bluuebunny/crossref_metadata_2025 huggingface dataset:
The incidence and natural history of ascites after liver transplantation
Authors: Bloom Patricia P. , Gilbert Timothy , Santos-Parker Keli , Memel Zoe , Przybyszewski Eric , Bethea Emily , Sonnenday Christopher J. , Tapper Elliot B. , Waits Seth
Published: May 2023

Background:

Ascites is common in cirrhosis but uncommon after liver transplant. We aimed to characterize the incidence, natural history, and current management strategies of post-transplant ascites.

Methods:

We performed a retrospective cohort study of patients who underwent liver transplantation at 2 centers. We included patients who underwent deceased donor whole graft liver transplants between 2002 and 2019. Chart review identified patients with post-transplant ascites, requiring a paracentesis between 1 and 6-month post-transplants. Detailed chart review identified clinical and transplant characteristics, evaluation of ascites etiology, and treatments.

Results:

Of 1591 patients who successfully underwent a first-time orthotopic liver transplant for chronic liver disease, 101 (6.3%) developed post-transplant ascites. Only 62% of these patients required large volume paracentesis for ascites before transplant. 36% of patients with post-transplant ascites had early allograft dysfunction. Most patients with post-transplant ascites (73%) required a paracentesis within 2 months of transplant, but 27% had delayed ascites onset. From 2002 to 2019, ascites studies were obtained less often, and hepatic vein pressure measurement was performed more often. Diuretics were the mainstay of treatment (58%). The use of albumin infusion and splenic artery embolization to treat post-transplant ascites increased over time. Larger pre-transplant spleen size was associated with a greater number of post-transplant paracenteses (r=0.32 and p=0.003). For patients who underwent splenic intervention, paracentesis frequency was significantly reduced (1.6–0.4 paracenteses/month, p=0.0001). The majority (72%) of patients had clinical resolution of their ascites at 6-month post-transplant.

Conclusions:

Persistent or recurrent ascites continues to be a clinical issue in the modern era of liver transplantation. Most had clinical resolution within 6 months, some requiring intervention.
Does Inclusion of Emergency Medicine (EM) Residents in ECG Screening for STEMI Change the Time to Catheterization Lab Activation?
Authors: Aly Sarah , Coolahan Kelsey , Tomlinson Kirk , Grossman Duncan , Bove Joseph , Hochman Steven
Published: May 2023

Background:

Emergency medicine physicians must rapidly obtain and interpret an electrocardiogram (ECG) to quickly identify life-threatening cardiac emergencies such as ST-elevation myocardial infarction (STEMI). Although ECG interpretation is a critical component of residency education, few high-powered studies exploring the accuracy of resident ECG interpretation exist.

Objectives:

This study aims to evaluate whether or not the inclusion of Third Year Emergency Medicine Resident ECG interpretations is noninferior to attending-only ECG interpretations in regard to time to STEMI activation.

Methods:

This was a retrospective noninferiority study of STEMI activation times before and after the inclusion of Third Year Emergency Medicine Resident resident ECG interpretations into the workflow at an academic, urban tertiary care center between November 2020 and April 2022, excluding prehospital activations. The primary outcome was the proportion of successful STEMI activations initiated within 5 minutes of ECG completion. An absolute decrease of 10% between groups was chosen as the noninferiority margin.

Results:

In the attending-only group, 26 (66.7%) cases resulted in successful STEMI activations compared to 31 cases (77.5%) in the combined group. The proportion of successful STEMI activations did not differ with resident screening, X2
= 1.15, P = 0.28. The absolute difference between groups’ successful activations was an increase of 11%, which lies within the noninferiority margin (+11%, 95% confidence interval, −8.68% to 30.7%). Average times to STEMI activation in the attending-only and combined groups were 7.59 minutes (Standard Deviation [SD], 10.19) and 5.13 minutes (SD, 6.95), respectively. Average door-to-balloon times for those undergoing Percutaneous Coronary Intervention were 72.74 minutes (SD, 20.76) in the attending-only group and 89.90 minutes (SD, 67.74) in the combination group. Two sample t-test showed no statistically significant difference between the 2 groups for average time to STEMI activation (difference = 2.46 minutes, 95% CI, −1.46 to 6.38) and average door-to-balloon time (difference = 17.16, 95% CI, −39.73 to 5.41).

Conclusion:

The inclusion of emergency medicine PGY-3 residents in the ECG screening workflow is noninferior to attending-only interpretation of ECGs with regard to STEMI activation time.
The Impact of Union Membership on Nursing Turnover and Job Satisfaction
Authors: Lee Doohee , Halleck Jamey , Lee Hana
Published: May 2023

Objective

The present study examines the scope of nursing unions and the relationship with turnover and job satisfaction among RNs.

Background

There is no recent empirical literature documenting evidence on workplace performance measures (turnover and job satisfaction) among unionized nurses at the national level.

Methods

This cross-sectional study analyzed secondary data (n = 43 960), the 2018 National Sample Survey of Registered Nurses.

Results

Approximately 16% of the sample reported being represented by labor unions. The overall nursing turnover rate for the sample was 12.8%. Unionized nurses were less likely than their counterparts to report turnover (mean, 10.9% vs 13.16%; P = 0.02) and less job satisfaction (mean, 3.20 vs 3.28). Union nurses were more likely than nonunion nurses to be male (12.72% vs 9.46%; P = 0.0004), minorities (37.65% vs 25.67%, P < 0.001), be employed in hospital settings (70.1% vs 57.9%, P = 0.001), but report fewer hours of work per week (mean, 36.73 vs 37.66; P = 0.003). Regression results revealed a positive association between union status and nursing turnover (odds ratio, 0.83; P < 0.05), whereas union status was inversely associated with job satisfaction (B = −0.13, P < 0.001) after adjusting for age, gender, race/ethnicity, care coordination time per week, weekly hours of work, and employment settings.

Conclusion

Overall, job satisfaction was high among all nurses, regardless of union membership. However, when comparing specifically union and nonunion members, unionized nurses were less likely to report turnover, but were more likely to experience job dissatisfaction.
Tnfa, Il6, Cxcl1 and Adam8 Genes are the Early Markers Post Mouse Tail Intervertebral Disc Injury
Authors: Lu Jiawei , Tian Zuozhen , Shofer Frances S. , Yao Lutian , Sandroni Alec Z. , Sun Honghong , Qin Ling , Zhang Yejia
Published: May 2023

Objectives

The early molecular events following intervertebral disc (IVD) injury remain unclear. In this study, we aimed to compare inflammatory markers from 1-day to 4-weeks post injury to have a comprehensive understanding of the IVD response to injury.

Design

Mouse tail IVD injury was induced by a needle puncture. Inflammatory marker gene expression and morphological changes was recorded at 1-day, 1- and 4-weeks following injury.

Results

Tnfa, Il6, and Cxcl1 gene expression peaked at day 1 post needle puncture of the mouse IVD, Adam8 gene expression peaked at 1-week time point, while Tipe2 gene expression was upregulated at week 4 post injury. F4/80 positive cells, likely to be macrophages, are present as early as day 1 in the injured IVDs and consistently present at week 4 post injury. Loss of Safranin O staining and increased histological scores of the injured IVDs are consistent with progressive degeneration following injury.

Conclusion

Inflammatory cytokines including Tnfa precedes Tipe2, suggesting that Tipe2 is likely induced by Tnfa. Upregulation of Adam8 and Cxcl1 gene expression persisted at week 4, suggesting that they play a role in the transition to chronic phase of IVD degeneration.
Delayed Reconstruction of Nasal Tip Amputation After a Dog Bite Using a Cartilage Graft and Paramedian Forehead Flap
Authors: Lee Mi Kyung , Woo Kyong-Je
Published: May 2023

The timing and method of reconstruction of an amputated nose due to a dog bite are still controversial. Here, we describe a delayed reconstruction using the paramedian forehead flap with a simultaneous cartilage graft to address a contracted nose from a dog bite. A healthy, 52-year-old patient was attacked by his acquaintance’s dog, resulting nasal tip amputation that included cartilage. The composite graft was performed, and secondary healing resulted in a short nose deformity. Five months after the injury, a conchal cartilage graft and paramedian forehead flap were performed simultaneously to correct the shape of the deformity. At 1 year postoperatively, the flap survived without complications, and the short nose deformity was successfully corrected. In summary, immediate composite graft after a dog bite could result in a contracted nose, but the deformity can be corrected by a simultaneous paramedian forehead flap and cartilage graft.
Incidence of Arterial and Venous Thromboembolism in Cancer Patients
Authors: Deng Hai-Wei , Li Jie , Mei Wei-Yi , Lin Xiao-Xiong , Xu Qing , Zhai Yuan-Sheng , Zheng Qian , Chen Jin-Sheng , Huang Zhi-Bin , Cheng Yun-Jiu
Published: May 2023

Background and Aims

The reported incidence of arterial thromboembolism (ATE) and venous thromboembolism (VTE) after cancer varies. A meta-analysis was performed to define the incidence of thromboembolism (TE) in cancer patients.

Methods

Articles were searched in PubMed and Embase from inception to November 1, 2022. Studies reporting the incidence data or data from which incidence could be estimated among patients with cancer and the explicit follow-up duration were included.

Results

Seventy-four studies involving 5059134 cancer patients were identified. The incidence rate per 1000 person-years was 11.60 (95% CI 7.62-15.58) for ATE, 6.11 (95% CI 3.70-8.53) for myocardial infarction, 9.07 (95% CI 7.48-10.66) for ischemic stroke, 2.11 (95% CI 0.89-3.31) for another ATE, 26.32 (95% CI 24.46-28.18) for VTE, 12.69 (95% CI 11.51-13.87) for deep vein thrombosis, 5.94 (95% CI 5.29-6.59) for pulmonary embolism, and 13.18 (95% CI 9.93-16.42) for another VTE. In addition, the highest incidence of ATE was observed in patients with gastrointestinal cancer, while patients with pancreatic cancer had the highest incidence of VTE. The risk of ATE and VTE increased at the initial stage of cancer, and then declined and became non-significant.

Conclusion

This meta-analysis provided overall estimates of ATE and VTE incidence in cancer patients, adding an important insight into the trajectory of the development of TE in cancer patients, which could help reduce the risk of TE in cancer patients in the future.
Subtle white matter intensity changes on FLAIR imaging in patients with ischemic stroke
Authors: Cougo Pedro , Colares Heber , Farinhas João Gabriel , Hämmerle Mariana , Neves Pedro , Bezerra Raquel , Balduíno Alex , Wu Ona , Pontes-Neto Octavio M.
Published: May 2023

Background

There is increasing evidence from pathology and neuroimaging suggesting that the structural abnormalities which characterize leukoaraiosis are present within regions of normal-appearing white matter. In this study, we aimed to verify whether signal intensity on FLAIR imaging in normal-appearing white matter is related to the leukoaraiosis burden.

Methods

We performed a cross-sectional study of adult patients admitted with a diagnosis of acute ischemic stroke or transient ischemic attack. Leukoaraiosis was segmented using a semi-automated method involving manual outlining and signal thresholding. White matter regions were segmented based on the probabilistic tissue maps from the International Consortium for Brain Mapping 152 atlas. Also, white matter was further segmented based on voxel-distance from leukoaraiosis borders. Normalized mean FLAIR signal intensity on normal-appearing white matter (NAWMM) was used as a dependent variable in univariate and multivariate statistical analysis, and leukoaraiosis volume quartiles (LKAV) and clinical data as independent variables.

Results

One-hundred consecutive patients were selected for analysis (53% female, mean age 68 years). NAWMMwas higher in the vicinity of leukoaraiosis and progressively lower at increasing distances from leukoaraiosis. NAWMMwas independently associated with leukoaraiosis volume. In voxels in the vicinity of leukoaraiosis borders, there was a linear association between LKAVand NAWMM(B=0.03;P<0.01). In voxels non-adjacent to leukoaraiosis borders, there was a non-linear association, with higher values of NAWMMamong patients in the second and third quartiles, and lower in the first and fourth quartiles (B=-0.21 for the second order term;P<0.01). In multivariate analysis, leukoaraiosis was the only variable independently related to NAWMM.

Conclusions

Our results show that normal-appearing white matter exhibits subtle signal intensity changes that are related to leukoaraiosis burden. The neuroimaging signature of these subtle changes suggests that they might not be a milder form of leukoaraiosis, but rather rather reflect widespread etiopathogenic processes underlying small-vessel disease and thus, leukoaraiosis development.
DrosophilaAHR limits tumor growth and stem cell proliferation in the intestine
Authors: Tsai Minghua , Sun Jiawei , Alexandre Cyrille , Shapiro Michael , Franchet Adrien , Li Ying , Gould Alex P. , Vincent Jean-Paul , Stockinger Brigitta , Diny Nicola Laura
Published: May 2023

The aryl hydrocarbon receptor (AHR) plays important roles in intestinal homeostasis, limiting tumour growth and promoting differentiation in the intestinal epithelium. Spineless, theDrosophilahomolog of AHR, has only been studied in the context of development but not in the adult intestine. Here, we show thatspinelessis upregulated in the adult intestinal epithelium after infection withPseudomonas entomophila(P.e.). Spineless knockdown increased stem cell proliferation following infection-induced injury. Spineless overexpression limited intestinal stem cell proliferation and reduced survival after infection. In two tumour models, using eitherNotchRNAi or constitutively active Yorkie, Spineless suppressed tumour growth and doubled the lifespan of tumour-bearing flies. At the transcriptional level it reversed the gene expression changes induced in Yorkie tumours, counteracting cell proliferation and altered metabolism. These findings demonstrate a new role for Spineless in the adultDrosophilamidgut and highlight the evolutionarily conserved functions of AHR/Spineless in the control of proliferation and differentiation of the intestinal epithelium.
The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs
Authors: Murray Gemma G. R. , Hossain A. S. Md. Mukarram , Miller Eric L. , Bruchman Sebastian , Balmer Andrew J. , Matuszewska Marta , Herbert Josephine , Hadjirin Nazreen F. , Mugabi Robert , Li Ganwu , Ferrando Maria Laura , Fernandes de Oliveira Isabela Maria , Nguyen Thanh , Yen Phung L. K. , Phuc Ho D. , Moe Aung Zaw , Wai Thiri Su , Gottschalk Marcelo , Aragon Virginia , Weigand Peter Valentin- , Heegaard Peter M. H. , Vrieling Manouk , Maw Min Thein , Myint Hnin Thidar , Win Ye Tun , Hoa Ngo Thi , Bentley Stephen D. , Clavijo Maria J. , Wells Jerry M. , Tucker Alexander W. , Weinert Lucy A.
Published: May 2023

The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species this can affect the health of humans as well as livestock. Here we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis ofStreptococcus suis, a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages ofS. suisemerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation ofS. suisand acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential ofS. suisis yet to be fully realised.
Characterisation of the genetic determinants of context specific DNA methylation in primary monocytes
Authors: Gilchrist James J. , Fang Hai , Danielli Sara , Tomkova Marketa , Nassiri Isar , Ng Esther , Tong Orion , Taylor Chelsea , Al Mossawi Hussein , Lau Evelyn , Neville Matt , Schuster-Boeckler Benjamin , Knight Julian C. , Fairfax Benjamin P.
Published: May 2023

DNA methylation (DNAm) has pervasive effects on gene expression and associations with ageing-related traits. Here we describe monocyte DNAm responses to inflammatory stimuli across 192 individuals. We find that, unlike the similarly widespread changes in gene expression elicited by LPS and IFNγ, DNAm is markedly more sensitive to LPS. Exposure to LPS caused differential methylation at 20,858 immune-modulated CpGs (imCpGs) which display distinct genomic localisation and transcription factor usage, dependent upon whether methylation is lost or gained. Demethylated imCpGs are profoundly enriched for enhancers, and are over-represented by genes implicated in human diseases, most notably cancer. We find LPS-induced demethylation follows hydroxymethylation and for most sites the degree of demethylation correlates with baseline signal. Notably, we find LPS exposure triggers gain in epigenetic age by approximately 6 months, identifying a potential cause of accelerated epigentic aging which has diverse negative health associations. Finally, we explore the effect of genetic variation on LPS-induced changes in DNAm, identifying 209 imCpGs under genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of human disease associated loci that also modulate imCpG formation.

In summary, our findings suggest innate immune activity continually remodels DNAm in a highly punctate, enhancerenriched fashion that is under tight genetic control and predominantly involves genes commonly mutated in cancer.
Identification of dynamical changes of rabies transmission under quarantine: community-based measures towards rabies elimination
Authors: Rysava Kristyna , Tildesley Michael J.
Published: May 2023

Quarantine has been long used as a public health response to emerging infectious diseases, particularly at the onset of an epidemic when the infected proportion of a population remains identifiable and logistically tractable. In theory, the same logic should apply to low-incidence infections; however, the application and impact of quarantine in low prevalence settings appears less common and lacks a formal analysis. Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites. We conclude that whilst comprehensive measures including sensitive surveillance and large-scale vaccination of dogs will be required to achieve disease elimination and sustained freedom given the persistent risk of rabies re-introductions, quarantine offers a low-cost community driven solution to intersectoral health burden.

Author summary

Canine rabies remains a human health risk in many countries around the world, particularly in lower and middle income settings where many dogs are free roaming and able to interact more easily with other dogs and humans. In this paper, we present results from a mathematical model that simulates the spread of rabies both between dogs and from dogs to humans and investigate the impact of quarantine and vaccination at reducing transmission. Our work demonstrates the effectiveness of quarantining both infected and exposed dogs - we observe that quarantine can have a substantial effect on reducing the number of new animals subsequently infected and thereby lowering the risk of humans being exposed to infection. Such a policy can have significant benefits, particularly in settings where access to vaccinations is challenging and resources are limited. Our research can therefore help to inform policy makers in countries where canine rabies is circulating to develop appropriate strategies to reduce the human health risks associated with canine rabies in the future.
Subchronic Toxicity Assessment of Perfluoroalkyl Substances by Mixed Exposure of Nine Substances at Daily Intake Relevant Concentration
Authors: Takeda Kazuki , Saito Taki , Sasaki Sakura , Eguchi Akifumi , Sugiyama Makoto , Suzuki Kio , Eto Saeka , Kamata Ryo
Published: May 2023

Per- and poly-fluoroalkyl substances (PFAS) have been utilized extensively for various applications owing to their distinctive chemical properties. They exhibit high persistence in the environment and accumulate within the human body, necessitating toxicity assessments. However, the consequences of prolonged, low-level exposure to PFAS and concurrent exposure to multiple PFAS have not been explored. In this study, male C57BL/6J mice (aged 8 weeks) were exposed to a composite of nine PFAS, which include long-chain PFAS (e.g. perfluorooctanoic acid and perfluorooctanesulfonic acid) and short-chain PFAS (e.g. perfluorobutanoic acid and perfluorobutanesulfonic acid) at concentrations equivalent to the estimated daily human intake in the composition reported (1 µg/L [sum of the nine compounds], the maximum reported exposure concentration) via drinking water. Histological examination revealed vacuolization of hepatocytes and irregular arrangement of hepatocyte cords, suggesting that exposure to low levels of the PFAS mixture causes morphological changes in liver tissues. Transcriptome analysis revealed that PFAS exposure mainly altered a group of genes related to metabolism and chemical carcinogenesis. Machine learning analysis of the liver metabolome showed a typical concentration-independent alteration upon PFAS exposure, and in addition to known substances such as glutathione, a compound with unknown biological function; 2,5-dihydro-2,4-dimethyloxazole was found. This study demonstrates that daily exposure to PFAS leads to morphological changes in liver tissues and alters the expression of metabolism-and cancer-related genes as well as phospholipid metabolism. Future studies are required to evaluate the chronic toxicity of prolonged, low-level exposure to PFAS mixtures and to investigate the health effects of PFAS.
labelSeg: segment annotation for tumor copy number alteration profiles
Authors: Zhao Hangjia , Baudis Michael
Published: May 2023

1

Somatic copy number alterations (SCNA) are a predominant type of oncogenomic alterations that affect a large proportion of the genome in the majority of cancer samples. Current technologies allow high-throughput measurement of such copy number aberrations, generating results consisting of frequently large sets of SCNA segments. However, the automated annotation and integration of such data are particularly challenging because the measured signals reflect biased, relative copy number ratios. In this study, we introducelabelSeg, an algorithm designed for rapid and accurate annotation of CNA segments, with the aim of enhancing the interpretation of tumor SCNA profiles. Leveraging density-based clustering and exploiting the length-amplitude relationships of SCNA, our algorithm proficiently identifies distinct relative copy number states from individual segment profiles. Its compatibility with most CNA measurement platforms makes it suitable for large-scale integrative data analysis. We confirmed its performance on both simulated and sample-derived data from The Cancer Genome Atlas (TCGA) reference dataset, and we demonstrated its utility in integrating heterogeneous segment profiles from different data sources and measurement platforms. Our comparative and integrative analysis revealed common SCNA patterns in cancer and protein-coding genes with a strong correlation between SCNA and mRNA expression, promoting the investigation into the role of SCNA in cancer development.
WITHDRAWN: Cholesterol mechanically stabilizes aquaporin-0 arrays by strengthening the association of adjacent tetramers
Authors: Orjuela Juan D. , Chiu Po-Lin , Walz Thomas , de Groot Bert L. , Aponte-Santamaría Camilo
Published: May 2023

Withdrawal Statement

The authors have withdrawn this manuscript owing to its merge with BIORXIV/2023/540959. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The merged preprint can be found atdoi.org/10.1101/2023.05.16.540959
Metabolic, Biochemical, Mineral and Fatty acid profiles of edibleBrassicaceaemicrogreens establish them as promising functional food
Authors: Pant Yogesh , Lingwan Maneesh , Masakapalli Shyam Kumar
Published: May 2023

Hidden hunger due to micronutrient deficiencies affecting one in three people is a global concern. Identifying functional foods which provide vital health beneficial components in addition to the nutrients is of immense health relevance. Microgreens are edible seedlings enriched with concentrated minerals and phytochemicals whose dietary potential as functional foods needs evaluation. In this study, comprehensive biochemical, mineral, metabolic, and fatty acid profiles of fourBrassicaceaemicrogreens - mustard (Brassica juncea), pak choi (Brassica rapa subsp. chinensis), radish pink (Raphanus sativus), and radish white (Raphanus ruphanistrum) was investigated. The biochemical and mineral profiling confirmed their promising nutritional and antioxidant nature and as excellent sources of minerals. Mineral profiling using inductively coupled plasma mass spectrometry (ICP-MS) exhibited promising levels of Fe, Mn, Mg, K, and Ca in microgreens. Gas chromatography-mass spectrometry (GC-MS) based metabolite profiling highlighted a range of phytochemicals-sugars, amino acids, organic acids, amines, fatty acids, phenol, and other molecules. Fatty acid profiling established promising levels of Oleic acid (C18:1; Monounsaturated fatty acids-MUFA) and linoleic acids (C18:2; omega-6 Poly unsaturated fatty acid-PUFA), which are health beneficial. It is estimated that fresh microgreens (100 g) can meet about 20 % to 50 % recommended dietary allowance (RDA) of macro- and micro-minerals along with providing useful fatty acids and antioxidants. Overall, the study highlightedBrassicaceaemicrogreens as an excellent nutrient source that can act as functional foods with promising potential to overcome “hidden hunger”.

Graphical Abstract

Highlights

Brassicaceaemicrogreens are rich in molecules with relevance to nutrition and health

The biochemical analysis supported the antioxidant nature of microgreens

Comprehensive metabolite profiles of edible microgreens ofBrassica juncea(Mustard),Brassica rapa subsp. chinensis(Pak Choi),Raphanus sativus(Radish Pink), andRaphanus ruphanistrum(Radish white) using GC-MS are reported

Ionomics analysis using theBrassicaceaemicrogreens exhibited promising levels of microminerals Fe, Mn, Mg, K, and Ca

Fatty acid profiles show promising levels of Linoleic acid and Oleic acid, which have health relevance
Shaping Synthetic Multicellular and Complex Multimaterial Tissues via Embedded Extrusion-Volumetric Printing of Microgels
Authors: Ribezzi Davide , Gueye Marième , Florczak Sammy , Dusi Franziska , de Vos Dieuwke , Manente Francesca , Hierholzer Andreas , Fussenegger Martin , Caiazzo Massimiliano , Blunk Torsten , Malda Jos , Levato Riccardo
Published: May 2023

In living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and therefore a bottleneck towards creating physiologically relevant models. Addressing this limitation, we introduced a novel technique, termed Embedded Extrusion-Volumetric Printing (EmVP), converging extrusion-bioprinting and layer-less, ultra-fast volumetric bioprinting, allowing to spatially pattern multiple inks/cell types. Light-responsive microgels were developed as permissive microenvironment for cell homing and self-organization, and as bioresins (µResins) for light-based bioprinting. Tuning the mechanical and optical properties of these gelatin-based microparticles enables their use as support bath for suspended extrusion printing, in which features containing high cell densities can be easily introduced. µResins can then be sculpted within seconds with tomographic light projections into centimetre-scale, granular hydrogel-based, convoluted constructs. Interstitial microvoids within microgels enhanced differentiation of multiple stem/progenitor cells (vascular, mesenchymal, neural), otherwise not possible with conventional bulk hydrogels. As proof-of-concept, EmVP was applied to create complex synthetic biology-inspired intercellular communication models, where adipocyte differentiation is regulated by optogenetic-engineered pancreatic cells. Overall, EmVP offers new avenues for producing regenerative grafts with enhanced functionality, and for developing engineered living systems and (metabolic) disease models.
Homeostatic, repertoire and transcriptional relationships between colon T regulatory cell subsets
Authors: Ramanan Deepshika , Chowdhary Kaitavjeet , Candéias Serge M. , Sassone-Corsi Martina , Mathis Diane , Benoist Christophe
Published: May 2023

Foxp3+regulatory T cells (Tregs) in the colon are key to promoting peaceful co-existence with symbiotic microbes. Differentiated in either thymic or peripheral locations, and modulated by microbes and other cellular influencers, colonic Treg subsets have been identified through key transcription factors (TF; Helios, Rorg, Gata3, cMaf), but their inter-relationships are unclear. Applying a multimodal array of immunologic, genomic, and microbiological assays, we find more overlap than expected between populations. The key TFs play different roles, some essential for subset identity, others driving functional gene signatures. Functional divergence was clearest under challenge. Single-cell genomics revealed a spectrum of phenotypes between the Helios+ and Rorγ+ poles, different Treg-inducing bacteria inducing the same Treg phenotypes to varying degrees, not distinct populations. TCR clonotypes in monocolonized mice revealed that Helios+ and Rorγ+ Tregs are related, and cannot be uniquely equated to tTreg and pTreg. We propose that rather than the origin of their differentiation, tissue-specific cues dictate the spectrum of colonic Treg phenotypes.
Investigating the Volume and Diversity of Data Needed for Generalizable Antibody-Antigen ∆∆G Prediction
Authors: Hummer Alissa M. , Schneider Constantin , Chinery Lewis , Deane Charlotte M.
Published: May 2023

Antibody-antigen binding affinity lies at the heart of therapeutic antibody development: efficacy is guided by specific binding and control of affinity. Here we present Graphinity, an equivariant graph neural network architecture built directly from antibody-antigen structures that achieves state-of-the-art performance on experimental ∆∆G prediction. However, our model, like previous methods, appears to be overtraining on the few hundred experimental data points available. To test if we could overcome this problem, we built a synthetic dataset of nearly 1 million FoldX-generated ∆∆G values. Graphinity achieved Pearson’s correlations nearing 0.9 and was robust to train-test cutoffs and noise on this dataset. The synthetic dataset also allowed us to investigate the role of dataset size and diversity in model performance. Our results indicate there is currently insufficient experimental data to accurately and robustly predict ∆∆G, with orders of magnitude more likely needed. Dataset size is not the only consideration – our tests demonstrate the importance of diversity. We also confirm that Graphinity can be used for experimental binding prediction by applying it to a dataset of>36,000 Trastuzumab variants.
SCN9A: Proposal of Voltage-Gated Ion Channels as a Novel Diagnostic Marker for Alzheimer’s Disease
Authors: Shah Divyash , Shah Raehash , Waldron Alyssa , Leonardi Donna
Published: May 2023

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that affects over 6 million adults each year. As individuals age, their cells do not repair themselves which leads to proliferation arrest known as senescence. In the nervous system, astrocyte senescence has been associated with neuroinflammation and other AD processes. Thus, studying senescence may be a unique approach to understanding AD pathology. This study looks at the correlation between SCN9A, a novel gene target, and AD. Results suggest SCN9A may be a potential diagnostic marker for AD. A model was created with an 80%+ accuracy rate in predicting AD. Overall, this study suggests SCN9A plays a large role in neurodegeneration and treating AD.
High Accuracy Machine Learning Model for Sarcopenia Severity Diagnosis based on Sit-to-stand Motion Measured by Two Micro Motion Sensors
Authors: Wang Keer , Zhang Hongyu , Cheng Clio Yuen Man , Chen Meng , Lai King Wai Chiu , Or Calvin Kalun , Chen Yonghua , Hu Yong , Vellaisamy Arul Lenus Roy , Lam Cindy Lo Kuen , Xi Ning , Lou Vivian W. Q. , Li Wen Jung
Published: May 2023

In this ageing society, sarcopenia as a geriatric condition that can have significant negative impacts on an individual’s quality of life. Sarcopenia is a kind of aged syndrome associated with loss of muscle mass and function, which may lead to falls, fractures, gait disorders or even mortality. There are multiple ways to diagnose sarcopenia, such as using Magnetic resonance imaging (MRI), Dual-energy X-ray absorptiometry (DEXA) and Bioelectrical impedance analysis (BIA) etc. to calculate muscle mass; using handgrip or sit-to-stand to measure muscle strength; using short physical performance battery (SPPB), gait, and 5-time sit-to-stand to evaluate physical performance.

In this work, we use two μIMUs worn on subjects to record their sit-to-stand motion, and then used several machine learning models to diagnose the severity of sarcopenia of the subjects. We recruited 53 elderly subjects in total for this work. The youngest subject is 65 years old and the oldest is 84 years old. Their average age is 70 years old. Among these 53 subjects, there are 12 healthy ones and 41 sarcopenia patients with different severity. The subject is instructed to do the single sit-to-stand (STS) three times, and two μIMUs attached to the subject’s waist and thigh transfer the data to a computer by Bluetooth. We separated the STS motion process into 4 phases based on the angle and angular velocity, extracted a total of 510 features for motion analytics. These features were futher analyzed by sequential feature selection with 5 different machine learning models (SVM, KNN, decision tree, LDA, and multilayer perceptron). With our proposed methodology, all 53 subjects could be classified as healthy or having sarcopenia with risk level 1, 2, or 3. The best accuracy to distinguish the healthy or sarcopenia subjects is 98.32%, and the best results to distinguish sarcopenia risk levels from 0 (healthy) to 3 (most severe) is 90.44%.
Beta blockers, digoxin or both following an incident diagnosis of atrial fibrillation – a prospective cohort study
Authors: Brophy James M , Nadeau Lyne
Published: May 2023

Background

Atrial fibrillation is one of the most common arrhythmias but the optimal drug choice for a rate control strategy remains uncertain. In particular, controversy and uncertainty exists regarding the safety of digoxin in this context.

Methods

This was a retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta blockers, digoxin or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovas-cular (CV) hospitalization. Secondary outcomes were the individual components of the primary outcome. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. In sensitivity analyses, baseline covariate imbalances were adjusted using a maximum likelihood algorithm and an overall average treatment effect estimand. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model.

Results

12,723 patients were discharged on beta blockers alone, 406 on digoxin alone, and 1,499 discharged on combined beta blocker / digoxin therapy with a median follow-up time of 356 days. In the unadjusted analyses, the primary outcome occured most frequently in the combined exposure group (15.5%) compared to the isolated digoxin (13.3%) and beta blocker (11.5%) groups (p < 0.001 for trend). There were more CV hospitalizations in the combined beta blocker / digoxin group (14.4%) compared to the BB (10.7%) or digoxin (10.6%) groups (p = 0.006 for trend). There were more deaths in the digoxin group (2.7%) and the combined group (1.1%) groups compared to the BB alone group (0.8%) (p < 0.001 for trend). However, after baseline covariate adjustment, the digoxin alone (hazard ratio (HR) 1.24, 95% CI 0.85 - 1.81) and the combined group (HR 1.09, 95% CI 0.90 - 1.31) were not associated with increased risk for the composite endpoint compared with the beta blocker alone group. These results were robust to sensitivity analyses.

Conclusion

After accounting for baseline imbalances, patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared to those discharged on isolated beta blocker therapy. However, additional studies are required to refine the precision of these estimates.
Five-year Transitions of Symptom Subtypes in Untreated Obstructive Sleep Apnea
Authors: Morris Jonna L. , Scott Paul W. , Magalang Ulysses , Keenan Brendan T , Patel Sanjay R. , Pack Allan I. , Mazzotti Diego R.
Published: May 2023

Objectives

It is unknown if symptom subtypes of obstructive sleep apnea (OSA) transition over time and what clinical factors may predict transitions.

Methods

Data from 2,643 participants of the Sleep Heart Health Study with complete baseline and 5-year follow-up visits were analyzed. Latent Class Analysis on 14 symptoms at baseline and follow up determined symptom subtypes. Individuals without OSA (AHI<5) were incorporated as a known class at each time point. Multinomial logistic regression assessed the effect of age, sex, body mass index (BMI) and AHI on specific class transitions.

Results

The sample consisted of 1,408 women (53.8%) and mean (SD) age 62.4 (10.5) years. We identified four OSA symptom subtypes at both baseline and follow-up visits:minimally symptomatic, disturbed sleep, moderately sleepyandexcessively sleepy. Nearly half (44.2%) of the sample transitioned to a different subtype from baseline to follow-up visits; transitions tomoderately sleepywere the most common (77% of all transitions). A five-year older age was associated with a 6% increase in odds to transit fromexcessively sleepytomoderately sleepy[OR (95% CI) = 1.06 (1.02, 1.12)]. Women had 2.35 times higher odds (95% CI: 1.27, 3.27) to transition frommoderately sleepytominimal symptoms. A 5-unit increase in BMI was associated with 2.29 greater odds (95% CI: 1.19, 4.38) to transition fromminimal symptomstoexcessively sleepy.

Interpretation

While over half of the sample did not transition their subtype over 5 years, among those who did, the likelihood of transitioning between subtypes was significantly associated with a higher baseline age, higher baseline BMI and with women, but was not predicted by AHI.

Clinical Trials

Sleep Heart Health Study (SHHS) Data Coordinating Center, (SHHS)https://clinicaltrials.gov/ct2/show/NCT00005275,NCT00005275

Statement of significance

There is very little research assessing symptom progression and its contributions to clinical heterogeneity in OSA. In a large sample with untreated OSA, we grouped common OSA symptoms into subtypes and assessed if age, sex, or BMI predicted transitions between the subtypes over 5 years. Approximately half the sample transitioned to a different symptom subtype and improvements in symptom subtype presentation were common. Women and older individuals were more likely to transition to less severe subtypes, while increased BMI predicted transition to more severe subtype. Determining whether common symptoms like disturbed sleep or excessive daytime sleepiness occur early in the course of the disease or as a result of untreated OSA over an extended period can improve clinical decisions concerning diagnosis and treatment.
Ordinary differential equations to construct invertible generative models of cell type and tissue-specific regulatory networks
Authors: Niktab Eliatan , Atkinson Paul H. , Walterfang Mark , Winship Ingrid , Sturley Stephen L. , Munkacsi Andrew B.
Published: May 2023

1

Single-cell RNA-Seq (scRNA-seq) transcriptomics can elucidate gene regulatory networks (GRNs) of complex phenotypes, but raw sequencing observations only provide ”snap-shots” of data and are inherently noisy. scRNA-seq trajectory inference has been utilized to solve for the missing observations, but disentangling complex dynamics of gene-gene interactions at different time points from aggregated data is a non-trivial task and computationally expensive. Here we describe our Non-Stiff Dynamic Invertible Model of CO-Regulatory Networks (NS-DIMCORN) to define the genetic nexus underpinning specific cellular functions using invertible warping of flexible multivariate Gaussian distributions by neural Ordinary differential equations. Our results yield a generative model with unbiased density estimation from RNA-seq read-count data only. This resulted in scalable time-flexible sampling of each gene’s expression level thence allowing ab initio assembly of gene regulatory networks in specific cells. We demonstrate our proposed methodology is superior to the state-of-the-art algorithms in accurately recovering genome-wide functional interactions, whether from synthetic or empirical data. We optimized our algorithm for GPU-based implementation thereby further enhancing the utility of our proposed methodology in comparison to the ten benchmarked methods.
Global diversity of enterococci and description of 18 novel species
Authors: Schwartzman Julia A. , Lebreton Francois , Salamzade Rauf , Martin Melissa J. , Schaufler Katharina , Urhan Aysun , Abeel Thomas , Camargo Ilana L.B.C , Sgardioli Bruna F. , Prichula Janira , Frazzon Ana Paula Guedes , Tyne Daria Van , Treinish Gregg , Innis Charles J. , Wagenaar Jaap A. , Whipple Ryan M. , Manson Abigail L. , Earl Ashlee M. , Gilmore Michael S.
Published: May 2023

Enterococci are commensal gut microbes of most land animals. They diversified over hundreds of millions of years adapting to evolving hosts and host diets. Of over 60 known enterococcal species,Enterococcus faecalisandE. faeciumuniquely emerged in the antibiotic era among leading causes of multidrug resistant hospital-associated infection. The basis for the association of particular enterococcal species with a host is largely unknown. To begin deciphering enterococcal species traits that drive host association, and to assess the pool ofEnterococcus-adapted genes from which known facile gene exchangers such asE. faecalisandE. faeciummay draw, we collected 886 enterococcal strains from nearly 1,000 specimens representing widely diverse hosts, ecologies and geographies. This provided data on the global occurrence and host associations of known species, identifying 18 new species in the process expanding genus diversity by >25%. The novel species harbor diverse genes associated with toxins, detoxification, and resource acquisition.E. faecalisandE. faeciumwere isolated from a wide diversity of hosts highlighting their generalist properties, whereas most other species exhibited more restricted distributions indicative of specialized host associations. The expanded species diversity permitted theEnterococcusgenus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades as well as genes associated with range expansion, such as B-vitamin biosynthesis and flagellar motility. Collectively, this work provides an unprecedentedly broad and deep view of the genusEnterococcus, potential threats to human health, and new insights into its evolution.

SIGNIFICANCE

Enterococci, host-associated microbes that are now leading drug-resistant hospital pathogens, arose as animals colonized land over 400 million years ago. To globally assess the diversity of enterococci now associated with land animals, we collected 886 enterococcal specimens from a wide range of geographies and ecologies, ranging from urban environments to remote areas generally inaccessible to humans. Species determination and genome analysis revealed host associations from generalists to specialists, and identified 18 new species, increasing the genus by over 25%. This added diversity provided greater resolution of the genus clade structure, identifying new features associated with species radiations. Moreover, the high rate of new species discovery shows that tremendous genetic diversity in Enterococcus remains to be discovered.