bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractMost 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

Abstract
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

AbstractDistinguishing 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

AbstractBackgroundTheapolipoprotein 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.MethodsUsing 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.ResultsWe 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.ConclusionsAPOEε4 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

AbstractBaricitinib 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

Abstract
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

Abstract
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

AbstractBackgroundTo 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 presentationIn 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.ConclusionHBO 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

AbstractAdipose-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

AbstractThe 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

AbstractThe 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

AbstractData 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.