bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review and meta-analysis of school-based interventions with health education to reduce body mass index in adolescents aged 10 to 19 years
Authors: Jacob Chandni Maria , Hardy-Johnson Polly Louise , Inskip Hazel M. , Morris Taylor , Parsons Camille M. , Barrett Millie , Hanson Mark , Woods-Townsend Kathryn , Baird Janis
Published: January 2021

Background

Adolescents are increasingly susceptible to obesity, and thus at risk of later non-communicable diseases, due to changes in food choices, physical activity levels and exposure to an obesogenic environment. This review aimed to synthesize the literature investigating the effectiveness of health education interventions delivered in school settings to prevent overweight and obesity and/ or reduce BMI in adolescents, and to explore the key features of effectiveness.

Methods

A systematic search of electronic databases including MEDLINE, CINAHL, PsychINFO and ERIC for papers published from Jan 2006 was carried out in 2020, following PRISMA guidelines. Studies that evaluated health education interventions in 10–19-year-olds delivered in schools in high-income countries, with a control group and reported BMI/BMI z-score were selected. Three researchers screened titles and abstracts, conducted data extraction and assessed quality of the full text publications. A third of the papers from each set were cross-checked by another reviewer. A meta-analysis of a sub-set of studies was conducted for BMI z-score.

Results

Thirty-three interventions based on 39 publications were included in the review. Most studies evaluated multi-component interventions using health education to improve behaviours related to diet, physical activity and body composition measures. Fourteen interventions were associated with reduced BMI/BMI z-score. Most interventions (n = 22) were delivered by teachers in classroom settings, 19 of which trained teachers before the intervention. The multi-component interventions (n = 26) included strategies such as environment modifications (n = 10), digital interventions (n = 15) and parent involvement (n = 16). Fourteen studies had a low risk of bias, followed by 10 with medium and nine with a high risk of bias. Fourteen studies were included in a random-effects meta-analysis for BMI z-score. The pooled estimate of this meta-analysis showed a small difference between intervention and control in change in BMI z-score (− 0.06 [95% CI -0.10, − 0.03]). A funnel plot indicated that some degree of publication bias was operating, and hence the effect size might be inflated.

Conclusions

Findings from our review suggest that school-based health education interventions have the public health potential to lower BMI towards a healthier range in adolescents. Multi-component interventions involving key stakeholders such as teachers and parents and digital components are a promising strategy.
Progranulin induces immune escape in breast cancer via up-regulating PD-L1 expression on tumor-associated macrophages (TAMs) and promoting CD8+ T cell exclusion
Authors: Fang Wenli , Zhou Ting , Shi He , Yao Mengli , Zhang Dian , Qian Husun , Zeng Qian , Wang Yange , Jin Fangfang , Chai Chengsen , Chen Tingmei
Published: January 2021

Background

Progranulin (PGRN), as a multifunctional growth factor, is overexpressed in multiple tumors, but the role of PGRN on tumor immunity is still unclear. Here, we studied the effect of PGRN on breast cancer tumor immunity and its possible molecular mechanism.

Methods

The changes of macrophage phenotypes after PGRN treatment were detected by western blot, quantitative polymerase chain reaction (PCR) and flow cytometry. Western blot was used to study the signal molecular mechanism of PGRN regulating this process. The number and localization of immune cells in Wild-type (WT) and PGRN−/− breast cancer tissues were analyzed by immunohistochemical staining and immunofluorescence techniques. The activation and proliferation of CD8+ T cells were measured by flow cytometry.

Results

After being treated with PGRN, the expressions of M2 markers and programmed death ligand 1 (PD-L1) on macrophages increased significantly. Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitor Stattic significantly inhibited the expression of PD-L1 and M2 related markers induced by PGRN. In WT group, CD8 were co-localized with macrophages and PD-L1, but not tumor cells. The number of immune cells in PGRN−/− breast cancer tissue increased, and their infiltration into tumor parenchyma was also enhanced. Moreover, in the co-culture system, WT peritoneal macrophages not only reduced the ratio of activated CD8+ T cells but also reduced the proportion of proliferating CD8+ T cells. The addition of programmed death receptor 1 (PD-1) and PD-L1 neutralizing antibodies effectively reversed this effect and restored the immune function of CD8+ T cells.

Conclusion

These results demonstrate that PGRN promotes M2 polarization and PD-L1 expression by activating the STAT3 signaling pathway. Furthermore, through PD-1/PD-L1 interaction, PGRN can promote the breast tumor immune escape. Our research may provide new ideas and targets for clinical breast cancer immunotherapy.
Choline kinase alpha impairment overcomes TRAIL resistance in ovarian cancer cells
Authors: Rizzo Andrea , Satta Alessandro , Garrone Giulia , Cavalleri Adalberto , Napoli Alessandra , Raspagliesi Francesco , Figini Mariangela , De Cecco Loris , Iorio Egidio , Tomassetti Antonella , Mezzanzanica Delia , Bagnoli Marina
Published: January 2021

Background

Choline kinase-α (ChoKα/CHKA) overexpression and hyper-activation sustain altered choline metabolism conferring the cholinic phenotype to epithelial ovarian cancer (OC), the most lethal gynecological tumor. We previously proved that CHKA down-modulation reduced OC cell aggressiveness and increased sensitivity to in vitro chemotherapeutics’ treatment also affecting intracellular content of one-carbon metabolites. In tumor types other than ovary, methionine decrease was shown to increase sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-receptor 2 triggering. These effects were suggestive of a potential role for ChoKα in regulating susceptibility to TRAIL cytokine.

Methods

The relationship between ChoKα/CHKA and TRAIL-receptor 2 (TRAIL-R2) expression was investigated in silico in OC patients’ GEO datasets and in vitro in a panel of OC cell lines upon transient CHKA silencing (siCHKA). The effect of siCHKA on metabolites content was assessed by LC-MS. The triggered apoptotic signalling was studied following soluble-TRAIL or anti-TRAIL-R2 agonist antibody treatment. Lipid rafts were isolated by Triton X-100 fractionation. Preclinical ex vivo studies were performed in OC cells derived from patients’ ascites using autologous PBLs as effectors and a bispecific anti-TRAIL-R2/anti-CD3 antibody as triggering agent.

Results

Here we demonstrate that siCHKA specifically overcomes resistance to TRAIL-mediated apoptosis in OC cells. Upon siCHKA we detected: a significant sensitization to caspase-dependent apoptosis triggered by both soluble TRAIL and anti-TRAIL-R2 agonist antibody, a specific increase of TRAIL-R2 expression and TRAIL-R2 relocation into lipid rafts. In siCHKA-OC cells the acquired TRAIL sensitivity was completely reverted upon recovery of ChoKα expression but, at variance of other tumor cell types, TRAIL sensitivity was not efficiently phenocopied by methionine deprivation. Of note, we were also able to show that siCHKA sensitized tumor cells derived ex vivo from OC patients’ ascites to the cytotoxic activity of autologous lymphocytes redirected by a bispecific anti-TRAIL-R2/anti-CD3 antibody.

Conclusions

Our findings suggest that ChoKα/CHKA impairment, by restoring drug-induced or receptor-mediated cell death, could be a suitable therapeutic strategy to be used in combination with chemotherapeutics or immunomodulators to improve OC patients’ outcome.
Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived from poor ovarian responders
Authors: Gong Yan , Li-Ling Jesse , Xiong Dongsheng , Wei Jiajing , Zhong Taiqing , Tan Hao
Published: January 2021

Background

Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes play important roles in folliculogenesis. Altered expression of the two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment.

Methods

A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed by the Bologna criteria and sub-divided into group A (< 35 year old), group B (35–40 year old), and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of the GDF9 and BMP15 genes in the FF and GCs was determined with enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.

Results

Compared with group C, groups A and B had significantly more two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P <  0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P <  0.05), showing a trend of decline along with age. The ratio of GDF9/BMP15 mRNA levels were similar among the three groups (P > 0.05). The relative levels of GDF9 and BMP15 proteins in GCs have correlated with the relative mRNA levels in GCs and protein concentrations in FF (P <  0.05).

Conclusions

For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined along with increased age and in accompany with poorer oocyte quality and IVF outcome, whilst the ratio of GDF9/BMP15 mRNA levels remained relatively constant.

Trial registration

Chinese Clinical Trial Registry Center (ChiCTR1800016107). Registered on 11 May 2018.
Comparison of anticoagulation strategies for veno-venous ECMO support in acute respiratory failure
Authors: Seeliger Benjamin , Döbler Michael , Friedrich Robert , Stahl Klaus , Kühn Christian , Bauersachs Johann , Steinhagen Folkert , Ehrentraut Stefan F. , Schewe Jens-Christian , Putensen Christian , Welte Tobias , Hoeper Marius M. , Tiede Andreas , David Sascha , Bode Christian
Published: January 2021

Background

Extracorporeal membrane oxygenation (ECMO) support in acute respiratory failure may be lifesaving, but bleeding and thromboembolic complications are common. The optimal anticoagulation strategy balancing these factors remains to be determined. This retrospective study compared two institutional anticoagulation management strategies focussing on oxygenator changes and both bleeding and thromboembolic events.

Methods

We conducted a retrospective observational cohort study between 04/2015 and 02/2020 in two ECMO referral centres in Germany in patients receiving veno-venous (VV)-ECMO support for acute respiratory failure for > 24 h. One centre routinely applied low-dose heparinization aiming for a partial thromboplastin time (PTT) of 35–40 s and the other routinely used a high-dose therapeutic heparinization strategy aiming for an activated clotting time (ACT) of 140–180 s. We assessed number of and time to ECMO oxygenator changes, 15-day freedom from oxygenator change, major bleeding events, thromboembolic events, 30-day ICU mortality, activated clotting time and partial thromboplastin time and administration of blood products. Primary outcome was the occurrence of oxygenator changes depending on heparinization strategy; main secondary outcomes were the occurrence of severe bleeding events and occurrence of thromboembolic events. The transfusion strategy was more liberal in the low-dose centre.

Results

Of 375 screened patients receiving VV-ECMO support, 218 were included in the analysis (117 high-dose group; 101 low-dose group). Disease severity measured by SAPS II score was 46 (IQR 36–57) versus 47 (IQR 37–55) and ECMO runtime was 8 (IQR 5–12) versus 11 (IQR 7–17) days (P = 0.003). There were 14 oxygenator changes in the high-dose group versus 48 in the low-dose group. Freedom from oxygenator change at 15 days was 73% versus 55% (adjusted HR 3.34 [95% confidence interval 1.2–9.4]; P = 0.023). Severe bleeding events occurred in 23 (19.7%) versus 14 (13.9%) patients (P = 0.256) and thromboembolic events occurred in 8 (6.8%) versus 19 (19%) patients (P = 0.007). Mortality at 30 days was 33.3% versus 30.7% (P = 0.11).

Conclusions

In this retrospective study, ECMO management with high-dose heparinization was associated with lower rates of oxygenator changes and thromboembolic events when compared to a low-dose heparinization strategy. Prospective, randomized trials are needed to determine the optimal anticoagulation strategy in patients receiving ECMO support.
Protective reactive thymus hyperplasia in COVID-19 acute respiratory distress syndrome
Authors: Cuvelier Pelagia , Roux Hélène , Couëdel-Courteille Anne , Dutrieux Jacques , Naudin Cécile , Charmeteau de Muylder Bénédicte , Cheynier Rémi , Squara Pierre , Marullo Stefano
Published: January 2021

Background

Patients with COVID-19 (COVID) may develop acute respiratory distress syndrome with or without sepsis, coagulopathy and visceral damage. While chest CT scans are routinely performed in the initial assessment of patients with severe pulmonary forms, thymus involvement and reactivation have not been investigated so far.

Methods

In this observational study, we systematically scored the enlargement of the thymus and the lung involvement, using CT scans, in all adult patients admitted to the ICU for COVID or any other cause (control group) at one centre between March and April 2020. Initial biological investigations included nasal detection of SARS-CoV-2 ribonucleic acid by polymerase chain reaction (PCR). In a subgroup of 24 patients with different degrees of pulmonary involvement and thymus hypertrophy, plasma cytokine concentrations were measured and the export of mature T cells from the thymus was estimated simultaneously by PCR quantification of T cell receptor excision circles (TRECs).

Results

Eighty-seven patients were studied: 50 COVID patients and 37 controls. Non-atrophic or enlarged thymus was more commonly observed in COVID patients than in controls (66% vs. 24%, p < 0.0001). Thymus enlargement in COVID patients was associated with more extensive lung injury score on CT scans (4 [3–5] vs. 2 [1.5–4], p = 0.01), but a lower mortality rate (8.6% vs. 41.2%, p < 0.001). Other factors associated with mortality were age, lymphopaenia, high CRP and co-morbidities. COVID patients had higher concentrations of IL-7 (6.00 [3.72–9.25] vs. 2.17 [1.76–4.4] pg/mL; p = 0.04) and higher thymic production of new lymphocytes (sj/βTREC ratio = 2.88 [1.98–4.51] vs. 0.23 [0.15–0.60]; p = 0.004). Thymic production was also correlated with the CT scan thymic score (r = 0.38, p = 0.03) and inversely correlated with the number of lymphocytes (r = 0.56, p = 0.007).

Conclusion

In COVID patients, thymus enlargement was frequent and associated with increased T lymphocyte production, which appears to be a beneficial adaptation to virus-induced lymphopaenia. The lack of thymic activity/reactivation in older SARS-CoV-2 infected patients could contribute to a worse prognosis.
Genome-wide association study implicates novel loci and reveals candidate effector genes for longitudinal pediatric bone accrual
Authors: Cousminer Diana L. , Wagley Yadav , Pippin James A. , Elhakeem Ahmed , Way Gregory P. , Pahl Matthew C. , McCormack Shana E. , Chesi Alessandra , Mitchell Jonathan A. , Kindler Joseph M. , Baird Denis , Hartley April , Howe Laura , Kalkwarf Heidi J. , Lappe Joan M. , Lu Sumei , Leonard Michelle E. , Johnson Matthew E. , Hakonarson Hakon , Gilsanz Vicente , Shepherd John A. , Oberfield Sharon E. , Greene Casey S. , Kelly Andrea , Lawlor Deborah A. , Voight Benjamin F. , Wells Andrew D. , Zemel Babette S. , Hankenson Kurt D. , Grant Struan F. A.
Published: January 2021

Background

Bone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype by modeling longitudinal bone accrual across 11,000 bone scans in a cohort of healthy children and adolescents, followed by genome-wide association studies (GWAS) and variant-to-gene mapping with functional follow-up.

Results

We identify 40 loci, 35 not previously reported, with various degrees of supportive evidence, half residing in topological associated domains harboring known bone genes. Of several loci potentially associated with later-life fracture risk, a candidate SNP lookup provides the most compelling evidence for rs11195210 (SMC3). Variant-to-gene mapping combining ATAC-seq to assay open chromatin with high-resolution promoter-focused Capture C identifies contacts between GWAS loci and nearby gene promoters. siRNA knockdown of gene expression supports the putative effector gene at three specific loci in two osteoblast cell models. Finally, using CRISPR-Cas9 genome editing, we confirm that the immediate genomic region harboring the putative causal SNP influences PRPF38A expression, a location which is predicted to coincide with a set of binding sites for relevant transcription factors.

Conclusions

Using a new longitudinal approach, we expand the number of genetic loci putatively associated with pediatric bone gain. Functional follow-up in appropriate cell models finds novel candidate genes impacting bone accrual. Our data also raise the possibility that the cell fate decision between osteogenic and adipogenic lineages is important in normal bone accrual.
Histone modifications during the life cycle of the brown alga Ectocarpus
Authors: Bourdareau Simon , Tirichine Leila , Lombard Bérangère , Loew Damarys , Scornet Delphine , Wu Yue , Coelho Susana M. , Cock J. Mark
Published: January 2021

Background

Brown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of developmental processes in this group is expected to provide important insights into the evolutionary events necessary for the emergence of complex multicellularity. Here, we focus on mechanisms of epigenetic regulation involving post-translational modifications of histone proteins.

Results

A total of 47 histone post-translational modifications are identified, including a novel mark H2AZR38me1, butEctocarpuslacks both H3K27me3 and the major polycomb complexes. ChIP-seq identifies modifications associated with transcription start sites and gene bodies of active genes and with transposons. H3K79me2 exhibits an unusual pattern, often marking large genomic regions spanning several genes. Transcription start sites of closely spaced, divergently transcribed gene pairs share a common nucleosome-depleted region and exhibit shared histone modification peaks. Overall, patterns of histone modifications are stable through the life cycle. Analysis of histone modifications at generation-biased genes identifies a correlation between the presence of specific chromatin marks and the level of gene expression.

Conclusions

The overview of histone post-translational modifications in the brown alga presented here will provide a foundation for future studies aimed at understanding the role of chromatin modifications in the regulation of brown algal genomes.
Integrated genomic and transcriptomic analysis reveals unique characteristics of hepatic metastases and pro-metastatic role of complement C1q in pancreatic ductal adenocarcinoma
Authors: Yang Jianyu , Lin Ping , Yang Minwei , Liu Wei , Fu Xueliang , Liu Dejun , Tao Lingye , Huo Yanmiao , Zhang Junfeng , Hua Rong , Zhang Zhigang , Li Yixue , Wang Liwei , Xue Jing , Li Hong , Sun Yongwei
Published: January 2021

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers due to its high metastasis rate in the liver. However, little is known about the molecular features of hepatic metastases due to difficulty in obtaining fresh tissues and low tumor cellularity.

Results

We conduct exome sequencing and RNA sequencing for synchronous surgically resected primary tumors and the paired hepatic metastases from 17 hepatic oligometastatic pancreatic ductal adenocarcinoma and validate our findings in specimens from 35 of such cases. The comprehensive analysis of somatic mutations, copy number alterations, and gene expressions show high similarity between primary tumors and hepatic metastases. However, hepatic metastases also show unique characteristics, such as a higher degree of 3p21.1 loss, stronger abilities of proliferation, downregulation of epithelial to mesenchymal transition activity, and metabolic rewiring. More interesting, altered tumor microenvironments are observed in hepatic metastases, especially a higher proportion of tumor infiltrating M2 macrophage and upregulation of complement cascade. Further experiments demonstrate that expression of C1q increases in primary tumors and hepatic metastases, C1q is mainly produced by M2 macrophage, and C1q promotes migration and invasion of PDAC cells.

Conclusion

Taken together, we find potential factors that contribute to different stages of PDAC metastasis. Our study broadens the understanding of molecular mechanisms driving PDAC metastasis.
Reference flow: reducing reference bias using multiple population genomes
Authors: Chen Nae-Chyun , Solomon Brad , Mun Taher , Iyer Sheila , Langmead Ben
Published: January 2021

Most sequencing data analyses start by aligning sequencing reads to a linear reference genome, but failure to account for genetic variation leads to reference bias and confounding of results downstream. Other approaches replace the linear reference with structures like graphs that can include genetic variation, incurring major computational overhead. We propose the reference flow alignment method that uses multiple population reference genomes to improve alignment accuracy and reduce reference bias. Compared to the graph aligner vg, reference flow achieves a similar level of accuracy and bias avoidance but with 14% of the memory footprint and 5.5 times the speed.
Comprehensive integrative profiling of upper tract urothelial carcinomas
Authors: Su Xiaoping , Lu Xiaofan , Bazai Sehrish Khan , Compérat Eva , Mouawad Roger , Yao Hui , Rouprêt Morgan , Spano Jean-Philippe , Khayat David , Davidson Irwin , Tannir Nizar N. , Yan Fangrong , Malouf Gabriel G.
Published: January 2021

Background

Crosstalk between genetic, epigenetic, and immune alterations in upper tract urothelial carcinomas and their role in shaping muscle invasiveness and patient outcome are poorly understood.

Results

We perform an integrative genome- and methylome-wide profiling of diverse non-muscle-invasive and muscle-invasive upper tract urothelial carcinomas. In addition to mutations of FGFR3 and KDM6A, we identify ZFP36L1 as a novel, significantly mutated tumor suppressor gene. Overall, mutations of ZFP36 family genes (ZFP36, ZFP36L1, and ZFP36L2) are identified in 26.7% of cases, which display a high mutational load. Unsupervised DNA methylation subtype classification identifies two epi-clusters associated with distinct muscle-invasive status and patient outcome, namely, EpiC-low and EpiC-high. While the former is hypomethylated, immune-depleted, and enriched for FGFR3-mutated, the latter is hypermethylated, immune-infiltrated, and tightly associated with somatic mutations of SWI/SNF genes.

Conclusions

Our study delineates for the first time the key role for convergence between genetic and epigenetic alterations in shaping clinicopathological and immune upper tract urothelial carcinoma features.
scMC learns biological variation through the alignment of multiple single-cell genomics datasets
Authors: Zhang Lihua , Nie Qing
Published: January 2021

Distinguishing biological from technical variation is crucial when integrating and comparing single-cell genomics datasets across different experiments. Existing methods lack the capability in explicitly distinguishing these two variations, often leading to the removal of both variations. Here, we present an integration method scMC to remove the technical variation while preserving the intrinsic biological variation. scMC learns biological variation via variance analysis to subtract technical variation inferred in an unsupervised manner. Application of scMC to both simulated and real datasets from single-cell RNA-seq and ATAC-seq experiments demonstrates its capability of detecting context-shared and context-specific biological signals via accurate alignment.
Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles
Authors: Walker Rosie M. , Vaher Kadi , Bermingham Mairead L. , Morris Stewart W. , Bretherick Andrew D. , Zeng Yanni , Rawlik Konrad , Amador Carmen , Campbell Archie , Haley Chris S. , Hayward Caroline , Porteous David J. , McIntosh Andrew M. , Marioni Riccardo E. , Evans Kathryn L.
Published: January 2021

Background

Theapolipoprotein E(APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease, whilst the ε2 allele confers protection. Previous studies report differential DNA methylation ofAPOEbetween ε4 and ε2 carriers, but associations with epigenome-wide methylation have not previously been characterised.

Methods

Using the EPIC array, we investigated epigenome-wide differences in whole blood DNA methylation patterns between Alzheimer’s disease-freeAPOEε4 (n = 2469) and ε2 (n = 1118) carriers from the two largest single-cohort DNA methylation samples profiled to date. Using a discovery, replication and meta-analysis study design, methylation differences were identified using epigenome-wide association analysis and differentially methylated region (DMR) approaches. Results were explored using pathway and methylation quantitative trait loci (meQTL) analyses.

Results

We obtained replicated evidence for DNA methylation differences in a ~ 169 kb region, which encompasses part ofAPOEand several upstream genes. Meta-analytic approaches identified DNA methylation differences outside ofAPOE: differentially methylated positions were identified inDHCR24,LDLRandABCG1(2.59 × 10−100 ≤ P ≤ 2.44 × 10−8) and DMRs were identified inSREBF2andLDLR(1.63 × 10−4 ≤ P ≤ 3.01 × 10−2). Pathway and meQTL analyses implicated lipid-related processes and high-density lipoprotein cholesterol was identified as a partial mediator of the methylation differences inABCG1andDHCR24.

Conclusions

APOEε4 vs. ε2 carrier status is associated with epigenome-wide methylation differences in the blood. The loci identified are located intransas well ascistoAPOEand implicate genes involved in lipid homeostasis.
Baricitinib inhibits structural joint damage progression in patients with rheumatoid arthritis—a comprehensive review
Authors: Emery Paul , Durez Patrick , Hueber Axel J. , de la Torre Inmaculada , Larsson Esbjörn , Holzkämper Thorsten , Tanaka Yoshiya
Published: January 2021

Baricitinib is an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 that has proved effective and well tolerated in the treatment of rheumatoid arthritis (RA) in an extensive programme of clinical studies of patients with moderate-to-severe disease. In a phase 2b dose-ranging study of baricitinib in combination with traditional disease-modifying antirheumatic drugs (DMARDs) in RA patients, magnetic resonance imaging showed that baricitinib 2 mg or 4 mg once daily provided dose-dependent suppression of synovitis, osteitis, erosion and cartilage loss at weeks 12 and 24 versus placebo. These findings correlated with clinical outcomes and were confirmed in three phase 3 studies (RA-BEGIN, RA-BEAM and RA-BUILD) using X-rays to assess structural joint damage. In patients naïve to DMARDs (RA-BEGIN study), baricitinib 4 mg once daily as monotherapy or combined with methotrexate produced smaller mean changes in structural joint damage than methotrexate monotherapy at week 24. Differences versus methotrexate were statistically significant for combined therapy. In patients responding inadequately to methotrexate (RA-BEAM study), baricitinib 4 mg plus background methotrexate significantly inhibited structural joint damage at week 24 versus placebo, and the results were comparable to those observed with adalimumab plus background methotrexate. In patients responding inadequately to conventional synthetic DMARDs (csDMARDs; RA-BUILD study), baricitinib 4 mg again significantly inhibited radiographic progression compared with placebo at week 24. Benefits were also observed with baricitinib 2 mg once daily, but the effects of baricitinib 4 mg were more robust. The positive effects of baricitinib 4 mg on radiographic progression continued over 1 and 2 years in the long-term extension study RA-BEYOND, with similar effects to adalimumab and significantly greater effects than placebo. Findings from the phase 3 studies of patients with RA were supported by preclinical studies, which showed that baricitinib has an osteoprotective effect, increasing mineralisation in bone-forming cells. In conclusion, baricitinib 4 mg once daily inhibits radiographic joint damage progression in patients with moderate-to-severe RA who are naïve to DMARDs or respond inadequately to csDMARDs, including methotrexate, and the beneficial effects are similar to those observed with adalimumab.
The complex microbiome in aquaponics: significance of the bacterial ecosystem
Authors: Kasozi Nasser , Abraham Benjamin , Kaiser Horst , Wilhelmi Brendan
Published: January 2021

Purpose

Aquaponics is a technology that has minimal impact on the environment and which is often promoted as a solution for sustainable food production. Developing aquaponics sustainably requires a thorough understanding of the biological components of the system. Recent reports on the bacterial populations of aquaponics systems using new DNA sequencing technologies are revealing a complex and diverse microbial ecosystem. The purpose of this review is to present information on microbial composition and various factors affecting bacterial activity in aquaponics systems. Approaches for establishing a bacterial ecosystem during the setup of an aquaponics system, and microbiological safety of aquaponics products are also highlighted.

Methods

This review was developed by evaluating and synthesising current literature of peer-reviewed publications related to aquaponics and microbial communities. Based on the results from credible academic journals, publications were categorised into five groups: methods used to characterise microbiomes, biofiltration microorganisms, bacterial diversity, biofilter establishment, and safety of aquaponics products.

Results

The microbial ecosystem is essential for biological filtration of water through the mineralisation of nutrients required for plant growth in an integrated system. The aquaponics microbiome is complex, and bacterial composition varies between the different compartments of these systems. Establishing these bacterial ecosystems is essential for optimal functioning of aquaponics. At the phylum level, Proteobacteria and Bacteroidetes are dominant in aquaponics systems. Despite bacteria being fundamental to aquaponics, there are currently no reports of human pathogens in aquaponics products.

Conclusion

Knowledge of the composition of bacterial populations in aquaponics systems will enhance understanding of relationships and functions within the microbiome. This in turn will allow for the establishment of sustainable and healthy aquaponics systems for food production.
Radiology departments as COVID-19 entry-door might improve healthcare efficacy and efficiency, and emergency department safety
Authors: García Santos José M. , Plasencia Martínez Juana M. , Fabuel Ortega Pablo , Lozano Ros Marina , Sánchez Ayala María Carmen , Pérez Hernández Gloria , Menchón Martínez Pedro
Published: January 2021

Background

Possible COVID-19 pneumonia patients (ppCOVID-19) generally overwhelmed emergency departments (EDs) during the first COVID-19 wave. Home-confinement and primary-care phone follow-up was the first-level regional policy for preventing EDs to collapse. But when X-rays were needed, the traditional outpatient workflow at the radiology department was inefficient and potential interpersonal infections were of concern. We aimed to assess the efficiency of a primary-care high-resolution radiology service (pcHRRS) for ppCOVID-19 in terms of time at hospital and decision’s reliability.

Methods

We assessed 849 consecutive ppCOVID-19 patients, 418 through the pcHRRS (home-confined ppCOVID-19 with negative—group 1- and positive—group 2-X-rays) and 431 arriving with respiratory symptoms to the ED by themselves (group 3). The pcHRRS provided X-rays and oximetry in an only-one-patient agenda. Radiologists made next-step decisions (group 1: pneumonia negative, home-confinement follow-up; group 2: pneumonia positive, ED assessment) according to X-ray results. We used ANOVA and Bonferroni correction, Student T, Chi2 tests to analyse changes in the ED workload, time-to-decision differences between groups, potential delays in patients acceding through the ED, and pcHRRS performance for deciding admission.

Results

The pcHRRS halved ED respiratory patients (49.2%), allowed faster decisions (group 1 vs. home-discharged group 2 and group 3 patients: 0:41 ± 1:05 h; 3:36 ± 2:58 h; 3:50 ± 3:16 h; group 1 vs. all group 2 and group 3 patients: 0:41 ± 1:05 h; 5.25 ± 3.08; 5:36 ± 4:36 h; group 2 vs. group 3 admitted patients: 5:27 ± 3:08 h vs. 7:42 ± 5:02 h; all p < 0.001) and prompted admission (84/93, 90.3%) while maintaining time response for ED patients.

Conclusions

Our pcHRRS may be a more efficient entry-door for ppCOVID-19 by decreasing ED patients and making expedited decisions while guaranteeing social distance.
The utility of hyperbaric oxygen therapy in post-transplant cyclophosphamide-induced hemorrhagic cystitis: a case report and review of the literature
Authors: Ibrahim Moayed , Bhyravabhotla Kshama , Khalaf Basil , Van Meter Keith , Saba Nakhle S. , Safah Hana , Socola Francisco
Published: January 2021

Background

To date, there are only a few case reports of cyclophosphamide (Cy)-induced hemorrhagic cystitis (HC) in adult or pediatric allogeneic stem cell transplant (SCT) patients treated successfully with hyperbaric oxygen (HBO). In all the reported cases, Cy was used as a part of the conditioning regimen, rather than post-transplant for graft-versus-host-disease (GVHD) prophylaxis. More recently, the risk of HC in allogeneic SCT is further increased by the widespread use of post-transplantation cyclophosphamide (PTCy) as a highly effective strategy for GVHD prophylaxis. This is the first case reported of PTCy-induced HC successfully treated with HBO to the best of our knowledge.

Case presentation

In this article, we present a 58-year-old Caucasian male case of allogeneic SCT complicated by severe HC following PTCy, which was successfully treated with HBO, eliminating the need for cystectomy.

Conclusion

HBO can be a safe, noninvasive, alternative treatment modality for PTCy-induced HC developing in allogeneic SCT patients.
Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19
Authors: Mazini Loubna , Ezzoubi Mohamed , Malka Gabriel
Published: January 2021

Adipose-derived stem cells (ADSCs) have raised big interest in therapeutic applications in regenerative medicine and appear to fulfill the criteria for a successful cell therapy. Their low immunogenicity and their ability to self-renew, to differentiate into different tissue-specific progenitors, to migrate into damaged sites, and to act through autocrine and paracrine pathways have been altogether testified as the main mechanisms whereby cell repair and regeneration occur. The absence of standardization protocols in cell management within laboratories or facilities added to the new technologies improved at patient’s bedside and the discrepancies in cell outcomes and engraftment increase the limitations on their widespread use by balancing their real benefit versus the patient safety and security. Also, comparisons across pooled patients are particularly difficult in the fact that multiple medical devices are used and there is absence of harmonized assessment assays despite meeting regulations agencies and efficient GMP protocols. Moreover, the emergence of the COVID-19 breakdown added to the complexity of implementing standardization. Cell- and tissue-based therapies are completely dependent on the biological manifestations and parameters associated to and induced by this virus where the scope is still unknown. The initial flow chart identified for stem cell therapies should be reformulated and updated to overcome patient infection and avoid significant variability, thus enabling more patient safety and therapeutic efficiency. The aim of this work is to highlight the major guidelines and differences in ADSC processing meeting the current good manufacturing practices (cGMP) and the cellular therapy-related policies. Specific insights on standardization of ADSCs proceeding at different check points are also presented as a setup for the cord blood and bone marrow.
A bio-inspired geometric model for sound reconstruction
Authors: Boscain Ugo , Prandi Dario , Sacchelli Ludovic , Turco Giuseppina
Published: January 2021

The reconstruction mechanisms built by the human auditory system during sound reconstruction are still a matter of debate. The purpose of this study is to propose a mathematical model of sound reconstruction based on the functional architecture of the auditory cortex (A1). The model is inspired by the geometrical modelling of vision, which has undergone a great development in the last ten years. There are, however, fundamental dissimilarities, due to the different role played by time and the different group of symmetries. The algorithm transforms the degraded sound in an ‘image’ in the time–frequency domain via a short-time Fourier transform. Such an image is then lifted to the Heisenberg group and is reconstructed via a Wilson–Cowan integro-differential equation. Preliminary numerical experiments are provided, showing the good reconstruction properties of the algorithm on synthetic sounds concentrated around two frequencies.
Noisy network attractor models for transitions between EEG microstates
Authors: Creaser Jennifer , Ashwin Peter , Postlethwaite Claire , Britz Juliane
Published: January 2021

The brain is intrinsically organized into large-scale networks that constantly re-organize on multiple timescales, even when the brain is at rest. The timing of these dynamics is crucial for sensation, perception, cognition, and ultimately consciousness, but the underlying dynamics governing the constant reorganization and switching between networks are not yet well understood. Electroencephalogram (EEG) microstates are brief periods of stable scalp topography that have been identified as the electrophysiological correlate of functional magnetic resonance imaging defined resting-state networks. Spatiotemporal microstate sequences maintain high temporal resolution and have been shown to be scale-free with long-range temporal correlations. Previous attempts to model EEG microstate sequences have failed to capture this crucial property and so cannot fully capture the dynamics; this paper answers the call for more sophisticated modeling approaches. We present a dynamical model that exhibits a noisy network attractor between nodes that represent the microstates. Using an excitable network between four nodes, we can reproduce the transition probabilities between microstates but not the heavy tailed residence time distributions. We present two extensions to this model: first, an additional hidden node at each state; second, an additional layer that controls the switching frequency in the original network. Introducing either extension to the network gives the flexibility to capture these heavy tails. We compare the model generated sequences to microstate sequences from EEG data collected from healthy subjects at rest. For the first extension, we show that the hidden nodes ‘trap’ the trajectories allowing the control of residence times at each node. For the second extension, we show that two nodes in the controlling layer are sufficient to model the long residence times. Finally, we show that in addition to capturing the residence time distributions and transition probabilities of the sequences, these two models capture additional properties of the sequences including having interspersed long and short residence times and long range temporal correlations in line with the data as measured by the Hurst exponent.
The identification and determination of toxin genes of Vibrio strains causing hemorrhagic disease on red drum (Sciaenops ocellatus) using PCR
Authors: Yen Pham Thi Hai , Linh Nguyen Quang , Tram Nguyen Duy Quynh
Published: January 2021

Data were collected from 30 strains of Vibrio and sampled on different organs (brain, hemorrhagic site and digestive tract) of Sciaenops ocellatus infection. The results showed that the nucleotide sequences 16S rRNA region are highly similar to those of V. alginolyticus, V. azureus, V. fluvialis, V. natriengens and V. orientalis, which were published on Genbank and other, ranging from 98.05 to 100%. The digestive tract has the most common Vibrio strains (V. alginolyticus [16] V. azureus [7] and V. fluvialis). Thereout, 25 of 30 strains of Vibrio contained 1 to 3 toxin genes, except V. parahaemolyticus. Six parameters were used to measure the DNA polymorphism of 33 homologous DNA sequences in this Vibrio bacteria population. The results indicated that number of separate polymorphic sites (S), total number of mutant sites (Eta), number of haplotype (h), haplotype diversity (Hd), average number of nucleotide differences (k), nucleotide diversity (Pi) were 98 (S), 103 (Eta), 9 (h), 0.887 ± 0.032 (Hd), 25.789 (k) and 17.980 × 10–3 ± 0.003 (Pi), respectively (P < 0,05). The G + C content above 1434 sites positions of nucleotide sequences accounted for 0.542. The phylogenetic tree showed that these strains are divided into six groups. As observed, the appearance of isolated Vibrio on 3 organs of fish (S. ocellatus) hemorrhagic are V. azureus (27,67%), V. alginolyticus (50%), V. orientalis (6,67%) and V. fluvialis (16,67%). Through this result, we found that the diversity of Vibrio species that appeared on the red drum was used in the 16S rRNA region and the presence of toxin genes in these Vibrio species.
Ammonium nitrate regulated the color characteristic changes of pigments in Monascus purpureus M9
Authors: Chen Di , Wang Yurong , Chen Mianhua , Fan Pei , Li Guiling , Wang Changlu
Published: January 2021

Monascus pigments (MPs) with different color characteristics, produced by submerged fermentation of Monascus purpureus M9, have potential application in food industry. In the present study, the effects and regulatory mechanisms of ammonium nitrate (AN) on the color characteristics of MPs were investigated. The concentration of intracellular pigments was significantly decreased when subjected to AN. The hue and lightness value indicated AN altered the total pigments appearance from original red to orange. The HPLC analysis for six major components of MPs showed that the production of rubropunctatin or monascorubrin, was significantly reduced to the undetectable level, whereas the yields of monascin, ankaflavin, rubropunctamine and monascorubramine, were apparently increased with AN supplement. To be noted, via real-time quantitative PCR strategy, the expression level of mppG, closely relative to orange pigments biosynthesis, was significantly down-regulated. However, the expression of mppE, involved in yellow pigments pathway, was up-regulated. Moreover, the broth pH value was dropped to 2.5–3.5 in the fermentation process resulted from AN treatment, along with the increased extracellular polysaccharide biosynthesis. Taken together, the change of MPs categories and amounts by AN might be the driving force for the color characteristics variation in M. purpureus M9. The present study provided useful data for producing MPs with different compositions and modified color characteristics.
On Cesàro and Copson sequence spaces with weights
Authors: Saker S. H. , Abuelwafa Maryam M. , Zidan Ahmed M. , Baleanu Dumitru
Published: January 2021

In this paper, we prove some properties of weighted Cesàro and Copson sequences spaces by establishing some factorization theorems. The results lead to two-sided norm discrete inequalities with best possible constants and also give conditions for the boundedness of the generalized discrete weighted Hardy and Copson operators.
Some new dynamic inequalities with several functions of Hardy type on time scales
Authors: Hamiaz Adnane , Abuelela Waleed , Saker Samir H. , Baleanu Dumitru
Published: January 2021

The aim of this article is to prove some new dynamic inequalities of Hardy type on time scales with several functions. Our results contain some results proved in the literature, which are deduced as limited cases, and also improve some obtained results by using weak conditions. In order to do so, we utilize Hölder’s inequality, the chain rule, and the formula of integration by parts on time scales.
Convergence rate of Euler–Maruyama scheme for SDDEs of neutral type
Authors: Ji Yanting
Published: January 2021

In this paper, we are concerned with the convergence rate of Euler–Maruyama (EM) scheme for stochastic differential delay equations (SDDEs) ofneutral type, where the neutral, drift, and diffusion terms are allowed to be of polynomial growth. More precisely, for SDDEs of neutral type driven by Brownian motions, we reveal that the convergence rate of the corresponding EM scheme is one-half; Whereas for SDDEs of neutral type driven by pure jump processes, we show that the best convergence rate of the associated EM scheme is slower than one-half. As a result, the convergence rate of general SDDEs of neutral type, which is dominated by pure jump process, is slower than one-half.
Sharp blowup rate for NLS with a repulsive harmonic potential
Authors: Zhou Rui
Published: January 2021

In this paper, we are concerned with the blowup solutions of the$L^{2}$L2critical nonlinear Schrödinger equation with a repulsive harmonic potential. By using the results recently obtained by Merle and Raphaël and by Carles’ transform we establish in a quite elementary way universal and sharp upper and lower bounds of the blowup rate for the blowup solutions of the aforementioned equation. As an application, we derive upper and lower bounds on the$L^{r}$Lr-norms of the singular solutions.
Mathematical model of SIR epidemic system (COVID-19) with fractional derivative: stability and numerical analysis
Authors: Alqahtani Rubayyi T.
Published: January 2021

In this paper, we study and analyze the susceptible-infectious-removed (SIR) dynamics considering the effect of health system. We consider a general incidence rate function and the recovery rate as functions of the number of hospital beds. We prove the existence, uniqueness, and boundedness of the model. We investigate all possible steady-state solutions of the model and their stability. The analysis shows that the free steady state is locally stable when the basic reproduction number $R_{0}$R0is less than unity and unstable when$R_{0} > 1$R0>1. The analysis shows that the phenomenon of backward bifurcation occurs when$R_{0}<1$R0<1. Then we investigate the model using the concept of fractional differential operator. Finally, we perform numerical simulations to illustrate the theoretical analysis and study the effect of the parameters on the model for various fractional orders.