bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in mating system and predicted parental conflict affect post-pollination reproductive isolation in a flowering plant
Authors: Petrén Hampus , Thosteman Hanna , Stift Marc , Toräng Per , Ågren Jon , Friberg Magne
Published: February 2023

Mating system shifts from outcrossing to selfing are frequent in plant evolution. Relative to outcrossing, selfing is associated with reduced parental conflict over seed provisioning, which may result in postzygotic, asymmetric, reproductive isolation in crosses between populations of different mating systems. To test the hypothesis that post-pollination reproductive isolation between populations increases with increasing differences in mating system and predicted parental conflict, we performed a crossing experiment involving all combinations of three self-compatible populations (with low outcrossing rates), and three self-incompatible populations (with high outcrossing rates) of the arctic-alpine herb Arabis alpina, assessing fitness-related seed and plant traits of the progeny. Predicted levels of parental conflict (“genome strength”) were quantified based on strength of self-incompatibility and estimates of outcrossing rates. Crosses between self-compatible and self-incompatible populations yielded very small seeds of low viability, resulting in strong reproductive isolation. In 14 of 15 reciprocal between-population crosses, seeds were heavier when the paternal plant had the stronger genome, and seed mass differences between cross directions increased with an increased difference in parental conflict. Overall, our results suggest that, when sufficiently large, differences in mating system and hence in expected parental conflict may result in strong post-pollination reproductive barriers contributing to speciation.
Mapping of meiotic recombination in human preimplantation blastocysts
Authors: Ma Yuanlin , Wang Jing , Li Rong , Ding Chenhui , Xu Yan , Zhou Canquan , Xu Yanwen
Published: February 2023

Recombination is essential for physical attachments and genetic diversity. The Han Chinese population is the largest ethnic group worldwide, therefore, the construction of a genetic map regarding recombination for the population is essential. In this study, 164 and 240 couples who underwent preimplantation genetic testing for monogenic diseases or segmental rearrangement were included in the analysis. Blastocysts and probands from couples who underwent preimplantation genetic testing for monogenic diseases by single nucleotide polymorphism array were included for recombination analysis. The location of recombination was determined from haplotype phase transitions in parent-offspring pairs at loci where the parents were heterozygous. The genetic map for Chinese in vitro fertilization embryos was constructed by the expectation–maximization algorithm with chip-level data. Our results confirmed that homologous recombination occurred more often in maternal chromosomes, and the age effect was more significant in maternal homologous recombination. A total of 6,494 homologous recombination hotspots (32.3%) were identified in genes of Online Mendelian Inheritance in Man. A uniform association between homologous recombination and aneuploidy was not established. In addition, carriers with identified breakpoints of reciprocal translocations were analyzed, and locations of breakpoints were found partly overlapped with homologous recombination hotspots, implying a possible similar mechanism behind both events. This study highlights the significance of constructing a recombination map, which may improve the accuracy of haplotype analysis for preimplantation genetic testing for monogenic diseases. Overlapping locations of translocation and recombination are worthy of further investigation.
Parvovirus dark matter in the cloaca of wild birds
Authors: Dai Ziyuan , Wang Haoning , Wu Haisheng , Zhang Qing , Ji Likai , Wang Xiaochun , Shen Quan , Yang Shixing , Ma Xiao , Shan Tongling , Zhang Wen
Published: February 2023

With the development of viral metagenomics and next-generation sequencing technology, more and more novel parvoviruses have been identified in recent years, including even entirely new lineages. The Parvoviridae family includes a different group of viruses that can infect a wide variety of animals. In this study, systematic analysis was performed to identify the “dark matter” (datasets that cannot be easily attributed to known viruses) of parvoviruses and to explore their genetic diversity from wild birds’ cloacal swab samples. We have tentatively defined this parvovirus “dark matter” as a highly divergent lineage in the Parvoviridae family. All parvoviruses showed several characteristics, including 2 major protein-coding genes and similar genome lengths. Moreover, we observed that the novel parvo-like viruses share similar genome organizations to most viruses in Parvoviridae but could not clustered with the established subfamilies in phylogenetic analysis. We also found some new members associated with the Bidnaviridae family, which may be derived from parvovirus. This suggests that systematic analysis of domestic and wild animal samples is necessary to explore the genetic diversity of parvoviruses and to mine for more of this potential dark matter.
Asymmetry in the rate of warming and the phenology of seasonal blooms in the Northeast US Shelf Ecosystem
Authors: Friedland Kevin D , Record Nicholas R , Pendleton Daniel E , Balch William M , Stamieszkin Karen , Moisan John R , Brady Damian C
Published: February 2023

Predicting the impact of marine ecosystem warming on the timing and magnitude of phytoplankton production is challenging. For example, warming can advance the progression of stratification thereby changing the availability of nutrients to surface phytoplankton, or influence the surface mixed layer depth, thus affecting light availability. Here, we use a time series of sea surface temperature (SST) and chlorophyll remote sensing products to characterize the response of the phytoplankton community to increased temperature in the Northeast US Shelf Ecosystem. The rate of change in SST was higher in the summer than in winter in all ecoregions resulting in little change in the timing and magnitude of the spring thermal transition compared to a significant change in the autumn transition. Along with little phenological shift in spring thermal conditions, there was also no evidence of a change in spring bloom timing and duration. However, we observed a change in autumn bloom timing in the Georges Bank ecoregion, where bloom initiation has shifted from late September to late October between 1998 and 2020—on average 33 d later. Bloom duration in this ecoregion also shortened from ∼7.5 to 5 weeks. The shortened autumn bloom may be caused by later overturn in stratification known to initiate autumn blooms in the region, whereas the timing of light limitation at the end of the bloom remains unchanged.  These changes in bloom timing and duration appear to be related to the change in autumn thermal conditions and the significant shift in autumn thermal transition. These results suggest that the spring bloom phenology in this temperate continental shelf ecosystem may be more resilient to thermal climate change effects than blooms occurring in other times of the year.
Cosets of Free Field Algebras via Arc Spaces
Authors: Linshaw Andrew R , Song Bailin
Published: February 2023

Using the invariant theory of arc spaces, we find minimal strong generating sets for certain cosets of affine vertex algebras inside free field algebras that are related to classical Howe duality. These results have several applications. First, for any vertex algebra ${{\mathcal {V}}}$, we have a surjective homomorphism of differential algebras $\mathbb {C}[J_{\infty }(X_{{{\mathcal {V}}}})] \rightarrow \text {gr}^{F}({{\mathcal {V}}})$; equivalently, the singular support of ${{\mathcal {V}}}$ is a closed subscheme of the arc space of the associated scheme $X_{{{\mathcal {V}}}}$. We give many new examples of classically free vertex algebras (i.e., this map is an isomorphism), including $L_{k}({{\mathfrak {s}}}{{\mathfrak {p}}}_{2n})$ for all positive integers $n$ and $k$. We also give new examples where the kernel of this map is nontrivial but is finitely generated as a differential ideal. Next, we prove a coset realization of the subregular ${{\mathcal {W}}}$-algebra of ${{\mathfrak {s}}}{{\mathfrak {l}}}_{n}$ at a critical level that was previously conjectured by Creutzig, Gao, and the 1st author. Finally, we give some new level-rank dualities involving affine vertex superalgebras.
Effects of replacing inorganic salts of trace minerals with organic trace minerals in the pre- and postpartum diets on mineral status, antioxidant biomarkers, and health of dairy cows
Authors: Mion Bruna , Ogilvie Lori , Van Winters Bryn , Spricigo Jose F W , Anan Sanjana , Duplessis Mélissa , McBride Brian W , LeBlanc Stephen J , Steele Michael A , Ribeiro Eduardo de Souza
Published: February 2023

Our objectives were to evaluate the effects of complete replacement of supplementary inorganic salts of trace minerals (ITM; cobalt (Co), copper (Cu), manganese (Mn), zinc (Zn) sulfates and sodium (Na) selenite) by organic trace minerals (OTM; Co, Cu, Mn, Zn proteinates, and selenized yeast) in both pre- and postpartum diets on trace minerals (TM) concentrations in body fluids and liver, antioxidant and inflammation biomarkers in blood, and postpartum health of dairy cows. Pregnant cows were blocked by parity and body condition score and randomly assigned to ITM (n = 136) or OTM (n = 137) 45 d before expected calving. Both groups received the same pre- and postpartum diets except for the source of supplementary TM. The day of calving was considered study d 0 and blood was collected on d –45, –21, –14, –10, –7, –3, 0, 3, 7, 10, 14, 23, 65, and 105 for analyses of TM and biomarkers. Concentrations of TM were also investigated in the liver (d 105), milk (d 7, 23, 65, 105), urine (d –21, 21, 65, 105), ruminal fluid and feces (d –21, 21, 65). Incidence of clinical and subclinical health conditions were evaluated. Complete replacement of ITM by OTM resulted in greater concentration of selenium (Se) in serum (0.084 vs. 0.086 µg/mL; P < 0.01), milk (0.24 vs. 0.31 µg/g; P < 0.01), and ruminal fluid (0.54 vs. 0.58 µg/g; P = 0.06), and reduced concentration of Se in urine (1.54 vs. 1.23 µg/g; P<0.01). For concentration of Co in serum, an interaction between treatment and time was detected (P < 0.01). Cows supplemented with OTM had greater concentrations of Co on d –7 and 0 (0.30 vs. 0.33 ng/mL; P < 0.01) but lower concentrations of Co on d 23, 65, and 105 (0.34 vs. 0.31 ng/mL; P < 0.05), in addition to reduced concentration of Co in feces (1.08 vs. 0.99 µg/g; P = 0.04) and, for multiparous only, in urine (0.019 vs. 0.014 µg/g; P < 0.01). Cows supplemented with OTM had lower postpartum concentrations of glutamate dehydrogenase (20.8 vs. 17.8 U/L; P < 0.05) and higher albumin on d –10 (36.0 vs. 36.7 g/L; P = 0.04) and 23 (36.9 vs. 37.6 g/L; P = 0.03) relative to calving. Primiparous cows fed OTM had lower concentration of ceruloplasmin in plasma (55 vs. 51 mg/L; P ≤ 0.05). Cows supplemented with OTM had less incidence of lameness (14% vs. 7%; P = 0.05), elevated nonesterified fatty acids (NEFA) (61% vs. 44%; P < 0.01), and multiple metabolic problems (35% vs. 20%; P < 0.01). Despite the lack of differences in Cu, Mn, and Zn concentrations and antioxidant capacity, complete replacement of ITM by OTM altered concentrations of Se and Co, supported liver and hoof health, and reduced the risk of postpartum elevated NEFA.
Code-free machine learning for classification of central nervous system histopathology images
Authors: Jungo Patric , Hewer Ekkehard
Published: February 2023

Machine learning (ML), an application of artificial intelligence, is currently transforming the analysis of biomedical data and specifically of biomedical images including histopathology. The promises of this technology contrast, however, with its currently limited application in routine clinical practice. This discrepancy is in part due to the extent of informatics expertise typically required for implementation of ML. Therefore, we assessed the suitability of 2 publicly accessible code-free ML platforms (Microsoft Custom Vision and Google AutoML), for classification of histopathological images of diagnostic central nervous system tissue samples. When trained with typically 100 to more than 1000 images, both systems were able to perform nontrivial classifications (glioma vs brain metastasis; astrocytoma vs astrocytosis, prediction of 1p/19q co-deletion in IDH-mutant tumors) based on hematoxylin and eosin-stained images with high accuracy (from ∼80% to nearly 100%). External validation of the predicted accuracy and negative control experiments were found to be crucial for verification of the accuracy predicted by the algorithms. Furthermore, we propose a possible diagnostic workflow for pathologists to implement classification of histopathological images based on code-free machine platforms.
Long-Term Health Care Costs for Service Members Injured in Iraq and Afghanistan
Authors: Stewart Ian J , Ambardar Shiva , Howard Jeffrey T , Janak Jud C , Walker Lauren E , Poltavskiy Eduard , Alcover Karl C , Watrous Jessica , V. Gundlapalli Adi , B. P. Pettey Warren , Suo Ying , Nelson Richard E
Published: February 2023

Introduction

Over the last two decades, the conflicts in Iraq and Afghanistan have cost the United States significantly in terms of lives lost, disabling injuries, and budgetary expenditures. This manuscript calculates the differences in costs between veterans with combat injuries vs veterans without combat injuries. This work could be used to project future costs in subsequent studies.

Materials and Methods

In this retrospective cohort study, we randomly selected 7,984 combat-injured veterans between February 1, 2002, and June 14, 2016, from Veterans Affairs Health System administrative data. We matched injured veterans 1:1 to noninjured veterans on year of birth (± 1 year), sex, and first service branch. We observed patients for a maximum of 10 years. This research protocol was reviewed and approved by the David Grant USAF Medical Center institutional review board (IRB), the University of Utah IRB, and the Research Review Committee of the VA Salt Lake City Health Care System in accordance with all applicable Federal regulations.

Results

Patients were primarily male (98.1% in both groups) and White (76.4% for injured patients, 72.3% for noninjured patients), with a mean (SD) age of 26.8 (6.6) years for the injured group and 27.7 (7.0) years for noninjured subjects. Average total costs for combat-injured service members were higher for each year studied. The difference was highest in the first year ($16,050 compared to $4,135 for noninjured). These differences remained significant after adjustment. Although this difference was greatest in the first year (marginal effect $12,386, 95% confidence interval $9,736-$15,036; P < 0.001), total costs continued to be elevated in years 2-10, with marginal effects ranging from $1,766 to $2,597 (P < 0.001 for all years). More severe injuries tended to increase costs in all categories.

Conclusions

Combat injured patients have significantly higher long-term health care costs compared to their noninjured counterparts. If this random sample is extrapolated to the 53,251 total of combat wounded service members, it implies a total excess cost of $1.6 billion to date after adjustment for covariates and a median follow-up time of 10 years. These costs are likely to increase as injured veterans age and develop additional chronic conditions.
Whole-brain radiotherapy associated with structural changes resembling aging as determined by anatomic surface-based deep learning
Authors: Rammohan Nikhil , Ho Alexander , Besson Pierre , Kruser Tim J , Bandt S Kathleen
Published: February 2023

Background

Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole-brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus has been demonstrated, global structural shape changes after WBRT remain to be studied.

Methods

We studied healthy controls and patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a validated graph convolutional neural network model to estimate patient’s “brain age”. We further developed a mixed-effects linear model to compare the estimated age of the whole brain and substructures before and after WBRT.

Results

4220 subjects were analyzed (4148 healthy controls and 72 patients). The median radiation dose was 30 Gy (range 25–37.5 Gy). The whole brain and substructures underwent structural change resembling rapid aging in radiated patients compared to healthy controls; the whole brain “aged” 9.32 times faster, the cortex 8.05 times faster, the subcortical structures 12.57 times faster, and the hippocampus 10.14 times faster. In a subset analysis, the hippocampus “aged” 8.88 times faster in patients after conventional WBRT versus after hippocampal avoidance (HA)-WBRT.

Conclusions

Our findings suggest that WBRT causes the brain and its substructures to undergo structural changes at a pace up to 13x of the normal aging pace, where hippocampal avoidance offers focal structural protection. Correlating these structural imaging changes with neurocognitive outcomes following WBRT or HA-WBRT would benefit from future analysis.
Adult intracranial ependymoma—relevance of DNA methylation profiling for diagnosis, prognosis, and treatment
Authors: Träger Malte , Schweizer Leonille , Pérez Eilís , Schmid Simone , Hain Elisabeth G , Dittmayer Carsten , Onken Julia , Fukuoka Kohei , Ichimura Koichi , Schüller Ulrich , Dührsen Lasse , Müther Michael , Paulus Werner , Thomas Christian , Gutt-Will Marielena , Schucht Philippe , Maragkou Theoni , Schittenhelm Jens , Eckert Franziska , Niyazi Maximilian , Fleischmann Daniel F , Dorostkar Mario M , Feyer Petra , May Sven-Axel , Moskopp Dag , Badakhshi Harun , Radke Cornelia , Walter Jan , Ehret Felix , Capper David , Kaul David
Published: February 2023

Background

A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas.

Methods

Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from 8 diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were correlated with progression-free survival (PFS).

Results

The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6%, and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE, and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (GTR) (P = .009) and postoperative radiotherapy (P = .007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of the prognosis within molecularly defined ependymoma classes.

Conclusions

DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. GTR and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.
Zooplankton community variability in the South Atlantic Bight (2015–2017)
Authors: López-Figueroa Natalia B , Walters Tina L , Laureano-Rosario Abdiel E , DiGeronimo Sebastian P , Hallock Pamela , Frischer Marc E , Rodríguez-Santiago Áurea E , Gibson Deidre M
Published: February 2023

In the South Atlantic Bight (SAB), responses of zooplankton communities to physical dynamics were evaluated monthly at two sites on the continental shelf offshore from Savannah, GA, USA, between December 2015 and December 2017. Zooplankton were collected in oblique net tows (202-μm). Samples were collected in two regions of the middle shelf: inner edge (Site 1: 25 m isobath, n = 22) and outer edge (Site 2: 40 m isobath, n = 21). Samples were also collected at a third site on the 40 m isobath, ~20 nm south of Site 2 in July and August 2016. Temperature, salinity and fluorescence data were recorded at each site. Overall, 57 taxa were identified with total abundances varying from 1 × 103 to 81 × 103 ind.m−3. Small copepods predominated; notably Paracalanus spp. The highest abundance was recorded in October 2016 at Site 1, following deep mixing induced by Hurricane Matthew. Interannual variability of zooplankton abundance was significant, with higher abundances in 2016 compared with 2017, reflecting higher river runoff in 2016. Samples from Site 3 yielded the largest Dolioletta gegenbauri bloom documented in the SAB. This 2-year time-series, for the first time, suggests that zooplankton communities on the SAB middle shelf region are significantly influenced by continental precipitation patterns.
Exercise effects on glucocorticoid-induced bone loss in adults: a systematic review and meta-analysis
Authors: Kast Stephanie , Jakob Franz , Kohl Matthias , von Stengel Simon , Kerschan-Schindl Katharina , Lange Uwe , Thomasius Friederike , Kemmler Wolfgang
Published: February 2023

Objectives

Due to their pronounced anti-inflammatory and immunosuppressive effects, glucocorticoids (GCs) are widely used in inflammatory conditions and organ transplants. Unfortunately, GC-induced osteoporosis is one of the most common causes of secondary osteoporosis. The aim of the present systematic review and meta-analysis was to determine the effect of exercise added to GC therapy on BMD at the lumbar spine or femoral neck in people on GC therapy.

Methods

A systematic literature search of five electronic databases included controlled trials with a duration of >6 months and at least two study arms [glucocorticoids (GCs) and GCs and exercise (GC + EX)] were conducted up to 20 September 2022. Studies involving other pharmaceutical therapies with relevant effects on bone metabolism were excluded. We applied the inverse heterogeneity model. Outcome measures were standardized mean differences (SMDs) with 95% CIs for BMD changes at the lumbar spine (LS) and femoral neck (FN).

Results

We identified three eligible trials with a total of 62 participants. In summary, the GC + EX intervention indicated statistically significantly higher SMDs for LS-BMD [SMD 1.50 (95% CI 0.23, 2.77)] but not for FN-BMD [0.64 (95% CI −0.89, 2.17)] compared with GC treatment alone. We observed substantial heterogeneity (LS-BMD I2 = 71%, FN-BMD I2 = 78%) between the study results.

Conclusion

Although more well-designed exercise studies are needed to address the issue of exercise effects on GC-induced osteoporosis (GIOP) in more detail, upcoming guidelines should pay more attention to the aspect of exercise for bone strengthening in GIOP.

Registration number

PROSPERO: CRD42022308155
The role of iTr35 cells in the inflammatory response and fibrosis progression of systemic sclerosis
Authors: Yang Chenxi , Lu Chunxiu , Pan Jie , Zhao Cheng , Chen Zhanrui , Qin Fang , Wen Jing , Wei Wanling , Lei Ling
Published: February 2023

Objective

To evaluate the role of induced immunosuppressive T regulatory (iTr) 35 cells in SSc-related inflammation and fibrosis.

Methods

Sixty-eight SSc patients were enrolled in this study. Subsets of iTr35 and Tr1 were measured by flow cytometry. IL-35 and IL-10 levels were measured using ELISA. Expressions of iTr35, Tr1, fibrosis-related genes and proteins associated with signalling pathways were determined using immunofluorescence, western blot and immunohistochemistry assays.

Results

In peripheral blood, the proportions of the iTr35 cells were higher and Tr1 cells were lower than the control group. Similarly, IL-35 expression was increased, while IL-10 levels were decreased. In fibroblasts from skin tissue, the expression levels of EBI3, IL-12Ap35, Foxp3 and IL-10 were decreased, but collagen I, TGF-β, alpha smooth muscle actin (α-SMA) and fibronectin levels were increased. Phosphorylated STAT3/6 were increased, but iTr35 and Tr1 cell levels were significantly decreased. When CD4+ cells were incubated with both recombinant human (rh)IL-35 and rhIL-10, the cell numbers of iTr35 and Tr1 were greater than the same type of cells treated with rhIL-35 or rhIL-10 alone. However, the viability of conventional CD4+ T cells was decreased by gradually increasing iTr35 cells. Moreover, iTr35 cells affected α-SMA expression through the STAT3/6 signalling pathway.

Conclusion

Both iTr35 and Tr1 cells are involved in SSc-related inflammation and fibrosis. IL-35 can induce iTr35 cells, showing a synergistic effect with IL-10. We also found that iTr35 cells can inhibit T cell proliferation and differentiation via the STAT3/6 signalling pathway, thereby causing fibrosis.
Using human genetics to understand the epidemiological association between obesity, serum urate, and gout
Authors: Zhang Li , Zhang Wenqiang , Xiao Chenghan , Wu Xueyao , Cui Huijie , Yan Peijing , Yang Chao , Tang Mingshuang , Wang Yutong , Chen Lin , Liu Yunjie , Zou Yanqiu , Alfredsson Lars , Klareskog Lars , Yang Yanfang , Yao Yuqin , Li Jiayuan , Liu Zhenmi , Yang Chunxia , Jiang Xia , Zhang Ben
Published: February 2023

Objectives

We aimed to clarify the genetic overlaps underlying obesity-related traits, serum urate, and gout.

Methods

We conducted a comprehensive genome-wide cross-trait analysis to identify genetic correlation, pleiotropic loci, and causal relationships between obesity (the exposure variable), gout (the primary outcome) and serum urate (the secondary outcome). Summary statistics were collected from the hitherto largest genome-wide association studies conducted for BMI (N = 806 834), waist-to-hip ratio (WHR; N = 697 734), WHR adjusted for BMI (WHRadjBMI; N = 694 649), serum urate (N = 288 649), and gout (Ncases = 13 179 and Ncontrols = 750 634).

Results

Positive overall genetic correlations were observed for BMI (rg = 0.27, P = 6.62 × 10−7), WHR (rg = 0.22, P = 6.26 × 10−7) and WHRadjBMI (rg = 0.07, P = 6.08 × 10−3) with gout. Partitioning the whole genome into 1703 LD (linkage disequilibrium)-independent regions, a significant local signal at 4q22 was identified for BMI and gout. The global and local shared genetic basis was further strengthened by the multiple pleiotropic loci identified in the cross-phenotype association study, multiple shared gene–tissue pairs observed by Transcriptome-wide association studies, as well as causal relationships demonstrated by Mendelian randomization [BMI–gout: OR (odds ratio) = 1.66, 95% CI = 1.45, 1.88; WHR–gout: OR = 1.57, 95% CI = 1.37, 1.81]. Replacing the binary disease status of gout with its latent pathological measure, serum urate, a similar pattern of correlation, pleiotropy and causality was observed with even more pronounced magnitude and significance.

Conclusion

Our comprehensive genome-wide cross-trait analysis demonstrates a shared genetic basis and pleiotropic loci, as well as a causal relationship between obesity, serum urate, and gout, highlighting an intrinsic link underlying these complex traits.
Gene-x-environment analysis supports protective effects of eveningness chronotype on self-reported and actigraphy-derived sleep duration among those who always work night shifts in the UK Biobank
Authors: Akimova Evelina T , Taiji Riley , Ding Xuejie , Mills Melinda C
Published: February 2023

Previous research has linked having an eveningness chronotype with a higher tolerance for night shift work, suggesting the ability to work nights without health consequences may partially depend upon having a circadian clock optimized for these times. As chronotypes entrain over time to environmental cues, it remains unclear whether higher relative eveningness among healthy night workers reflects a moderating or mediating effect of chronotype on health. We address these concerns conducting a genome-wide association study and utilizing a polygenic score (PGS) for eveningness as a time-invariant measure of chronotype. On a sample of 53 211 workers in the UK Biobank (2006–2018), we focus on the effects of night shift work on sleep duration, a channel through which night shift work adversely affects health. We ask whether a higher predisposition toward eveningness promotes night shift work tolerance. Results indicate that regular night shift work is associated with a 13-minute (3.5%) reduction in self-reported sleep per night relative to those who never work these hours (95% confidence interval [CI] = −17:01, −8:36). We find that eveningness has a strong protective effect on night workers: a one-SD increase in the PGS is associated with a 4-minute (28%) reduction in the night shift work sleep penalty per night (CI = 0:10, 7:04). This protective effect is pronounced for those working the longest hours. Consistent patterns are observed with an actigraphy-derived measure of sleep duration. These findings indicate that solutions to health consequences of night shift work should take individual differences in chronotype into account.
First Report of the Root Lesion Nematode Pratylenchus penetrans Parasitizing Hemp (Cannabis sativa) in the United States
Authors: Núñez-Rodríguez Lester A. , Rivedal Hannah , Peetz Amy , Ocamb Cynthia M. , Zasada Inga
Published: February 2023

In 2022, during a survey of plant-parasitic nematodes affecting hemp in Washington and Oregon, a Pratylenchus sp. was found parasitizing hemp roots. Morphology and morphometrics, as well as molecular techniques, confirmed the identity of the nematodes extracted from hemp roots as Pratylenchus penetrans. A pathogenicity assay done in the greenhouse confirmed hemp as a host to P. penetrans, with an average reproduction factor of 2.2 at 60 days postinoculation. To our knowledge, this is the first report of P. penetrans on hemp in the United States.
Delineating Marker-Trait Associations for Fusarium Wilt in Chickpea Using the Axiom®CicerSNP Array
Authors: Rasool Bushra , Summuna Baby , Djalovic Ivica , Shah Tariq Ahmad , Sheikh Parveez Ahmed , Gupta Sachin , Tyagi Sandhya , Bilal Sierra , Varshney Rajeev Kumar , Abidi Ishfaq , Kumar Jitendra , Penmetsa R. Varma , Khandey Imtiyaz , Kumar Upendra , Sofi Parvaze Ahmad , Khan Mohd Anwar , Bhat Mohd Ashraf , Wani Fahim Jeelani , Thudi Mahendar , Mir Reyazul Rouf
Published: February 2023

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. ciceri is a devastating disease of chickpea ( Cicer arietinum). To identify promising resistant genotypes and genomic loci for FW resistance, a core set of 179 genotypes of chickpea was tested for FW reactions at the seedling and reproductive stages under field conditions and controlled conditions in the greenhouse. Our results revealed that at the seedling stage, most of the genotypes were resistant, whereas at the reproductive stage, most of the genotypes were susceptible. Genotyping using a 50K Axiom®CicerSNP Array and trait data of FW together led to the identification of 26 significant ( P ≤ E-05) marker-trait associations (MTAs) for FW resistance. Among the 26 MTAs, 12 were identified using trait data recorded in the field (three at the seedling and nine at the reproductive stage), and 14 were identified using trait data recorded under controlled conditions in the greenhouse (six at the seedling and eight at the reproductive stage). The phenotypic variation explained by these MTAs varied from 11.75 to 15.86%, with an average of 13.77%. Five MTAs were classified as major, explaining more than 15% of the phenotypic variation for FW, and two were declared stable, being identified in two environments. One of the promising stable and major MTAs (Affx_123280060) detected in field conditions at the reproductive stage was also detected in greenhouse conditions at the seedling and reproductive stages. The stable and major (>15% PVE) MTAs can be used in chickpea breeding programs.
A whole blood approach improves speed and accuracy when measuring mitochondrial respiration in intact avian blood cells
Authors: Nord Andreas , Chamkha Imen , Elmér Eskil
Published: February 2023

Understanding mitochondrial biology and pathology is key to understanding the evolution of animal form and function. However, mitochondrial measurement often involves invasive, or even terminal, sampling, which can be difficult to reconcile in wild models or longitudinal studies. Non‐mammal vertebrates contain mitochondria in their red blood cells, which can be exploited for minimally invasive mitochondrial measurement. Several recent bird studies have measured mitochondrial function using isolated blood cells. Isolation adds time in the laboratory and might be associated with physiological complications. We developed and validated a protocol to measure mitochondrial respiration in bird whole blood. Endogenous respiration was comparable between isolated blood cells and whole blood. However, respiration towards oxidative phosphorylation was higher in whole blood, and whole blood mitochondria were better coupled and had higher maximum working capacity. Whole blood measurement was also more reproducible than measurement on isolated cells for all traits considered. Measurements were feasible over a 10‐fold range of sample volumes, although both small and large volumes were associated with changes to respiratory traits. The protocol was compatible with long‐term storage: after 24 h at 5°C without agitation, all respiration traits but maximum working capacity remained unchanged, the latter decreasing by 14%. Our study suggests that whole blood measurement provides faster, more reproducible, and more biologically and physiologically relevant (mitochondrial integrity) assessment of mitochondrial respiration. We recommend future studies to take a whole blood approach unless specific circumstances require the use of isolated blood cells.
Help me stay afloat
Authors: Burras-Sando Jessica , Jensen Megan , Wong Kelsey
Published: February 2023

Building cohesion while working apart
Richard Hader Visionary Leader Award 2022 Visionary Leader Finalist Justin Precourt
Authors: Uttaro Karen
Published: February 2023

The following manuscript, selected as a finalist for the 2022 Richard Hader Visionary Leader Award entry, was submitted to Nursing Management in recognition of Justin Precourt, DNP, RN, NEA-BC, chief nurse executive at UMass Memorial Health and CNO at UMass Memorial Medical Center in Worcester, Mass.
Post–acute Withdrawal Syndrome
Authors: Grover Casey , Sturgill Drew , Goldman Lee
Published: February 2023

Post–acute withdrawal syndrome is an underresearched topic that affects many patients with substance use disorders after the cessation of substance use. Post–acute withdrawal syndrome is exemplified by the occurrence of substance-specific withdrawal signs and symptoms lasting well past the known timeframe for acute withdrawal of a used substance. Post–acute withdrawal syndrome may also include signs and symptoms that are not substance specific that persist, evolve, or appear well past the expected acute withdrawal timeframe. Unfortunately, there is very little scientific literature on post–acute withdrawal syndrome. As a result of this, there are no diagnostic criteria for post–acute withdrawal syndrome, and there is no consensus on the proper name for the condition. We present a case of a 38-year-old man who developed post–acute withdrawal syndrome after treatment with buprenorphine for opioid use disorder and review the limited existing literature on post–acute withdrawal syndrome.
Opioid Use Disorder Among the Economically Disadvantaged in the Rural South
Authors: Albright David L. , Suntai Zainab , McDaniel Justin T. , Johnson Karen , Henson Harvey , Robertson Ellen , McIntosh Shanna
Published: February 2023

Objective

This study aimed to identify county-level hotspots and associated risk factors for opioid use disorder (OUD) in the state of Alabama.

Methods

Using 2015 to 2019 Alabama Medicaid administrative claims data, Medicaid recipients with OUD were identified. We performed local indicators of spatial association analysis to identify hotspots of OUD rates. Using logistic regression, we examined county-level social determinants of health associated with county OUD hotspots.

Results

There was a +14.13% percentage change from 2015 to 2019. The county level local indicators of spatial association analysis found that 5 counties in the northwestern part of Alabama remained “hotspots” throughout the entire study period. Results of the logistic regression model showed that location within the Appalachian region was an independent predictor of high OUD rates (b = 2.58; adjusted odds ratio, 13.27, P = 0.04).

Conclusions

The high rates of OUD may reflect the economic distress and lack of access to resources germane to the Appalachian region in Alabama.
Pregnancy Outcomes in Patients After Completion of the mRNA Coronavirus Disease 2019 (COVID-19) Vaccination Series Compared With Unvaccinated Patients
Authors: Morgan John A. , Biggio Joseph R. , Martin Jane K. , Mussarat Naiha , Elmayan Ardem , Chawla Harsheen K. , Kandalaft Savannah , Magalski Gabrielle R. , Puri Priya , Williams Frank B.
Published: February 2023

OBJECTIVE:

To compare frequency of perinatal death between pregnant patients who completed the mRNA coronavirus disease 2019 (COVID-19) vaccination series and unvaccinated patients.

METHODS:

This retrospective cohort study included 15,865 pregnant patients who delivered 16,132 newborns after 20 weeks of gestation within a large regional health system between January 1, 2021, and December 31, 2021. Patients who received two doses of mRNA vaccine (Pfizer–BioNTech [BNT162b2] or Moderna [mRNA-1273]) were included in the vaccinated group and were compared with unvaccinated patients. Exclusions included partial vaccination, viral-vector vaccine, major congenital anomalies, and higher-order multiple gestation. Our primary outcome was perinatal death, including stillbirth and neonatal death, which was evaluated by logistic regression. Unadjusted odds ratios and adjusted odds ratios (aORs) were reported, controlling for age, body mass index (BMI), diabetes, hypertension, smoking, twin gestation, and insurance status. Propensity score matching was also performed.

RESULTS:

A total of 15,865 patients were included in the final analysis: 2,069 in the vaccination group and 13,796 in the control group. Only 13.0% of the cohort was included in the vaccination group; however, the vaccination rate increased over the course of the study period as the vaccine became more widely available and accepted. Vaccinated patients were older, with higher rates of people of non-Black racial non-Hispanic ethnic backgrounds, people with private insurance, and those with higher BMIs. Vaccination was associated with a lower incidence of perinatal death (0.5% vaccinated group vs 0.8% unvaccinated group, aOR 0.20 0.05–0.88). Vaccination against COVID-19 was also associated with lower rates of preterm delivery (aOR 0.63, 0.48–0.82), neonates with very low birth weight (aOR 0.35, 0.15–0.84), and neonatal intensive care unit (NICU) admission (aOR 0.66, 0.52–0.85). The association between vaccination and lower rates of perinatal death was no longer significant after propensity score matching.

CONCLUSION:

In a large retrospective cohort study, receipt of the primary mRNA COVID-19 vaccination series was associated with a lower rate of several adverse pregnancy outcomes, including perinatal death, preterm delivery, neonates with very low birth weight, and NICU admission. Although the decreased rates of perinatal death did not remain significant after propensity score matching, there was evidence of directional benefit for vaccinated patients.
Ultrasonography of the Explanted Uterus in Placenta Accreta Spectrum
Authors: Einerson Brett D. , Kennedy Anne , Silver Robert M. , Branch D. Ware , Comstock Jessica , Woodward Paula J.
Published: February 2023

OBJECTIVE:

To better understand placenta accreta spectrum (PAS) by correlating postoperative ultrasonographic findings of the explanted uteroplacental interface with intraoperative findings and gross pathology.

METHODS:

We enrolled consecutive pregnant patients aged 18 years and older with a prior cesarean delivery and antenatal diagnosis of lower uterine segment PAS who planned to undergo hysterectomy into this prospective, descriptive study. All underwent cesarean hysterectomy with standardized intraoperative photography. Ultrasonography of explanted postsurgical uteruses was performed by expert radiologists to obtain standard detailed images of the myometrial–placental interface and other areas of interest. Sagittal views of the gross pathologic specimen were photographed. We correlated the intraoperative, ultrasonographic, and gross pathologic findings as a study team and report four consistent patterns that emerged from this systematic evaluation.

RESULTS:

Thirty-four consecutive eligible patients were enrolled. The following consistent observations emerged: 1) The uteroplacental interface in the explanted specimen was smooth and distinct. At the point of maximal placental protrusion, the myometrium was imperceptible, but the placenta was confined by a smooth thin echogenic line of uterine serosa (the scar shell) unless surgically disrupted. 2) Every specimen of PAS grade 2–3 showed placenta bulging through the lower uterine segment in the region of prior hysterotomy. 3) Placentas extended to, but not through, the uterovesical interface or scar shell. Dense adhesive disease was found between the placenta and bladder. There were no cases of true bladder invasion. 4) Placental extension beyond the serosa (invasion) has a distinct appearance on postoperative ultrasonography with irregular frond-like protrusion of placental tissue. This appearance was always the result of surgical manipulation and was not present before delivery of the neonate.

CONCLUSION:

These findings suggest that PAS severity is likely mediated by progressive scar dehiscence and uterine remodeling, not placental invasion. This challenges the existence of in situ invasive percreta as it is currently described.
The Quality of Preoperative Glycemic Control Predicts Insulin Sensitivity During Major Upper Abdominal Surgery: A Case-Control Study
Authors: Omiya Keisuke , Sato Hiroaki , Sato Tamaki , Nooh Abdulwahaab , Koo Bon-Wook , Kandelman Stanislas , Schricker Thomas
Published: February 2023

Objective:

To examine the association of the quality of preoperative glycemic control and insulin sensitivity during major upper abdominal surgery.

Background:

In cardiac surgery, glycated hemoglobin A1c (HbA1c), an indicator of glycemic control during the preceding 3 months, correlated with intraoperative insulin sensitivity. Furthermore, insulin resistance showed a significant association with adverse clinical outcomes.

Methods:

This study is a post hoc exploratory analysis of a randomized controlled trial in patients undergoing elective hepatectomy and receiving the hyperinsulinemic-normoglycemic clamp (HNC) as a potential intervention to reduce surgical site infections (ClinicalTrials.gov NCT01528189). Immediately before skin incision, the HNC was initiated by infusing insulin at the rate of 2 mU/kg/min. Dextrose was administered at rates titrated to maintain normoglycemia (4.0–6.0 mmol/L). The average of 3 consecutive dextrose infusion rates during steady state was used as a measure of insulin sensitivity. Primary outcome was the relationship between preoperative HbA1c and insulin sensitivity during surgery. Secondary outcomes were the associations of insulin sensitivity with the patient’s body mass index (BMI) and postoperative morbidity.

Results:

Thirty-four patients were studied. HbA1c (Y = −0.52X + 4.8, P < 0.001, R
2 = 0.29), BMI (Y = −0.12X + 5.0, P < 0.001, R
2 = 0.43) showed negative correlations with insulin sensitivity. The odds ratio of postoperative complications within 30 days of surgery for every increase in insulin sensitivity by 1 mg/kg/min was 0.22 (95% confidential interval, 0.06–0.59; P = 0.009).

Conclusions:

We demonstrate significant associations of the quality of preoperative glycemic control and body mass index with insulin sensitivity during hepatectomy. The degree of insulin resistance correlated with postoperative morbidity.
Novel Coagulation Test Detects Anticoagulation Resistance and Is Associated With Thrombotic Events in Pediatric Patients Requiring Extracorporeal Membrane Oxygenation
Authors: Frydman Galit H. , Berger Barry M. , Kostousov Vadim , Bruzdovski Karen , Papageorgiou Dimitrios P. , Navaei Amir , Hui Shiu-Ki Rocky , Teruya Jun
Published: February 2023

OBJECTIVES:

Bivalirudin, an IV direct thrombin inhibitor, and unfractionated heparin (UFH) are frequently used anticoagulants in the pediatric critical care setting. An accurate, specific, point-of-care test to quantify and detect anticoagulation resistance is not currently available. This study evaluates the ability of a rapid (< 10 min), micro-volume (< 50 uL) coagulation test to detect and quantify the anticoagulation effect of bivalirudin and UFH using a functional, clot time endpoint in pediatric critical care patients.

DESIGN:

Single-site retrospective laboratory sample analysis and chart review.

SETTING:

A 105-bed pediatric and cardiac ICUs delivering extracorporeal membrane oxygenation.

SUBJECTS:

Forty-one citrated, frozen, biobanked plasma specimens comprising 21 with bivalirudin and 20 with UFH from 15 anticoagulated pediatric patients were analyzed. Thirteen patients were on extracorporeal membrane oxygenation, one had a submassive pulmonary embolism, and one was on a left ventricular assist device.

INTERVENTIONS:

None.

MEASUREMENT AND MAIN RESULTS:

A Clotting Time Score (CTS) was derived on each sample. The CTS detected patients that had developed a pathologic clotting event with 100% sensitivity and 82% specificity compared with prothrombin time with 25% sensitivity/76% specificity and activated partial thromboplastin time with 0% sensitivity/0% specificity. Additionally, the CTS detected subtherapeutic anticoagulation in response to UFH in patients that were clinically determined to be UFH resistant requiring alternative anticoagulation with bivalirudin.

CONCLUSIONS:

The CTS appears to be a clinically valuable indicator of coagulation status in patients treated with either UFH or bivalirudin. Results outside of the therapeutic range due to inadequate dosing or anticoagulation resistance appeared to be associated with clot formation. CTS testing may reduce the risk of anticoagulation-related complications via the rapid identification of patients at high risk for pathologic thrombotic events.