bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Analysis of Synonymous Single Nucleotide Polymorphisms in Mycobacterium tuberculosis Complex Organisms: Resolution of Genetic Relationships Among Closely Related Microbial Strains
Authors: Gutacker Michaela M , Smoot James C , Migliaccio Cristi A Lux , Ricklefs Stacy M , Hua Su , Cousins Debby V , Graviss Edward A , Shashkina Elena , Kreiswirth Barry N , Musser James M
Published: April 2021

Several human pathogens (e.g., Bacillus anthracis, Yersinia pestis, Bordetella pertussis, Plasmodium falciparum, and Mycobacterium tuberculosis) have very restricted unselected allelic variation in structural genes, which hinders study of the genetic relationships among strains and strain-trait correlations. To address this problem in a representative pathogen, 432 M. tuberculosis complex strains from global sources were genotyped on the basis of 230 synonymous (silent) single nucleotide polymorphisms (sSNPs) identified by comparison of four genome sequences. Eight major clusters of related genotypes were identified in M. tuberculosis sensu stricto, including a single cluster representing organisms responsible for several large outbreaks in the United States and Asia. All M. tuberculosis sensu stricto isolates of previously unknown phylogenetic position could be rapidly and unambiguously assigned to one of the eight major clusters, thus providing a facile strategy for identifying organisms that are clonally related by descent. Common clones of M. tuberculosis sensu stricto and M. bovis are distinct, deeply branching genotypic complexes whose extant members did not emerge directly from one another in the recent past. sSNP genotyping rapidly delineates relationships among closely related strains of pathogenic microbes and allows construction of genetic frameworks for examining the distribution of biomedically relevant traits such as virulence, transmissibility, and host range.
Candida albicans Mds3p, a Conserved Regulator of pH Responses and Virulence Identified Through Insertional Mutagenesis
Authors: Davis Dana A , Bruno Vincent M , Loza Lucio , Filler Scott G , Mitchell Aaron P
Published: April 2021

Candida albicans is a commensal fungus that causes diverse infections after antibiotic use or immune debilitation. Gene discovery has been limited because the organism is an asexual diploid. We have developed a strategy that yields random homozygous insertion mutants. The strategy has permitted identification of several prospective essential genes. Many of these genes are homologous to nonessential Saccharomyces cerevisiae genes, and some have no S. cerevisiae homolog. These findings may expand the range of antifungal drug targets. We have also identified new genes required for pH-dependent filamentation, a trait previously associated with virulence. One newly identified gene, MDS3, is required for expression in alkaline media of two filamentation-associated genes, HWP1 and ECE1, but is not required for expression of other pH-response genes. In S. cerevisiae, the two MDS3 homologs are required for growth in alkaline media, thus arguing that Mds3p function in adaptation to external pH changes is conserved. Epistasis tests show that Mds3p contributes to virulence and alkaline pH responses independently of the well-characterized Rim101p pH-response pathway.
A Drosophila Homologue of Sir2 Modifies Position-Effect Variegation but Does Not Affect Life Span
Authors: Newman Brenda L , Lundblad James R , Chen Yang , Smolik Sarah M
Published: April 2021

Control of chromosome structure is important in the regulation of gene expression, recombination, DNA repair, and chromosome stability. In a two-hybrid screen for proteins that interact with the Drosophila CREB-binding protein (dCBP), a known histone acetyltransferase and transcriptional coactivator, we identified the Drosophila homolog of a yeast chromatin regulator, Sir2. In yeast, Sir2 silences genes via an intrinsic NAD+-dependent histone deacetylase activity. In addition, Sir2 promotes longevity in yeast and in Caenorhabditis elegans. In this report, we characterize the Drosophila Sir2 (dSir2) gene and its product and describe the generation of dSir2 amorphic alleles. We found that dSir2 expression is developmentally regulated and that dSir2 has an intrinsic NAD+-dependent histone deacetylase activity. The dSir2 mutants are viable, fertile, and recessive suppressors of position-effect variegation (PEV), indicating that, as in yeast, dSir2 is not an essential function for viability and is a regulator of heterochromatin formation and/or function. However, mutations in dSir2 do not shorten life span as predicted from studies in yeast and worms.
A Role for the Drosophila SU(VAR)3-9 Protein in Chromatin Organization at the Histone Gene Cluster and in Suppression of Position-Effect Variegation
Authors: Ner Sarbjit S , Harrington Michael J , Grigliatti Thomas A
Published: April 2021

Mutations in the gene for Su(var)3-9 are dominant suppressors of position-effect variegation (PEV). We show that SU(VAR)3-9 is a chromatin-associated protein and identify the large multicopy histone gene cluster (HIS-C) as one of its target loci. The organization of nucleosomes over the entire HIS-C region is altered in Su(var)3-9 mutants and there is a concomitant increase in expression of the histone genes. SU(VAR)3-9 is a histone H3 methyltransferase and, using chromatin immunoprecipitation, we show that SU(VAR)3-9 is present at the HIS-C locus and that the histone H3 at the HIS-C locus is methylated. We propose that SU(VAR)3-9 is involved in packaging HIS-C into a distinct chromatin domain that has some of the characteristics of β-heterochromatin. We suggest that methylation of histone H3 is important for the chromatin structure at HIS-C. The chromosomal deficiency for the HIS-C is also a suppressor of PEV. In contrast to what might be expected, we show that hemizygosity for the HIS-C locus leads to a substantial increase in the histone transcripts.
Accelerated Protein Evolution and Origins of Human-Specific Features: FOXP2 as an Example
Authors: Zhang Jianzhi , Webb David M , Podlaha Ondrej
Published: April 2021

Genes responsible for human-specific phenotypes may have been under altered selective pressures in human evolution and thus exhibit changes in substitution rate and pattern at the protein sequence level. Using comparative analysis of human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and FOXP2) with significantly enhanced evolutionary rates in the hominid lineage. PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely target of sexual selection in humans and chimpanzees. FOXP2 is a transcription factor involved in speech and language development. Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated two fixed amino acid changes in a broadly defined transcription suppression domain. A survey of a diverse group of placental mammals reveals the uniqueness of the human FOXP2 sequence and a population genetic analysis indicates possible adaptive selection behind the accelerated evolution. Taken together, our results suggest an important role that FOXP2 may have played in the origin of human speech and demonstrate a strategy for identifying candidate genes underlying the emergences of human-specific features.
Expression Patterns and Mutant Phenotype ofteosinte branched1Correlate With Growth Suppression in Maize and Teosinte
Authors: Hubbard Lauren , McSteen Paula , Doebley John , Hake Sarah
Published: April 2021

The evolution of domesticated maize from its wild ancestor teosinte is a dramatic example of the effect of human selection on agricultural crops. Maize has one dominant axis of growth, whereas teosinte is highly branched. The axillary branches in maize are short and feminized whereas the axillary branches of teosinte are long and end in a male inflorescence under normal growth conditions. Previous QTL and molecular analysis suggested that the teosinte branched1 (tb1) gene of maize contributed to the architectural difference between maize and teosinte. tb1 mutants of maize resemble teosinte in their overall architecture. We analyzed the tb1 mutant phenotype in more detail and showed that the highly branched phenotype was due to the presence of secondary and tertiary axillary branching, as well as to an increase in the length of each node, rather than to an increase in the number of nodes. Double-mutant analysis with anther ear1 and tassel seed2 revealed that the sex of the axillary inflorescence was not correlated with its length. RNA in situ hybridization showed that tb1 was expressed in maize axillary meristems and in stamens of ear primordia, consistent with a function of suppressing growth of these tissues. Expression in teosinte inflorescence development suggests a role in pedicellate spikelet suppression. Our results provide support for a role for tb1 in growth suppression and reveal the specific tissues where suppression may occur.
The pam1 Gene Is Required for Meiotic Bouquet Formation and Efficient Homologous Synapsis in Maize (Zea mays L.)
Authors: Golubovskaya Inna N , Harper Lisa C , Pawlowski Wojciech P , Schichnes Denise , Cande W Zacheus
Published: April 2021

The clustering of telomeres on the nuclear envelope (NE) during meiotic prophase to form the bouquet arrangement of chromosomes may facilitate homologous chromosome synapsis. The pam1 (plural  abnormalities of  meiosis  1) gene is the first maize gene that appears to be required for telomere clustering, and homologous synapsis is impaired in pam1. Telomere clustering on the NE is arrested or delayed at an intermediate stage in pam1. Telomeres associate with the NE during the leptotene-zygotene transition but cluster slowly if at all as meiosis proceeds. Intermediate stages in telomere clustering including miniclusters are observed in pam1 but not in wild-type meiocytes. The tight bouquet normally seen at zygotene is a rare event. In contrast, the polarization of centromeres vs. telomeres in the nucleus at the leptotene-zygotene transition is the same in mutant and wild-type cells. Defects in homologous chromosome synapsis include incomplete synapsis, nonhomologous synapsis, and unresolved interlocks. However, the number of RAD51 foci on chromosomes in pam1 is similar to that of wild type. We suggest that the defects in homologous synapsis and the retardation of prophase I arise from the irregularity of telomere clustering and propose that pam1 is involved in the control of bouquet formation and downstream meiotic prophase I events.
The Influence of Linkage and Inbreeding on Patterns of Nucleotide Sequence Diversity at Duplicate Alcohol Dehydrogenase Loci in Wild Barley (Hordeum vulgare ssp. spontaneum)
Authors: Lin Jing-Zhong , Morrell Peter L , Clegg Michael T
Published: April 2021

Patterns of nucleotide sequence diversity are analyzed for three duplicate alcohol dehydrogenase loci (adh1-adh3) within a species-wide sample of 25 accessions of wild barley (Hordeum vulgare ssp. spontaneum). The adh1 and adh2 loci are tightly linked (recombination fraction <0.01) while the adh3 locus is inherited independently. Wild barley is predominantly self-fertilizing (∼98%), and as a consequence, effective recombination is restricted by the extreme reduction in heterozygosity. Large reductions in effective recombination, in turn, widen the conditions for linkage to influence nucleotide sequence diversity through the action of selective sweeps or background selection. These considerations would appear to predict (1) homogeneity in patterns of nucleotide sequence diversity, especially between closely linked loci, and (2) extensive linkage disequilibrium relative to random-mating species. In contrast to these expectations, the wild barley data reveal heterogeneity in patterns of nucleotide sequence diversity and levels of linkage disequilibrium that are indistinguishable from those observed at adh1 in maize, an outbreeding grass species.
Approximate Bayesian Computation in Population Genetics
Authors: Beaumont Mark A , Zhang Wenyang , Balding David J
Published: April 2021

We propose a new method for approximate Bayesian statistical inference on the basis of summary statistics. The method is suited to complex problems that arise in population genetics, extending ideas developed in this setting by earlier authors. Properties of the posterior distribution of a parameter, such as its mean or density curve, are approximated without explicit likelihood calculations. This is achieved by fitting a local-linear regression of simulated parameter values on simulated summary statistics, and then substituting the observed summary statistics into the regression equation. The method combines many of the advantages of Bayesian statistical inference with the computational efficiency of methods based on summary statistics. A key advantage of the method is that the nuisance parameters are automatically integrated out in the simulation step, so that the large numbers of nuisance parameters that arise in population genetics problems can be handled without difficulty. Simulation results indicate computational and statistical efficiency that compares favorably with those of alternative methods previously proposed in the literature. We also compare the relative efficiency of inferences obtained using methods based on summary statistics with those obtained directly from the data using MCMC.
Linkage Disequilibrium Patterns Across a Recombination Gradient in African Drosophila melanogaster
Authors: Andolfatto Peter , Wall Jeffrey D
Published: April 2021

Previous multilocus surveys of nucleotide polymorphism have documented a genome-wide excess of intralocus linkage disequilibrium (LD) in Drosophila melanogaster and D. simulans relative to expectations based on estimated mutation and recombination rates and observed levels of diversity. These studies examined patterns of variation from predominantly non-African populations that are thought to have recently expanded their ranges from central Africa. Here, we analyze polymorphism data from a Zimbabwean population of D. melanogaster, which is likely to be closer to the standard population model assumptions of a large population with constant size. Unlike previous studies, we find that levels of LD are roughly compatible with expectations based on estimated rates of crossing over. Further, a detailed examination of genes in different recombination environments suggests that markers near the telomere of the X chromosome show considerably less linkage disequilibrium than predicted by rates of crossing over, suggesting appreciable levels of exchange due to gene conversion. Assuming that these populations are near mutation-drift equilibrium, our results are most consistent with a model that posits heterogeneity in levels of exchange due to gene conversion across the X chromosome, with gene conversion being a minor determinant of LD levels in regions of high crossing over. Alternatively, if levels of exchange due to gene conversion are not negligible in regions of high crossing over, our results suggest a marked departure from mutation-drift equilibrium (i.e., toward an excess of LD) in this Zimbabwean population. Our results also have implications for the dynamics of weakly selected mutations in regions of reduced crossing over.
Green Fluorescent Protein Tagging Drosophila Proteins at Their Native Genomic Loci With Small P Elements
Authors: Clyne Peter J , Brotman Jennie S , Sweeney Sean T , Davis Graeme
Published: April 2021

We describe a technique to tag Drosophila proteins with GFP at their native genomic loci. This technique uses a new, small P transposable element (the Wee-P) that is composed primarily of the green fluorescent protein (GFP) sequence flanked by consensus splice acceptor and splice donor sequences. We demonstrate that insertion of the Wee-P can generate GFP fusions with native proteins. We further demonstrate that GFP-tagged proteins have correct subcellular localization and can be expressed at near-normal levels. We have used the Wee-P to tag genes with a wide variety of functions, including transmembrane proteins. A genetic analysis of 12 representative fusion lines demonstrates that loss-of-function phenotypes are not caused by the Wee-P insertion. This technology allows the generation of GFP-tagged reagents on a genome-wide scale with diverse potential applications.
Compositional Biases and Polyalanine Runs in Humans
Authors: Cocquet Julie , De Baere Elfride , Caburet Sandrine , Veitia Reiner A
Published: April 2021

Human proteins containing polyalanine tracts tend to have runs of other amino acids and their open reading frames (ORFs) display a biased codon usage. Their alanine, glycine, proline, and histidine content strongly correlates with the GC content of the third codon base, suggesting that the compositional specificity of these proteins is dictated to a great extent by the evolution of their ORFs.
Staff Reports of Behavioral Expressions of Persons With Dementia in 250 Assisted Living Communities
Authors: Dobbs Debra , Zimmerman Sheryl , Carder Paula , Beeber Anna S , Palmertree Stephanie J
Published: April 2021

Background and Objectives

Assisted living (AL) residents with dementia commonly exhibit behavioral expressions (BEs), yet no study has examined how AL staff perceive and respond to BEs in terms of the “ABC” model of antecedents, behaviors, and consequences, or how perceptions relate to organizational characteristics. Understanding staff perceptions may inform interventions.

Research Design and Methods

A convergent, mixed methods design was used in a study of health care supervisors from 250 AL communities in 7 states who reported 366 cases of resident BEs (one successful and one unsuccessful case). Qualitative analysis identified antecedents, BEs, staff responses, resident outcomes, and disposition (aging in place or discharge). Content analysis identified themes and compared case types. Descriptive statistics examined organizational characteristics associated with identifying antecedents.

Results

One quarter of cases recognized antecedents; slightly more were identified in successful (28%) compared to unsuccessful cases (20%); staff in dementia-only and smaller communities identified antecedents more often. Combativeness and anxiety were the most frequently reported BEs. The majority of both types of cases reported staff responses. Medication management was enacted as a response in 40% of cases compared to psychiatric assessment in 33% of cases.

Discussion and Implications

Staff training is indicated to increase AL staff recognition of antecedents; doing so might reduce the use of antipsychotic medications. Psychiatric assessment plays an important role in dementia care in AL and warrants further examination. Results could be helpful for applied behavioral researchers interested in developing ways to improve the identification of antecedents of BEs of persons with dementia.
Using citizen science to empower older adults to improve a food security initiative in Australia
Authors: Tuckett Anthony G , Rowbotham Samantha , Hetherington Sharon , Goddard Jodie , King Abby C
Published: April 2021

Food security is an increasing problem for older adults who are living longer and having to stretch their resources further. Initiatives such as subsidized community market days are increasingly important in bolstering food security amongst these groups but there have been few attempts to understand these initiatives from the perspective of community members. This exploratory study examined the utility of a novel citizen science approach to engage older adults in evaluating and improving a local food security initiative. Using the Our Voice methodology, citizen scientists recorded their perceptions of their local Market Day via photographs and audio narratives. Thirteen citizen scientists captured 127 photographs and 125 commentaries. Citizen scientists participated in workshops to discuss, code and synthesize their data, and used their findings to advocate for change. A number of improvements to the Market Day were made by key stakeholders on the basis of citizen scientist recommendations, including improving the processes for sourcing and storing food and changing the layout to improve access. This study demonstrates that citizen science is a useful and feasible approach to engaging community members in capturing data and advocating for change to ensure that local initiatives meet the needs of communities.
Genome-wide association study of cardiac troponin I in the general population
Authors: Moksnes Marta R , Røsjø Helge , Richmond Anne , Lyngbakken Magnus N , Graham Sarah E , Hansen Ailin Falkmo , Wolford Brooke N , Gagliano Taliun Sarah A , LeFaive Jonathon , Rasheed Humaira , Thomas Laurent F , Zhou Wei , Aung Nay , Surakka Ida , Douville Nicholas J , Campbell Archie , Porteous David J , Petersen Steffen E , Munroe Patricia B , Welsh Paul , Sattar Naveed , Smith George Davey , Fritsche Lars G , Nielsen Jonas B , Åsvold Bjørn Olav , Hveem Kristian , Hayward Caroline , Willer Cristen J , Brumpton Ben M , Omland Torbjørn
Published: April 2021

Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes are unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study, and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. We further use two-sample Mendelian randomization to investigate the causal effects of circulating cTnI on acute myocardial infarction (AMI) and heart failure (HF). We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1. Phenome-wide association tests in 1688 phecodes and 83 continuous traits in UK Biobank showed associations between a genetic risk score for cTnI and cardiac arrhythmias, metabolic and anthropometric measures. Using two-sample Mendelian randomization, we confirmed the non-causal role of cTnI in AMI (5948 cases, 355 246 controls). We found indications for a causal role of cTnI in HF (47 309 cases and 930 014 controls), but this was not supported by secondary analyses using left ventricular mass as outcome (18 257 individuals). Our findings clarify the biology underlying the heritable contribution to circulating cTnI and support cTnI as a non-causal biomarker for AMI in the general population. Using genetically informed methods for causal inference helps inform the role and value of measuring cTnI in the general population.
Transient upper limb ischaemia during veno-arterial extracorporeal membrane oxygenation in a child
Authors: Izquierdo-Blasco Jaume , Riaza Lucía , Pujol Montse , Gran Ferran , Fernández-Doblas Joaquín , Pérez-Andreu Joaquín , Abella Raul F , Balcells Joan
Published: April 2021

Neck cannulation is the most common cannulation strategy performed to provide veno-arterial extracorporeal membrane oxygenation support in paediatric patients, especially in small children. Upper limb ischaemia is a rare complication of neck cannulation and is likely caused by arterial cannula malposition. We describe a case of right arm ischaemia caused by extrinsic compression of the right subclavian artery by the venous drainage cannula inserted through the right internal jugular vein. Upper limb hypoperfusion was resolved immediately after changing the venous drainage cannula from the right jugular vein to the right femoral vein.
Cognitive and Affective Processes Associated with Social Biases
Authors: Kaneko Asuka , Asaoka Yui , Lee Young-A , Goto Yukiori
Published: April 2021

Background

Our social activities are quite often erroneous and irrational, based on biased judgements and decision-making, known as social biases. However, the cognitive and affective processes that produce such biases remain largely unknown. In this study, we investigated associations between social schemas, such as social judgment and conformity, entailing social biases and psychological measurements relevant to cognitive and affective functions.

Method

This study recruited 42 healthy adult subjects. A psychological test and a questionnaire were administered to assess biased social judgements by superficial attributes and social conformity by adherence to social norms, respectively, along with additional questionnaires and psychological tests for cognitive and affective measurements, including negative affects, autistic traits, and Theory of Mind (ToM). Associations of social judgment and conformity with cognitive and affective functions were examined using a multiple regression analysis and structural equation modeling.

Results

Anxiety and the cognitive realm of ToM were mutually associated with both social judgments and conformity, although social judgements and conformity were still independent processes. Social judgements were also associated with autistic traits and the affective realm of ToM, whereas social conformity was associated with negative affects other than anxiety and an intuitive decision-making style.

Conclusions

These results suggest that ToM and negative affects may play important roles in social judgements and conformity, and the social biases connoted in these social schemas.
Prevalence and predictors of teenage pregnancy in Pakistan: a trend analysis from Pakistan Demographic and Health Survey datasets from 1990 to 2018
Authors: Ali Anna , Khaliq Asif , Lokeesan Laavanya , Meherali Salima , Lassi Zohra S
Published: April 2021

Background

Teenage pregnancies carry an increased risk of adverse obstetric and health outcomes for mothers and children.

Methods

This study assessed the prevalence and predictors of teenage pregnancies over time in Pakistan using the Pakistan Demographic and Health Survey (PDHS). Data on 400 076 ever-married pregnant women aged 15–49 y from four PDHS datasets were used. Teenage pregnancy was the outcome variable, whereas a woman's and her partner's education, occupation, wealth quintile, region, place of residence and access to knowledge on family planning were the explanatory variables. Pooled prevalence was estimated and regression analysis was undertaken to produce an adjusted prevalence ratio with 95% CIs.

Results

Although the prevalence of teenage pregnancy decreased from 54.4% in 1990–1991 to 43.7% in 2017–2018, the pooled prevalence was 42.5% (95% CI 37.9 to 49.6%). The prevalence of teenage pregnancy was significantly associated with place of residence, wealth quintile, education and occupation.

Conclusion

Despite a growing focus on women's education, access to sexual and reproductive health (SRH) services and contraception in the last decade in Pakistan, the prevalence of teenage pregnancy is still high. There is a pressing need to develop appropriate strategies for increasing access to education, SRH services and use of contraception in Pakistan.
“P3”: an adaptive modeling tool for post-COVID-19 restart of surgical services
Authors: Joshi Divya , Jalali Ali , Whipple Todd , Rehman Mohamed , Ahumada Luis M
Published: April 2021

Objective

To develop a predictive analytics tool that would help evaluate different scenarios and multiple variables for clearance of surgical patient backlog during the COVID-19 pandemic.

Materials and Methods

Using data from 27 866 cases (May 1 2018–May 1 2020) stored in the Johns Hopkins All Children’s data warehouse and inputs from 30 operations-based variables, we built mathematical models for (1) time to clear the case backlog (2), utilization of personal protective equipment (PPE), and (3) assessment of overtime needs.

Results

The tool enabled us to predict desired variables, including number of days to clear the patient backlog, PPE needed, staff/overtime needed, and cost for different backlog reduction scenarios.

Conclusions

Predictive analytics, machine learning, and multiple variable inputs coupled with nimble scenario-creation and a user-friendly visualization helped us to determine the most effective deployment of operating room personnel. Operating rooms worldwide can use this tool to overcome patient backlog safely.
Breast Imaging After Dark
Authors: Lane Deanna L , Parikh Jay R
Published: April 2021

Patients may present to the emergency department with breast complaints due to traumatic or nontraumatic changes in the breast. Benign and malignant breast pathologies may mimic each other both in clinical presentation and imaging appearance. A complex cystic and solid mass seen on ultrasound in a patient with a palpable mass can represent breast cancer, abscess, or hematoma. A unilateral swollen breast may result from inflammatory breast cancer, mastitis, or other benign etiologies; correlation with clinical history, physical exam, and close follow-up are required to ensure complete resolution of symptoms. Uncommon breast entities such as granulomatous mastitis and breast implant–associated anaplastic large-cell lymphoma may cause changes in the appearance of the breast that prompt a patient to seek initial evaluation in the emergency department. Imaging evaluation of the breast in the emergency department is limited, and it is important that patients with a breast complaint be referred to a dedicated breast center for complete evaluation at an appropriate time interval after their discharge from the emergency department.
Patient-Reported Outcomes in Pediatric Cancer Registration Trials: A US Food and Drug Administration Perspective
Authors: Murugappan Meena N , King-Kallimanis Bellinda L , Reaman Gregory H , Bhatnagar Vishal , Horodniceanu Erica G , Bouchkouj Najat , Kluetz Paul G
Published: April 2021

Pediatric patient-reported outcome (PRO) data can help inform the US Food and Drug Administration’s (FDA’s) benefit-risk assessment of cancer therapeutics by quantifying symptom and functional outcomes from the patient’s perspective.

 

This study assessed use of PROs in commercial pediatric oncology trials submitted to the FDA for regulatory review. FDA databases were searched to identify pediatric oncology product applications approved between 1997 and 2020. Sponsor-submitted documents were reviewed to determine whether PRO data were collected, which instruments were used, and the quality of collected data (ie, sample size, completion rates, and use of fit-for-purpose instruments). The role of PROs in each trial (endpoint hierarchy) was also recorded in addition to whether any PRO endpoints were included in product labeling.

 

We reviewed 17 pediatric oncology applications, 4 of which included PRO data: denosumab, tisagenlecleucel, larotrectinib, and selumetinib. In these 4 instances, PROs served as exploratory endpoints and were not incorporated in product labeling. Trials that collected PRO data were phase II or phase I/II single-arm studies with sample sizes of 28 to 88 patients. Symptomatic adverse events (AEs) were characterized using clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without additional patient self-report.

 

PROs were infrequently used in pediatric cancer registration trials. When PROs were used, PRO data were limited by lack of a clear research objective and corresponding prospective statistical analysis plan. Contemporary PRO symptom libraries, such as the National Cancer Institute’s Pediatric PRO-CTCAE, may provide an opportunity to better evaluate the occurrence and impact of symptomatic AEs, from the patient’s perspective, in pediatric oncology trials.
Predictive Value of Developmental Assessment in a Neonatal Intensive Care Unit (NICU) Follow-Up Clinic
Authors: Kalstabakken Amanda W , Molitor Stephen J , Gross Amy C , Georgieff Michael K , Boys Christopher J
Published: April 2021

Objective

Neonatal Intensive Care Unit (NICU) Follow-Up programs vary in the duration for which they monitor child development and neurocognitive outcomes. This study explores the early predictive value of a widely used developmental measure for intellectual functioning during early childhood to better inform whether there is value added in continued monitoring.

Methods

Participants were 209 children who had at least two assessments between the ages of 1 and 6 years old as part of NICU Follow-Up clinic. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) was administered when children were 1 and 2 years old and the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was administered when children were 3 years and older.

Results

The Bayley-III at 1 year of age was a significant predictor of Bayley-III performance at age 2. Similarly, Bayley-III at ages 1 year and 2 years were significant predictors of WPPSI-IV performance. Strength of prediction was moderate with the majority of variance unexplained. Exploratory analyses examining whether early developmental abilities as assessed on the Bayley-III could identify patients at risk for poorer WPPSI-IV performance indicated appropriate specificity but inadequate sensitivity.

Conclusions

This study supports ongoing assessment of children who were born with perinatal complications into at least early childhood. Assessing development only during the infant and toddler years did not sufficiently identify children who went on to have lower cognitive functioning in preschool and the early school years.
Drivers of avian species richness and community structure in urban courtyard gardens
Authors: Pirzio Biroli Alessandro , Van Doren Benjamin M , Grabowska-Zhang Ada
Published: April 2021

Increasing global urbanisation has steered research towards understanding biodiversity in urban areas. Old city spaces throughout Europe have a proliferation of urban court gardens, which can create a mosaic of habitat pockets in an urban area. This article examines the patterns and drivers of avian species richness and community structure in 20 gardens of the constituent colleges of the University of Oxford. We conducted morning surveys across 7 weeks in May and June 2017 and used an information-theoretic approach and model averaging to identify important habitat predictors of species richness. We also studied community structure with Sorensen indices and non-metric multi-dimensional analysis. A total of 43 avian species were observed across all sites. Our sites generally differed in their avian assemblages, with greater species turnover than nestedness between sites. Site area was the strongest predictor of site species richness and surrounding habitat composition was the dominant driver of community structure. Thus, the largest gardens were the most species rich, but species composition among gardens differed based on the habitats in which they were embedded. We support using island biogeography theory to understand the avian species assemblages of urban ecosystems and stress the suitability of our study sites for future urban ecosystem research and generating wildlife awareness.
Growth of magnetorotational instability in circumstellar discs around class 0 protostars
Authors: Kawasaki Yoshihiro , Koga Shunta , Machida Masahiro N
Published: April 2021

We investigate the possibility of the growth of magnetorotational instability (MRI) in discs around Class 0 protostars. We construct a disc model and calculate the chemical reactions of neutral and charged atoms, molecules, and dust grains to derive the abundance of each species and the ionization degree of the disc. Then, we estimate the diffusion coefficients of non-ideal magnetohydrodynamics effects such as ohmic dissipation, ambipolar diffusion, and the Hall effect. Finally, we evaluate the linear growth rate of MRI in each area of the disc. We investigate the effect of changes in the strength and direction of the magnetic field in our disc model and we adopt four different dust models to investigate the effect of dust size distribution on the diffusion coefficients. Our results indicate that an MRI-active region possibly exists with a weak magnetic field in a region far from the protostar where the Hall effect plays a role in the growth of MRI. On the other hand, in all models, the disc is stable against MRI in the region within <20 au from the protostar on the equatorial plane. Since the size of the discs in the early stage of star formation is limited to ≲10–20 au, it is difficult to develop MRI-driven turbulence in such discs.
Astraeus – II. Quantifying the impact of cosmic variance during the Epoch of Reionization
Authors: Ucci Graziano , Dayal Pratika , Hutter Anne , Yepes Gustavo , Gottlöber Stefan , Legrand Laurent , Pentericci Laura , Castellano Marco , Choudhury Tirthankar Roy
Published: April 2021

Next-generation telescopes such as the James Webb Space Telescope (JWST) and the Nancy Grace Roman Space Telescope (NGRST) will enable us to study the first billion years of our Universe in unprecedented detail. In this work, we use the astraeus (semi-numerical rAdiative tranSfer coupling of galaxy formaTion and Reionization in N-body dArk mattEr simUlationS) framework, which couples galaxy formation and reionization (for a wide range of reionization feedback models), to estimate the cosmic variance expected in the UV Luminosity Function (UV LF) and the stellar mass function in JWST surveys. We find that different reionization scenarios play a minor role in the cosmic variance. Most of the cosmic variance is completely driven by the underlying density field and increases above $100{{\ \rm per\ cent}}$ for ${\it M}_{\rm UV}\sim -17.5 ~ (-20)$ at z = 12 (6) for the JADES-deep survey (the deep JWST Advanced Extragalactic Survey with an area of 46 arcmin2); the cosmic variance decreases with an increasing survey area roughly independently of redshift. We find that the faint-end (${\it M}_{\rm UV}\gtrsim -17$) slope of the Lyman Break Galaxies (LBGs) UV LF becomes increasingly shallower with increasing reionization feedback and show how JWST observations will be able to distinguish between different models of reionization feedback at z > 9, even accounting for cosmic variance. We also show the environments (in terms of density and ionization fields) of LBGs during the EoR, finding that the underlying overdensity and ionization fraction scale positively with the UV luminosity. Finally, we also provide a public software tool to allow interested readers to compute cosmic variance for different redshifts and survey areas.
Search for dormant black holes in ellipsoidal variables – III. The OGLE BULGE short-period sample
Authors: Gomel Roy , Faigler Simchon , Mazeh Tsevi , Pawlak Michał
Published: April 2021

This is the third of a series of papers that presents an algorithm to search for close binaries with massive, possibly compact, unseen secondaries. The detection of such a binary is based on identifying a star that displays a large ellipsoidal periodic modulation, induced by tidal interaction with its companion. In the second paper of the series, we presented a simple approach to derive a robust modified minimum mass ratio (mMMR), based on the observed ellipsoidal amplitude, without knowing the primary mass and radius, assuming the primary fills its Roche lobe. The newly defined mMMR is always smaller than the actual mass ratio. Therefore, a binary with an mMMR larger than unity is a good candidate for having a massive secondary, which might be a black hole or a neutron star. This paper considers 10 956 OGLE short-period ellipsoidals observed towards the Galactic bulge. We re-analyse their modulation and identify 136 main-sequence systems with mMMR significantly larger than unity as candidates for having compact-object secondaries, assuming their observed periodic modulations reflect indeed the ellipsoidal effect. Obviously, one needs follow-up observations to find out the true nature of these companions.
Cancer-causingBRCA2missense mutations disrupt an intracellular protein assembly mechanism to disable genome maintenance
Authors: Lee Miyoung , Shorthouse David , Mahen Robert , Hall Benjamin A , Venkitaraman Ashok R
Published: April 2021

Cancer-causing missense mutations in the 3418 amino acid BRCA2 breast and ovarian cancer suppressor protein frequently affect a short (∼340 residue) segment in its carboxyl-terminal domain (DBD). Here, we identify a shared molecular mechanism underlying their pathogenicity. Pathogenic BRCA2 missense mutations cluster in the DBD’s helical domain (HD) and OB1-fold motifs, which engage the partner protein DSS1. Pathogenic - but not benign – DBD mutations weaken or abolish DSS1-BRCA2 assembly, provoking mutant BRCA2 oligomers that are excluded from the cell nucleus, and disable DNA repair by homologous DNA recombination (HDR). DSS1 inhibits the intracellular oligomerization of wildtype, but not mutant, forms of BRCA2. Remarkably, DSS1 expression corrects defective HDR in cells bearing pathogenic BRCA2 missense mutants with weakened, but not absent, DSS1 binding. Our findings identify a DSS1-mediated intracellular protein assembly mechanism that is disrupted by cancer-causing BRCA2 missense mutations, and suggest an approach for its therapeutic correction.
DomainViz: intuitive visualization of consensus domain distributions across groups of proteins
Authors: Schläpfer Pascal , Mehta Devang , Ridderikhoff Cameron , Uhrig R Glen
Published: April 2021

The prediction of functional domains is typically among the first steps towards understanding the function of new proteins and protein families. There are numerous databases of annotated protein domains that permit researchers to identify domains on individual proteins of interest. However, it is necessary to perform high-throughput domain searches to gain evolutionary insight into the functions of proteins and protein families. Unfortunately, at present, it is difficult to search for, and visualize domain conservation across multiple proteins and/or multiple groups of proteins in an intuitive manner. Here we present DomainViz, a new web-server that streamlines the identification and visualization of domains across multiple protein sequences. Currently, DomainViz uses the well-established PFAM and Prosite databases for domain searching and assembles intuitive, publication-ready ‘monument valley’ plots (mv-plots) that display the extent of domain conservation along two dimensions: positionality and frequency of occurrence in the input protein sequences. In addition, DomainViz produces a conventional domain-ordering figure. DomainViz can be used to explore the conservation of domains within a single protein family, across multiple families, and across families from different species to support studies into protein function and evolution. The web-server is publicly available at: https://uhrigprotools.biology.ualberta.ca/domainviz.
The effect of energy and fat content labeling on food consumption pattern: a systematic review and meta-analysis
Authors: Agarwal Deepali , Ravi Priyanka , Purohit Bharathi , Priya Harsh
Published: April 2021

Context

Consumption of high-energy food has increased globally, thereby leading to an increase in many diseases. One strategy for addressing this is to make people aware of their energy intake through energy and fat labels. However, the effectiveness of this remains debatable.

Objective

This review aims to pool the mixed outcomes of recent studies assessing the effect of energy and fat content labeling on food consumption pattern.

Data Sources

Google Scholar, MEDLINE, and Cochrane Library databases were searched. Randomized controlled and quasi-experimental controlled trials published from 2014 to 2019 were included.

Data Extraction

Two reviewers screened 413 abstracts independently. Qualitative and quantitative data was extracted from 10 articles; meta-analysis was carried out on 6 of those studies.

Results

The majority of the included papers were conducted in the regions of America, the Western Pacific, and Europe. Overall, the 6 studies claimed that labeling did not reduce the consumption of energy or fat. However, meta-analysis showed that fat and energy content labeling of food had a statistically significant effect on consumption. Subgroup analysis showed no difference with respect to types of labels, ie, context labeling vs traffic-light labeling, but energy content labels seemed to be more effective than fat content labels in influencing healthy food choices.

Conclusion

Energy and fat content labeling were shown to reduce the consumption of each significantly. However, the outcome was influenced by the study setting and the population concerned. There is a need for research in other regions in order to assess the global effectiveness of nutrition labels on food consumption.

Systematic Review Registration

PROSPERO registration no. CRD42020172675.
Post-traumatic tenosynovial chondromatosis following a triquetrum fracture: a case report
Authors: Mangual Danny , Olivella Gerardo , Ramirez Norman , Astacio Eric , Bibiloni Juan , Foy-Parrilla Christian
Published: April 2021

Tenosynovial chondromatosis (TC) is a rare progressive benign tumor from the synovial lining of tendon sheath. The TC mostly affects males between the ages 30 to 50 years old at the ventral side of wrist. There are two different forms of TC that have been proposed in previous studies: an idiopathic cause (primary TC) and a joint related diseases cause (secondary TC). Even though trauma has been written to be a common reason for TC, a case of a secondary TC affecting the dorsal wrist following a triquetrum fracture has never been written before. The aim of this report is to present a rare case of a solitary post-traumatic TC at the dorsal wrist following a triquetrum fracture. We describe the clinical presentation, imaging modalities, histopathological and treatment challenges to manage this difficult lesion.
A near miss: subclinical saddle pulmonary embolism diagnosed by handheld ultrasound
Authors: Skipina Travis M , Petty S Allan , Kelly Christopher T
Published: April 2021

Introduction: Pulmonary embolism (PE) is a life-threatening condition characterized by occlusive disease of the pulmonary vasculature. Point-of-care ultrasound (POCUS) of right ventricular strain patterns have high specificity and low sensitivity for diagnosis. Here, we describe a patient with a saddle PE and low pre-test probability who was diagnosed primarily by handheld POCUS.

Case Report: An 80-year old female was admitted to the intensive care unit with hypotension and lactic acidosis. She also had mild leukocytosis and troponinemia. No other clinical or metabolic abnormalities were present. After transfer to the floor, handheld POCUS demonstrated D-sign and McConnell’s sign. Computed tomography angiography showed a saddle PE involving both main pulmonary arteries. The patient was immediately initiated on anticoagulation without further complications.

Conclusion: Handheld POCUS is inexpensive, carries a low risk of harm and is an invaluable extension of the physical exam when interpreted in the appropriate context.
Cystic fibrosis and coeliac disease: a case report of an unusual association
Authors: Doya Leen Jamel , Hassan Naya Talal , Hajo Narmin , Bijow Fareeda Wasfy , Ibrahim Alexander , Ibrahim Ali
Published: April 2021

Coeliac disease (CD) and cystic fibrosis (CF) are well known as the most common causes of chronic intestinal malabsorption in childhood. The coexistence of coeliac disease with cystic fibrosis is uncommon. Here, we describe the case of cystic fibrosis in a patient diagnosed with coeliac disease who failed to respond clinically to a gluten-free diet and had persistent steatorrhea and failure to thrive.