bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin Sample Prediction and Spatial Modeling of Antimicrobial Resistance in Metagenomic Sequencing Data
Authors: Zhelyazkova Maya , Yordanova Roumyana , Mihaylov Iliyan , Kirov Stefan , Tsonev Stefan , Danko David , Mason Christopher , Vassilev Dimitar
Published: March 2021

The steady elaboration of the Metagenomic and Metadesign of Subways and Urban Biomes (MetaSUB) international consortium project raises important new questions about the origin, variation, and antimicrobial resistance of the collected samples. CAMDA (Critical Assessment of Massive Data Analysis,http://camda.info/) forum organizes annual challenges where different bioinformatics and statistical approaches are tested on samples collected around the world for bacterial classification and prediction of geographical origin. This work proposes a method which not only predicts the locations of unknown samples, but also estimates the relative risk of antimicrobial resistance through spatial modeling. We introduce a new component in the standard analysis as we apply a Bayesian spatial convolution model which accounts for spatial structure of the data as defined by the longitude and latitude of the samples and assess the relative risk of antimicrobial resistance taxa across regions which is relevant to public health. We can then use the estimated relative risk as a new measure for antimicrobial resistance. We also compare the performance of several machine learning methods, such as Gradient Boosting Machine, Random Forest, and Neural Network to predict the geographical origin of the mystery samples. All three methods show consistent results with some superiority of Random Forest classifier. In our future work we can consider a broader class of spatial models and incorporate covariates related to the environment and climate profiles of the samples to achieve more reliable estimation of the relative risk related to antimicrobial resistance.
Mycobacterium tuberculosis RipA Dampens TLR4-Mediated Host Protective Response Using a Multi-Pronged Approach Involving Autophagy, Apoptosis, Metabolic Repurposing, and Immune Modulation
Authors: Shariq Mohd , Quadir Neha , Sharma Neha , Singh Jasdeep , Sheikh Javaid A. , Khubaib Mohd , Hasnain Seyed E. , Ehtesham Nasreen Z.
Published: March 2021

Reductive evolution has endowedMycobacterium tuberculosis(M. tb) with moonlighting in protein functions. We demonstrate that RipA (Rv1477), a peptidoglycan hydrolase, activates the NFκB signaling pathway and elicits the production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-12, through the activation of an innate immune-receptor, toll-like receptor (TLR)4. RipA also induces an enhanced expression of macrophage activation markers MHC-II, CD80, and CD86, suggestive of M1 polarization. RipA harbors LC3 (Microtubule-associated protein 1A/1B-light chain 3) motifs known to be involved in autophagy regulation and indeed alters the levels of autophagy markers LC3BII and P62/SQSTM1 (Sequestosome-1), along with an increase in the ratio of P62/Beclin1, a hallmark of autophagy inhibition. The use of pharmacological agents, rapamycin and bafilomycin A1, reveals that RipA activates PI3K-AKT-mTORC1 signaling cascade that ultimately culminates in the inhibition of autophagy initiating kinase ULK1 (Unc-51 like autophagy activating kinase). This inhibition of autophagy translates into efficient intracellular survival, within macrophages, of recombinantMycobacterium smegmatisexpressingM. tbRipA. RipA, which also localizes into mitochondria, inhibits the production of oxidative phosphorylation enzymes to promote a Warburg-like phenotype in macrophages that favors bacterial replication. Furthermore, RipA also inhibited caspase-dependent programed cell death in macrophages, thus hindering an efficient innate antibacterial response. Collectively, our results highlight the role of an endopeptidase to create a permissive replication niche in host cells by inducing the repression of autophagy and apoptosis, along with metabolic reprogramming, and pointing to the role of RipA in disease pathogenesis.
Combination of the Probiotics Lacticaseibacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis, BB-12 Has Limited Effect on Biomarkers of Immunity and Inflammation in Older People Resident in Care Homes: Results From the Probiotics to Reduce Infections iN CarE home reSidentS Randomized, Controlled Trial
Authors: Castro-Herrera Vivian M. , Fisk Helena L. , Wootton Mandy , Lown Mark , Owen-Jones Eleri , Lau Mandy , Lowe Rachel , Hood Kerenza , Gillespie David , Hobbs F. D. Richard , Little Paul , Butler Christopher C. , Miles Elizabeth A. , Calder Philip C.
Published: March 2021

Aging is associated with a decline in many components of the immune system (immunosenescence). Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67–97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3–1.6 × 109 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly (p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).
Effects of Coastal Construction on Indo-Pacific Humpback Dolphin (Sousa chinensis) Behavior and Habitat-Use Off Hong Kong
Authors: Piwetz Sarah , Jefferson Thomas A. , Würsig Bernd
Published: March 2021

Construction-related loss of habitat, degradation of existing habitat, noise pollution, and vessel activity are growing issues for Indo-Pacific humpback dolphins (Sousa chinensis) that occur in the shallow, near-shore, highly industrialized waters off Lantau Island, Hong Kong. We studied the occurrence of dolphins in discrete locations, fine-scale movement patterns, and dolphin behavioral activity states. Potential explanatory variables varied and included year, season, time of day, dolphin group size and behavioral activity state, proximity to construction activity, and vessel type and number. Land-based observations and theodolite tracking of dolphins and vessels were conducted from seven locations to the north of Lantau Island, Hong Kong, and marine construction activities near survey sites were identified. A total of 636 groups of dolphins were recorded, totaling 150.91 h of tracking, from 405 days of observation effort. Hurdle models were used to analyze dolphin occurrence, multivariate generalized additive models were used to analyze fine-scale movement patterns, and log-likelihood ratio and binomialzscorepost hoctests were used to analyze behavioral activity states. Dolphin occurrence was lower in historically important areas near long-term, low-intensity construction activity, and dolphin swimming speed was higher in response to vessel presence. Overall, foraging and traveling were the most frequently observed behavioral activity states and resting behavior was observed off only one location that was not in proximity to construction activities. Temporal overlap in adjacent marine construction areas may displace animals for extended periods and nearby ecologically similar habitats should be identified and designated as marine protected areas to mitigate effects of such disturbance.
Diet Composition and Isotopic Analysis of Nine Important Fisheries Resources in the Eastern Adriatic Sea (Mediterranean)
Authors: Zorica Barbara , Ezgeta-Balić Daria , Vidjak Olja , Vuletin Vedran , Šestanović Marija , Isajlović Igor , Čikeš Keč Vanja , Vrgoč Nedo , Harrod Chris
Published: March 2021

We examined how the trophic ecology of nine economically important marine taxa varied across three distinct areas of the Adriatic Sea. These taxa included three species of demersal fishes (European hake Merluccius merluccius, red mullet Mullus barbatus, black-bellied angler Lophius budegassa) and two species of decapod crustaceans (Norway lobster Nephrops norvegicus, deep-water rose shrimp Parapenaeus longirostris) and four species of pelagic fishes (sardine Sardina pilchardus, anchovy Engraulis encrasicolus, Mediterranean horse mackerel Trachurus mediterraneus, Atlantic horse mackerel Trachurus trachurus). We used two complementary methods that differed in their temporal context to examine and compare diet. Stomach contents analysis was used to describe the short term diet while stable isotope analysis was used compare long-term assimilated diet. Results showed that although there were spatial differences in what each species consumed, and in their trophic and isotopic niches, each species fed at similar trophic position across locations, indicating similar ecological function. Comparisons of biomass-weighted trophic position (δ15N) and consumer body size (log2 mass) showed evidence for a common isotopic size spectrum across areas, indicating the existence of a size-structured food web. In turn this allowed us to provide a first estimate of the predator–prey body mass ratio (PPMR) for this area (655:1). Results obtained within this study, in future, could be used for ecological modeling and improved long-term management of the Adriatic Sea’s marine resources.
Transcriptome Sequencing of the Endangered Species Elongate Loach (Leptobotia elongata) From the Yangtze River: De novo Transcriptome Assembly, Annotation, Identification and Validation of EST-SSR Markers
Authors: Zhang Yunbang , Gao Jian , Zhang Yunhai , Zou Yuanchao , Cao Xiaojuan
Published: March 2021

Elongate loach (Leptobotia elongata) is endemic to middle and upper reaches of the Yangtze River in China. Due to overfishing and habitat destruction, this loach has become an endangered species. So far, lack of reliable genetic information and molecular markers has hindered the conservation and utilization of elongate loach resources. Therefore, we here performed an Illumina sequencing and de novo transcriptome assembly in elongate loach, and then developed polymorphic simple sequence repeat markers (SSRs). After assembly, 51,185 unigenes were obtained, with an average length of 1,496 bp. A total of 23,901 expressed sequence tag-simple sequence repeats (EST-SSRs) were identified, distributing in 14,422 unigenes, with a distribution frequency of 28.18%. Out of 16,885 designed EST-SSR primers, 150 primers (3 or 4 base repetition-dominated) were synthesized for polymorphic EST-SSR development. Then, 52 polymorphic EST-SSRs were identified, with polymorphism information contents (PIC) ranging from 0.03 to 0.88 (average 0.54). In conclusion, this was the first report of transcriptome sequencing of elongate loach. Meanwhile, we developed a set of polymorphic EST-SSRs for the loach. This study will provide an important basis, namely genetic information and polymorphic SSRs, for further population genetics and breeding studies of this endangered and economic loach in China.
Systematic Assessment of Safety Threshold for Donor Age in Cadaveric Liver Transplantation
Authors: Wang Wenchao , Liu Zhengtao , Qian Junjie , Xu Jun , Que Shuping , Zhuang Li , Geng Lei , Zhou Lin , Zheng Shusen
Published: March 2021

Background: Donor age affects allograft quality and the prognosis of recipients after liver transplantation (LT). Clinicians have assessed the quality of grafts from older donors based on their appearance and texture, with no reliable quantitative evidence. Our study aimed to assess the quantitative impact of donor age on post-transplant outcomes and its safety threshold for LT, based on the published literature.

Methods: Relevant studies were retrieved from the Embase, PubMed, and ISI Web of Science databases. Pooled dichotomous relative risks (RRs) were calculated using metan. Continuous RRs were calculated using a two-stage random-effects model.

Results: Eleven studies including 30,691 LT cases were included for further analysis. For categorical comparison, the RR of death within the first post-transplant year was significantly higher among patients who received grafts from older donors. Similarly, the RR of graft failure (GF) was increased within the 3 years after transplantation. For continuous comparison, advanced donor age affected transplant outcomes in a linear manner (P > 0.05). A 10-year increment in donor age was associated with RRs 1.10, 1.12, 1.15, 1.10, and 1.08 for 90-day, 180-day, 1-year, 3-year, and 5-year patient mortality and 1.08, 1.06, 1.10, 1.11, and 1.12, for 90-day, 180-day, 1-year, 2-year, and 3-year GF, respectively (all P < 0.05). A spline model showed that transplants using grafts from donors <43 years old were not associated with age-related risks (P > 0.05). The risk of GF was increased in subgroups with fewer LT cases, longer cold ischemic time, fewer male donors, and recipients with viral hepatitis (P < 0.05).

Conclusion: Donor age might affect post-LT outcomes in a dose-dependent manner. The safety threshold for donor age in terms of GF should be lowered to 43 years as an early warning for the guarantee of satisfactory outcomes. Clinicians should weigh the benefits against the risks carefully for patients receiving grafts from older donors. Further studies are warranted to investigate the mechanisms responsible for the relationship between donor age and graft quality.
Prevalence and Antifungal Susceptibility of Candida parapsilosis Species Complex in Eastern China: A 15-Year Retrospective Study by ECIFIG
Authors: Guo Jian , Zhang Min , Qiao Dan , Shen Hui , Wang Lili , Wang Dongjiang , Li Li , Liu Yun , Lu Huaiwei , Wang Chun , Ding Hui , Zhou Shuping , Zhou Wanqing , Wei Yingjue , Zhang Haomin , Xi Wei , Zheng Yi , Wang Yueling , Tang Rong , Zeng Lingbing , Xu Heping , Wu Wenjuan
Published: March 2021

Candida parapsilosis complex is one of the most common non-albicans Candida species that cause candidemia, especially invasive candidiasis. The purpose of this study was to evaluate the antifungal susceptibilities of both colonized and invasive clinical C. parapsilosis complex isolates to 10 drugs: amphotericin (AMB), anidulafungin (AFG), caspofungin (CAS), micafungin (MFG), fluconazole (FLZ), voriconazole (VRZ), itraconazole (ITZ), posaconazole (POZ), 5-flucytosine (FCY), and isaconazole (ISA). In total, 884 C. parapsilosis species complex isolates were gathered between January 2005 and December 2020. C. parapsilosis, Candida metapsilosis, and Candida orthopsilosis accounted for 86.3, 8.1, and 5.5% of the cryptic species, respectively. The resistance/non-wild-type rate of bloodstream C. parapsilosis to the drugs was 3.5%, of C. metapsilosis to AFG and CAS was 7.7%, and of C. orthopsilosis to FLZ and VRZ was 15% and to CAS, MFG, and POZ was 5%. The geometric mean (GM) minimum inhibitory concentrations (MICs) of non-bloodstream C. parapsilosis for CAS (0.555 mg/L), MFG (0.853 mg/L), FLZ (0.816 mg/L), VRZ (0.017 mg/L), ITZ (0.076 mg/L), and POZ (0.042 mg/L) were significantly higher than those of bloodstream C. parapsilosis, for which the GM MICs were 0.464, 0.745, 0.704, 0.015, 0.061, and 0.033 mg/L, respectively (P < 0.05). The MIC distribution of the bloodstream C. parapsilosis strains collected from 2019 to 2020 for VRZ, POZ, and ITZ were 0.018, 0.040, and 0.073 mg/L, significantly higher than those from 2005 to 2018, which were 0.013, 0.028, and 0.052 mg/L (P < 0.05). Additionally, MIC distributions of C. parapsilosis with FLZ and the distributions of C. orthopsilosis with ITZ and POZ might be higher than those in Clinical and Laboratory Standards Institute studies. Furthermore, a total of 143 C. parapsilosis complex isolates showed great susceptibility to ISA. Overall, antifungal treatment of the non-bloodstream C. parapsilosis complex isolates should be managed and improved. The clinicians are suggested to pay more attention on azoles usage for the C. parapsilosis complex isolates. In addition, establishing the epidemiological cutoff values (ECVs) for azoles used in Eastern China may offer better guidance for clinical treatments. Although ISA acts on the same target as other azoles, it may be used as an alternative therapy for cases caused by FLZ- or VRZ-resistant C. parapsilosis complex strains.
The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1
Authors: Laval Kathlyn , Poelaert Katrien C. K. , Van Cleemput Jolien , Zhao Jing , Vandekerckhove Annelies P. , Gryspeerdt Annick C. , Garré Barbara , van der Meulen Karen , Baghi Hossein B. , Dubale Haileleul N. , Zarak Ines , Van Crombrugge Eline , Nauwynck Hans J.
Published: March 2021

Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus related to pseudorabies virus (PRV) and varicella-zoster virus (VZV). This virus is one of the major pathogens affecting horses worldwide. EHV-1 is responsible for respiratory disorders, abortion, neonatal foal death and equine herpes myeloencephalopathy (EHM). Over the last decade, EHV-1 has received growing attention due to the frequent outbreaks of abortions and/or EHM causing serious economical losses to the horse industry worldwide. To date, there are no effective antiviral drugs and current vaccines do not provide full protection against EHV-1-associated diseases. Therefore, there is an urgent need to gain a better understanding of the pathogenesis of EHV-1 in order to develop effective therapies. The main objective of this review is to provide state-of-the-art information on the pathogenesis of EHV-1. We also highlight recent findings on EHV-1 immune evasive strategies at the level of the upper respiratory tract, blood circulation and endothelium of target organs allowing the virus to disseminate undetected in the host. Finally, we discuss novel approaches for drug development based on our current knowledge of the pathogenesis of EHV-1.
Effect of Levodopa Initiation on the Gut Microbiota in Parkinson's Disease
Authors: Palacios Natalia , Hannoun Anas , Flahive Julie , Ward Doyle , Goostrey Kelsey , Deb Anindita , Smith Kara M.
Published: March 2021

Background: The impact of Levodopa on the gut microbiota of Parkinson's disease (PD) patients has not been sufficiently addressed.

Methods: We conducted a longitudinal study to examine the impact of Levodopa initiation on the gut microbiota composition of 19 PD patients who had not previously been exposed to Levodopa. Patients provided two stool samples prior to and two samples 90 days after starting Levodopa. Motor impairment (MDS-UPDRS Part III), diet, and other patient characteristics were assessed. 16S rRNA gene amplicon sequencing was used to characterize the microbiota. We examined, cross-sectionally and longitudinally, the associations between Levodopa use and alpha and beta diversity and performed feature-wise, multivariate modeling to identify taxa associated longitudinally with Levodopa use and with improvement in motor function after Levodopa administration.

Results: We did not observe significant differences in alpha or beta diversity before vs. after initiation of Levodopa. In longitudinal feature-wise analyses, at the genus level, no taxa were significantly associated with Levodopa use after false discovery rate (FDR) correction (q < 0.05). We observed a marginally lower relative abundance of bacteria belonging to Clostridium group IV in PD patients who experienced a medium or large improvement in motor impairment in response to Levodopa compared to those with a small response [β = −0.64 (SE: 0.18), p-trend: 0.00015 p-FDR: 0.019].

Conclusions: In this study, Levodopa was not associated with changes in microbiota composition in this longitudinal analysis. The association between abundance of Clostridium group IV and short-term motor symptom response to Levodopa is preliminary and should be investigated in larger, longer-term studies, that include a control group.
Association Between Circular RNAs and Intracranial Aneurysm Rupture Under the Synergistic Effect of Individual Environmental Factors
Authors: Huang Qing , Sun Yi , Huang Qiuyu , Zeng Yile , Lin Shaowei , Huang Shuna , Cai Yingying , Xu Xingyan , Kang Dezhi , Li Huangyuan , Wu Siying
Published: March 2021

Introduction: To study the association between specific circular RNAs and rupture of intracranial aneurysm. To explore its clinical diagnostic significance and synergistic effects with individual environmental influencing factors.

Methods: Three hundred and forty seven cases and controls were included in this study. Multivariate analysis was used to explore the main individual environmental factors. Intracranial aneurysm rupture related circular RNAs screened based on sequencing was verified in peripheral blood by PCR. ROC curve, logistic regression model and fork analysis were used to study the association, diagnostic values, and synergistic effects of circular RNA with intracranial aneurysms and individual environmental factors.

Results: Smoking, hair dyeing, sitting time ≥6 h/day, single animal oil intake and hypertension are the main risk factors for intracranial aneurysm rupture; People with higher education, sleeping time ≥7 h/day, tea drinking, diabetes, higher levels of (hemoglobin, low density lipoprotein, serum calcium, and apolipoprotein-A1) have a low risk of intracranial aneurysm rupture. Hsa_circ_0008433 and hsa_circ_0001946 are closely related to intracranial aneurysm rupture and have certain clinical diagnostic significance (AUC = 0.726; 95% CI: 0.668~0.784). Hsa_circ_0008433 (OR = 0.497, 95% CI: 0.338~0.731), hsa_circ_0001946 (OR = 0.682, 95% CI: 0.509~0.914) were independent epigenetic factors affecting intracranial aneurysm rupture, and have a multiplicative interaction with age (OR = 3.052, 95% CI: 1.006~9.258).

Conclusions: Low expressions of hsa_circ_0008433 and hsa_circ_0001946 are risk factors for intracranial aneurysms rupture and have good clinical diagnostic value. There was a multiplicative interaction between epigenetic score and age. The older and the higher the epigenetic score was, the more likely to have intracranial aneurysm rupture.
Complement Activation in the Central Nervous System: A Biophysical Model for Immune Dysregulation in the Disease State
Authors: Peoples Nicholas , Strang Candace
Published: March 2021

Complement, a feature of the innate immune system that targets pathogens for phagocytic clearance and promotes inflammation, is tightly regulated to prevent damage to host tissue. This regulation is paramount in the central nervous system (CNS) since complement proteins degrade neuronal synapses during development, homeostasis, and neurodegeneration. We propose that dysregulated complement, particularly C1 or C3b, may errantly target synapses for immune-mediated clearance, therefore highlighting regulatory failure as a major potential mediator of neurological disease. First, we explore the mechanics of molecular neuroimmune relationships for the regulatory proteins: Complement Receptor 1, C1-Inhibitor, Factor H, and the CUB-sushi multiple domain family. We propose that biophysical and chemical principles offer clues for understanding mechanisms of dysregulation. Second, we describe anticipated effects to CNS disease processes (particularly Alzheimer's Disease) and nest our ideas within existing basic science, clinical, and epidemiological findings. Finally, we illustrate how the concepts presented within this manuscript provoke new ways of approaching age-old neurodegenerative processes. Every component of this model is testable by straightforward experimentation and highlights the untapped potential of complement dysregulation as a driver of CNS disease. This includes a putative role for complement-based neurotherapeutic agents and companion biomarkers.
The Impact of Lockdown During the COVID-19 Outbreak on Dietary Habits in Various Population Groups: A Scoping Review
Authors: Bennett Grace , Young Elysia , Butler Isabel , Coe Shelly
Published: March 2021

Background: Since the beginning of the COVID-19 pandemic, access to fresh food has been restricted, and people are spending more time inside and have limited their physical activity. However, more time at home may have resulted in some positive habits including an increase in cooking. The aim of this review was to assess dietary changes during the first lockdown. Themes and patterns were considered and associations with other lifestyle factors were assessed.

Methods: Between June and July 2020, the PubMed, Google Scholar, and Science Direct databases were searched, and results were screened for eligibility based on title, abstract, and full text. The inclusion criteria of this search included: papers published (or in pre-print) in the year 2020; studies that investigated the impact of COVID-19 lockdown on diet; papers published in English. Exclusion criteria were as follows: papers examining dietary changes in those following a structured diet based on diagnosed conditions or dietetic advice; literature, systematic, or narrative studies reviewing previous research. Researchers agreed on the study characteristics for extraction from final papers.

Results: Four thousand three hundred and twenty-two studies were originally considered with 23 final full-text papers included. Four themes were identified: dietary patterns, dietary habits (favorable), dietary habits (unfavorable), and other (includes physical activity levels, weight gain). A total of 10 studies reported an increase in the number of snacks consumed, while six studies found that participants increased their meal number and frequency during quarantine. Eleven studies reported favorable changes in dietary habits with an increase in fresh produce and home cooking and reductions in comfort food and alcohol consumption. However, nine studies found a reduction in fresh produce, with a further six reporting an increase in comfort foods including sweets, fried food, snack foods, and processed foods. Two studies reported an increase in alcohol consumption. In eight studies participants reported weight gain with seven studies reporting a reduction in physical exercise.

Conclusion: The effect of COVID-19 lockdown both negatively and positively impacted dietary practices throughout Europe and globally, and negative diet habits were associated with other poor lifestyle outcomes including weight gain, mental health issues, and limited physical activity. Both in the short term and if sustained in the long term, these changes may have significant impacts on the health of the population.
Prediction of Microvascular Invasion of Hepatocellular Carcinoma Based on Contrast-Enhanced MR and 3D Convolutional Neural Networks
Authors: Zhou Wu , Jian Wanwei , Cen Xiaoping , Zhang Lijuan , Guo Hui , Liu Zaiyi , Liang Changhong , Wang Guangyi
Published: March 2021

Background and Purpose

It is extremely important to predict the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) before surgery, which is a key predictor of recurrence and helps determine the treatment strategy before liver resection or liver transplantation. In this study, we demonstrate that a deep learning approach based on contrast-enhanced MR and 3D convolutional neural networks (CNN) can be applied to better predict MVI in HCC patients.

Materials and Methods

This retrospective study included 114 consecutive patients who were surgically resected from October 2012 to October 2018 with 117 histologically confirmed HCC. MR sequences including 3.0T/LAVA (liver acquisition with volume acceleration) and 3.0T/e-THRIVE (enhanced T1 high resolution isotropic volume excitation) were used in image acquisition of each patient. First, numerous 3D patches were separately extracted from the region of each lesion for data augmentation. Then, 3D CNN was utilized to extract the discriminant deep features of HCC from contrast-enhanced MR separately. Furthermore, loss function for deep supervision was designed to integrate deep features from multiple phases of contrast-enhanced MR. The dataset was divided into two parts, in which 77 HCCs were used as the training set, while the remaining 40 HCCs were used for independent testing. Receiver operating characteristic curve (ROC) analysis was adopted to assess the performance of MVI prediction. The output probability of the model was assessed by the independent student’s t-test or Mann-Whitney U test.

Results

The mean AUC values of MVI prediction of HCC were 0.793 (p=0.001) in the pre-contrast phase, 0.855 (p=0.000) in arterial phase, and 0.817 (p=0.000) in the portal vein phase. Simple concatenation of deep features using 3D CNN derived from all the three phases improved the performance with the AUC value of 0.906 (p=0.000). By comparison, the proposed deep learning model with deep supervision loss function produced the best results with the AUC value of 0.926 (p=0.000).

Conclusion

A deep learning framework based on 3D CNN and deeply supervised net with contrast-enhanced MR could be effective for MVI prediction.
Novel Long Noncoding RNA 005620 Induces Epirubicin Resistance in Triple-Negative Breast Cancer by Regulating ITGB1 Expression
Authors: Wang Fengliang , Yang Sujin , Lv Mingming , Chen Fei , Yin Hong , Gao Sheng , Tang Jinhai , Yu Jing
Published: March 2021

Triple-negative breast cancer (TNBC) is often treated with anthracyclines (e.g., epirubicin or doxorubicin), but very little is known about anthracycline resistance, especially epirubicin resistance in TNBC. To identify novel long noncoding RNAs (lncRNAs) involved in epirubicin resistance in TNBC, we established a new TNBC MDA-MB-231 cell line that was resistant to epirubicin (Epi-R). A total of 12 differentially expressed lncRNAs were identified using RNA sequencing analysis of Epi-R cells. Among these lncRNAs, we found a novel intronic lncRNA, lnc005620, was highly expressed in Epi-R cells and human TNBC tissues. Further gain- and loss-of-function studies demonstrated that lnc005620 played an oncogenic role and partially abrogated the effects of epirubicin on TNBC cells. Using iTRAQ proteomics analysis, we found that three members of the integrin family, integrin β4, integrin β1 and integrin α6, were all upregulated in Epi-R MDA-MB-231 cells. Integrin β1, encoded by the ITGB1 gene, was validated to be a downstream target of lnc005620 in Epi-R MDA-MB-231 cells. Our study demonstrates that novel lnc005620 promotes TNBC progression and chemoresistance to epirubicin via integrin β1 both in vitro and in vivo and provides a promising therapeutic target for TNBC patients in terms of enhancing the benefits of epirubicin treatment.
Feasibility of Wave Intensity Analysis in Patients With Conotruncal Anomalies Before and After Pregnancy: New Physiological Insights?
Authors: Ordonez Maria Victoria , Neumann Sandra , Caputo Massimo , Curtis Stephanie , Biglino Giovanni
Published: March 2021

Background: Conotruncal anomalies (CTA) are associated with ongoing dilation of the aortic root, as well as increased aortic stiffness, which may relate to intrinsic properties of the aorta. Pregnancy hormones lead to hemodynamic changes and remodeling of the tunica media, resulting in the opposite effect, i.e., increasing distensibility. These changes normalize post-pregnancy in healthy women but have not been fully investigated in CTA patients.

Methods: We examined aortic distensibility and ventriculo-arterial coupling before and after pregnancy using cardiovascular magnetic resonance (CMR)-derived wave intensity analysis (WIA). Pre- and post-pregnancy CMR data were retrospectively analyzed. Aortic diameters were measured before, during, and after pregnancy by cardiac ultrasound and before and after pregnancy by CMR. Phase contrast MR flow sequences were used for calculating wave speed (c) and intensity (WI). A matched analysis was performed comparing results before and after pregnancy.

Results: Thirteen women (n = 5, transposition of the great arteries; n = 6, tetralogy of Fallot; n = 1, double outlet right ventricle, n = 1, truncus arteriosus) had 19 pregnancies. Median time between delivery and second CMR was 2.3 years (range: 1–6 years). The aortic diameter increased significantly after pregnancy in nine (n = 9) patients by a median of 4 ± 2.3 mm (range: 2–7.0 mm, p = 0.01). There was no difference in c pre-/post-pregnancy (p = 0.73), suggesting that increased compliance, typically observed during pregnancy, does not persist long term. A significant inverse relationship was observed between c and heart rate (HR) after pregnancy (p = 0.01, r = 0.73). There was no significant difference in cardiac output, aortic/pulmonary regurgitation, or WI peaks pre-/post-pregnancy.

Conclusions: WIA is feasible in this population and could provide physiological insights in larger cohorts. Aortic distensibility and wave intensity did not change before and after pregnancy in CTA patients, despite an increase in diameter, suggesting that pregnancy did not adversely affect coupling in the long-term.
Case Report: Recurring Peritonitis and Dialysis Failure in a Toddler on Peritoneal Dialysis
Authors: Mohammed Enas H. , Chandy Sajimol , Kadhi Abderrahman E. , Shatat Ibrahim F.
Published: March 2021

We report a case of a 2-year-old-boy with end stage renal disease (ESRD) secondary to posterior urethral valves (PUV) on peritoneal dialysis (PD). Our patient developed multiple episodes of peritonitis, refractory anemia and feeding intolerance over a 12-month-period. He was treated with multiple courses of intraperitoneal antibiotics. Despite being on high-calorie formula, he was slowly thriving. The feeding intolerance was attributed to past history of prematurity, gastro-esophageal reflux disease and ESRD co-morbidities. He had anemia resistant to erythrocyte stimulating agents and iron supplementation. His family received re-training and mastered the PD techniques. They reported no breach of the aseptic techniques. His workup which included multiple AP abdominal XR-plain films were read as unremarkable and showed the gastrostomy tube (GT) and the PD catheter in good position. He completed his antibiotic courses as prescribed after each peritonitis episode, peritoneal fluid cultures repeated after each treatment completion showed no growth. During the last peritonitis episode, our patient developed ultrafiltration failure. A cross-table abdominal XR was obtained to evaluate the peritoneal catheter position and showed an intra-abdominal foreign body. During surgery, a needle was laparoscopically removed from the ileum and the PD catheter was replaced. Subsequently, our patient's feeding intolerance and resistant anemia resolved. Finally PD was successfully resumed.
Using Topological Data Analysis (TDA) and Persistent Homology to Analyze the Stock Markets in Singapore and Taiwan
Authors: Yen Peter Tsung-Wen , Cheong Siew Ann
Published: March 2021

In recent years, persistent homology (PH) and topological data analysis (TDA) have gained increasing attention in the fields of shape recognition, image analysis, data analysis, machine learning, computer vision, computational biology, brain functional networks, financial networks, haze detection, etc. In this article, we will focus on stock markets and demonstrate how TDA can be useful in this regard. We first explain signatures that can be detected using TDA, for three toy models of topological changes. We then showed how to go beyond network concepts like nodes (0-simplex) and links (1-simplex), and the standard minimal spanning tree or planar maximally filtered graph picture of the cross correlations in stock markets, to work with faces (2-simplex) or any k-dim simplex in TDA. By scanning through a full range of correlation thresholds in a procedure called filtration, we were able to examine robust topological features (i.e. less susceptible to random noise) in higher dimensions. To demonstrate the advantages of TDA, we collected time-series data from the Straits Times Index and Taiwan Capitalization Weighted Stock Index (TAIEX), and then computed barcodes, persistence diagrams, persistent entropy, the bottleneck distance, Betti numbers, and Euler characteristic. We found that during the periods of market crashes, the homology groups become less persistent as we vary the characteristic correlation. For both markets, we found consistent signatures associated with market crashes in the Betti numbers, Euler characteristics, and persistent entropy, in agreement with our theoretical expectations.
Stick-Slip Dynamics in Fiber Bundle Models with Variable Stiffness and Slip Number
Authors: Halász Zoltán , Kállai Imre , Kun Ferenc
Published: March 2021

We present an extension of fiber bundle models to describe the mechanical response of systems which undergo a sequence of stick-slip cycles taking into account the changing stiffness and the fluctuating number of slip events of local material elements. After completing all stick-slip cycles allowed, fibers can either ultimately break or can keep their final stiffness leading to softening or hardening of the bundle, respectively. Under the assumption of global load sharing we derive analytic expressions for the constitutive response of the bundle with both quenched and annealed disorder of the failure thresholds where consecutive slips occur. Our calculations revealed that on the macro-scale the bundle exhibits a plastic behavior, which gets more pronounced when fibers undergo a higher number of stick-slip cycles with a gradually degrading stiffness. Releasing the load a permanent deformation remains, which increases monotonically for hardening bundles with the maximum deformation reached before unloading starts, however, in the softening case a non-monotonous behavior is obtained. We found that the macroscopic response of hardening bundles is more sensitive to fluctuations of the number of stick-slip cycles allowed than of the softening ones. The quenched and annealed disorder of failure thresholds gives rise to the same qualitative macro-scale behavior, however, the plastic response is found to be stronger in the annealed case.
Plant Defense Responses to Biotic Stress and Its Interplay With Fluctuating Dark/Light Conditions
Authors: Iqbal Zahra , Iqbal Mohammed Shariq , Hashem Abeer , Abd_Allah Elsayed Fathi , Ansari Mohammad Israil
Published: March 2021

Plants are subjected to a plethora of environmental cues that cause extreme losses to crop productivity. Due to fluctuating environmental conditions, plants encounter difficulties in attaining full genetic potential for growth and reproduction. One such environmental condition is the recurrent attack on plants by herbivores and microbial pathogens. To surmount such attacks, plants have developed a complex array of defense mechanisms. The defense mechanism can be either preformed, where toxic secondary metabolites are stored; or can be inducible, where defense is activated upon detection of an attack. Plants sense biotic stress conditions, activate the regulatory or transcriptional machinery, and eventually generate an appropriate response. Plant defense against pathogen attack is well understood, but the interplay and impact of different signals to generate defense responses against biotic stress still remain elusive. The impact of light and dark signals on biotic stress response is one such area to comprehend. Light and dark alterations not only regulate defense mechanisms impacting plant development and biochemistry but also bestow resistance against invading pathogens. The interaction between plant defense and dark/light environment activates a signaling cascade. This signaling cascade acts as a connecting link between perception of biotic stress, dark/light environment, and generation of an appropriate physiological or biochemical response. The present review highlights molecular responses arising from dark/light fluctuations vis-à-vis elicitation of defense mechanisms in plants.
Biosynthesis and Cellular Functions of Tartaric Acid in Grapevines
Authors: Burbidge Crista Ann , Ford Christopher Michael , Melino Vanessa Jane , Wong Darren Chern Jan , Jia Yong , Jenkins Colin Leslie Dow , Soole Kathleen Lydia , Castellarin Simone Diego , Darriet Philippe , Rienth Markus , Bonghi Claudio , Walker Robert Peter , Famiani Franco , Sweetman Crystal
Published: March 2021

Tartaric acid (TA) is an obscure end point to the catabolism of ascorbic acid (Asc). Here, it is proposed as a “specialized primary metabolite”, originating from carbohydrate metabolism but with restricted distribution within the plant kingdom and lack of known function in primary metabolic pathways. Grapes fall into the list of high TA-accumulators, with biosynthesis occurring in both leaf and berry. Very little is known of the TA biosynthetic pathway enzymes in any plant species, although recently some progress has been made in this space. New technologies in grapevine research such as the development of global co-expression network analysis tools and genome-wide association studies, should enable more rapid progress. There is also a lack of information regarding roles for this organic acid in plant metabolism. Therefore this review aims to briefly summarize current knowledge about the key intermediates and enzymes of TA biosynthesis in grapes and the regulation of its precursor, ascorbate, followed by speculative discussion around the potential roles of TA based on current knowledge of Asc metabolism, TA biosynthetic enzymes and other aspects of fruit metabolism.
A Way to Improve Adolescents’ Life Satisfaction: School Altruistic Group Games
Authors: Lu Caixia , Liang Lichan , Chen Wenting , Bian Yufang
Published: March 2021

Previous studies have shown that adolescents are experiencing growing pains due to their unbalanced physical and mental development. Their life satisfaction showed a steady downward trend with age. Altruism may be an effective way to improve their life satisfaction. Against this background, the current study carried out school altruistic group games (SAGGs) for the first time to explore the role of altruistic group activities in the school context in improving adolescents’ life satisfaction. There were 176 adolescents in the study, including 90 in the experimental group and 86 in the control group, who were enrolled from a junior high school in East China. A 10-week school altruism group game was carried out for the experimental group. The participants in the control group participated in activities that were not related to altruism. Participants in both groups reported their life satisfaction and emotions before and after the games. The findings of this study were as follows: (1) SAGGs can effectively improve adolescents’ life satisfaction, especially school satisfaction; (2) SAGGs can significantly improve adolescents’ emotional state; that is, SAGGs can enhance positive emotions and reduce negative emotions; and (3) SAGGs have different effects on the life satisfaction of adolescents with different initial emotional states. The results of this study not only enrich the existing literature but also provide enlightenment and a reference for schools to improve adolescents’ life satisfaction.
Drivers or Drifters? The “Who” and “Why” of Leader Role Occupancy—A Mixed-Method Study
Authors: Auvinen Elina , Huhtala Mari , Rantanen Johanna , Feldt Taru
Published: March 2021

This study investigated the reasons that leaders have given for their leader role occupancy. By using a mixed-method approach and large leader data, we aimed to provide a more nuanced picture of how leader positions are occupied in real life. We examined how individual leadership motivation may associate with other reasons for leader role occupancy. In addition, we aimed to integrate the different reasons behind leader role occupancy into the framework of sustainable leader careers and its two indicators: leader’s health (occupational well-being) and performance (measured indirectly as followers’ occupational well-being). The survey data consisted of 1,031 leaders from various sectors of working life. Qualitative analysis revealed that leaders mention various factors behind their leader role occupancy, resulting 26 themes. After inductive investigation of the data, theory-driven analysis focused on the sustainable career components (person, context, time) and agency vs. non-agency. Qualitative data was quantitized based on the theory-driven categories for statistical analysis. Based on the these analysis, we found out that only Affective-Identity MTL predicted all of the studied reasons behind leader role occupancy, whereas the other motivation types (Non-calculative MTL and Social-Normative MTL) did not. All of the reasons for leader role occupancy except non-agentic ones were related to both leaders’ own and their followers’ occupational well-being. Leaders with more person-related and agentic reasons for leader role occupancy experienced better occupational well-being. Person- and context-related and agentic reasons behind leader role occupancy associated also with followers’ occupational well-being, but the associations differed from those of leaders’ well-being: person-related and agentic reasons associated with followers’ exhaustion, but this association was not found among leaders. Our study provided important information for practitioners in the field of human resources and development, as it has shown that if the reasons for leader role occupancy mainly reflect circumstances or other non-person-related reasons, the experienced occupational well-being and person-career fit may remain weak. It is necessary to try to support the leadership motivation for those leaders, or to shape the job description in such a way that it can also offer the experiences of meaningfulness from aspects other than self-realization through a managerial role.
Physical Activity With Eduball Stimulates Graphomotor Skills in Primary School Students
Authors: Wawrzyniak Sara , Cichy Ireneusz , Matias Ana Rita , Pawlik Damian , Kruszwicka Agnieszka , Klichowski Michal , Rokita Andrzej
Published: March 2021

Despite the general agreement that the interdisciplinary model of physical education (PE), based on the incorporation of core academic subjects into the PE curriculum, stimulates the holistic development of students, there is still a lack of methods for its implementation. Therefore, Eduball was created, i.e., a method that uses educational balls with printed letters, numbers, and other signs. Numerous studies have shown that children participating in activities with Eduballs can develop their physical fitness while simultaneously improving their academic performance, particularly in math and language, including some writing skills. However, little is known about the effects of Eduball on children’s graphomotor skills, which are key for the academic performance of students throughout the entire schooling process. Here, we investigate whether 6-month participation in PE with Eduball stimulates graphomotor skills in primary school students, such as drawing prehandwriting letter patterns on unlined or lined paper and rewriting text on unlined or lined paper. Our results show that the Eduball class (N= 28) significantly improved these skills compared to the control class (N= 26) participating in traditional PE. For example, students from the experimental group wrote with a lower pen pressure and better stability of the line, in contrast to those from the control group. Therefore, this study demonstrates that the Eduball method successfully supports teachers in developing graphomotor skills in children. More broadly, our findings make clear once again that there is the need to integrate physical and cognitive development in education, which can be achieved by using an interdisciplinary model of PE.