR-untransduced and CAR-transduced T cells before infusion into the patient. Eighteen of these distinct epigenetic loci were associated with complete response (CR), adjusting by multiple testing. Using the sites linked to CR, an epigenetic signature, referred to hereafter as the EPICART signature, was established in the initial discovery cohort (n = 79), which was associated with CR (Fisher exact test, P < .001) and enhanced event-free survival (hazard ratio [HR] = 0.36; 95% confidence interval [CI] = 0.19 to 0.70; P = .002; log-rank P = .003) and overall survival (HR = 0.45; 95% CI = 0.20 to 0.99; P = .047; log-rank P = .04;). Most important, the EPICART profile maintained its clinical course predictive value in the validation cohort (n = 35), where it was associated with CR (Fisher exact test, P < .001) and enhanced overall survival (HR = 0.31; 95% CI = 0.11 to 0.84; P = .02; log-rank P = .02).

Conclusions

We show that the DNA methylation landscape of patient CART19 cells influences the efficacy of the cellular immunotherapy treatment in patients with B-cell malignancy.
State Compliance and the Track Record of International Security Institutions: Evidence from the Nuclear Nonproliferation Regime
Authors: Kaplow Jeffrey M
Published: September 2021

Why do states choose to comply with international security institutions, and what factors drive changes in compliance behavior over time? This article argues that these institutions are based on a fundamental bargain among members—each is willing to comply only so long as others do—but there is often uncertainty about the compliance of others. The track record of the institution provides information that helps to resolve this uncertainty. As time passes with few violations, states will be more likely to comply themselves; evidence of increasing noncompliance, on the other hand, will make states more likely to cheat. Analysis of data on nuclear weapons programs from 1968 to 2010 finds that members of the nuclear nonproliferation regime are more likely to pursue nuclear weapons when there have been a greater number of recent violations of the regime. These findings point to a more dynamic view of international security institutions than has generally been recognized in the literature.
Ion acceleration to 100 keV by the ExB wave mechanism in collision-less shocks
Authors: Stasiewicz Krzysztof , Eliasson Bengt
Published: September 2021

It is shown that ions can be accelerated to about 100 keV in the direction perpendicular to the magnetic field by the ExB mechanism of electrostatic waves. The acceleration occurs in discrete steps of duration being a small fraction of the gyroperiod and can explain observations of ion energization to 10 keV at quasi-perpendicular shocks and to hundreds keV at quasi-parallel shocks. A general expression is provided for the maximum energy of ions accelerated in shocks of arbitrary configuration. The waves involved in the acceleration are related to three cross-field current-driven instabilities: the lower hybrid drift (LHD) instability induced by the density gradients in shocks and shocklets, followed by the modified two-stream (MTS) and electron cyclotron drift (ECD) instabilities, induced by the ExB drift of electrons in the strong LHD wave electric field. The ExB wave mechanism accelerates heavy ions to energies proportional to the atomic mass number, which is consistent with satellite observations upstream of the bow shock and also with observations of post-shocks in supernovae remnants. The results are compared with other acceleration mechanisms traditionally discussed in the literature.
A slim disc approach to external photoevaporation of discs
Authors: Owen James E , Altaf Noumahn
Published: September 2021

The photoevaporation of protoplanetary discs by nearby massive stars present in their birth cluster plays a vital role in their evolution. Previous modelling assumes that the disc behaves like a classical Keplerian accretion disc out to a radius where the photoevaporative outflow is launched. There is then an abrupt change in the angular velocity profile, and the outflow is modelled by forcing the fluid parcels to conserve their specific angular momenta. Instead, we model externally photoevaporating discs using the slim disc formalism. The slim disc approach self-consistently includes the advection of radial and angular momentum as well as angular momentum redistribution by internal viscous torques. Our resulting models produce a smooth transition from a rotationally supported Keplerian disc to a photoevaporative driven outflow, where this transition typically occurs over ∼4–5 scale heights. The penetration of ultraviolet photons predominately sets the radius of the transition and the viscosity’s strength plays a minor role. By studying the entrainment of dust particles in the outflow, we find a rapid change in the dust size and surface density distribution in the transition region due to the steep gas density gradients present. This rapid change in the dust properties leaves a potentially observable signature in the continuum spectral index of the disc at mm wavelengths. Using the slim disc formalism in future evolutionary calculations will reveal how both the gas and dust evolve in their outer regions and the observable imprints of the external photoevaporation process.
TYGS and LPSN: a database tandem for fast and reliable genome-based classification and nomenclature of prokaryotes
Authors: Meier-Kolthoff Jan P , Carbasse Joaquim Sardà , Peinado-Olarte Rosa L , Göker Markus
Published: September 2021

Microbial systematics is heavily influenced by genome-based methods and challenged by an ever increasing number of taxon names and associated sequences in public data repositories. This poses a challenge for database systems, particularly since it is obviously advantageous if such data are based on a globally recognized approach to manage names, such as the International Code of Nomenclature of Prokaryotes. The amount of data can only be handled if accurate and reliable high-throughput platforms are available that are able to both comply with this demand and to keep track of all changes in an efficient and flexible way. The List of Prokaryotic names with Standing in Nomenclature (LPSN) is an expert-curated authoritative resource for prokaryotic nomenclature and is available at https://lpsn.dsmz.de. The Type (Strain) Genome Server (TYGS) is a high-throughput platform for accurate genome-based taxonomy and is available at https://tygs.dsmz.de. We here present important updates of these two previously introduced, heavily interconnected platforms for taxonomic nomenclature and classification, including new high-level facilities providing access to bioinformatic algorithms, a considerable expansion of the database content, and new ways to easily access the data.
SignaLink3: a multi-layered resource to uncover tissue-specific signaling networks
Authors: Csabai Luca , Fazekas Dávid , Kadlecsik Tamás , Szalay-Bekő Máté , Bohár Balázs , Madgwick Matthew , Módos Dezső , Ölbei Márton , Gul Lejla , Sudhakar Padhmanand , Kubisch János , Oyeyemi Oyebode James , Liska Orsolya , Ari Eszter , Hotzi Bernadette , Billes Viktor A , Molnár Eszter , Földvári-Nagy László , Csályi Kitti , Demeter Amanda , Pápai Nóra , Koltai Mihály , Varga Máté , Lenti Katalin , Farkas Illés J , Türei Dénes , Csermely Péter , Vellai Tibor , Korcsmáros Tamás
Published: September 2021

Signaling networks represent the molecular mechanisms controlling a cell's response to various internal or external stimuli. Most currently available signaling databases contain only a part of the complex network of intertwining pathways, leaving out key interactions or processes. Hence, we have developed SignaLink3 (http://signalink.org/), a value-added knowledge-base that provides manually curated data on signaling pathways and integrated data from several types of databases (interaction, regulation, localisation, disease, etc.) for humans, and three major animal model organisms. SignaLink3 contains over 400 000 newly added human protein-protein interactions resulting in a total of 700 000 interactions for Homo sapiens, making it one of the largest integrated signaling network resources. Next to H. sapiens, SignaLink3 is the only current signaling network resource to provide regulatory information for the model species Caenorhabditis elegans and Danio rerio, and the largest resource for Drosophila melanogaster. Compared to previous versions, we have integrated gene expression data as well as subcellular localization of the interactors, therefore uniquely allowing tissue-, or compartment-specific pathway interaction analysis to create more accurate models. Data is freely available for download in widely used formats, including CSV, PSI-MI TAB or SQL.
General one-loop contributions to the decay $H\rightarrow \nu_l\bar{\nu}_l\gamma$
Authors: Phan Khiem Hong , Hue Le Tho , Tran Dzung Tri
Published: September 2021

General one-loop contributions to the decay amplitudes $H\rightarrow \nu_l\bar{\nu}_l\gamma$ are presented, considering all possible contributions of additional heavy vector gauge bosons, fermions, and charged (and also neutral) scalar particles appearing in the loop diagrams. Moreover, the results can be applied directly when extra neutrinos (apart from three ones in the standard model) are taken into account in final states. Analytic results are expressed in terms of Passarino–Veltman scalar functions which can be evaluated numerically using $\texttt{LoopTools}$. In the standard model framework, these analytical results are generated and cross-checked with previous computations. We find that our results are well consistent with these computations. Within the standard model limit, phenomenological results for the decay channels are also studied using the present input parameters at the Large Hadron Collider. Lastly, the calculation is also applied to the Two Higgs Doublet Model framework as another example.
Asporin regulated by miR-26b-5p mediates chondrocyte senescence and exacerbates osteoarthritis progression via TGF-β1/Smad2 pathway
Authors: Liu Liangliang , Zhao Chang , Zhang Haiyan , Lu Yuheng , Luo Bingsheng , Yao Zihao , Shao Yan , Zeng Hua , Zeng Chun , Zhang Rongkai , Fang Hang , Pan Jianying , Bai Xiaochun , Cai Daozhang
Published: September 2021

Objectives

This study aimed to investigate the role and mechanism of asporin in modulating chondrocyte senescence in OA pathology.

Methods

Asporin and senescence-related hallmark expression were examined in human and experimental OA mouse cartilage samples. Twelve-week-old male C57 mice were administered with recombinant protein (rm-asporin)- or asporin-siRNA-expressing lentiviruses via intra-articular injection once a week after destabilization of the medial meniscus (DMM) surgery to induce OA. Cartilage damage was measured using the Osteoarthritis Research Society International score. Senescence-associated β-galactosidase (SA-β-Gal) staining, γH2AX, p21 and p16INK4a were analysed by immunofluorescence staining and western blot to assess the specific role of asporin in chondrocyte senescence. The TGF-β1–Smad2 signalling pathway and miR-26b-5p were further evaluated to explore the mechanism of asporin in OA.

Results

Asporin was upregulated in articular chondrocytes of OA patients and DMM mice and accompanied by accumulation of senescent cells. Asporin overexpression exaggerated OA progression, whereas silencing asporin restored chondrocyte homeostasis and deferred chondrocyte senescence, leading to markedly attenuated DMM-induced OA. Cellular and molecular analyses showed that asporin can be inhibited by miR-26b-5p, which was significantly downregulated in OA cartilage, leading to exacerbation of experimental OA partially through inhibition of TGF-β1–Smad2 signalling in chondrocytes.

Conclusions

Our findings indicate that asporin plays an essential role in chondrocyte senescence and OA pathogenesis. Upregulated by miR-26b-5p, asporin inhibits the TGF-β1–Smad2 pathway to accelerate chondrocyte senescence and exacerbate cartilage degeneration. Targeting the miR-26b-5p–asporin–Smad2 axis may serve as a practical therapeutic strategy to delay chondrocyte senescence and OA development.
Embedding Racism: City Government Credit Ratings and the Institutionalization of Race in Markets
Authors: Norris Davon
Published: September 2021

How does racism and racial inequality manifest in contemporary markets? Leveraging insights from the sociology of race and economic sociology, I highlight how ratings and scores operate as key mechanisms institutionalizing racism in markets according to an epistemology of racial ignorance. While ratings and scores give a veneer of individualized objectivity, their actual inputs reflect decades of racial disadvantage. The use of such racialized inputs embeds historical racism in ratings allowing racial inequality to persist and escape cognition as seemingly race-neutral inputs “explain away” racial disparities. I demonstrate this argument using an original dataset to approximate the evaluative criteria used in rating city government creditworthiness. I show that cities with larger proportions of Black residents receive worse credit ratings when controlling for the non-racialized inputs in the evaluative criteria. This racial disparity only attenuates after the inclusion of the criterion median family income, which I argue is a fundamentally racialized input owing to the legacy of racism in the United States. Establishing this point provides key theoretical takeaways at the intersection of race and economic sociology as scores and ratings pervade more corners of social life and push up against the epistemological seams of how we understand and identify inequality.
The Impact of Volunteering at a Family Camp for Children and Adolescents With Cancer: The Experience of Pediatric Intensive Care Nurses
Authors: Butterworth Lori , Nasr Annette , Pyke-Grimm Kimberly A. , Swisher Darcy , Johnson Kelly
Published: September 2021

OBJECTIVE

This study explored the experience of pediatric ICU (PICU) nurses who volunteered at a camp for families of children and adolescents with cancer.

BACKGROUND

PICU nurses are at risk of developing symptoms of posttraumatic stress disorder, compassion fatigue, depression, and burnout due to exposure(s) to traumatic events. Spending time with patients, families, and nurse colleagues at camp may reduce the effects of this exposure.

METHODS

A qualitative descriptive study was conducted using content analysis. Fifteen nurse participants completed a precamp questionnaire and semistructured focus groups immediately following camp. Individual interviews were conducted 6 months after camp.

RESULTS

Three categories emerged: 1) personal factors, changes in the nurses themselves; 2) patient and family factors, changes in how nurses perceived patients and families; and 3) work-related factors, relationships with colleagues.

CONCLUSIONS

Supporting PICU nurses to participate with patients, families, and colleagues outside of the hospital may reduce burnout and support nurses' well-being.
Bee flowers drive macroevolutionary diversification in long-horned bees
Authors: Dorchin Achik , Shafir Anat , Neumann Frank H. , Langgut Dafna , Vereecken Nicolas J. , Mayrose Itay
Published: September 2021

The role of plant–pollinator interactions in the rapid radiation of the angiosperms have long fascinated evolutionary biologists. Studies have brought evidence for pollinator-driven diversification of various plant lineages, particularly plants with specialized flowers and concealed rewards. By contrast, little is known about how this crucial interaction has shaped macroevolutionary patterns of floral visitors. In particular, there is currently no empirical evidence that floral host association has increased diversification in bees, the most prominent group of floral visitors that essentially rely on angiosperm pollen. In this study, we examine how floral host preference influenced diversification in eucerine bees (Apidae, Eucerini), which exhibit large variations in their floral associations. We combine quantitative pollen analyses with a recently proposed phylogenetic hypothesis, and use a state speciation and extinction probabilistic approach. Using this framework, we provide the first evidence that multiple evolutionary transitions from host plants with accessible pollen to restricted pollen from ‘bee-flowers’ have significantly increased the diversification of a bee clade. We suggest that exploiting host plants with restricted pollen has allowed the exploitation of a new ecological niche for eucerine bees and contributed both to their colonization of vast regions of the world and their rapid diversification.
Lifelong exposure to artificial light at night impacts stridulation and locomotion activity patterns in the cricketGryllus bimaculatus
Authors: Levy Keren , Wegrzyn Yoav , Efronny Ronny , Barnea Anat , Ayali Amir
Published: September 2021

Living organisms experience a worldwide continuous increase in artificial light at night (ALAN), negatively affecting their behaviour. The field cricket, an established model in physiology and behaviour, can provide insights into the effect of ALAN on insect behaviour. The stridulation and locomotion patterns of adult male crickets reared under different lifelong ALAN intensities were monitored simultaneously for five consecutive days in custom-made anechoic chambers. Daily activity periods and acrophases were compared between the experimental groups. Control crickets exhibited a robust rhythm, stridulating at night and demonstrating locomotor activity during the day. By contrast, ALAN affected both the relative level and timing of the crickets' nocturnal and diurnal activity. ALAN induced free-running patterns, manifested in significant changes in the median and variance of the activity periods, and even arrhythmic behaviour. The magnitude of disruption was light intensity dependent, revealing an increase in the difference between the activity periods calculated for stridulation and locomotion in the same individual. This finding may indicate the existence of two peripheral clocks. Our results demonstrate that ecologically relevant ALAN intensities affect crickets’ behavioural patterns, and may lead to decoupling of locomotion and stridulation behaviours at the individual level, and to loss of synchronization at the population level.
When fossil clades ‘compete’: local dominance, global diversification dynamics and causation
Authors: Lidgard Scott , Di Martino Emanuela , Zágoršek Kamil , Liow Lee Hsiang
Published: September 2021

Examining the supposition that local-scale competition drives macroevolutionary patterns has become a familiar goal in fossil biodiversity studies. However, it is an elusive goal, hampered by inadequate confirmation of ecological equivalence and interactive processes between clades, patchy sampling, few comparative analyses of local species assemblages over long geological intervals, and a dearth of appropriate statistical tools. We address these concerns by reevaluating one of the classic examples of clade displacement in the fossil record, in which cheilostome bryozoans surpass the once dominant cyclostomes. Here, we analyse a newly expanded and vetted compilation of 40 190 fossil species occurrences to estimate cheilostome and cyclostome patterns of species proportions within assemblages, global genus richness and genus origination and extinction rates while accounting for sampling. Comparison of time-series models using linear stochastic differential equations suggests that inter-clade genus origination and extinction rates are causally linked to each other in a complex feedback relationship rather than by simple correlations or unidirectional relationships, and that these rates are not causally linked to changing within-assemblage proportions of cheilostome versus cyclostome species.
Hoverflies use a time-compensated sun compass to orientate during autumn migration
Authors: Massy Richard , Hawkes Will L. S. , Doyle Toby , Troscianko Jolyon , Menz Myles H. M. , Roberts Nicholas W. , Chapman Jason W. , Wotton Karl R.
Published: September 2021

The sun is the most reliable celestial cue for orientation available to daytime migrants. It is widely assumed that diurnal migratory insects use a ‘time-compensated sun compass’ to adjust for the changing position of the sun throughout the day, as demonstrated in some butterfly species. The mechanisms used by other groups of diurnal insect migrants remain to be elucidated. Migratory species of hoverflies (Diptera: Syrphidae) are one of the most abundant and beneficial groups of diurnal migrants, providing multiple ecosystem services and undergoing directed seasonal movements throughout much of the temperate zone. To identify the hoverfly navigational strategy, a flight simulator was used to measure orientation responses of the hoverfliesScaeva pyrastriandScaeva seleniticato celestial cues during their autumn migration. Hoverflies oriented southwards when they could see the sun and shifted this orientation westward following a 6 h advance of their circadian clocks. Our results demonstrate the use of a time-compensated sun compass as the primary navigational mechanism, consistent with field observations that hoverfly migration occurs predominately under clear and sunny conditions.
Computational systematics of nutritional support of vaccination against viral and bacterial pathogens as prolegomena to vaccinations against COVID-19
Authors: Torshin Ivan Y. , Gromova Olga A. , Chuchalin Alexander G.
Published: September 2021

A total of 6,628 PUBMED-registered publications on the relationships between the effects of vaccination and the provision of micronutrients have been studied by methods of topological analysis of text data. In case of insufficient intake of certain micronutrients, the functioning of the acquired immunity is disrupted resulting in an imbalance of populations of T-cells CD4+/CD8+ and of B-lymphocytes. Nutritional supplements of folate, vitamins A, D and B12, which are recognized regulators of cell division, support a wide range of lymphocyte populations. Trace elements zinc, iron, selenium, manganese and omega-3 polyunsaturated fatty acids are also important for supporting the mechanisms of acquired immunity. The data presented show that a course intake of these micronutrients by patients planning vaccination can significantly improve its effectiveness. In particular, these micronutrients can increase the titers of antibodies to pathogens, and to reduce the percentage of patients who still contract infection after vaccination. Supplements of these micronutrients can also contribute to the safety of vaccination: to prevent malaise and, in the unfortunate case of contracting infection despite the vaccine, to reduce the severity of the course and the mortality from the corresponding infection.
COVID-19 epidemics monitored through the logarithmic growth rate and SIR model
Authors: Konishi Tomokazu
Published: September 2021

Background

The SIR model is often used to analyse and forecast the expansion of an epidemic. In this model, the number of patients exponentially increases and decreases, resulting in two phases. Therefore, in these phases, the logarithm of infectious patients changes at a constant rate, the logarithmic growth rate K. However, in the case of the coronavirus disease 2019 (COVID19) epidemic, K never remains constant but increases and decreases linearly; therefore, the SIR model does not fit that seen in reality. We would like to clarify the cause of this phenomenon and predict the occurrence of COVID19 epidemics.

Methods

We simulated a situation in which smaller epidemics were repeated with short time intervals. The results were compared with the epidemic data from 279 countries and regions.

Results

In the simulations, the K values increased and decreased linearly, similar to the real data. Because the previous peak covered the initial increase in the epidemic, K did not increase as much as expected; rather, the difference in the basic reproduction number R0 appeared in the slope of increasing K. Additionally, the mean infectious time τ appeared in the negative peaks of K. By using the R0 and τ estimated from the changes in K, changes in the number of patients could be approximated using the SIR model. This supports the appropriateness of the model for evaluating COVID-19 epidemics. By using the model, the distributions of the parameters were identified. On average, an epidemic started every eleven days in a country. The worldwide mean R0 was 2.9; however, this value showed an exponential character and could thus increase explosively. In addition, the average τ was 12 days; this is not the native value but represents a shortened period because of the isolation of patients. As τ represents the half-life, the infectious time varies among patients; hence, prior testing should be performed before isolation is lifted. The changes in K represented the state of epidemics and were several weeks to a month ahead of the changes in the number of confirmed cases. In the actual data, when K was positive on consecutive days, the number of patients increased a few weeks later. In addition, if the negative peaks of K could not be reduced to as small as 0.1, the number of patients remained high. Thus, the number of K-positive days and mean infectious time had a clear correlation with the total number of patients. In such cases, mortality, which was lognormally distributed, with a mean of 1.7%, increased. To control the epidemic, it is important to observe K daily, not to allow K to remain positive continuously, and to terminate a peak with a series of K-negative days. To do this, it was necessary to shorten τ by finding and isolating a patient earlier. The effectiveness of the countermeasures is apparent in τ. The effect of vaccination, in terms of controlling the epidemic, was limited.
Time-dependent prediction of mortality and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation using machine learning
Authors: Eisenberg Lisa ,   the XplOit consortium, Brossette Christian , Rauch Jochen , Grandjean Andrea , Ottinger Hellmut , Rissland Jürgen , Schwarz Ulf , Graf Norbert , Beelen Dietrich W. , Kiefer Stephan , Pfeifer Nico , Turki Amin T.
Published: September 2021

Allogeneic hematopoietic cell transplantation (HCT) effectively treats high-risk hematologic diseases but can entail HCT-specific complications, which may be minimized by appropriate patient management, supported by accurate, individual risk estimation. However, almost all HCT risk scores are limited to a single risk assessment before HCT without incorporation of additional data. We developed machine learning models which integrate both baseline patient data and time-dependent laboratory measurements to individually predict mortality and cytomegalovirus (CMV) reactivation after HCT at multiple time points per patient. These gradient boosting machine models provide well-calibrated, time-dependent risk predictions and achieved areas under the receiver-operating characteristic of 0.92 and 0.83 and areas under the precision-recall curve of 0.58 and 0.62 for prediction of mortality and CMV reactivation, respectively, in a 21-day time window. Both models were successfully validated in a prospective, non-interventional study and performed on par with expert hematologists in a pilot comparison.
Vaccination or restriction?: COVID-19 vaccine hesitancy and vaccine passports
Authors: Okamoto Shohei , Kamimura Kazuki , Komamura Kohei
Published: September 2021

Objectives

While the development of vaccines against the novel coronavirus (COVID-19) brought the hope of establishing herd immunity, which might help end the global pandemic, vaccine hesitancy can hinder the progress towards herd immunity. In this study, we assess the determinants of vaccine hesitancy, reasons for hesitation, and effectiveness of vaccine passports in relaxing public health restrictions.

Methods

Through an online survey that includes a conjoint experiment of a demographically representative sample of 5,000 Japanese adults aged 20–74, we assess the determinants of vaccine hesitancy, reasons for hesitation, and effectiveness of hypothetical vaccine passports.

Results

We found that about 30% of respondents did not intend to vaccinate or have not yet decided, with major reasons for vaccine hesitancy being related to concerns about the safety and side effects of the vaccine. In line with previous findings, younger age, lower socioeconomic status, and psychological factors such as weaker COVID-19 fear were associated with vaccine hesitancy. The easing of public health restrictions such as travel, wearing face masks, and dining out at night was associated with an increase in vaccine acceptance by 4–10%.

Conclusion

Vaccine hesitancy can be reduced by mitigating the concerns about vaccine safety and side effects, as well as by relaxing public health restrictions. However, the feasibility of vaccine passports needs to be sufficiently assessed, taking the ethical issues of passports and the public health impacts of the relaxation of restrictions into careful consideration.

Strengths and limitations of this study

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This study includes timely data on COVID-19 vaccine hesitancy, obtained from a demographically representative sample of 5,000 Japanese adults.

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A conjoint experiment allows assessing the effectiveness of easing public health restrictions on vaccine acceptance.

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Actual behaviour may diverge from the survey responses or fluctuate due to the pandemic situation and the timing of the survey.

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Results may not be applicable in other countries, since the pandemic situation, government responses to the pandemic, and reasons for vaccine hesitancy can vary across countries.
Ontogeny of plasma lipid metabolism in pregnancy and early childhood: a longitudinal population study
Authors: Burugupalli Satvika , Smith Adam Alexander T. , Olshansky Gavriel , Huynh Kevin , Giles Corey , Paul Sudip , Nguyen Anh , Duong Thy , Mellett Natalie , Cinel Michelle , Mir Sartaj Ahmad , Chen Li , Wenk Markus R. , Karnani Neerja , Collier Fiona , Saffery Richard , Vuillermin Peter , Ponsonby Anne-Louise , Burgner David , Meikle Peter J. ,   Barwon Infant Study Investigator team
Published: September 2021

Background

There is mounting evidence thatin uteroand early life exposures may predispose an individual to metabolic disorders in later life; and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. In this study, we aim to understand the lipid metabolism in pregnancy, and from birth to four years.

Methods and findings

We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population based pre-birth cohort and measured 776 distinct lipid species across 42 lipid classes using ultra high-performance liquid chromatography (UHPLC). We measured lipids in 1032 maternal serum samples at 28 weeks’ gestation, 893 cord serum samples at birth, 793, 735, and 511 plasma samples at six, twelve months, and four years, respectively. The lipidome differed between mother and newborn and changed markedly with increasing postnatal age. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. Alkenyl-phosphatidylethanolamine species containing LC-PUFAs increased with postnatal age, whereas the corresponding lysophospholipids and triglycerides decreased. We performed regression analyses to investigate the associations of cord serum lipid species with birth factors: gestational age, birth weight, mode of birth and duration of labor. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids.

Conclusions

There were marked changes in the plasma lipidome over the first four years of life. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood.

Funding Statement

This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Toward Using Twitter Data to Monitor Covid-19 Vaccine Safety in Pregnancy
Authors: Klein Ari Z. , O’Connor Karen , Gonzalez-Hernandez Graciela
Published: September 2021

Background

Coronavirus Disease 2019 (Covid-19) during pregnancy is associated with an increased risk of maternal death, intensive care unit (ICU) admission, and preterm birth; however, many people who are pregnant refuse to receive Covid-19 vaccination because of a lack of safety data.

Objective

The objective of this preliminary study was to assess whether we could identify (1) users who have reported on Twitter that they received Covid-19 vaccination during pregnancy or the periconception period, and (2) reports of their pregnancy outcomes.

Methods

We searched for reports of Covid-19 vaccination in a large collection of tweets posted by users who have announced their pregnancy on Twitter. To help determine if users were vaccinated during pregnancy, we drew upon a natural language processing (NLP) tool that estimates the timeframe of the prenatal period. For users who posted tweets with a timestamp indicating they were vaccinated during pregnancy, we drew upon additional NLP tools to help identify tweets that report their pregnancy outcomes.

Results

Upon manually verifying the content of tweets detected automatically, we identified 150 users who reported on Twitter that they received at least one dose of Covid-19 vaccination during pregnancy or the periconception period. Among the 60 completed pregnancies, we manually verified at least one reported outcome for 45 (75%) of them.

Conclusions

Given the limited availability of data on Covid-19 vaccine safety in pregnancy, Twitter can be a complementary resource for potentially increasing the acceptance of Covid-19 vaccination in pregnant populations. Directions for future work include developing machine learning algorithms to detect a larger number of users for observational studies.
Reduction of Major Adverse Cardiovascular Events (MACE) after Bariatric Surgery in Obese Patients with Cardiovascular Diseases: A Systematic Review and Meta-Analysis
Authors: Sutanto Andryanto , Sutanto Henry
Published: September 2021

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and obesity is a major risk factor which increases morbidity and mortality of CVDs. Lifestyle modifications (e.g., diet control, physical exercise and behavioral changes) have been the first-line managements of obesity for decades. Nonetheless, when such interventions fail, pharmacotherapies and bariatric surgery are considered. Interestingly, a sudden weight loss (e.g., due to bariatric surgery) could also increase mortality (i.e., “obesity paradox”). Thus, it remains unclear whether the bariatric-surgery-associated weight reduction in patients with obesity and CVDs is beneficial for the reduction of Major Adverse Cardiovascular Events (MACE). Here, we performed a systematic literature search and meta-analysis of published studies comparing the MACE in patients with obesity and CVDs underwent bariatric surgery with control patients (no surgery). Studies’ data, including odds ratio (OR), were pooled and analyzed in a meta-analysis using a random effect model. Ten studies with a total of 1,772,305 patients, consisted of 74,042 patients underwent any form of bariatric surgery and 1,698,263 patients with no-surgery, were included in the meta-analysis. A random effect model was employed for analysis and showed that bariatric surgery group had significantly lower odds of MACE as compared to no surgery (OR = 0.49; 95% CI 0.40-0.60;p<0.00001;I2=93%), suggesting the benefit of bariatric surgery in reducing the occurrence of MACE in obese patients with CVDs.
Considerations regarding a diagnosis of Alzheimer’s Disease before dementia: a systematic review
Authors: van der Schaar Jetske , Visser Leonie N.C. , Bouwman Femke H. , Scheltens Philip , Bredenoord Annelien L. , van der Flier Wiesje M.
Published: September 2021

Introduction

The NIA-AA research framework proposes a purely biological definition of Alzheimer’s Disease (AD). This implies AD can be diagnosed based on biomarker abnormalities. While this brings opportunities, it also raises challenges.

Methods

We conducted a systematic review by searching PubMed for publications on conveying AD biomarker results to individuals without dementia. Content was analyzed inductively.

Results

We included 25 publications. From these we extracted 26 considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations include (lack of) validity, utility, and disclosure protocols. Personal considerations cover psychological and behavioral implications, as well as the right to (not) know. Societal considerations comprise the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory.

Discussion

Perceptions on a diagnosis of AD before dementia vary widely. Empirical research is required, taking perspectives of medical professionals and the general public into account.