bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Chromosome-level Genome Assembly ofCheumatopsyche charitesMalicky and Chantaramongkol, 1997 (Trichoptera: Hydropsychidae) Reveals How It Responds to Pollution
Authors: Ge Xinyu , Jin Jianfeng , Peng Lang , Zang Haoming , Wang Beixin , Sun Changhai
Published: September 2022

Trichoptera is a highly adapted group of freshwater insects. They are generally more sensitive to dissolved oxygen and water quality than most freshwater organisms, and this sensitivity allows them to be used as reliable biological indicators of water quality. At present, there exists no chromosome-level genome of a hydropsychid species. Cheumatopsyche charites Malicky & Chantaramongkol, 1997 can successfully survive and thrive in polluted streams where other caddisflies are infrequent, suggesting that they are tolerant to latent contamination. Here we report a high-quality chromosome-level genome assembly of C. charites generated combining PacBio long reads and Hi-C reads. We obtained a genome assembly of 223.23 Mb, containing 68 scaffolds with an N50 length of 13.97 Mb, and 155 contigs (99.67%) anchored into 16 pseudochromosomes. We identified 36.12 Mb (16.18%) of the genome as being composed of repetitive elements, identified 369 noncoding RNAs, and predicted 8,772 protein-coding genes (96.80% BUSCO completeness). Gene family evolution analyses identified 7,148 gene families, of which 41 experienced rapid evolution. The expanded gene families were shown to be involved in detoxification metabolism, digestive absorption, and resistance to viruses or bacteria. This high-quality genome provides a valuable genomic basis for the study of trichopteran evolution.
Social Support for Informal Caregivers of Spouses and Parents(-in-Law) Aged 60 Years and Older During the COVID-19 Pandemic: Findings From a Representative German Online Survey
Authors: Zwar Larissa , König Hans-Helmut , Hajek André
Published: September 2022

Objectives

We analyzed whether spousal and adult child caregivers of older adults differed from each other and from noncaregivers in terms of the social support available to them during the coronavirus disease 2019 pandemic, whether available support differed by gender, and whether the perception of pandemic restrictions moderated these differences.

Methods

Participants (≥40 years) were randomly drawn from the population-based German online panel forsa.omninet. Between March 4 and 19, 2021, 2,520 noncaregivers, 337 adult child caregivers, and 55 spousal caregivers were questioned about social support, perception of pandemic restrictions, health, and sociodemographic information. Adjusted regression analyses and moderator analyses were conducted.

Results

Adult child caregivers had higher social support from family and friends than noncaregivers, and more support from friends than spousal caregivers. Spousal caregivers had less social support from friends compared to both groups. The perceived restrictions of the pandemic moderated the differences in support from family and friends between spousal caregivers and noncaregivers, and the differences between spousal and adult child caregivers in support from friends. Gender moderated the difference in support by friends between caregiving and noncaregiving wives and sons(-in-law).

Discussion

Informal caregivers seemed to have a supportive informal network during the pandemic. However, spousal caregivers only had similar levels of support as adult child caregivers if they strongly perceived restrictions of the pandemic, and had the lowest support level of all 3 groups—in particular from friends. Thus, spousal caregivers may benefit most from support actions, and these should focus on their wider social network.
Overprediction of Carbapenemase-Containing Isolates by an Automated AST Instrument’s Computer Algorithm
Authors: Rice Kathryn S , Luethy Paul M
Published: September 2022

Background

The VITEK® 2 is generally accepted as a reliable method for predicting antibiotic resistance mechanisms including aminoglycoside phenotypes, beta lactam phenotypes, impermeability, and penicillinases. However, when it comes to predicting carbapenemases, the research that has been done is inconsistent in both methods and results.

Methods

We compared the predictions of the VITEK 2 and Advanced Expert System™ (AES) with the results of the modified carbapenemase inactivation method in an academic medical center lab to evaluate the clinical reliability of the VITEK 2 and AES in routine workflow for the detection of carbapenemases.

Results

Our findings show that the positive predictive value of carbapenemase detection on the VITEK2 and AES is 30.3% (91/300) in our patient population.

Conclusions

In light of these results, we propose that the VITEK 2 and AES be used as a screening tool for carbapenemase-containing organisms rather than as a definitive test.
Extension of the reduced animal model to single-step methods
Authors: Nilforooshan Mohammad Ali
Published: September 2022

For a few decades, animal models (AMs) in the form of best linear unbiased prediction (BLUP) have been used for the genetic evaluation of animals. An equation system is set in the order of all the effects in the model, including all the animals in the pedigree. Solving these large equation systems has been a challenge. Reduced AM (RAM) was introduced in 1980, which allowed setting up equations for parents instead of all animals. That greatly reduced the number of equations to be solved. The RAM is followed by a back-solving step, in which progenies’ breeding values are obtained conditional on parental breeding values. Initially, pedigree information was utilized to model genetic relationships between animals. With the availability of genomic information, genomic BLUP (GBLUP), single-step GBLUP (ssGBLUP), and single-step marker models were developed. Single-step methods utilize pedigree and genomic information for simultaneous genetic evaluation of genotyped and nongenotyped animals. There has been a shortage of studies on RAM development for genetic evaluation models utilizing genomic information. This study extended the concept of RAM from BLUP to the single-step methods. Using example data, three RAMs were described for ssGBLUP. The order of animal equations was reduced from the total number of animals to (1) genotyped animals and nongenotyped parents, (2) genotyped animals and nongenotyped phenotyped animals, and (3) genotyped animals and nongenotyped parents of phenotyped nongenotyped nonparents. Solutions for the remaining animals are obtained following a back-solving step. All the RAMs produced identical results to the full ssGBLUP. Advances in computational hardware have alleviated many computational limitations, but, on the other hand, the size of data is growing rapidly by the number of animals, traits, phenotypes, genotypes, and genotype density. There is an opportunity for a RAM comeback for the single-step methods to reduce the computational demands by reducing the number of equations.
Antimicrobial Stewardship in Cystic Fibrosis
Authors: Lloyd Elizabeth C , Cogen Jonathan D , Maples Holly , Bell Scott C , Saiman Lisa
Published: September 2022

The chronic airway infection and inflammation characteristic of cystic fibrosis (CF) ultimately leads to progressive lung disease, the primary cause of death in persons with CF (pwCF). Despite many recent advances in CF clinical care, efforts to preserve lung function in many pwCF still necessitate frequent antimicrobial use. Incorporating antimicrobial stewardship (AMS) principles into management of pulmonary exacerbations (PEx) would facilitate development of best practices for antimicrobial utilization at CF care centers. However, AMS can be challenging in CF given the unique aspects of chronic, polymicrobial infection in the CF airways, lack of evidence-based guidelines for managing PEx, limited utility for antimicrobial susceptibility testing, and increased frequency of adverse drug events in pwCF. This article describes current evidence-based antimicrobial treatment strategies for pwCF, highlights the potential for AMS to beneficially impact CF care, and provides practical strategies for integrating AMS programs into the management of PEx in pwCF.
A correlation between H α trough depth and inclination in quiescent X-ray transients: evidence for a low-mass black hole in GRO J0422+32
Authors: Casares J , Muñoz-Darias T , Torres M A P , Mata Sánchez D , Britt C T , Armas Padilla M , Álvarez-Hernández A , Cúneo V A , González Hernández J I , Jiménez-Ibarra F , Jonker P G , Panizo-Espinar G , Sánchez-Sierras J , Yanes-Rizo I V
Published: September 2022

We present a new method to derive binary inclinations in quiescent black hole (BH) X-ray transients (XRTs), based on the depth of the trough (T) from double-peaked H α emission profiles arising in accretion discs. We find that the inclination angle (i) is linearly correlated with T in phase-averaged spectra with sufficient orbital coverage (≳50 per cent) and spectral resolution, following i(deg) = 93.5 × T + 23.7. The correlation is caused by a combination of line opacity and local broadening, where a leading (excess broadening) component scales with the deprojected velocity of the outer disc. Interestingly, such scaling allows to estimate the fundamental ratio M1/Porb by simply resolving the intrinsic width of the double-peak profile. We apply the T–i correlation to derive binary inclinations for GRO J0422+32 and Swift J1357−0933, two BH XRTs where strong flickering activity has hindered determining their values through ellipsoidal fits to photometric light curves. Remarkably, the inclination derived for GRO J0422+32 (i = 55.6 ± 4.1○) implies a BH mass of $2.7^{+0.7}_{-0.5}$ M⊙ thus placing it within the gap that separates BHs from neutron stars. This result proves that low-mass BHs exist in nature and strongly suggests that the so-called ‘mass gap’ is mainly produced by low number statistics and possibly observational biases. On the other hand, we find that Swift J1357−0933 contains a $10.9^{+1.7}_{-1.6}$ M⊙ BH, seen nearly edge on ($i=87.4^{+2.6}_{-5.6}$ deg). Such extreme inclination, however, should be treated with caution since it relies on extrapolating the T–i correlation beyond i ≳ 75○, where it has not yet been tested.
SPARKESX: Single-dish PARKES data sets for finding the uneXpected – a data challenge
Authors: Yong Suk Yee , Hobbs George , Huynh Minh T , Rolland Vivien , Petersson Lars , Norris Ray P , Dai Shi , Luo Rui , Zic Andrew
Published: September 2022

New classes of astronomical objects are often discovered serendipitously. The enormous data volumes produced by recent high-time resolution, radio-telescope surveys imply that efficient algorithms are required for a discovery. Such algorithms are usually tuned to detect specific, known sources. Existing data sets therefore likely contain unknown astronomical sources, which will remain undetected unless algorithms are developed that can detect a more diverse range of signals. We present the Single-dish PARKES data sets for finding the uneXpected (SPARKESX), a compilation of real and simulated high-time resolution observations. SPARKESX comprises three mock surveys from the Parkes ‘Murriyang’ radio telescope. A broad selection of simulated and injected expected signals (such as pulsars and fast radio bursts), poorly characterized signals (plausible flare star signatures), and ‘unknown unknowns’ are generated for each survey. The goal of this challenge is to aid in the development of new algorithms that can detect a wide range of source types. We show how successful a typical pipeline based on the standard pulsar search software, presto, is at finding the injected signals. The data set is publicly available at https://doi.org/10.25919/fd4f-0g20 (Yong et al. 2022).
Low Sensitivity of International Classification of Diseases, Tenth Revision Coding for Culture-Confirmed Candidemia Cases in an Active Surveillance System: United States, 2019–2020
Authors: Benedict Kaitlin , Gold Jeremy A W , Jenkins Emily N , Roland Jeremy , Barter Devra , Czaja Christopher A , Johnston Helen , Clogher Paula , Farley Monica M , Revis Andrew , Harrison Lee H , Tourdot Laura , Davis Sarah Shrum , Phipps Erin C , Felsen Christina B , Tesini Brenda L , Escutia Gabriela , Pierce Rebecca , Zhang Alexia , Schaffner William , Lyman Meghan
Published: September 2022

We evaluated healthcare facility use of International Classification of Diseases, Tenth Revision (ICD-10) codes for culture-confirmed candidemia cases detected by active public health surveillance during 2019–2020. Most cases (56%) did not receive a candidiasis code, suggesting that studies relying on ICD-10 codes likely underestimate disease burden.
Magnetic Resonance Imaging of the Lumbar Spine: Recommendations for Acquisition and Image Evaluation from the BACPAC Spine Imaging Working Group
Authors: Sollmann Nico , Fields Aaron J , O’Neill Conor , Nardo Lorenzo , Majumdar Sharmila , Chin Cynthia T , Tosun Duygu , Han Misung , Vu An T , Ozhinsky Eugene , Shah Lubdha M , Harris Richard E , Lobo Remy , Anderst William , Herzog Richard , Psioda Matthew A , Standaert Christopher J , Price River T , Lotz Jeffrey C , Link Thomas M , Krug Roland
Published: September 2022

Management of patients suffering from low back pain (LBP) is challenging and requires development of diagnostic techniques to identify specific patient subgroups and phenotypes in order to customize treatment and predict clinical outcome. The Back Pain Consortium (BACPAC) Research Program Spine Imaging Working Group has developed standard operating procedures (SOPs) for spinal imaging protocols to be used in all BACPAC studies. These SOPs include procedures to conduct spinal imaging assessments with guidelines for standardizing the collection, reading/grading (using structured reporting with semi-quantitative evaluation using ordinal rating scales), and storage of images. This article presents the approach to image acquisition and evaluation recommended by the BACPAC Spine Imaging Working Group. While the approach is specific to BACPAC studies, it is general enough to be applied at other centers performing magnetic resonance imaging (MRI) acquisitions in patients with LBP. The herein presented SOPs are meant to improve understanding of pain mechanisms and facilitate patient phenotyping by codifying MRI-based methods that provide standardized, non-invasive assessments of spinal pathologies. Finally, these recommended procedures may facilitate the integration of better harmonized MRI data of the lumbar spine across studies and sites within and outside of BACPAC studies.
A filarial parasite-encoded human IL-10 receptor antagonist reveals a novel strategy to modulate host responses
Authors: Ricciardi Alessandra , Hassan Sergio A , Kamenyeva Olena , Bennuru Sasisekhar , Andersen John , Nutman Thomas B
Published: September 2022

Interleukin (IL)-10 is the primary cytokine driving the modulation of the host response in filarial infections. We performed binding assays with Brugia malayi antigen extracts and human IL-10R1. Bm5539 was the top-binding hit. We identified a short sequence, termed truncated Bm5339, that has structural similarities to the human IL-10 functional dimer. Sequence comparisons revealed that other filarial parasites possess Bm5539 orthologues. Using recombinant Bm5539 in a modified Luciferase Immunoprecipitation System assay, we confirmed that both the truncated and full-length forms of the protein can bind to human IL-10R1. Truncated Bm5539 could inhibit human IL-10-driven phosphorylation of STAT3, thereby demonstrating that Bm5539 acts as an IL-10 antagonist, most likely through competitive binding to the receptor. We provide a structural basis for these observations using computational modeling and simulations. This parasite-encoded cytokine receptor antagonist provides an additional lens through which parasite-induced modulation of the host immune response can be examined.
Time Consistency and Duration of Government Debt: A Model of Quantitative Easing
Authors: Bhattarai Saroj , Eggertsson Gauti B , Gafarov Bulat
Published: September 2022

This article presents a model of quantitative easing (QE) at the zero lower bound (ZLB) on the short-term nominal interest rate. QE, which reduces the maturity of government debt, is effective at the ZLB because it generates expectations of future monetary expansion in a time-consistent equilibrium. Numerical experiments show that this effect can be substantial.
Mental Health Impacts of Hurricane Harvey: Examining the Roles of Intimate Partner Violence and Resilience
Authors: First Jennifer M , Ravi Kristen E , Smith-Frigerio Sarah , Houston J Brian
Published: September 2022

Prior research has found that the prevalence and severity of intimate partner violence (IPV) increase in communities experiencing a disaster. Less studied are the associations between IPV, disaster exposure, and mental health outcomes following disaster events. In the current study, authors examined the prevalence of IPV before and after Hurricane Harvey and the direct and indirect effects of risk (i.e., disaster exposure, IPV) and resilience on mental health outcomes using structural equation modeling with 382 adults. Results indicate that exposure to Hurricane Harvey was significantly associated with risk for IPV, posttraumatic stress (PTS) symptoms, and depression symptoms. In addition, IPV mediated the relationships between disaster exposure and PTS and depression symptoms. These findings support the need to incorporate IPV services and resources into disaster mental health services.
Mosaic Evolution of the Skull in Labrid Fishes Involves Differences in Both Tempo and Mode of Morphological Change
Authors: Larouche Olivier , Gartner Samantha M , Westneat Mark W , Evans Kory M
Published: September 2022

Modularity is a ubiquitous feature of organismal design that plays an important role in structuring patterns of morphological diversification. Modularity can facilitate evolutionary changes by allowing subsets of traits to coevolve as integrated units and follow quasi-independent evolutionary trajectories, a pattern that may be particularly consequential in the case of highly complex morphological structures. Here we examine modularity in a complex and highly kinetic structure, the teleost skull, and ask if a modular organization of the skull has influenced the diversification dynamics of the shapes of its osteological components across the labrid phylogeny. We compiled one of the largest 3D morphological data sets of fishes to date and used geometric morphometrics to quantify patterns of cranial shape evolution across 184 species of wrasses (Labridae). We then tested several hypotheses of modularity inspired by functional and developmental relationships between cranial bones and compared phenotypic rates among modules. We also compared the fit of models of trait evolution for the entire skull and the various articulated bones that it comprises. Our analyses indicated strong support for a 2-module hypothesis, one that encompasses the oral and pharyngeal jaws and another module comprised of the neurocranium, hyoid apparatus, and operculum. This functional hypothesis yielded one of the highest significant rate differentials across modules, yet we also found that the best-fitting models of trait evolution differed among skull bones. These results suggest that modularity can influence morphological diversification in complex biological structures via differences in both the tempo and mode of evolutionary change. [3D geometric morphometrics, cranial morphology, evolutionary modularity, Labridae, phenotypic rates, structural complexity.]
Blended Learning in Health Care Education: An Overview and Overarching Meta-analysis of Systematic Reviews
Authors: Lockey Andrew , Bland Andrew , Stephenson John , Bray Janet , Astin Felicity
Published: September 2022

Introduction:

Blended learning is an educational approach that integrates face-to-face with online instruction. This overview of existing systematic reviews aims to evaluate the impact of blended learning on educational outcomes in health care professional education, identify gaps in the current evidence, and direction for future reviews.

Methods:

Five databases were searched (January 1, 2000 to January 14, 2021) for systematic reviews of blended versus nonblended learning approaches for health care education. “Flipped classroom”, unpublished studies, abstracts, and study protocols were excluded. The extracted data included details of included reviews, description of populations, and outcomes according to Kirkpatrick levels. A narrative review is presented, along with an overarching meta-analysis, which evaluates a synthesized estimate of the effect of blended learning based on standardized mean differences.

Results:

Eleven systematic reviews were included, comprising of 160 primary studies (including 117 randomized controlled trials) from 56 countries with over 18,000 participants. The overall level of evidence was very low quality. An overarching meta-analysis of 93 studies addressing knowledge acquisition favored blended over nonblended learning methods (standardized mean difference 0.768 [95% confidence interval 0.594–0.941]; P < .001). None of the reviews identified an adverse effect on other educational outcomes.

Discussion:

Blended learning may be superior to traditional teaching approaches in improving knowledge acquisition. We recommend further research to describe the relative benefits of blended learning in each individual context and identify which elements of instructional design are beneficial for each outcome. Finally, we recommend the use of clear and consistent terminology in reported studies.
Which fetal growth charts should be used? A retrospective observational study in China
Authors: Zhao Jianxin , Yuan Ying , Tao Jing , Chen Chunyi , Wu Xiaoxia , Liao Yimei , Wu Linlin , Zeng Qing , Chen Yin , Wang Ke , Li Xiaohong , Liu Zheng , Zhou Jiayuan , Zhou Yangwen , Li Shengli , Zhu Jun
Published: September 2022

Background:

The fetal growth charts in widest use in China were published by Hadlock >35 years ago and were established on several hundred of American pregnant women. After that, >100 fetal growth charts were published around the world. We attempted to assess the impact of applying the long-standing Hadlock charts and other charts in a Chinese population and to compare their ability to predict newborn small for gestational age (SGA).

Methods:

For this retrospective observational study, we reviewed all pregnant women (n = 106,455) who booked prenatal care with ultrasound measurements for fetal biometry at the Shenzhen Maternity and Child Healthcare Hospital between 2012 and 2019. A fractional polynomial regression model was applied to generate Shenzhen fetal growth chart ranges for head circumference (HC), biparietal diameter, abdominal circumference (AC), and femur length (FL). The differences between Shenzhen charts and published charts were quantified by calculating the Z-score. The impact of applying these published charts was quantified by calculating the proportions of fetuses with biometric measurements below the 3rd centile of these charts. The sensitivity and area under the receiver operating characteristic curves of published charts to predict neonatal SGA (birthweight <10th centile) were assessed.

Results:

Following selection, 169,980 scans of fetal biometry contributed by 41,032 pregnancies with reliable gestational age were analyzed. When using Hadlock references (<3rd centile), the proportions of small heads and short femurs were as high as 8.9% and 6.6% in late gestation, respectively. The INTERGROWTH-21st standards matched those of our observed curves better than other charts, in particular for fat-free biometry (HC and FL). When using AC<10th centile, all of these references were poor at predicting neonatal SGA.

Conclusions:

Applying long-standing Hadlock references could misclassify a large proportion of fetuses as SGA. INTERGROWTH-21st standard appears to be a safe option in China. For fat-based biometry, AC, a reference based on the Chinese population is needed. In addition, when applying published charts, particular care should be taken due to the discrepancy of measurement methods.
New Recommendations of a Height-Based Dosing Regimen of Tobramycin for Cystic Fibrosis in Adults: A Population Pharmacokinetic Analysis
Authors: Koloskoff Kevin , Thirion Daniel J. G. , Matouk Elias , Marsot Amélie
Published: September 2022

Background:

Acute pulmonary exacerbations (APEs) in patients with adult cystic fibrosis (CF) are treated with a beta-lactam and an aminoglycoside for activity against Pseudomonas aeruginosa (PA). Emerging drug resistance and changing pharmacokinetic profile in an aging population involve a reevaluation of tobramycin dosing recommendations. The objective of this study was to develop a population pharmacokinetic model and establish optimal dosing recommendations for tobramycin using Monte Carlo simulations.

Methods:

This retrospective clinical study and data collection were performed at the CF center of the McGill University Health Center (MUHC), Canada. Model development and simulations were performed using a nonlinear mixed-effect modeling approach (NONMEM, version 7.4.2). The ratios of maximal concentration (Cmax) to the minimal inhibitory concentration (MIC) (Cmax/MIC ≥8 and ≥10) and area under the curve (AUC) to the MIC (AUC/MIC ≥70 and ≥100) were evaluated.

Results:

Adult patients with CF (n = 51) treated with tobramycin were included in the study. Plasma concentrations of tobramycin were obtained for 699 samples from the MUHC database. The two-compartmental model best described the pharmacokinetics of tobramycin. The association of patient height with the central volume of distribution significantly improved this model. Height, rather than weight, induced the best reduction in objective function. According to simulations, doses between 3.4 mg/cm and 4.4 mg/cm were necessary to achieve Cmax/MIC values of ≥8 and ≥10, respectively. However, higher doses were required to achieve the AUC/MIC targets.

Conclusions:

This study demonstrated that height of the patients seems to be more suitable than their weight for dosing adjustments in adult patients with CF. According to this model, initial doses of tobramycin between 3.4 and 4.4 mg/cm should be recommended for patients with a median height of 164 cm and weight of 55 kg to achieve the target plasma concentrations.
“Should I Tell My Leader or Not?”—Health-Oriented Leadership and Stigma as Antecedents of Employees' Mental Health Information Disclosure Intentions at Work
Authors: Pischel Sarah , Felfe Jörg
Published: September 2022

Objective

To investigate how health-oriented leadership and stigma facilitate or impede employees' disclosure intentions to leaders.

Methods

In two studies—an experimental vignette (n = 73) and a cross-sectional study (n = 220)—we manipulated or measured health-oriented leadership, transformational leadership, and organizational stigma and compared different reasons for disclosure (mental health problems and severe error) to separate general and specific disclosure decisions.

Results

Health-oriented leadership fostered disclosure above and beyond transformational leadership. High organizational stigma was associated with lower disclosure. Health-oriented leadership had a stronger effect on disclosing mental problems than on disclosing a severe error and slightly mitigated the negative relationship between stigma and disclosure in study 1. Findings were not influenced by employees' current mental health status.

Conclusions

Our findings highlight the importance of health-oriented leadership as a facilitator and organizational stigma as a barrier to disclosure intentions.
The Effect of Shiftwork on Body Composition
Authors: Sooriyaarachchi Piumika , Jayawardena Ranil , Pavey Toby , King Neil A.
Published: September 2022

Objective

This study compared the body composition parameters between shiftworkers and nonshiftworkers in a hospital setting in Sri Lanka.

Methods

A comparative cross-sectional study was carried out among a sample of 78 health care workers, recruited by a stratified random sampling technique. Subjects underwent anthropometric and bioimpedentiometric analysis for body composition parameters.

Results

The mean (SD) body fat percentage (BF%) of shiftworking women (40.8 [SD, 6.8%]) was significantly higher than day-working women (36.7% [SD, 5.9%]) (P < 0.05). Mean BF% between day and shift groups did not significantly differ (33.0% [SD, 6.9%] vs 32.4% [SD, 10.7%]). Body mass index and waist circumference were significantly higher among shiftworking women (P < 0.05), whereas male workers showed the opposite trend.

Conclusion

Prolonged exposure to shiftwork was associated with a higher BF%. Therefore, interventions for shiftworkers must be addressed, focusing on improving body composition.
Disease Status at Diagnosis in Danish Children with α1‐antitrypsin Deficiency
Authors: Winther Christina Louise , Nyrann Sofie , Nielsen Rasmus Gaardskaer , Duno Morten , Johansen Klaus Birkelund , Helt Thora Wesenberg , Christensen Vibeke Brix
Published: September 2022

Objectives:

The aim of this cross‐sectional study was to assess the state of disease at the time of diagnosis in Danish children with α1‐antitrypsin deficiency as Denmark has a high prevalence of ZZ‐homozygosity.

Methods:

Children either heterozygous, compound heterozygous, or homozygous for Z‐ and S‐variants in the SERPINA1‐gene were included. Clinical characteristics, SERPINA1‐genotype, and blood serum (S) concentrations were recorded concurrently with genetic testing. Serum liver marker concentrations were compared using T tests and Wilcoxon‐Mann‐Whitney tests. Generalized estimating equation (GEE) linear regression models, both univariable and multivariable adjusted for age and sex, were applied to identify correlations with serum α1‐antitrypsin (S‐AAT). The relationship between S‐AAT concentration and genotype was assessed using logistic regression with GEE.

Results:

The study included 183 of 225 children genetically tested for alpha‐1‐antitrypsin deficiency (AATD). Of these, 36.6% were homozygous for the Z‐variant. Of the heterozygotes, 89.7% had a ZM genotype and the remaining had either an MS genotype or were compound heterozygous. At diagnosis, ZZ‐homozygous children had higher serum concentrations of liver enzymes and conjugated bilirubin, but lower concentrations of S‐AAT compared with heterozygotes. Serum concentrations of conjugated bilirubin and liver enzymes were negatively associated with S‐AAT. Children under 6 months of age had higher total S‐bilirubin concentrations than children over 6 months of age.

Conclusions:

A low S‐AAT concentration is a strong indicator of homozygosity, and homozygous children have higher enzymatic and cholestatic parameters compared with heterozygous children at diagnosis. This underlines the importance of measuring the S‐AAT concentration in children with prolonged neonatal jaundice.
Health‐related Quality of Life in a Prospective Study of Ultrasound to Detect Cystic Fibrosis–related Liver Disease in Children
Authors: Schwarzenberg Sarah Jane , Palermo Joseph J. , Ye Wen , Huang Suiyuan , Magee John C. , Alazraki Adina , Freeman A. Jay , Harned Roger , Karmazyn Boaz , Karnsakul Wikrom , Leung Daniel H. , Ling Simon C. , Masand Prakash , Molleston Jean P. , Murray Karen F. , Navarro Oscar M. , Nicholas Jennifer L. , Otto Randolph K. , Paranjape Shruti M. , Siegel Marilyn J. , Stoll Janis , Towbin Alexander J. , Narkewicz Michael R. , Alonso Estella M. ,   CFLD NET, Freeman A. Jay , Romero Rene , Alazraki Adina L. , Karnsakul Wikrom W. , Paranjape Shruti M. , Dunn Emily , Alonso Estella M. , McColley Susanna , Nicholas Jennifer L. , Palermo Joseph J. , Ziady Assem G. , Towbin Alexander J. , Narkewicz Michael R. , Harned Roger K. , Leung Daniel H. , Masand Prakash , Molleston Jean P. , Bozic Molly , Karmazyn Boaz W. , Schwarzenberg Sarah Jane , Seidel Glenn F. , Stoll Janis , Kulkarni Sakil , Siegel Marilyn , Green Nicole , Murray Karen , Otto Randolph K. , Ling Simon C. , Navarro Oscar M. , Magee John C. , Ye Wen , Doo Edward , Sherker Averell H.
Published: September 2022

Objectives:

Cystic fibrosis liver disease (CFLD) begins early in life. Symptoms may be vague, mild, or nonexistent. Progressive liver injury may be associated with decrements in patient health before liver disease is clinically apparent. We examined Health‐Related Quality of Life (HRQOL) in children enrolled in a multi‐center study of CFLD to determine the impact of early CFLD on general and disease‐specific QOL.

Methods:

Ultrasound (US) patterns of normal (NL), heterogeneous (HTG), homogeneous (HMG), or nodular (NOD) were assigned in a prospective manner to predict those at risk for advanced CFLD. Parents were informed of results. We assessed parent/child‐reported (age ≥5 years) HRQOL by PedsQL 4.0 Generic Core and CF Questionnaire‐revised (CFQ‐R) prior to US and annually. HRQOL scores were compared by US pattern at baseline (prior to US), between baseline and 1 year and at 5 years. Multivariate analysis of variance (MANOVA) with Hotelling‐Lawley trace tested for differences among US groups.

Results:

Prior to US, among 515 participants and their parents there was no evidence that HTG or NOD US was associated with reduced PedsQL/CFQ‐R at baseline. Parents of NOD reported no change in PedsQL/CFQ‐R over the next year. Child‐report PedsQL/CFQ‐R (95 NL, 20 NOD) showed improvement between baseline and year 5 for many scales, including Physical Function. Parents of HMG children reported improved CFQ‐R scores related to weight.

Conclusions:

Early undiagnosed or pre‐symptomatic liver disease had no impact on generic or disease‐specific HRQoL, and HRQoL was remarkably stable in children with CF regardless of liver involvement.
Magnetic Resonance Imaging to Assess Body Composition Change in Adolescents With Obesity After Sleeve Gastrectomy
Authors: Berg Elizabeth A. , Huang Zixing , Wang Youya , Woo Baidal Jennifer , Fennoy Ilene , Lavine Joel E. , Zitsman Jeffrey , Shen Wei
Published: September 2022

Objectives:

Metabolic and bariatric surgery is the most effective weight loss treatment for severe obesity. The number of adolescents undergoing sleeve gastrectomy is increasing. We investigated changes in body composition in adolescents undergoing sleeve gastrectomy 12–26 weeks post-operatively using whole-body magnetic resonance imaging (WB-MRI).

Methods:

This prospective cohort study assessed changes in adipose tissue compartments (ie, visceral, subcutaneous, and intermuscular) and muscle in 18 obese adolescents, ages 14–19, 89% female, with body mass index z-score of 2.6 ± 0.25 (range 2.16–3.2). All underwent WB-MRI 1.5–17 weeks pre-operatively and 12–26 weeks post-operatively.

Results:

Pre- and post-operative WB-MRI showed decreases in all adipose tissue compartments, as well as decreased skeletal muscle and liver fat fraction (P < 0.0001). The post-operative percentage loss of adipose tissue in subcutaneous, visceral, and intermuscular compartments (89.0%, 5.8%, 5.2%, respectively) was similar to the pre-operative percentages of corresponding adipose tissue compartments (90.5%, 5.0%, 4.5%, respectively). Of note, participants with obstructive sleep apnea had significantly higher pre-operative volume of subcutaneous and intermuscular adipose tissue than participants without obstructive sleep apnea (P = 0.003).

Conclusions:

We found, contrary to what is reported to occur in adults, that pre-operative percentage loss of adipose tissue in subcutaneous, visceral, and intermuscular compartments was similar to the post-operative percentage loss of corresponding adipose tissue compartments in adolescents 12–26 weeks after sleeve gastrectomy.
SWI/SNF-deficient Malignancies: Optimal Candidates for Immune-oncological Therapy?
Authors: Agaimy Abbas
Published: September 2022

Inactivation of different subunits of the SWItch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex has emerged as one of the most frequent genetic pathways driving a variety of neoplasms of diverse histogenesis, originating in different organs. With few exceptions, most SWI/SNF-deficient malignancies pursue a highly aggressive clinical course resulting in widespread disease dissemination either at or soon after diagnosis, ultimately causing patients’ death soon after diagnosis, despite the apparently curative treatment intention. To date, no satisfactorily effective systemic chemotherapy has been established for treating these diseases. This disappointing finding underlines the urgent need for an effective systemic therapy that would enable sufficient intermediate to long-term disease control. Recently, SWI/SNF-deficiency has increasingly emerged as pivotal in cancer immunogenicity and hence a promising biomarker predicting response to immune-checkpoint inhibition therapy utilizing several recently established drugs. This review summarizes the most recent literature on this topic with emphasis on the entities that most likely represent suitable candidates for immune therapy.
Analysis of Cross-sectional and Longitudinal HLA and Anti-viral Responses After COVID Infection in Renal Allograft Recipients: Differences and Correlates
Authors: Girnita Alin L. , Wang Lin , Colovai Adriana I. , Ahearn Patrick , Azzi Yorg , Menon Madhav C. , Fernandez-Vina Marcelo , Gebel Howard M. , Steve Woodle E. , Cravedi Paolo , Maltzman Jonathan S. , Akalin Enver
Published: September 2022

Background.

Characterization of anti-HLA versus anti-severe acute respiratory syndrome coronavirus 2 (anti–SARS-CoV-2) immune globulin isotypes in organ transplant recipients after coronavirus disease 2019 (COVID-19) infection has not been reported. We aimed to determine changes in anti-HLA antibodies in renal transplant patients with COVID-19 and compare the immunoglobulin and epitope-binding pattern versus anti–SARS-CoV-2 antibodies.

Methods.

This is a cross-sectional study of 46 kidney transplant recipients including 21 with longitudinal sampling. Using a semi-quantitative multiplex assay, we determined immunoglobulin (Ig) M, IgA, IgG, and IgG1-2-3-4 antibodies against Class I and Class II HLA, and 5 SARS-CoV-2 epitopes including the nucleocapsid protein and multiple regions of the spike protein.

Results.

Fourteen of 46 (30%) patients had donor-specific anti-HLA antibodies (donor-specific antibody [DSA]), 12 (26%) had non-DSA anti-HLA antibodies and 45 (98%) had anti–SARS-CoV-2 antibodies. Most DSAs targeted HLA-DQ (71%), with a dominant IgG isotype and IgG1 subtype prevalence (93%), and/or IgG3 (64%), followed by IgG2 (36%). Comparatively, there was a higher prevalence of IgA (85% versus 14%, P = 0.0001) and IgM (87%, versus 36%, P = 0.001) in the anti–SARS-CoV-2 antibody profile, when compared to DSAs, respectively. Anti–SARS-CoV-2 antibody profile was characterized by increased prevalence of IgM and IgA, when compared to DSAs. The median calculated panel reactive antibody before COVID-19 diagnosis (24%) tended to decrease after COVID-19 diagnosis (10%) but it was not statistically significant (P = 0.1).

Conclusions.

Anti-HLA antibody strength and calculated panel reactive antibody in kidney transplant recipients after COVID-19 do not significantly increase after infection. Although the IgG isotype was the dominant form in both HLA and SARS-CoV-2 antigens, the alloimmune response had a low IgA pattern, whereas anti–SARS-CoV-2 antibodies were high IgA/IgM.
Social effects of rabies infection in male vampire bats (
Desmodus rotundus
)
Authors: Cárdenas-Canales Elsa M. , Stockmaier Sebastian , Cronin Eleanor , Rocke Tonie E. , Osorio Jorge E. , Carter Gerald G.
Published: September 2022

Rabies virus (RABV) transmitted by the common vampire bat (
Desmodus rotundus
) poses a threat to agricultural development and public health throughout the Neotropics. The ecology and evolution of rabies host–pathogen dynamics are influenced by two infection-induced behavioural changes. RABV-infected hosts often exhibit increased aggression which facilitates transmission, and rabies also leads to reduced activity and paralysis prior to death. Although several studies document rabies-induced behavioural changes in rodents and other dead-end hosts, surprisingly few studies have measured these changes in vampire bats, the key natural reservoir throughout Latin America. Taking advantage of an experiment designed to test an oral rabies vaccine in captive male vampire bats, we quantify for the first time, to our knowledge, how rabies affects allogrooming and aggressive behaviours in this species. Compared to non-rabid vampire bats, rabid individuals reduced their allogrooming prior to death, but we did not detect increases in aggression among bats. To put our results in context, we review what is known and what remains unclear about behavioural changes of rabid vampire bats (resumen en español, electronic supplementary material, S1).
GNL3
is an evolutionarily conserved stem cell gene influencing cell proliferation, animal growth and regeneration in the hydrozoan
Hydractinia
Authors: Quiroga-Artigas Gonzalo , de Jong Danielle , Schnitzler Christine E.
Published: September 2022

Nucleostemin
(
NS
) is a vertebrate gene preferentially expressed in stem and cancer cells, which acts to regulate cell cycle progression, genome stability and ribosome biogenesis.
NS
and its paralogous gene,
GNL3-like
(
GNL3L
), arose in the vertebrate clade after a duplication event from their orthologous gene,
G protein Nucleolar 3
(
GNL3
). Research on invertebrate
GNL3
, however, has been limited. To gain a greater understanding of the evolution and functions of the
GNL3
gene, we have performed studies in the hydrozoan cnidarian
Hydractinia symbiolongicarpus
, a colonial hydroid that continuously generates pluripotent stem cells throughout its life cycle and presents impressive regenerative abilities. We show that
Hydractinia GNL3
is expressed in stem and germline cells. The knockdown of
GNL3
reduces the number of mitotic and S-phase cells in
Hydractinia
larvae of different ages. Genome editing of
Hydractinia GNL3
via CRISPR/Cas9 resulted in colonies with reduced growth rates, polyps with impaired regeneration capabilities, gonadal morphological defects, and low sperm motility. Collectively, our study shows that
GNL3
is an evolutionarily conserved stem cell and germline gene involved in cell proliferation, animal growth, regeneration and sexual reproduction in
Hydractinia
, and sheds new light into the evolution of
GNL3
and of stem cell systems.
Macrolactonization of methyl 15-hydroxypentadecanoate to cyclopentadecanolide using KF-La/γ-Al
2
O
3
catalyst
Authors: Cheng Haijun , Yu Chang , Wang Hongyun , Liu Xiongmin , Ma Li , Lai Fang
Published: September 2022

It has been a challenge to synthesize macrolide musk in excellent yields with high purity. KF-La/γ-Al
2
O
3
catalyst was prepared from a highly basic mesoporous framework using a mild method. The prepared KF-La/γ-Al
2
O
3
catalyst was employed for the synthesis of cyclopentadecanolide from methyl 15-hydroxypentadecanoate. The morphology and structure of prepared catalysts were characterized using XRD, TG-DTG, SEM, EDX, TEM, BET and CO
2
-TPD. The results revealed that the K
3
AlF
6
and LaOF are produced on the surface of KF-La/γ-Al
2
O
3
, and LaO can promote the dispersion of KF on the surface of Al
2
O
3
. Catalysts pore size main distribution ranges between 10 and 30 nm, the maximum CO
2
desorption temperature is 715°C when the La loading is 25%. Because F
−
ion has a higher electronegativity than O
2−
ion, the KF-promoted metal oxide (Al
2
O
3
or/and La
2
O
3
) contained more strong basic sites, compared with that of the corresponding metal oxide. The yield of cyclopentadecanolide obtained at 0.5 g KF-25La/γ-Al
2
O
3
catalyst and a reaction temperature of 190°C for 7 h were 58.50%, and the content after reactive distillation is 98.8%. The KF-La/γ-Al
2
O
3
catalyst has a larger pore size and basic strength, which is more conducive to the macrolactonization of long-chain hydroxy ester.
Estimating the effective reproduction number for heterogeneous models using incidence data
Authors: Jorge D. C. P. , Oliveira J. F. , Miranda J. G. V. , Andrade R. F. S. , Pinho S. T. R.
Published: September 2022

The effective reproduction number,

R

(
t
)

, plays a key role in the study of infectious diseases, indicating the current average number of new infections caused by an infected individual in an epidemic process. Estimation methods for the time evolution of

R

(
t
)

, using incidence data, rely on the generation interval distribution,
g
(
τ
), which is usually obtained from empirical data or theoretical studies using simple epidemic models. However, for systems that present heterogeneity, either on the host population or in the expression of the disease, there is a lack of data and of a suitable general methodology to obtain
g
(
τ
). In this work, we use mathematical models to bridge this gap. We present a general methodology for obtaining explicit expressions of the reproduction numbers and the generation interval distributions, within and between model sub-compartments provided by an arbitrary compartmental model. Additionally, we present the appropriate expressions to evaluate those reproduction numbers using incidence data. To highlight the relevance of such methodology, we apply it to the spread of COVID-19 in municipalities of the state of Rio de Janeiro, Brazil. Using two meta-population models, we estimate the reproduction numbers and the contributions of each municipality in the generation of cases in all others.
Defence mitigation by predators of chemically defended prey integrated over the predation sequence and across biological levels with a focus on cardiotonic steroids
Authors: Mohammadi Shabnam , Yang Lu , Bulbert Matthew , Rowland Hannah M.
Published: September 2022

Predator–prey interactions have long served as models for the investigation of adaptation and fitness in natural environments. Anti-predator defences such as mimicry and camouflage provide some of the best examples of evolution. Predators, in turn, have evolved sensory systems, cognitive abilities and physiological resistance to prey defences. In contrast to prey defences which have been reviewed extensively, the evolution of predator counter-strategies has received less attention. To gain a comprehensive view of how prey defences can influence the evolution of predator counter-strategies, it is essential to investigate how and when selection can operate. In this review we evaluate how predators overcome prey defences during (i) encounter, (ii) detection, (iii) identification, (iv) approach, (v) subjugation, and (vi) consumption. We focus on prey that are protected by cardiotonic steroids (CTS)—defensive compounds that are found in a wide range of taxa, and that have a specific physiological target. In this system, coevolution is well characterized between specialist insect herbivores and their host plants but evidence for coevolution between CTS-defended prey and their predators has received less attention. Using the predation sequence framework, we organize 574 studies reporting predators overcoming CTS defences, integrate these counter-strategies across biological levels of organization, and discuss the costs and benefits of attacking CTS-defended prey. We show that distinct lineages of predators have evolved dissecting behaviour, changes in perception of risk and of taste perception, and target-site insensitivity. We draw attention to biochemical, hormonal and microbiological strategies that have yet to be investigated as predator counter-adaptations to CTS defences. We show that the predation sequence framework will be useful for organizing future studies of chemically mediated systems and coevolution.