bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Trained Innate Immunity on T Cell Responses; Clinical Implications and Knowledge Gaps for Future Research
Authors: Murphy Dearbhla M. , Mills Kingston H. G. , Basdeo Sharee A.
Published: August 2021

The burgeoning field of innate immune training, also called trained immunity, has given immunologists new insights into the role of innate responses in protection against infection and in modulating inflammation. Moreover, it has led to a paradigm shift in the way we think about immune memory and the interplay between innate and adaptive immune systems in conferring immunity against pathogens. Trained immunity is the term used to describe the medium-term epigenetic and metabolic reprogramming of innate immune cells in peripheral tissues or in the bone marrow stem cell niche. It is elicited by an initial challenge, followed by a significant period of rest that results in an altered response to a subsequent, unrelated challenge. Trained immunity can be associated with increased production of proinflammatory mediators, such as IL-1β, TNF and IL-6, and increased expression of markers on innate immune cells associated with antigen presentation to T cells. The microenvironment created by trained innate immune cells during the secondary challenge may have profound effects on T cell responses, such as altering the differentiation, polarisation and function of T cell subtypes, including Th17 cells. In addition, the Th1 cytokine IFN-γ plays a critical role in establishing trained immunity. In this review, we discuss the evidence that trained immunity impacts on or can be impacted by T cells. Understanding the interplay between innate immune training and how it effects adaptive immunity will give insights into how this phenomenon may affect the development or progression of disease and how it could be exploited for therapeutic interventions or to enhance vaccine efficacy.
Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products
Authors: Murata Makoto , Teshima Takanori
Published: August 2021

Acute graft-versus-host disease (GVHD) is a life-threatening complication that can develop after allogeneic hematopoietic stem cell transplantation. In particular, the prognosis of patients with steroid-refractory acute GVHD is extremely poor. Ryoncil™ (remestemcel-L), a human bone marrow-derived mesenchymal stem cell (MSC) product, failed to show superiority over placebo in patients with steroid-refractory acute GVHD, but it was approved for use in pediatric patients in Canada and New Zealand based on the results of a subgroup analysis. Temcell®, an equivalent manufactured MSC product to remestemcel-L, was approved in Japan based on small single-arm studies by using a regulation for regenerative medicine in 2016. The efficacy of Temcell was evaluated in 381 consecutive patients treated with Temcell during the initial 3 years after its approval. Interestingly, its real-world efficacy was found to be equivalent to that observed in a prospective study of remestemcel-L with strict eligibility criteria. In this article, the potential of MSC therapy in the treatment of acute GVHD is discussed. A meticulous comparison of studies of remestemcel-L and Temcell, remestemcel-L/Temcell and ruxolitinib, and remestemcel-L/Temcell and thymoglobulin showed that the precise position of remestemcel-L/Temcell therapy in the treatment of acute GVHD remains to be determined.
Testing the Seamount Refuge Hypothesis for Predators and Scavengers in the Western Clarion-Clipperton Zone
Authors: Leitner Astrid B. , Drazen Jeffrey C. , Smith Craig R.
Published: August 2021

Seamounts are common in all ocean basins, and most have summit depths >3,000 m. Nonetheless, these abyssal seamounts are the least sampled and understood seamount habitats. We report bait-attending community results from the first baited camera deployments on abyssal seamounts. Observations were made in the Clarion Clipperton Zone (CCZ), a manganese nodule region stretching from south of Hawaii nearly to Mexico. This zone is one of the main target areas for (potential) large-scale deep-sea nodule mining in the very near future. The Seamount Refuge Hypothesis (SRH) posits that the seamounts found throughout the CCZ provide refugia for abyssal fauna likely to be disturbed by seabed mining, yielding potential source populations for recolonization of mined areas. Here we use baited cameras to test a prediction of this hypothesis, specifically that predator and scavenger communities are shared between abyssal seamounts and nearby abyssal plains. We deployed two camera systems on three abyssal seamounts and their surrounding abyssal plains in three different Areas of Particular Environmental Interests (APEIs), designated by the International Seabed Authority as no-mining areas. We found that seamounts have a distinct community, and differences in community compositions were driven largely by habitat type and productivity changes. In fact, community structures of abyssal-plain deployments hundreds of kilometers apart were more similar to each other than to deployments ∼15 km away on seamounts. Seamount communities were found to have higher morphospecies richness and lower evenness than abyssal plains due to high dominance by synaphobranchid eels or penaeid shrimps. Relative abundances were generally higher on seamounts than on the plains, but this effect varied significantly among the taxa. Seven morphotypes were exclusive to the seamounts, including the most abundant morphospecies, the cutthroat eel Ilyophis arx. No morphotype was exclusive to the abyssal plains; thus, we cannot reject the SRH for much of the mobile megafaunal predator/scavenging fauna from CCZ abyssal plains. However, the very small area of abyssal seamounts compared to abyssal plains suggest that seamounts are likely to provide limited source populations for recolonizing abyssal plains post-mining disturbance. Because seamounts have unique community compositions, including a substantial number of predator and scavenger morphospecies not found on abyssal plains, they contribute to the beta biodiversity of the Clarion-Clipperton Zone, and thus indirect mining impacts on those distinct communities are of concern.
Combining Multiple Markers in Environmental DNA Metabarcoding to Assess Deep-Sea Benthic Biodiversity
Authors: Liu Jun , Zhang Haibin
Published: August 2021

Environmental DNA (eDNA) metabarcoding is an emerging tool to estimate diversity by combining DNA from the environmental samples and the high-throughput sequencing. Despite its wide use in estimating eukaryotic diversity, many factors may bias the results. Maker choice and reference databases are among the key issues in metabarcoding analyses. In the present study, we compared the performance of a novel 28S rRNA gene marker designed in this study and two commonly used 18S rRNA gene markers (V1-2 and V9) in estimating the eukaryotic diversity in the deep-sea sediments. The metabarcoding analyses based on the sediment surveys of the Okinawa Trough found that more eukaryotic taxa were discovered by 18S V9 than 28S and 18S V1-2, and that 18S V9 also performed better in metazoan recovery than the other two markers. Although a broad range of taxa were detected by the three metabarcoding markers, only a small proportion of taxa were shared between them even at the phylum level. The non-metric multidimensional scaling (NMDS) analysis also supported that communities detected by the three markers were distinct from each other. In addition, different communities were resolved by different reference databases (NCBI nt vs. SILVA) for the two 18S markers. Combining the three markers, annelids were found to be the most abundant (44.9%) and diverse [179 operational taxonomic units (OTUs)] metazoan group in the sediments of the Okinawa Trough. Therefore, multiple independent markers are recommended to be used in metabarcoding analyses during marine diversity surveys, especially for the poorly understood deep-sea sediments.
Distribution of Megabenthic Communities Under Contrasting Settings in Deep-Sea Cold Seeps Near Northwest Atlantic Canyons
Authors: Cleland Jason , Kazanidis Georgios , Roberts J. Murray , Ross Steve W.
Published: August 2021

Cold seeps support fragile deep-sea communities of high biodiversity and are often found in areas with high commercial interest. Protecting them from encroaching human impacts (bottom trawling, oil and gas exploitation, climate change) requires an advanced understanding of the drivers shaping their spatial distribution and biodiversity. Based on the analysis of 2,075 high-quality images from six remotely operated vehicle dives, we examined cold seep megabenthic community composition, richness, density, and biodiversity at a relatively shallow (∼400 m water depth) site near Baltimore Canyon (BC) and a much deeper site (∼1,500 m) near Norfolk Canyon (NC), in the northwest Atlantic. We found sharp differences in the megabenthic composition between the sites, which were driven mostly by bathymetric gradients. At both BC and NC there were significant differences in megabenthic composition across habitats. Hard habitats in and around cold seeps had significantly higher values of species richness, density, and biodiversity than soft habitats. Depth and habitat complexity were the leading environmental variables driving megabenthic variability. The presence of microbial mats and gas bubbling sites had a statistically significant contribution to explaining megabenthic variability mainly in the shallower BC and less in the deeper NC areas examined; drivers behind this discrepancy could be related to differences between BC and NC in terms of chemical compound fluxes and megafaunal life history characteristics. Our surveys revealed marine litter, primarily from commercial fisheries. This study highlights the importance of habitat complexity for the proliferation of highly diverse cold-seep ecosystems and underscores the importance of discovery science to inform spatial management of human activities in the deep and open ocean.
New Constraints on the Physical and Biological Controls on the Silicon Isotopic Composition of the Arctic Ocean
Authors: Brzezinski Mark A. , Closset Ivia , Jones Janice L. , de Souza Gregory F. , Maden Colin
Published: August 2021

The silicon isotope composition of silicic acid, δ30Si(OH)4, in the deep Arctic Ocean is anomalously heavy compared to all other deep ocean basins. To further evaluate the mechanisms leading to this condition, δ30Si(OH)4 was examined on US GEOTRACES section GN01 from the Bering Strait to the North Pole. Isotope values in the polar mixed layer showed a strong influence of the transpolar drift. Drift waters contained relatively high [Si(OH)4] with heavy δ30Si(OH)4 consistent with the high silicate of riverine source waters and strong biological Si(OH)4 consumption on the Eurasian shelves. The maximum in silicic acid concentration, [Si(OH)4], within the double halocline of the Canada Basin formed a local minimum in δ30Si(OH)4 that extended across the Canada Basin, reflecting the high-[Si(OH)4] Pacific source waters and benthic inputs of Si(OH)4 in the Chukchi Sea. δ30Si(OH)4 became lighter with the increase in [Si(OH)4] in intermediate and deep waters; however, both Canada Basin deep water and Eurasian Basin deep water were heavier than deep waters from other ocean basins. A preliminary isotope budget incorporating all available Arctic δ30Si(OH)4 data confirms the importance of isotopically heavy inflows in creating the anomalous deep Arctic Si isotope signature, but also reveals a surprising similarity in the isotopic composition of the major inflows compared to outflows across the main gateways connecting the Arctic with the Pacific and the Atlantic. This similarity implies a major role of biological productivity and opal burial in removing light isotopes entering the Arctic Ocean from rivers.
Ocean Sound Analysis Software for Making Ambient Noise Trends Accessible (MANTA)
Authors: Miksis-Olds Jennifer L. , Dugan Peter J. , Martin S. Bruce , Klinck Holger , Mellinger David K. , Mann David A. , Ponirakis Dimitri W. , Boebel Olaf
Published: August 2021

Making Ambient Noise Trends Accessible (MANTA) software is a tool for the community to enable comparisons between soundscapes and identification of ambient ocean sound trends required by ocean stakeholders. MANTA enhances the value of individual datasets by assisting users in creating thorough calibration metadata and internationally recommended products comparable over time and space to ultimately assess ocean sound at any desired scale up to a global level. The software package combines of two applications: MANTA Metadata App, which allows users to specify information about their recordings, and MANTA Data Mining App, which applies that information to acoustic recordings to produce consistently processed, calibrated time series products of sound pressure levels in hybrid millidecade bands. The main outputs of MANTA are daily.csv and NetCDF files containing 60-s spectral energy calculations in hybrid millidecade bands and daily statistics images. MANTA data product size and formats enable easy and compact transfer and archiving among researchers and programs, allowing data to be further averaged and explored to address user-specified questions.
The Wind Effect on Biogeochemistry in Eddy Cores in the Northern South China Sea
Authors: Chow Chun Hoe , Shih Yung-Yen , Chien Ya-Tang , Chen Jing Yi , Fan Ning , Wu Wei-Chang , Hung Chin-Chang
Published: August 2021

Cyclonic and anticyclonic eddies are usually characterized by upwelling and downwelling, respectively, which are induced by eddy pumping near their core. Using a repeated expendable bathythermograph transect (XBT) and Argo floats, and by cruise experiments, we determined that not all eddies in the northern South China Sea (NSCS) were accompanied by eddy pumping. The weakening of background thermocline was attributed to the strengthening of eddy pumping, affected by (1) wind-induced meridional Sverdrup transports and (2) Kuroshio intrusion into the NSCS. Higher particulate organic carbon (POC) fluxes (> 100 mg-C m−2 day−1) were found near the eddy cores with significant eddy pumping (defined by a depth change of 22°C isotherm near the thermocline for over 10 m), although the satellite-estimated POC fluxes were inconsistent with the in-situ POC fluxes. nitrogen limitation transition and high POC flux were even found near the core of a smaller mesoscale (diameter < 100 km) cyclonic eddy in May 2014, during the weakening of the background thermocline in the NSCS. This finding provides evidence that small mesoscale eddies can efficiently provide nutrients to the subsurface, and that they can remove carbon from the euphotic zone. This is important for global warming, which generally strengthens upper ocean stratification.
Modulation of Antioxidant Enzymes, Heat Shock Protein, and Intestinal Microbiota of Large Yellow Croaker (Larimichthys crocea) Under Acute Cold Stress
Authors: Lv Huirong , Liu Yanli , Li Haidong , Yin Xiaolong , Wang Ping , Qu Xiaoyu , Gao Yang , Li Weiye , Chu Zhangjie
Published: August 2021

The experiment was conducted in a sealed, temperature-controlled room. The initial water temperature of the treatment group was 12°C, lowered by 1°C a day to 8°C using a chiller, and maintained at that temperature for 3 days. The water temperature was then increased by 1°C per day to 12°C using a heater. The control group were the fish that kept at 12°C at the beginning of the experiment; T1 represents the group that sampled on the first day when the water temperature reached 8 from 12°C; T2 represents the group that sampled when the fish had been kept at 8°C for 3 days; T3 represents the group sampled when the water temperature was increased to 12 from 8°C. The antioxidant abilities of the liver, muscle, and intestine of large yellow croaker at different temperatures and times were determined, and the expression of HSP70 and HSP90 in the liver as well as the changes in intestinal microbiota were investigated. The results showed that the activities of SOD, CAT, GSH-Px, and MDA content increased significantly when the water temperature decreased from 12 to 8°C, significantly higher than those in the control group. The gene expression levels of HSP70 and HSP90 in the liver of large yellow croaker significantly increased under low temperature stress and were significantly higher than those in the control group. The diversity and abundance of intestinal microbiota of large yellow croaker were altered when the water temperature was maintained at 8°C, although the change was not obvious. Proteobacteria, Firmicutes, and Bacteroidetes were the dominate phyla in both the 12 and 8°C groups, and the temperature variation did not change the functional pathways of the microbiota. In conclusion, the acute temperature variation affected the antioxidant ability and heat shock protein expression of large yellow croaker but did not affect the diversity or abundance of the intestinal microbiota. These results will provide a theoretical basis for studying the mechanisms of large yellow croaker overwintering and adaptation to low temperatures.
A Novel Imprinted Gene (Sp-Pol) With Sex-Specific SNP Locus and Sex-Biased Expression Pattern Provides Insights Into the Gonad Development of Mud Crab (Scylla paramamosain)
Authors: Farhadi Ardavan , Shi Xi , Zhang Yin , Zhang Yueling , Li Shengkang , Zheng Huaiping , Ikhwanuddin Mhd , Ma Hongyu
Published: August 2021

Identification and exploring the role of novel sex-related genes is a crucial step for understanding the regulation mechanism of sexual development. In the present study, we identified a novel sex-related gene (designated as Sp-Pol) upstream of a sex-specific single nucleotide polymorphism (SNP). SNP1888 together with Sp-Pol were mapped on LG32 (which is a sex-related linkage group) of a high-density genetic map. The full-length cDNA of Sp-Pol consists of 1703 bp with an open reading frame (ORF) encoding 204 amino acids, a 344 bp 5′-UTR and a 744 bp 3′-UTR. Phylogenetic analysis showed that Sp-Pol may need to be classified as a new gene family due to the very low sequence identity with other known genes (less than 25% identity). The sex-biased expression pattern of Sp-Pol starts from crablet stage V (C5) with approximately three- to four-fold higher in males than in females. Sp-Pol was expressed at a higher level in gonads compared to other tissues, with the highest expression level in the testis. In testis, a downward trend was observed in the expression level of Sp-Pol from the testis stage I (T1) to testis stage III (T3). After unilateral eyestalk ablation, the expression level of Sp-Pol significantly increased in testis and hepatopancreas in males, while it was downregulated in the hepatopancreas of females. Fluorescence in situ hybridization (FISH) assay revealed that Sp-Pol transcripts were strongly localized in the epithelia of seminiferous tubules of the testis, and in the ovary, it was detected in the oogonium cells. These findings showed that Sp-Pol may play crucial roles in the gonad development of S. paramamosain.
Synthesis of Comb-Polyurethane-Modified Polycarboxylate at Indoor Temperature and Its Interaction With Portland Cement
Authors: Xiang Shuncheng , Tan Yansheng , Gao Yingli
Published: August 2021

According to the principle of radical polymerization reaction, different polycarboxylates with comb structures were synthesized. With the other two commercial polycarboxylates (C-PCE-1 and C-PCE-2), the effects of all the polycarboxylates on adsorption, hydration, zeta potential, liquid surface tension, and flowability in Portland cement were determined. Compared to O-PCE and C-PCEs, the adsorption value of M-PCE increased by 14.1% and the adsorption rate increased by 24% maximum. O-PCE, C-PCE-1, and C-PCE-2 have a delayed effect on the hydration of the cementitious materials, but M-PCE does not. Due to higher adsorption amount, M-PCE with siloxane groups has an excellent comprehensive performance of zeta potential, liquid surface tension, and flowability in cementitious materials.
Corksorb Enhances Alkane Degradation by Hydrocarbonoclastic Bacteria
Authors: Martins Valdo R. , Freitas Carlos J. B. , Castro A. Rita , Silva Rita M. , Gudiña Eduardo J. , Sequeira João C. , Salvador Andreia F. , Pereira M. Alcina , Cavaleiro Ana J.
Published: August 2021

Biosorbent materials are effective in the removal of spilled oil from water, but their effect on hydrocarbonoclastic bacteria is not known. Here, we show that corksorb, a cork-based biosorbent, enhances growth and alkane degradation by Rhodococcus opacus B4 (Ro) and Alcanivorax borkumensis SK2 (Ab). Ro and Ab degraded 96 ± 1% and 72 ± 2%, respectively, of a mixture of n-alkanes (2 g L–1) in the presence of corksorb. These values represent an increase of 6 and 24%, respectively, relative to the assays without corksorb. The biosorbent also increased the growth of Ab by 51%. However, no significant changes were detected in the expression of genes involved in alkane uptake and degradation in the presence of corksorb relative to the control without the biosorbent. Nevertheless, transcriptomics analysis revealed an increased expression of rRNA and tRNA coding genes, which confirms the higher metabolic activity of Ab in the presence of corksorb. The effect of corksorb is not related to the release of soluble stimulating compounds, but rather to the presence of the biosorbent, which was shown to be essential. Indeed, scanning electron microscopy images and downregulation of pili formation coding genes, which are involved in cell mobility, suggest that cell attachment on corksorb is a determinant for the improved activity. Furthermore, the existence of native alkane-degrading bacteria in corksorb was revealed, which may assist in situ bioremediation. Hence, the use of corksorb in marine oil spills may induce a combined effect of sorption and stimulated biodegradation, with high potential for enhancing in situ bioremediation processes.
Antibiotic Resistance Profiles and Molecular Characteristics of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Escherichia coli and Klebsiella pneumoniae Isolated From Shrimp Aquaculture Farms in Kerala, India
Authors: Sivaraman Gopalan Krishnan , Rajan Vineeth , Vijayan Ardhra , Elangovan Ravikrishnan , Prendiville Alison , Bachmann Till T.
Published: August 2021

This study was undertaken to evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae in selected shrimp aquaculture farms (n = 37) in Kerala, South India and to characterize the isolates using molecular tools. Overall, a low prevalence of ESBL-producers was found in the farms, most likely due to the reduced antibiotic usage in the shrimp farming sector. Out of the 261 samples (77 shrimp and 92 each of water and sediment), 14 (5.4%) tested positive for ESBL-E. coli or ESBL-K. pneumoniae. A total of 32 ESBL-E. coli and 15 ESBL- K. pneumoniae were recovered from these samples. All ESBL isolates were cefotaxime-resistant with minimal inhibitory concentration (MIC) ≥32 μg/ml. Of all isolates, 9 (28.1%) E. coli and 13 (86.7%) K. pneumoniae showed simultaneous resistance to tetracycline, ciprofloxacin, and trimethoprim-sulfamethoxazole. PCR analysis identified CTX-M group 1 (blaCTX–M–15) as the predominant ESBL genotype in both E. coli (23, 71.9%) and K. pneumoniae (15, 100%). Other beta-lactamase genes detected were as follows: blaTEM and blaSHV (11 K. pneumoniae), blaCTX–M group 9 (9 E. coli), and blaCMY–2 (2 E. coli). Further screening for AMR genes identified tetA and tetB (13, 40.6%), sul1 (11, 34.4%), sul2 (9, 28.1%), catA and cmlA (11, 34.4%), qepA and aac(6′)-Ib-cr (9, 28.1%) and strAB and aadA1 (2, 6.3%) in E. coli, and qnrB (13, 86.7%), qnrS (3, 20%), oqxB (13, 86.7%), tetA (13, 86.7%), and sul2 (13, 86.7%) in K. pneumoniae isolates. Phylogenetic groups identified among E. coli isolates included B1 (4, 12.5%), B2 (6, 18.8%), C (10, 31.3%), D (3, 9.4%), and E (9, 28.1%). PCR-based replicon typing (PBRT) showed the predominance of IncFIA and IncFIB plasmids in E. coli; however, in K. pneumoniae, the major replicon type detected was IncHI1. Invariably, all isolates of K. pneumoniae harbored virulence-associated genes viz., iutA, entB, and mrkD. Epidemiological typing by pulsed-field gel electrophoresis (PFGE) revealed that E. coli isolates recovered from different farms were genetically unrelated, whereas isolates of K. pneumoniae showed considerable genetic relatedness. In conclusion, our findings provide evidence that shrimp aquaculture environments can act as reservoirs of multi-drug resistant E. coli and K. pneumoniae.
Oxidative Phosphorylation Is Dysregulated Within the Basocortical Circuit in a 6-month old Mouse Model of Down Syndrome and Alzheimer’s Disease
Authors: Alldred Melissa J. , Lee Sang Han , Stutzmann Grace E. , Ginsberg Stephen D.
Published: August 2021

Down syndrome (DS) is the primary genetic cause of intellectual disability (ID), which is due to the triplication of human chromosome 21 (HSA21). In addition to ID, HSA21 trisomy results in a number of neurological and physiological pathologies in individuals with DS, including progressive cognitive dysfunction and learning and memory deficits which worsen with age. Further exacerbating neurological dysfunction associated with DS is the concomitant basal forebrain cholinergic neuron (BFCN) degeneration and onset of Alzheimer’s disease (AD) pathology in early mid-life. Recent single population RNA sequencing (RNA-seq) analysis in the Ts65Dn mouse model of DS, specifically the medial septal cholinergic neurons of the basal forebrain (BF), revealed the mitochondrial oxidative phosphorylation pathway was significantly impacted, with a large subset of genes within this pathway being downregulated. We further queried oxidative phosphorylation pathway dysregulation in Ts65Dn mice by examining genes and encoded proteins within brain regions comprising the basocortical system at the start of BFCN degeneration (6 months of age). In select Ts65Dn mice we demonstrate significant deficits in gene and/or encoded protein levels of Complex I-V of the mitochondrial oxidative phosphorylation pathway in the BF. In the frontal cortex (Fr Ctx) these complexes had concomitant alterations in select gene expression but not of the proteins queried from Complex I-V, suggesting that defects at this time point in the BF are more severe and occur prior to cortical dysfunction within the basocortical circuit. We propose dysregulation within mitochondrial oxidative phosphorylation complexes is an early marker of cognitive decline onset and specifically linked to BFCN degeneration that may propagate pathology throughout cortical memory and executive function circuits in DS and AD.
Alterations in Urine Metabolomics Following Sport-Related Concussion: A 1H NMR-Based Analysis
Authors: Wanner Zachary R. , Southam Cormac G. , Sanghavi Prachi , Boora Naveenjyote S. , Paxman Eric J. , Dukelow Sean P. , Benson Brian W. , Montina Tony , Metz Gerlinde A. S. , Debert Chantel T.
Published: August 2021

Objective: Millions of sport-related concussions (SRC) occur annually in North America, and current diagnosis of concussion is based largely on clinical evaluations. The objective of this study was to determine whether urinary metabolites are significantly altered post-SRC compared to pre-injury.

Setting: Outpatient sports medicine clinic.

Participants: Twenty-six male youth sport participants.

Methods: Urine was analyzed pre-injury and after SRC by 1H NMR spectroscopy. Data were analyzed using multivariate statistics, pairwise t-test, and metabolic pathway analysis. Variable importance analysis based on random variable combination (VIAVC) was applied to the entire data set and resulted in a panel of 18 features. Partial least square discriminant analysis was performed exploring the separation between pre-injury and post-SRC groups. Pathway topography analysis was completed to identify biological pathway involvement. Spearman correlations provide support for the relationships between symptom burden and length of return to play and quantifiable metabolic changes in the human urinary metabolome.

Results: Phenylalanine and 3-indoxysulfate were upregulated, while citrate, propylene glycol, 1-methylhistidine, 3-methylhistidine, anserine, and carnosine were downregulated following SRC. A receiver operator curve (ROC) tool constructed using the 18-feature classifier had an area under the curve (AUC) of 0.887. A pairwise t-test found an additional 19 altered features, 7 of which overlapped with the VIAVC analysis. Pathway topology analysis indicated that aminoacyl-tRNA biosynthesis and beta-alanine metabolism were the two pathways most significantly changed. There was a significant positive correlation between post-SRC 2-hydroxybutyrate and the length of return to play (ρ = 0.482, p = 0.02) as well as the number of symptoms and post-SRC lactose (ρ = 0.422, p = 0.036).

Conclusion: We found that 1H NMR metabolomic urinary analysis can identify a set of metabolites that can correctly classify SRC with an accuracy of 81.6%, suggesting potential for a more objective method of characterizing SRC. Correlations to both the number of symptoms and length of return to play indicated that 2-hydroxybutyrate and lactose may have potential applications as biomarkers for sport-related concussion.
Headache Characteristics in the Neurological Emergency Department: A Retrospective Study
Authors: Rimmele Florian , Janke Josephine , Kropp Peter , Grossmann Annette , Hamann Till , Walter Uwe , Jürgens Tim P.
Published: August 2021

Background: The care of patients with headache in the emergency department (ED) represents a diagnostic and clinical challenge. Data on the prevalence and characteristics of headache patients in purely neurological EDs are sparse. The aim of the present study is to examine patient profiles with the cardinal symptom of headache in an academic neurological ED, to analyze correlations between headache characteristics and search for differences compared to the interdisciplinary ED.

Methods: This retrospective cross-sectional study assessed all patients who presented to the ED of the Department of Neurology at Rostock University Medical Center between November 2013 and November 2016 with the main symptom of headache. Epidemiological, clinical, diagnostic data as well as key data regarding the care structure were recorded. Correlations between headache characteristics and diagnosis at discharge were analyzed and risk profiles were identified using binary logistic regression analysis.

Conclusion: This study comprehensively characterized a large collective of patients with the cardinal symptom of headache presenting to a purely neurology emergency department.
A Validation of Supervised Deep Learning for Gait Analysis in the Cat
Authors: Lecomte Charly G. , Audet Johannie , Harnie Jonathan , Frigon Alain
Published: August 2021

Gait analysis in cats and other animals is generally performed with custom-made or commercially developed software to track reflective markers placed on bony landmarks. This often involves costly motion tracking systems. However, deep learning, and in particular DeepLabCutTM (DLC), allows motion tracking without requiring placing reflective markers or an expensive system. The purpose of this study was to validate the accuracy of DLC for gait analysis in the adult cat by comparing results obtained with DLC and a custom-made software (Expresso) that has been used in several cat studies. Four intact adult cats performed tied-belt (both belts at same speed) and split-belt (belts operating at different speeds) locomotion at different speeds and left-right speed differences on a split-belt treadmill. We calculated several kinematic variables, such as step/stride lengths and joint angles from the estimates made by the two software and assessed the agreement between the two measurements using intraclass correlation coefficient or Lin’s concordance correlation coefficient as well as Pearson’s correlation coefficients. The results showed that DLC is at least as precise as Expresso with good to excellent agreement for all variables. Indeed, all 12 variables showed an agreement above 0.75, considered good, while nine showed an agreement above 0.9, considered excellent. Therefore, deep learning, specifically DLC, is valid for measuring kinematic variables during locomotion in cats, without requiring reflective markers and using a relatively low-cost system.
Effect of Megestrol Acetate Combined With Oral Nutrition Supplement in Malnourished Lung Cancer Patients: A Single-Center Prospective Cohort Study
Authors: Duan Baojun , Zhang Yan , Wang Xi , Zhang Yulian , Hou Yinyin , Bai Jun , Liu Linhua , Chen Yaohua , Zhang Rong , Jin Ronghui , He Li , Pu Yansong
Published: August 2021

Background: The optimal treatment of cancer-related malnutrition remains unknown. A single-center prospective cohort study was performed to compare the efficacy of megestrol acetate (MA) combined with oral nutrition supplement (ONS) and MA alone for the treatment of lung cancer-related malnutrition.

Methods: 76 eligible patients were prospectively enrolled in two arms, Arm 1 patients (n = 40, 52.6%) received MA 160 mg/d, and Arm 2 patients (n = 36, 47.4%) received MA 160 mg/d combined with ONS 55.8 g/t.i.d, all orally. All patients received anticancer therapy. Treatment duration was 3 months. The primary endpoints were improvements in body mass index (BMI) and Eastern Cooperative Oncology Group (ECOG) score. Secondary endpoints were assessed by appetite, mid-upper arm circumference (MAC), serum pre-albumin levels, and serum albumin levels.

Results: Baseline levels were comparable between Arm 1 and Arm 2 patients. Compared with Arm 1, primary endpoints (BMI, P = 0.018; ECOG, P = 0.022) and secondary endpoints (MAC, P = 0.025; serum pre-albumin, P = 0.043; and serum albumin, P = 0.034) were improved significantly after treatment in Arm 2. While toxicity was negligible and comparable between Arm 1 and Arm 2.

Conclusion: MA combined with ONS may be an effective and safe treatment option for lung cancer-related malnutrition patients.

Clinical Trial Registration:www.clinicaltrials.gov, identifier ChiCTR2100049007.
Selenium Intake and Glycemic Control in Young Adults With Normal-Weight Obesity Syndrome
Authors: Santos Acsa de Castro , Passos Anna Flavia Ferreira , Holzbach Luciana Carla , Cominetti Cristiane
Published: August 2021

Numerous endogenous functions related to antioxidant processes, reproduction, and thyroid metabolism, as well as actions related to glycemic control, have been attributed to selenium. This study aimed to evaluate whether dietary selenium consumption is associated with variables of glycemic control in a sample of young Brazilian adults with Normal-Weight Obesity (NWO) syndrome. This was a cross-sectional study that evaluated 270 individuals with adequate body weight and excess body fat, who had their body composition assessed by dual-energy X-ray absorptiometry. Socioeconomic, health, and lifestyle questionnaires and three 24-h food records were applied. Glycemic control markers were also evaluated. The prevalence of inadequate selenium intake was analyzed by the Estimated Average Requirement (EAR) cut-point method. The prevalence of disturbances in glycemic control markers according to selenium consumption was compared by either the chi-square or the Fisher's exact test, with individuals classified according to the EAR values for selenium. The associations were evaluated by multiple linear regressions, using the backward strategy. The mean ± standard deviation (SD) age was 23.7 ± 3.3 years, and the mean ± SD daily selenium intake was 59.2 ± 26.4 μg. The overall prevalence of inadequate selenium intake was 59.2%. Individuals with selenium intakes below the EAR (≤45 μg/day) showed higher concentrations of glycated hemoglobin (HbA1c) (P = 0.002) and a higher prevalence of disturbances in HbA1c than those with selenium intakes above the EAR (>45 μg/day) (P = 0.001). Dietary selenium intake was directly associated with female sex (β = 19.95, 95% CI 5.00 to 34.89; P = 0.001) and weight (β = 6.69, 95% CI 0.56 to 12.81; P = 0.010), and inversely associated with the percentage of total body fat (β = −0.80, 95% CI −1.56 to −0,04; P = 0.010) and HbA1c (β = −7.41, 95% CI −13.06 to −1.75; P = 0.010). Considering the noticeable young age of the individuals evaluated and the high frequency of disturbances in HbA1c concentrations in those with selenium consumption below the recommendation, it is suggested that adequate dietary intake or supplementation of this micronutrient should be guaranteed to prevent future possible complications associated with glycemic control disturbances.
Effects of Lactococcus lactis on the Intestinal Functions in Weaning Piglets
Authors: Yu Dongming , Xia Yaoyao , Ge Liangpeng , Tan Bie , Chen Shuai
Published: August 2021

Post-weaning diarrhea of piglets is associated with gut microbiota dysbiosis and intestinal pathogen infection. Recent studies have shown that Lactococcus lactis (L.lactis) could help suppress pathogen infection. This study aimed to investigate the effects of L.lactis on various factors related to growth and immunity in weaning piglets. The results showed that L.lactis improved the growth performance, regulated the amino acid profile (for example, increasing serum tryptophan and ileal mucosal cystine) and the intestinal GABAergic system (including inhibiting ileal gene expression of SLC6A13, GABAAρ1, π, θ, and γ1, and promoting ileal GABAAα5 expression). L.lactis also modulated intestinal immunity by promoting jejunal interleukin 17, 18, 22, ileal toll-like receptor 2, 5, 6, and myeloid differentiation primary response protein 88 gene expression while inhibiting jejunal interferon-γ and ileal interleukin 22 expressions. L.lactis highly affected the intestinal microbiota by improving the beta diversity of gut microbiota and the relative abundance of Halomonas and Shewanella. In conclusion, L.lactis improved the growth performance and regulated amino acid profiles, intestinal immunity and microbiota in weaning piglets.
HOXA1 Is an Antagonist of ERα in Breast Cancer
Authors: Belpaire Magali , Ewbank Bruno , Taminiau Arnaud , Bridoux Laure , Deneyer Noémie , Marchese Damien , Lima-Mendez Gipsi , Baurain Jean-François , Geerts Dirk , Rezsohazy René
Published: August 2021

Breast cancer is a heterogeneous disease and the leading cause of female cancer mortality worldwide. About 70% of breast cancers express ERα. HOX proteins are master regulators of embryo development which have emerged as being important players in oncogenesis. HOXA1 is one of them. Here, we present bioinformatic analyses of genome-wide mRNA expression profiles available in large public datasets of human breast cancer samples. We reveal an extremely strong opposite correlation between HOXA1 versus ER expression and that of 2,486 genes, thereby supporting a functional antagonism between HOXA1 and ERα. We also demonstrate in vitro that HOXA1 can inhibit ERα activity. This inhibition is at least bimodal, requiring an intact HOXA1 DNA-binding homeodomain and involving the DNA-binding independent capacity of HOXA1 to activate NF-κB. We provide evidence that the HOXA1-PBX interaction known to be critical for the transcriptional activity of HOXA1 is not involved in the ERα inhibition. Finally, we reveal that HOXA1 and ERα can physically interact but that this interaction is not essential for the HOXA1-mediated inhibition of ERα. Like other HOX oncoproteins interacting with ERα, HOXA1 could be involved in endocrine therapy resistance.
Identification of PAFAH1B3 as Candidate Prognosis Marker and Potential Therapeutic Target for Hepatocellular Carcinoma
Authors: Xu Weikang , Lu Xinyu , Liu Jing , Chen Qianhui , Huang Xuan , Huang Kuiyuan , Liu Hongyan , Zhu Wei , Zhang Xiaoyong
Published: August 2021

Background

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. PAFAH1B3 plays an important role on occurrence and development in a variety tumor. However, the function of PAFAH1B3 in HCC remains unclear.

Methods

The TIMER, ONCOMINE, Human Protein Atlas (HPA), GEPIA, The Cancer Genome Atlas (TCGA), HCCDB, UALCAN and LinkedOmics database were used to analyze the prognostic value, co-expression genes and regulator networks of PAFAH1B3 in HCC. siRNA transfections and inhibitor of PAFAH1B3 P11 were used to verify the anti-tumor effect on HCC cell lines. Gene expression was detected by qRT-PCR. The functions of PAFAH1B3 downregulation in HCC cell lines were investigated using cell cycle analysis, apoptosis detection, CCK8 assay and transwell assay. Western blot was used to evaluate the role of PAFAH1B3 on metabolic pathways in HCC cells.

Results

Based on the data from databases, the expression of PAFAH1B3 was remarkably increased in HCC patients. High expression of PAFAH1B3 was associated with poorer overall survival (OS) and disease-free survival (DFS). And PAFAH1B3 was notably linked to age, sex, grade, stage, race, and TP53 mutational status. Then, the functional network analysis showed PAFAH1B3 may be involved in HCC through cell cycle, cell metabolism, spliceosome, and RNA transport. Furthermore, the mRNA expression of PAFAH1B3 was also increased in HCC cell lines. Flow cytometry analysis showed that PAFAH1B3 manipulated apoptosis and cell cycle regulation. CCK8 assay showed that PAFAH1B3 silencing or pharmacologic inhibitor of PAFAH1B3 inhibited the proliferation of HepG2, Huh7 and MHCC-97H cells. Transwell assay results showed that PAFAH1B3 silencing also significantly impaired the invasion and migratory ability of HCC cells. In addition, PAFAH1B3 silencing significantly downregulated the expression of glycolysis and lipid synthesis signaling pathways.

Conclusion

Our findings suggested that PAFAH1B3 plays a critical role in progression of HCC. PAFAH1B3 as a prognosis marker and potential target for HCC has prospective clinical significance.
Efficacy and Safety of Anti-HER2 Agents in Combination With Chemotherapy for Metastatic HER2-Positive Breast Cancer Patient: A Network Meta-Analysis
Authors: Zhang Xiaohui , Leng Junsheng , Zhou Yidong , Mao Feng , Lin Yan , Shen Songjie , Sun Qiang
Published: August 2021

Background

The presence of anti-HER2 agents, such as trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1), significantly improved the prognosis of metastatic HER2-positive (HER2+) breast cancers (BC). However, drug resistance and disease progression are still common. In order to further improve the treatment efficacy, new clinical trials about anti-HER2 agents in combination with chemotherapy are growing rapidly. We conducted the network meta-analysis to synthesize evidences of clinical trials to identify the best therapy for metastatic HER2+ BC.

Methods

A systematic search of randomized controlled trials regarding anti-HER2 agents in combination with chemotherapy for advanced or metastatic breast cancers up to May 2020 was conducted in Embase, PubMed, and the Cochrane Library. The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS), objective response rate (ORR), and safety. Bayesian network meta-analysis was conducted to synthesize the results and rank the therapies.

Results

Twenty-six studies, including 16 studies for first-line treatments and 10 studies for second- or later-line treatments were included in the network meta-analysis. For first-line studies, the THP (taxanes + trastuzumab + pertuzumab) regimen exhibited the highest probability to be the optimal treatment in all efficacy outcomes and moderate safety. For second- or later-line studies, the T-DM1 and XHTuC (capecitabine + trastuzumab + tucatinib) regimens ranked top two in all efficacy outcomes according to the surface under the cumulative ranking (SUCRA) results. T-DM1 ranked first in PFS and OS whereas XHTuC ranked first in ORR. The safety outcomes of T-DM1 and XHTuC were acceptable.

Conclusions

THP was still the optimal first-line treatment for metastatic HER2+ BC. T-DM1 and XHTuC were recommended for second-line treatments.

Systematic Review Registration

INPLASY.com, identifier (INPLASY202090086).
Pyroptotic and Necroptotic Cell Death in the Tumor Microenvironment and Their Potential to Stimulate Anti-Tumor Immune Responses
Authors: Scarpitta Allan , Hacker Ulrich T. , Büning Hildegard , Boyer Olivier , Adriouch Sahil
Published: August 2021

Cancer remains the second most common cause of death worldwide affecting around 10 million patients every year. Among the therapeutic options, chemotherapeutic drugs are widely used but often associated with side effects. In addition, toxicity against immune cells may hamper anti-tumor immune responses. Some chemotherapeutic drugs, however, preserve immune functions and some can even stimulate anti-tumor immune responses through the induction of immunogenic cell death (ICD) rather than apoptosis. ICD stimulates the immune system by several mechanisms including the release of damage-associated molecular patterns (DAMPs) from dying cells. In this review, we will discuss the consequences of inducing two recently characterized forms of ICD, i.e., pyroptosis and necroptosis, in the tumor microenvironment (TME) and the perspectives they may offer to increase the immunogenicity of the so-called cold tumors and to stimulate effective anti-tumor immune responses.
Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, HEC30654, in Healthy Chinese Subjects
Authors: Li Xiaojiao , Gao Lei , Liu Jingrui , Zhang Hong , Chen Hong , Yang Lizi , Wu Min , Li Cuiyun , Zhu Xiaoxue , Ding Yanhua , Sun Li
Published: August 2021

Background and Objective: HEC30654 is a selective 5-HT6 receptor antagonist that was safe and well-tolerated in preclinical models of Alzheimer’s disease. The objective of this double-blind, randomized, placebo-controlled clinical trial was to evaluate the safety, tolerability, and pharmacokinetic profile of HEC30654 after single ascending doses in healthy Chinese subjects.

Methods: Healthy volunteers received a single oral dose of HEC30654 (5, 10, 15, 30, 60 mg). Safety and tolerability assessments included adverse events, vital signs, and findings on electrocardiograms, electroencephalograms, physical examination, and clinical laboratory tests. Pharmacokinetic analysis of HEC30654 and its major metabolite HEC93263 were conducted in blood, urine, and fecal samples.

Results: Single doses of HEC30654 up to 30 mg were generally safe and well tolerated, but dose escalation was terminated early as the 60 mg HEC30654 treatment group met the pre-defined stopping rules specified in the protocol. Median tmax of HEC30654 was 6 h (range, 4–12 h), t1/2 of 10–60 mg HEC30654 ranged from 52.1 to 63.8 h. Exposure to HEC30654 across the dose range explored in this study increased more than in proportion to dose. Metabolism of HEC30654 to HEC93263 was slow (<10%), and HEC30654 was mainly eliminated unchanged through feces.

Conclusion: Single doses of HEC30654 up to 30 mg were generally safe and well tolerated. Based on preclinical efficacy in various models of cognition, HEC30654 may represent a therapeutic option for symptomatic treatment of cognitive disorders.