bluuebunny/crossref_metadata_2025 huggingface dataset:
Harnessing feature extraction capacities from a pre-trained convolutional neural network (VGG-16) for the unsupervised distinction of aortic outflow velocity profiles in patients with severe aortic stenosis
Authors: Lachmann Mark , Rippen Elena , Rueckert Daniel , Schuster Tibor , Xhepa Erion , von Scheidt Moritz , Pellegrini Costanza , Trenkwalder Teresa , Rheude Tobias , Stundl Anja , Thalmann Ruth , Harmsen Gerhard , Yuasa Shinsuke , Schunkert Heribert , Kastrati Adnan , Joner Michael , Kupatt Christian , Laugwitz Karl Ludwig
Published: April 2022

Aims

Hypothesizing that aortic outflow velocity profiles contain more valuable information about aortic valve obstruction and left ventricular contractility than can be captured by the human eye, features of the complex geometry of Doppler tracings from patients with severe aortic stenosis (AS) were extracted by a convolutional neural network (CNN).

Methods and results

After pre-training a CNN (VGG-16) on a large data set (ImageNet data set; 14 million images belonging to 1000 classes), the convolutional part was employed to transform Doppler tracings to 1D arrays. Among 366 eligible patients [age: 79.8 ± 6.77 years; 146 (39.9%) women] with pre-procedural echocardiography and right heart catheterization prior to transcatheter aortic valve replacement (TAVR), good quality Doppler tracings from 101 patients were analysed. The convolutional part of the pre-trained VGG-16 model in conjunction with principal component analysis and k-means clustering distinguished two shapes of aortic outflow velocity profiles. Kaplan–Meier analysis revealed that mortality in patients from Cluster 2 (n = 40, 39.6%) was significantly increased [hazard ratio (HR) for 2-year mortality: 3; 95% confidence interval (CI): 1–8.9]. Apart from reduced cardiac output and mean aortic valve gradient, patients from Cluster 2 were also characterized by signs of pulmonary hypertension, impaired right ventricular function, and right atrial enlargement. After training an extreme gradient boosting algorithm on these 101 patients, validation on the remaining 265 patients confirmed that patients assigned to Cluster 2 show increased mortality (HR for 2-year mortality: 2.6; 95% CI: 1.4–5.1, P-value: 0.004).

Conclusion

Transfer learning enables sophisticated pattern recognition even in clinical data sets of limited size. Importantly, it is the left ventricular compensation capacity in the face of increased afterload, and not so much the actual obstruction of the aortic valve, that determines fate after TAVR.
Genetic analysis of daf-18/PTEN missense mutants for starvation resistance and developmental regulation during Caenorhabditis elegans L1 arrest
Authors: Chen Jingxian , Tang Linda Y , Powell Maya E , Jordan James M , Baugh L Ryan
Published: April 2022

Mutations in the well-known tumor suppressor PTEN are observed in many cancers. PTEN is a dual-specificity phosphatase that harbors lipid and protein-phosphatase activities. The Caenorhabditis elegans PTEN ortholog is daf-18, which has pleiotropic effects on dauer formation, aging, starvation resistance, and development. Function of 3 daf-18 point-mutants, G174E, D137A, and C169S, had previously been investigated using high-copy transgenes in a daf-18 null background. These alleles were generated based on their mammalian counterparts and were treated as though they specifically disrupt lipid or protein-phosphatase activity, or both, respectively. Here, we investigated these alleles using genome editing of endogenous daf-18. We assayed 3 traits relevant to L1 starvation resistance, and we show that each point mutant is essentially as starvation-sensitive as a daf-18 null mutant. Furthermore, we show that G174E and D137A do not complement each other, suggesting overlapping effects on lipid and protein-phosphatase activity. We also show that each allele has strong effects on nucleocytoplasmic localization of DAF-16/FoxO and dauer formation, both of which are regulated by PI3K signaling, similar to a daf-18 null allele. In addition, each allele also disrupts M-cell quiescence during L1 starvation, though D137A has a weaker effect than the other alleles, including the null. Our results confirm that daf-18/PTEN is important for promoting starvation resistance and developmental arrest and that it is a potent regulator of PI3K signaling, and they highlight challenges of using genetic analysis to link specific DAF-18/PTEN enzymatic activities to particular phenotypes.
Subgenome dominance and its evolutionary implications in crop domestication and breeding
Authors: Wang Zheng , Yang Jinghua , Cheng Feng , Li Peirong , Xin Xiaoyun , Wang Weihong , Yu Yangjun , Zhang Deshuang , Zhao Xiuyun , Yu Shuancang , Zhang Fenglan , Dong Yang , Su Tongbing
Published: April 2022

Polyploidization or whole-genome duplication (WGD) is a well-known speciation and adaptation mechanism in angiosperms, while subgenome dominance is a crucial phenomenon in allopolyploids, established following polyploidization. The dominant subgenomes contribute more to genome evolution and homoeolog expression bias, both of which confer advantages for short-term phenotypic adaptation and long-term domestication. In this review, we firstly summarize the probable mechanistic basis for subgenome dominance, including the effects of genetic [transposon, genetic incompatibility, and homoeologous exchange (HE)], epigenetic (DNA methylation and histone modification), and developmental and environmental factors on this evolutionary process. We then move to Brassica rapa, a typical allopolyploid with subgenome dominance. Polyploidization provides the B. rapa genome not only with the genomic plasticity for adapting to changeable environments, but also an abundant genetic basis for morphological variation, making it a representative species for subgenome dominance studies. According to the ‘two-step theory’, B. rapa experienced genome fractionation twice during WGD, in which most of the genes responding to the environmental cues and phytohormones were over-retained, enhancing subgenome dominance and consequent adaption. More than this, the pangenome of 18 B. rapa accessions with different morphotypes recently constructed provides further evidence to reveal the impacts of polyploidization and subgenome dominance on intraspecific diversification in B. rapa. Above and beyond the fundamental understanding of WGD and subgenome dominance in B. rapa and other plants, however, it remains elusive why subgenome dominance has tissue- and spatiotemporal-specific features and could shuffle between homoeologous regions of different subgenomes by environments in allopolyploids. We lastly propose acceleration of the combined application of resynthesized allopolyploids, omics technology, and genome editing tools to deepen mechanistic investigations of subgenome dominance, both genetic and epigenetic, in a variety of species and environments. We believe that the implications of genomic and genetic basis of a variety of ecologically, evolutionarily, and agriculturally interesting traits coupled with subgenome dominance will be uncovered and aid in making new discoveries and crop breeding.
Circulating Hormones and Dominance Status Predict Female Behavior during Courtship in a Lekking Species
Authors: Earl Alexis D , Kimmitt Abigail A , Yorzinski Jessica L
Published: April 2022

Female competitive behaviors during courtship can have substantial fitness consequences, yet we know little about the physiological and social mechanisms underlying these behaviors—particularly for females of polygynous lek mating species. We explored the hormonal and social drivers of female intersexual and intrasexual behavior during courtship by males in a captive population of Indian peafowl. We investigated whether (1) female non-stress induced circulating estradiol (E2) and corticosterone (CORT) levels or (2) female dominance status in a dyad predicts female solicitation behavior. We also tested whether female circulating E2 and CORT predict dominant females’ aggressive behaviors toward subordinate females in the courtship context. Our findings demonstrate that females with higher levels of circulating E2 as well as higher levels of circulating CORT solicit more courtships from males. Dominant females also solicit more courtships from males than subordinate females. Female intrasexual aggressive behaviors during courtship, however, were not associated with circulating levels of E2 or CORT. Overall, we conclude that circulating steroid hormones in conjunction with social dominance might play a role in mediating female behaviors associated with competition for mates. Experimental manipulation and measures of hormonal flexibility throughout the breeding season in relation to competitive and sexual behaviors will be necessary to further examine the link between hormonal mechanisms and female behavior in polygynous lekking systems.
Discards of cod (Gadus morhua) in the Norwegian coastal fisheries: improving past and future estimates
Authors: Berg Hilde Sofie Fantoft , Clegg Thomas L , Blom Geir , Kolding Jeppe , Ono Kotaro , Nedreaas Kjell
Published: April 2022

Discarding can be an unknown source of biases and uncertainties in stock assessments. Discarding patterns and quantities vary so a routine methodology for estimating discards is important to give a better picture of total catches, and potentially mortality, in fisheries. Using data from the Norwegian Reference Fleet between 2012 and 2018, this study presents a revised methodology for estimating discards of cod (Gadus morhua) in the Norwegian coastal gillnet fisheries, which accounts for variations in discarding between vessels and uncertainties in the conversion of numbers to weight discarded. The estimated average discard rate of cod (weight of cod discarded as percentage of total weight caught) is 0.55% (95% confidence interval: 0.45–0.70%), although discard rates in southern areas were an order of magnitude higher than in northern areas. We also present an exploratory analysis of the drivers behind discarding using a random forest regression model. Spatial variations and fishing intensity were identified as the most important drivers of discarding. Results from this study suggest ways in which self-sampled data can be used to estimate discards in Norwegian coastal fisheries, and where the accuracy of future estimates can be improved when a higher resolution data collection programme is established.
Machine Learning Quantifies Accelerated White-Matter Aging in Persons With HIV
Authors: Petersen Kalen J , Strain Jeremy , Cooley Sarah , Vaida Florin , Ances Beau M
Published: April 2022

Background

Persons with HIV (PWH) undergo white matter changes, which can be quantified using the brain-age gap (BAG), the difference between chronological age and neuroimaging-based brain-predicted age. Accumulation of microstructural damage may be accelerated in PWH, especially with detectable viral load (VL).

Methods

In total, 290 PWH (85% with undetectable VL) and 165 HIV-negative controls participated in neuroimaging and cognitive testing. BAG was measured using a Gaussian process regression model trained to predict age from diffusion magnetic resonance imaging in publicly available normative controls. To test for accelerated aging, BAG was modeled as an age × VL interaction. The relationship between BAG and global neuropsychological performance was examined. Other potential predictors of pathological aging were investigated in an exploratory analysis.

Results

Age and detectable VL had a significant interactive effect: PWH with detectable VL accumulated +1.5 years BAG/decade versus HIV-negative controls (P = .018). PWH with undetectable VL accumulated +0.86 years BAG/decade, although this did not reach statistical significance (P = .052). BAG was associated with poorer global cognition only in PWH with detectable VL (P < .001). Exploratory analysis identified Framingham cardiovascular risk as an additional predictor of pathological aging (P = .027).

Conclusions

Aging with detectable HIV and cardiovascular disease may lead to white matter pathology and contribute to cognitive impairment.
Osamu Tezuka’sBuddha, Canonical Authority, and Remix Theory in the Study of Religion
Authors: Walker Seth M
Published: April 2022

Contemporary narrative repositories of religious traditions are often the ambiguous product of dialogic oral transmissions that occurred over many years, undergoing variation based on audience, context, or ideological purpose. Through an application of remix theory, both official and unauthorized narrative developments among the sacred stories of religious traditions can be understood as sampling processes in which select elements are sourced from archival spaces of narrative data in the creation of unique versions for the contexts in which they emerge. This is specifically demonstrated through Osamu Tezuka’s Buddha manga series, but the questions it raises and the conceptual challenges it presents for doctrinal notions of authority and authenticity are also relevant outside the immediate context of Buddhism for the canonical traditions within other religious systems. Thus, this article demonstrates how remix theory can be utilized to better challenge the ways such concepts are understood and taken for granted in religious traditions.
Targeted protein degradation and drug discovery
Authors: Naito Mikihiko
Published: April 2022

Targeted protein degradation attracts attention as a novel modality for drug discovery, as well as for basic research. Various types of degrader molecules have been developed so far, which include proteolysis-targeting chimaeras (PROTACs) and specific and nongenetic IAP-dependent protein erasers (SNIPERs), E3 modulators, hydrophobic tagging molecules, IAP antagonists and deubiquitylase inhibitors. PROTACs and SNIPERs are chimeric degrader molecules consisting of a target ligand linked to another ligand that binds to an E3 ubiquitin ligase. In the cells, they recruit an E3 ligase to the target protein, thereby inducing ubiquitylation and proteasomal degradation of the target protein. Because of their modular structure, novel PROTACs and SNIPERs targeting proteins of your interest can be rationally developed by substituting target ligands. In this article, various compounds capable of inducing protein degradation were overviewed, including SNIPER compounds developed in our laboratory.
Effects of Elevated Temperatures on the Growth and Development of Adult Anopheles gambiae (s.l.) (Diptera: Culicidae) Mosquitoes
Authors: Agyekum Thomas P , Arko-Mensah John , Botwe Paul K , Hogarh Jonathan N , Issah Ibrahim , Dwomoh Duah , Billah Maxwell K , Dadzie Samuel K , Robins Thomas G , Fobil Julius N
Published: April 2022

Higher temperatures expected in a future warmer climate could adversely affect the growth and development of mosquitoes. This study investigated the effects of elevated temperatures on longevity, gonotrophic cycle length, biting rate, fecundity, and body size of Anopheles gambiae (s.l.) (Diptera: Culicidae) mosquitoes. Anopheles gambiae (s.l.) eggs obtained from laboratory established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40°C), and 80 ± 10% RH. All adults were allowed to feed on a 10% sugar solution soaked in cotton wool; however, some mosquitoes were provided blood meal using guinea pig. Longevity was estimated for both blood-fed and non-blood-fed mosquitoes and analyzed using the Kaplan–Meier survival analysis. One-way ANOVA was used to test the effect of temperature on gonotrophic cycle length, biting rate, and fecundity. Adult measurement data were log-transformed and analyzed using ordinary least square regression with robust standard errors. Increasing temperature significantly decreased the longevity of both blood-fed (Log-rank test; X2(4) = 904.15, P < 0.001) and non-blood-fed (Log-rank test; X2(4) = 1163.60, P < 0.001) mosquitoes. In addition, the fecundity of mosquitoes decreased significantly (ANOVA; F(2,57) = 3.46, P = 0.038) with an increase in temperature. Body size (β = 0.14, 95% CI, 0.16, 0.12, P < 0.001) and proboscis length (β = 0.13, 95% CI, 0.17, 0.09, P < 0.001) significantly decreased with increasing temperature from 25 to 34°C. Increased temperatures expected in a future warmer climate could cause some unexpected effects on mosquitoes by directly influencing population dynamics and malaria transmission.
Nonparametric Differentially Private Confidence Intervals for the Median
Authors: Drechsler Jörg , Globus-Harris Ira , Mcmillan Audra , Sarathy Jayshree , Smith Adam
Published: April 2022

Differential privacy is a restriction on data processing algorithms that provides strong confidentiality guarantees for individual records in the data. However, research on proper statistical inference, that is, research on properly quantifying the uncertainty of the (noisy) sample estimate regarding the true value in the population, is currently still limited. This article proposes and evaluates several strategies to compute valid differentially private confidence intervals for the median. Instead of computing a differentially private point estimate and deriving its uncertainty, we directly estimate the interval bounds and discuss why this approach is superior if ensuring privacy is important. We also illustrate that addressing both sources of uncertainty—the error from sampling and the error from protecting the output—simultaneously should be preferred over simpler approaches that incorporate the uncertainty in a sequential fashion. We evaluate the performance of the different algorithms under various parameter settings in extensive simulation studies and demonstrate how the findings could be applied in practical settings using data from the 1940 Decennial Census.
Low Complexity Regions in Mammalian Proteins are Associated with Low Protein Abundance and High Transcript Abundance
Authors: Dickson Zachery W. , Golding G. Brian
Published: April 2022

Low Complexity Regions (LCRs) are present in a surprisingly large number of eukaryotic proteins. These highly repetitive and compositionally biased sequences are often structurally disordered, bind promiscuously, and evolve rapidly. Frequently studied in terms of evolutionary dynamics, little is known about how LCRs affect the expression of the proteins which contain them. It would be expected that rapidly evolving LCRs are unlikely to be tolerated in strongly conserved, highly abundant proteins, leading to lower overall abundance in proteins which contain LCRs. To test this hypothesis and examine the associations of protein abundance and transcript abundance with the presence of LCRs, we have integrated high-throughput data from across mammals. We have found that LCRs are indeed associated with reduced protein abundance, but are also associated with elevated transcript abundance. These associations are qualitatively consistent across 12 human tissues and nine mammalian species. The differential impacts of LCRs on abundance at the protein and transcript level are not explained by differences in either protein degradation rates or the inefficiency of translation for LCR containing proteins. We suggest that rapidly evolving LCRs are a source of selective pressure on the regulatory mechanisms which maintain steady-state protein abundance levels.
Associations between Music Therapy, Pain and Heart Rate for Children Receiving Palliative Care
Authors: Delaney Angela M , Herbert Anthony R , Bradford Natalie , Bernard Anne
Published: April 2022

Music therapy (MT) is a widely used non-pharmacological intervention in pediatric health care, an integral part of pediatric palliative care (PPC). Yet, there is a lack of evidence of efficacy, and best practices are not well established. The nature and extent of physiologic impacts of MT in PPC have not previously been reported. This study explores how MT contributes to psycho-physiological changes in children receiving palliative care. We used a convergent mixed-methods feasibility study with a pre–post design. MT sessions were delivered to children (0–18 years), who were registered with a statewide Pediatric Palliative Care Service. Pre–post measures of pain and heart rate were collected using validated and objective measures and analyzed using mixed-model analysis. Analysis of 36 MT sessions demonstrated a statistically significant reduction in pain scores and heart rate after MT sessions. Post measures of pain measured with Face, Legs, Activity, Cry, Consolability scale (FLACC scale) scores were −1.57 (95% confidence interval [CI] −2.31 to −0.83) and by Likert pain scale −2.03 (95% CI −2.79 to −1.27). Heart rate reduced by a mean of −7.6 beats per minute (95% CI −10.74 to −3.37). Five parents participated in semi-structured interviews. Following thematic analysis, two major themes emerged: (1) MT has a positive impact on physiological symptoms and (2) MT enhances the opportunity to experience joy. Results demonstrate the feasibility of study components and may inform future research design for a larger study. This research contributes to the limited evidence about non-pharmacological interventions enhancing the quality of life for children receiving PPC.
vRhyme enables binning of viral genomes from metagenomes
Authors: Kieft Kristopher , Adams Alyssa , Salamzade Rauf , Kalan Lindsay , Anantharaman Karthik
Published: April 2022

Genome binning has been essential for characterization of bacteria, archaea, and even eukaryotes from metagenomes. Yet, few approaches exist for viruses. We developed vRhyme, a fast and precise software for construction of viral metagenome-assembled genomes (vMAGs). vRhyme utilizes single- or multi-sample coverage effect size comparisons between scaffolds and employs supervised machine learning to identify nucleotide feature similarities, which are compiled into iterations of weighted networks and refined bins. To refine bins, vRhyme utilizes unique features of viral genomes, namely a protein redundancy scoring mechanism based on the observation that viruses seldom encode redundant genes. Using simulated viromes, we displayed superior performance of vRhyme compared to available binning tools in constructing more complete and uncontaminated vMAGs. When applied to 10,601 viral scaffolds from human skin, vRhyme advanced our understanding of resident viruses, highlighted by identification of a Herelleviridae vMAG comprised of 22 scaffolds, and another vMAG encoding a nitrate reductase metabolic gene, representing near-complete genomes post-binning. vRhyme will enable a convention of binning uncultivated viral genomes and has the potential to transform metagenome-based viral ecology.
Rare central nervous system tumors in adults: a population-based study of ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors
Authors: Ho Vincent K Y , Gijtenbeek Anja (J) M M , Wagemakers Michiel , Taal Walter , van Linde Myra E , Swaak-Kragten Annemarie T , Kurt Erkan , van der Weide Hiske L , Wesseling Pieter , de Vos Filip Y , Bromberg Jacoline E C
Published: April 2022

Background

Ependymomas, pilocytic astrocytomas, medulloblastomas, and intracranial germ cell tumors occur relative frequently in children, but are rare central nervous system (CNS) tumors in adults. In this population-based survey, we established incidence, treatment, and survival patterns for these tumors diagnosed in adult patients (≥18 years) over a 30-year period (1989–2018).

Methods

Data on 1384 ependymomas, 454 pilocytic astrocytomas, 205 medulloblastomas, and 112 intracranial germ cell tumors were obtained from the Netherlands Cancer Registry (NCR) on the basis of a histopathological diagnosis. For each tumor type, age-standardized incidence rates and estimated annual percentage change were calculated. Trends in incidence and main treatment modalities were reported per 5-year periods. Overall survival was calculated using the Kaplan–Meier method, and relative survival rates were estimated using the Pohar-Perme estimator.

Results

Incidence and survival rates remained generally stable for pilocytic astrocytomas, medulloblastomas, and germ cell tumors. Increasing incidence was observed for spinal ependymomas, mostly for myxopapillary ependymomas, and survival improved over time for grade II ependymomas (P < .01). Treatment patterns varied over time with shifting roles for surgery in ependymomas and for chemotherapy and radiation in medulloblastomas and germinomas.

Conclusions

The study provides baseline information for highly needed national and international standard treatment protocols, and thus for further improving patient outcomes in these rare CNS tumors.
Crabgrass as an equine pasture forage: impact of establishment method on yield, nutrient composition, and horse preference
Authors: Weinert-Nelson Jennifer R , Meyer William A , Williams Carey A
Published: April 2022

Warm-season grasses (WSG) incorporated into traditional cool-season rotational grazing systems to increase summer yields are typically established in monoculture in separate pasture areas. Few studies have evaluated alternative interseeded establishment of WSG, despite potential benefits for improving biodiversity and land-use efficiency. The objective of this study was to determine the impact of establishment method (monoculture vs. interseeded) on crabgrass pasture forage yield, nutritive value, and preference under equine grazing. Three adult standardbred mares grazed two main plots on two consecutive days (8 hr/d) for three grazing events in 2019: Jul 28/29 (GRAZE 1), Aug 20/30 (GRAZE 2), Oct 1/2 (GRAZE 3). Each main plot contained four replicates of three treatments: mixed cool-season grass (CSG); Quick-N-Big crabgrass (CRB) [Digitaria sanguinalis (L.) Scop.] interseeded into existing cool-season grass (INT), and CRB established as a monoculture (MON). The cool-season grass mix included Inavale orchardgrass [Dactylis glomerata (L.)], Tower tall fescue [Lolium arundinaceum (Schreb.) Darbysh.], and Argyle Kentucky bluegrass [Poa pratensis (L.)]. Herbage mass (HM) and sward height (SH) were measured prior to each grazing event and samples were collected (0800–1000 h) for chemical composition analysis. Observed grazing time (GT) in each sub-plot as determined by 5-min scan sampling was utilized as marker of horse preference. Forage HM was greater in MON (8043 ± 1220 kg/ha) than CSG (5001 ± 1308 kg/ha; P = 0.003), with a trend for greater total HM in MON vs. INT (6582 ± 1220 kg/ha: P = 0.06), but HM did not differ between INT and CSG. The SH was also greatest for MON (28 ± 1.11; INT: 23.6 ± 1.11; CSG: 19.7 ± 1.37 cm; P < 0.003). Forage nutrients (digestible energy and crude protein) were largely similar across treatments and met requirements of horses at maintenance. Horse GT was lower in MON (22.6 ± 3.77 min/sub-plot) than in INT (31.9 ± 3.79 min/sub-plot; P = 0.003) and there was a trend for lower GT in MON vs. CSG (29.9 ± 4.17 min/sub-plot: P = 0.07). These results indicate interseeding CRB would not effectively increase yields of traditional cool-season grass equine rotational grazing systems and would not supply similar levels of summer forage provided by monoculture establishment. Results of this study also suggest horses may prefer cool-season grass pasture forage over warm-season crabgrass.
Exposure to 3,3′,4,4′,5-Pentachlorobiphenyl (PCB126) Causes Widespread DNA Hypomethylation in Adult Zebrafish Testis
Authors: Aluru Neelakanteswar , Engelhardt Jan
Published: April 2022

Exposure to environmental toxicants during preconception has been shown to affect offspring health and epigenetic mechanisms such as DNA methylation are hypothesized to be involved in adverse outcomes. However, studies addressing the effects of exposure to environmental toxicants during preconception on epigenetic changes in gametes are limited. The objective of this study is to determine the effect of preconceptional exposure to a dioxin-like polychlorinated biphenyl (3,3′,4,4′,5-pentachlorobiphenyl [PCB126]) on DNA methylation and gene expression in testis. Adult zebrafish were exposed to 3 and 10 nM PCB126 for 24 h and testis tissue was sampled at 7 days postexposure for histology, DNA methylation, and gene expression profiling. Reduced representation bisulfite sequencing revealed 37 and 92 differentially methylated regions (DMRs) in response to 3 and 10 nM PCB126 exposures, respectively. Among them, 19 DMRs were found to be common between both PCB126 treatment groups. Gene ontology (GO) analysis of DMRs revealed that enrichment of terms such as RNA processing, iron-sulfur cluster assembly, and gluconeogenesis. Gene expression profiling showed differential expression of 40 and 1621 genes in response to 3 and 10 nM PCB126 exposures, respectively. GO analysis of differentially expressed genes revealed enrichment of terms related to xenobiotic metabolism, oxidative stress, and immune function. There is no overlap in the GO terms or individual genes between DNA methylation and RNA sequencing results, but functionally many of the altered pathways have been shown to cause spermatogenic defects.
Food Inflation and Child Health
Authors: Woldemichael Andinet , Kidane Daniel , Shimeles Abebe
Published: April 2022

Malnutrition is one of the most important early life shocks that have lasting effects on health. An often neglected cause of malnutrition and hidden hunger is high food inflation, particularly in developing countries. This study uses the Ethiopian Demographic and Health Survey data, matching each child's early life age in months from the time of conception with the corresponding local monthly food price data to examine the medium-term and long-term impacts of exposure to food inflation during the critical early life window—pregnancy and infancy—on child health. Exposure to one percentage point higher month-to-month food inflation while in utero increases the risk of under-five stunting by 0.95 percent. The impacts are heterogeneous depending on the month of exposure, highlighting the complicated biological mechanisms through which malnutrition during early life affects human growth. The results are robust to various empircal specifications and potential biases arising from survivor sample selection and age misreporting.
Proximal Femoral Screw Hemiepiphysiodesis in Children With Cerebral Palsy Improves the Radiographic Measures of Hip Subluxation
Authors: Zakrzewski Allyson M. , Carl Jacob R. , McCarthy James J.
Published: April 2022

Background:

Proximal femoral screw hemiepiphysiodesis (PFSH) is a promising technique for treatment of hip subluxation in children with cerebral palsy (CP). The aim of this study is to report radiographic outcomes of PFSH and to evaluate its role in changing the natural history of hip displacement in children with CP.

Methods:

This is a single center retrospective chart review of children with CP that underwent PFSH with at least 2 years of radiographic follow-up. Demographic information, surgical details, complications, additional surgical procedures, and need for screw exchange were recorded. Radiographs were assessed for migration percentage (MP), neck shaft angle (NSA), head shaft angle (HSA), and articular trochanter distance preoperatively as well as at 6 months, 1 year, 2 year, and latest follow-up postoperatively. Hips were divided into group 1 (no previous hip surgery) and group 2 (PFSH performed after hip reconstruction). Hips with 2 years of preoperative radiographic data were included in the natural history cohort.

Results:

Twenty-three patients (44 hips) met inclusion criteria with an average age of 7.3±1.7 years and a mean follow-up of 33.5 months. Group 1 and group 2 had 32 and 12 hips, respectively. Group 1 had significant improvement in all parameters (ΔMP=5%, ΔNSA=13 degrees, ΔHSA=15 degrees) group 2 showed improvements in NSA and HSA (ΔNSA=4 degrees ΔHSA=8 degrees) with only HSA reaching significance and MP remaining unchanged. All radiographic measurements worsened in the 2 years before surgery (N=25, natural history group) and improved after PFSH. Screw exchange occurred in 12 hips (27.2%) at an average of 33 months (range 27 to 42 mo) with 2 hips also undergoing pelvic osteotomy at that time. Three hips had a MP >50% at follow-up with 2 hips in group 1 undergoing hip reconstruction. No complications were noted.

Conclusion:

PFSH effectively alters proximal femoral growth and can improve hip subluxation in children with CP. Screws often need to be exchanged and hips should be carefully monitored.

Level of Evidence:

Level III—retrospective comparative study.
A Comparison of Generalized and Individualized Vestibular Rehabilitation Therapy in a Military TBI Sample
Authors: Vander Vegt Christina B. , Hill-Pearson Candace A. , Hershaw Jamie N. , Loftin Megan C. , Bobula Selena A. , Souvignier Alicia R.
Published: April 2022

Objective:

To compare clinical outcomes between active duty service members receiving generalized versus individualized vestibular rehabilitation treatment (GVRT and IVRT, respectively) for persistent vestibular-related symptoms following mild traumatic brain injury (mTBI).

Setting:

An outpatient TBI rehabilitation clinic.

Participants:

Fifty-seven participants with persistent vestibular-related symptoms following mTBI were randomly assigned to the GVRT (n = 28) or IVRT (n = 29) group, stratified by dizziness-related impairment severity. Forty-two participants (n = 21 per group) completed the posttreatment evaluation and were included in analyses.

Design:

We employed a single-site, randomized, pre-/posttest experimental design. The GVRT program consisted of eight 45-minute group-based treatment sessions and IVRT consisted of three 30-minute one-on-one treatment sessions both to be completed within 8 weeks. Group assignment was not blinded to study personnel or participants. Research evaluations were completed approximately 2 weeks prior to treatment initiation and following treatment completion.

Main Measures:

Outcome measures included Dizziness Handicap Inventory (DHI) and Activities-specific Balance Confidence Scale (ABC) total scores, Sensory Organization Test (SOT) composite equilibrium and sensory input ratio scores, Head Shake SOT (HS-SOT) conditions 2 and 5, and horizontal and vertical Dynamic Visual Acuity. Separate mixed-effects models were used to compare clinical outcomes between the GVRT and IVRT groups.

Results:

Both groups demonstrated significant improvement from pre- to posttreatment on self-reported dizziness-related impairment (DHI [F
(1,41) = 16.28, P < .001]) and balance performance with and without head movement (composite equilibrium score [F
(1,41) = 16.58, P < .001, effect size [ES] = 0.43], somatosensory [F
(1,41) = 6.79, P = .013, ES = 0.26], visual [F
(1,41) = 6.49, P = .015, ES = 0.29], vestibular [F
(1,41) = 22.31, P < .001, ES = 0.55], and HS-SOT condition 5 [F
(1,38) = 23.98, P < .001, ES = 0.64]). Treatment effects did not differ between groups on any of the outcome measures.

Conclusions:

We provide preliminary evidence that differences in clinical outcomes do not exist between participants receiving generalized versus individualized VR. Further research is needed to determine comparative effectiveness between these 2 treatment approaches for persistent vestibular-related symptoms following mTBI.
The effect of asynchronous group discussions on nurse practitioner student debriefing experience in virtual simulation
Authors: Casler Kelly , Bobek Heidi , Pittman Oralea , Tornwall Joni
Published: April 2022

Debriefing facilitates student learning of critical concepts and faculty evaluation of simulation learning outcomes. However, effective practices in debriefing after virtual simulation, including the impact of software-generated performance feedback and asynchronous group debriefing, are not well understood. Student perceptions of two different methods of postsimulation debriefing were explored by comparing software-generated performance feedback only versus software-generated feedback combined with an asynchronous, faculty-facilitated, online discussion based on the 3D Model of Debriefing. The Debriefing Experience Scale was used to evaluate self-reported debriefing experiences in 68 advanced practice nursing students before and after implementation of an online discussion-board debriefing strategy. Students reported an improved debriefing experience when simulation software-generated feedback was combined with asynchronous online discussion compared with automated software-generated feedback alone. Implications for faculty are discussed including lessons learned to support online, asynchronous debriefing experiences, and how to engage students in meaningful discussions that triangulate feedback from the simulation software, peers, and their instructor.
Management of adverse effects associated with pegylated Escherichia coli asparaginase on coagulation in the treatment of patients with NK/T-cell lymphoma
Authors: Yang Jing , Guo Xiangyun , Guo Sutang , Yan Hongxia , Chai Limin , Guo Yimeng , Li Zhenhua , Hao Zhiying , Su Liping
Published: April 2022

Natural killer/T-cell lymphoma (NK/TL) is a chemotherapy-sensitive disease, and asparaginase-based chemotherapy has become the standard primary treatment for patients with this malignancy recently. The objective of this study was to evaluate the adverse reactions on blood coagulation of the administered pegylated Escherichia coli (E coli) asparaginase (PEG-ASP) to the NK/TL patients. Clinical data of 71 NK/TL patients (range 13–73 years), who received 239 cycles of chemotherapy treatment containing PEG-ASP in the Hematology Department of Shanxi Province Cancer Hospital of China from January 2016 to December 2019 were analyzed retrospectively. Data of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), and antithrombinIII (ATIII) were obtained at the time points routinely and statistically analyzed. There were statistical differences between the monitored parameters of baseline day0 (the day before use of PEG-ASP, named day0) and those of day3 (the 3rd day after treatment) to day6, and data showed all of the indicators could recover within 21 days. The events included PT prolonged in 33 patients (46.5%), APPT prolonged in 41 patients (57.7%, 20 patients with APTT >60 seconds), FBG decreased in 49 patients (69.0%, 12 patients with FBG <1 g/L), and ATIII decreased in 52 patients (73.2%). The patients’ average number of cycles received was 2.3 for PT (>14 seconds), 2.5 for APTT (>35 seconds), 2.7 for FBG (<2 g/L), and 2.6 for D-dimer (>550 ng/mL). Compared with those at day0, PT and APTT prolonged sharply at day3 (P < .05), reached the peak at day12, maintained the prolonged level from day3 to day15, and gradually recovered at day 21. FBG and ATIII significantly decreased at day6 and day3 respectively (P < .05), both of them fell to the minimum at day12, and then returned the normal. The D-dimer levels were no significantly change during the whole treatment course. The APTT >60 seconds or FBG <1 g/L side effects were improved by symptomatic treatment of supplementation of fresh frozen plasma or cryoprecipitate infusion, no concomitant bleeding or thrombotic events emerging. Our data suggested although chemotherapy including PEG-ASP impacted moderately on the coagulation function of NK/TL patients, clinically monitored regularly were necessary and most NK/TL patients can complete the chemotherapy cycles successfully.
Acupuncture and moxibustion for cancer-related psychological disorders
Authors: Jiang Yan , Liang Dan , He Yadi , Wang Jing , Xu Guixing , Wang Jun
Published: April 2022

Introduction:

Cancer-related psychological disorders (CRPD) with high incidence are often underdiagnosed and undertreated. Although, some studies suggested that acupuncture and moxibustion (AM) are effective and safe for CRPD, lacking strong evidence, for instance, the relevant systematic review, meta-analysis, and randomized control trial (RCT) of a large sample, multicenter, makes the effects and safety remain uncertain. The aim of protocol is to evaluating the RCTs of AM for CRPD to verify the association of AM with the improvement of CRPD.

Methods and analysis:

Eight electric databases (4 English databases and 4 Chinese databases) will be searched from inception to Mar. 2022. There will be no restrictions on the category of the language. The RCTs of AM for CRPD unlimited to any type of cancer will be included. Depression and anxiety scores will be the primary outcome indicators. Two researchers will independently complete study selection, evaluate the risk of bias, and extract the data. The RevMan 5.2 software will be used to conduct data synthesis using the random-effects model. The weighted mean differences or standardized mean differences with 95% CIs will be used to present the results of measurement data, and the risk ratios with 95% CIs will be used to express the counting data. Additionally, we will use the Grading of Recommendations Assessment, Development, and Evaluation to assess evidence quality.

Main results:

The results of the meta-analysis will be presented with tables and figures.

Ethics and dissemination:

The results of this meta-analysis and meta-regression will be disseminated via publication in peer-reviewed journals and will be published at relevant conferences. The data to be used will not contain individual patient data; therefore, there is no need to worry about patient privacy.

PROSPERO registration number:

CRD42020177219.
Identification of a novel mutation in CYBB gene in a Chinese neonate with X-linked chronic granulomatous disease
Authors: Zhang Jie , Fan Meili , Chen Mengmeng , Wang Huihui , Miao Na , Yu Haihua , Zhang Lehai , Deng Qianqian , Yi Changying
Published: April 2022

Rationale:

X-linked chronic granulomatous disease (X-CGD) is an X-linked recessive disorder of the Nicotinamide adenine dinucleotide phosphate oxidase system that can cause primary immunodeficiency. Mutations in the CYBB gene located in Xp21.1 were accounting for X-CGD disease. More than 600 mutations have been identified as the cause of X-CGD in various populations worldwide.

Patient concerns and diagnosis:

In this study, the proband suffered from elevated white blood cells (WBC, 23.65 × 109/L), mainly in neutral (16.4 × 109/L). The neutrophil oxidative index of the patient was 2.13, which was extremely low, whereas his mother was 69.0 (Ref >100). Next, next-generation sequencing of the primary immunodeficiency diseases -related gene panel was performed. One novel mutation was identified in the CYBB gene in the CGD case: c.55C>G in exon 2. The mutation was verified by Sanger sequencing. The mother of the patient was heterozygous for the c.55C>G mutation, and the father was normal. These mutations were not present in the 100 unrelated normal controls.

Interventions and outcomes:

The patient died from severe and uncontrollable pulmonary infection at 3 months of age.

Lessons:

The identification of these mutations in this study further expands the spectrum of known CYBB gene mutations and contributes to the genetic counseling and prenatal molecular diagnosis of X-CGD.
Cancer and obstructive sleep apnea
Authors: Cao Yuan , Ning Pu , Li Qiao , Wu Shuang
Published: April 2022

Objective:

The relationship between cancers and obstructive sleep apnea (OSA) has been discussed for decades. However, the previous meta-analysis led to opposite conclusions. To further investigate this controversial issue, we performed this systematic review and meta-analysis update.

Methods:

PubMed, Embase, and the Cochrane Library were systematically searched and studies on “cancer and OSA” were all included. Two reviewers independently searched articles, extracted data, and assessed the quality of included studies. Moreover, the overall incidence of cancer and OSA in corresponding populations was calculated.

Results:

Of the 1434 titles identified, 22 articles involving more than 32.1 million patients were included in this meta-analysis. An overall incidence of OSA positive individuals in cancer was 46 (95%CI, 27–67)%, and the prevalence of cancers in OSA patients reached 1.53 (95%CI, 1.01–2.31) times higher than non-OSA individuals.

Conclusion:

This meta-analysis indicated that there was a high prevalence of OSA in cancer patients, and individuals with OSA were more likely to develop tumors, and the incidence was related to the severity of OSA.
Performance characterization of PCR-free whole genome sequencing for clinical diagnosis
Authors: Zhou Guiju , Zhou Meizhen , Zeng Fanwei , Zhang Ningzhi , Sun Yan , Qiao Zhihong , Guo Xueqin , Zhou Shihao , Yun Guojun , Xie Jiansheng , Wang Xiaodan , Liu Fengxia , Fan Chunna , Wang Yaoshen , Fang Zhonghai , Tian Zhongming , Dai Wentao , Sun Jun , Peng Zhiyu , Song Lijie
Published: April 2022

To evaluate the performance of polymerase chain reaction (PCR)-free whole genome sequencing (WGS) for clinical diagnosis, and thereby revealing how experimental parameters affect variant detection.

Five NA12878 samples were sequenced using MGISEQ-2000. NA12878 samples underwent WGS with differing deoxyribonucleic acid (DNA) input and library preparation protocol (PCR-based vs PCR-free protocols for library preparation). The depth of coverage and genotype quality of each sample were compared. The performance of each sample was measured for sensitivity, coverage of depth and breadth of coverage of disease-related genes, and copy number variants. We also developed a systematic WGS pipeline (PCR-free) for the analysis of 11 clinical cases.

In general, NA12878-2 (PCR-free WGS) showed better depth of coverage and genotype quality distribution than NA12878-1 (PCR-based WGS). With a mean depth of ∼40×, the sensitivity of homozygous and heterozygous single nucleotide polymorphisms (SNPs) of NA12878-2 showed higher sensitivity (>99.77% and >99.82%) than NA12878-1, and positive predictive value exceeded 99.98% and 99.07%. The sensitivity and positive predictive value of homozygous and heterozygous indels for NA12878-2 (PCR-free WGS) showed great improvement than NA128878-1. The breadths of coverage for disease-related genes and copy number variants are slightly better for samples with PCR-free library preparation protocol than the sample with PCR-based library preparation protocol. DNA input also influences the performance of variant detection in samples with PCR-free WGS. All the 19 previously confirmed variants in 11 clinical cases were successfully detected by our WGS pipeline (PCR free).

Different experimental parameters may affect variant detection for clinical WGS. Clinical scientists should know the range of sensitivity of variants for different methods of WGS, which would be useful when interpreting and delivering clinical reports.
Effect of resisted exercise on autonomic cardiac modulation in elderly women
Authors: Isidoro Naerton José Xavier , Oliveira Fernando Rocha , Raimundo Rodrigo Daminello
Published: April 2022

Heart rate variability (HRV) is an important cardiac health marker, with lower values indicating a reduction in vagal control of cardiac rhythm and decreasing significantly with advancing age. In this study, we evaluated the effects of strength exercises for the upper and lower limbs on cardiac autonomic modulation in elderly women.

We registered 29 participants using a portable RS800CX heart rate monitor to record the RR intervals. For the collection of HRV data, the volunteers remained seated at rest for 10 minutes. After the rest period, the participants performed the exercises. Immediately after the exercise protocol, the subjects remained seated at rest for 30 minutes. HRV indices were analyzed in the following periods: rest, 0 to 10 minutes, 5 to 10 minutes, 10 to 20 minutes, and 20 to 30 minutes. Systolic arterial pressure and diastolic arterial pressure were measured in the following periods: rest, immediately after exercise, and 30 minutes after exercise.

Regarding the mean of the RR intervals, heart rate, and indexes of the time and frequency domains surveyed, there were no statistically significant differences between the 4 moments in the protocols for upper and lower limbs. No significant differences were found in systolic and diastolic pressures between the 3 time points surveyed in the protocols for the upper and lower limbs.

Resistance exercises performed with low-intensity loads and a greater number of repetitions did not promote significant variations in cardiac autonomic modulation and blood pressure levels, showing good safety in elderly women.