bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous globe subluxation: a case report and review of the literature
Authors: Yadete Tesfaye , Isby Ian , Patel Ketan , Lin Alex 
Published: December 2021

Abstract
Background
Spontaneous globe subluxation (SGS) is an atraumatic anterior dislocation of the eyeball. It is exceedingly rare. Understanding SGS predisposing factors may help uncover its etiology and undertake vision-saving management.

Case presentation
A 48-year-old female presented to the ED with her right eye out of its socket. She reported blurry vision, photophobia, and pain in the affected eye. She was unable to close her right eyelid and was in obvious distress. On arrival, her blood pressure was elevated. Her medical history was notable for hypertension and obesity. On physical examination, extraocular eye movements were not intact, and the globe appeared whole and round. She was also unable to count fingers with the affected eye. There was no visible trauma to the face. Multiple wet gauzes with sterile saline were placed over the displaced eyeball. Direct and even pressure was applied on the globe. Within 30 s, the globe was reduced back in. The patient was able to close her eyelids and reports substantial pain relief with reduction. A CT scan of the orbits was then obtained, demonstrating mild bilateral proptosis. The globes were normal and symmetric. No intraconal or extraconal abscess or infection was seen. There were no intraconal or extraconal masses. There was no acute orbital traumatic injury, no avulsion of the optic nerve, ocular rupture, or retrobulbar hematoma. After reviewing the case with an ophthalmologist, a follow-up appointment with the ophthalmologist was arranged. The patient was discharged on erythromycin ointment. Post-discharge investigation of the CT imaging revealed dilated optic nerve sheaths, tortuosity of the optic nerve, and empty sella.

Conclusions
In addition to causing distress and severe anxiety, SGS poses numerous immediate as well as long-term complications. Traction of the optic nerve and retinal vasculature may potentially cause retinal venous congestion and loss of visual acuity with potential vision loss. In the absence of known risk factors or disease processes, orbital imaging and serological studies for thyroid ophthalmopathy should be considered.
GraphOmics: an interactive platform to explore and integrate multi-omics data
Authors: Wandy Joe , Daly Rónán 
Published: December 2021

Abstract
Background
An increasing number of studies now produce multiple omics measurements that require using sophisticated computational methods for analysis. While each omics data can be examined separately, jointly integrating multiple omics data allows for deeper understanding and insights to be gained from the study. In particular, data integration can be performed horizontally, where biological entities from multiple omics measurements are mapped to common reactions and pathways. However, data integration remains a challenge due to the complexity of the data and the difficulty in interpreting analysis results.

Results
Here we present GraphOmics, a user-friendly platform to explore and integrate multiple omics datasets and support hypothesis generation. Users can upload transcriptomics, proteomics and metabolomics data to GraphOmics. Relevant entities are connected based on their biochemical relationships, and mapped to reactions and pathways from Reactome. From the Data Browser in GraphOmics, mapped entities and pathways can be ranked, sorted and filtered according to their statistical significance (p values) and fold changes. Context-sensitive panels provide information on the currently selected entities, while interactive heatmaps and clustering functionalities are also available. As a case study, we demonstrated how GraphOmics was used to interactively explore multi-omics data and support hypothesis generation using two complex datasets from existing Zebrafish regeneration and Covid-19 human studies.

Conclusions
GraphOmics is fully open-sourced and freely accessible from https://graphomics.glasgowcompbio.org/. It can be used to integrate multiple omics data horizontally by mapping entities across omics to reactions and pathways. Our demonstration showed that by using interactive explorations from GraphOmics, interesting insights and biological hypotheses could be rapidly revealed.
Integrated analysis of DNA methylome and transcriptome reveals the differences in biological characteristics of porcine mesenchymal stem cells
Authors: Feng Zheng , Yang Yalan , Liu Zhiguo , Zhao Weimin , Huang Lei , Wu Tianwen , Mu Yulian 
Published: December 2021

Abstract
Background
Bone marrow (BM) and umbilical cord (UC) are the main sources of mesenchymal stem cells (MSCs). These two MSCs display significant differences in many biological characteristics, yet the underlying regulation mechanisms of these cells remain largely unknown.

Results
BMMSCs and UCMSCs were isolated from inbred Wuzhishan miniature pigs and the first global DNA methylation and gene expression profiles of porcine MSCs were generated. The osteogenic and adipogenic differentiation ability of porcine BMMSCs is greater than that of UCMSCs. A total of 1979 genes were differentially expressed and 587 genes were differentially methylated at promoter regions in these cells. Integrative analysis revealed that 102 genes displayed differences in both gene expression and promoter methylation. Gene ontology enrichment analysis showed that these genes were associated with cell differentiation, migration, and immunogenicity. Remarkably, skeletal system development-related genes were significantly hypomethylated and upregulated, whereas cell cycle genes were opposite in UCMSCs, implying that these cells have higher cell proliferative activity and lower differentiation potential than BMMSCs.

Conclusions
Our results indicate that DNA methylation plays an important role in regulating the differences in biological characteristics of BMMSCs and UCMSCs. Results of this study provide a molecular theoretical basis for the application of porcine MSCs in human medicine.
Comprehensive epigenomic profiling of human alveolar epithelial differentiation identifies key epigenetic states and transcription factor co-regulatory networks for maintenance of distal lung identity
Authors: Zhou B. , Stueve T. R. , Mihalakakos E. A. , Miao L. , Mullen D. , Wang Y. , Liu Y. , Luo J. , Tran E. , Siegmund K. D. , Lynch S. K. , Ryan A. L. , Offringa I. A. , Borok Z. , Marconett C. N. 
Published: December 2021

Abstract
Background
Disruption of alveolar epithelial cell (AEC) differentiation is implicated in distal lung diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung adenocarcinoma that impact morbidity and mortality worldwide. Elucidating underlying disease pathogenesis requires a mechanistic molecular understanding of AEC differentiation. Previous studies have focused on changes of individual transcription factors, and to date no study has comprehensively characterized the dynamic, global epigenomic alterations that facilitate this critical differentiation process in humans.

Results
We comprehensively profiled the epigenomic states of human AECs during type 2 to type 1-like cell differentiation, including the methylome and chromatin functional domains, and integrated this with transcriptome-wide RNA expression data. Enhancer regions were drastically altered during AEC differentiation. Transcription factor binding analysis within enhancer regions revealed diverse interactive networks with enrichment for many transcription factors, including NKX2–1 and FOXA family members, as well as transcription factors with less well characterized roles in AEC differentiation, such as members of the MEF2, TEAD, and AP1 families. Additionally, associations among transcription factors changed during differentiation, implicating a complex network of heterotrimeric complex switching in driving differentiation. Integration of AEC enhancer states with the catalog of enhancer elements in the Roadmap Epigenomics Mapping Consortium and Encyclopedia of DNA Elements (ENCODE) revealed that AECs have similar epigenomic structures to other profiled epithelial cell types, including human mammary epithelial cells (HMECs), with NKX2–1 serving as a distinguishing feature of distal lung differentiation.

Conclusions
Enhancer regions are hotspots of epigenomic alteration that regulate AEC differentiation. Furthermore, the differentiation process is regulated by dynamic networks of transcription factors acting in concert, rather than individually. These findings provide a roadmap for understanding the relationship between disruption of the epigenetic state during AEC differentiation and development of lung diseases that may be therapeutically amenable.
Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift
Authors: Migdał Maciej , Tralle Eugeniusz , Abu Nahia Karim , Bugajski Łukasz , Kędzierska Katarzyna Zofia , Garbicz Filip , Piwocka Katarzyna , Winata Cecilia Lanny , Pawlak Michał 
Published: December 2021

Abstract
Background
Liver fibrosis is a wound-healing response to tissue injury and inflammation hallmarked by the extracellular matrix (ECM) protein deposition in the liver parenchyma and tissue remodelling. Different cell types of the liver are known to play distinct roles in liver injury response. Hepatocytes and liver endothelial cells receive molecular signals indicating tissue injury and activate hepatic stellate cells which produce ECM proteins upon their activation. Despite the growing knowledge on the molecular mechanism underlying hepatic fibrosis in general, the cell-type-specific gene regulatory network associated with the initial response to hepatotoxic injury is still poorly characterized.

Results
In this study, we used thioacetamide (TAA) to induce hepatic injury in adult zebrafish. We isolated three major liver cell types - hepatocytes, endothelial cells and hepatic stellate cells - and identified cell-type-specific chromatin accessibility and transcriptional changes in an early stage of liver injury. We found that TAA induced transcriptional shifts in all three cell types hallmarked by significant alterations in the expression of genes related to fatty acid and carbohydrate metabolism, as well as immune response-associated and vascular-specific genes. Interestingly, liver endothelial cells exhibit the most pronounced response to liver injury at the transcriptome and chromatin level, hallmarked by the loss of their angiogenic phenotype.

Conclusion
Our results uncovered cell-type-specific transcriptome and epigenome responses to early stage liver injury, which provide valuable insights into understanding the molecular mechanism implicated in the early response of the liver to pro-fibrotic signals.
Bioinformatic comparison of Kunitz protease inhibitors in Echinococcus granulosus sensu stricto and E. multilocularis and the genes expressed in different developmental stages of E. granulosus s.s.
Authors: Zhang Hui , Tian Mengxiao , Qi Wenjing , Wu Juan , Zheng Huajun , Guo Gang , Zhang Liang , Ranasinghe Shiwanthi L. , McManus Donald P. , Li Jun , Zhang Wenbao 
Published: December 2021

Abstract
Background

Cystic and alveolar echinococcosis caused by the tapeworms Echinococcus granulosus sensu stricto (s.s.) and E. multilocularis, respectively, are important zoonotic diseases. Protease inhibitors are crucial for the survival of both Echinococcus spp. Kunitz-type inhibitors play a regulatory role in the control of protease activity. In this study,we identified Kunitz-type domain protease inhibitors(KDPIs) present in the genomes of these two tapeworms and analyzed the gene sequences using computational, structural bioinformatics and phylogenetic approaches to evaluate the evolutionary relationships of these genes. Hi-seq transcriptome analysis showed that E. granulosuss.s. KDPIs were differentially expressed in the different developmental stages. We validated some of the genes expressed in adult worm, protoscolex and cyst germinal membrane of E. granulosuss.s. and E. multilocularis by quantitative PCR.

Results
A total of 19 genes from E. multilocularis and 23 genes from E. granulosuss.s. were predicted to be KDPIs with the most containing a single Kunitz-domain. A maximum likelihood method phylogenetic tree indicated that the E. granulosuss.s. and E. multilocularis Kunitz domain peptides were divided into three branches containing 9 clusters. The ratio of positively charged residues and neutral residues are different between E. multilocularis and E. granulosuss.s. KDPIs. We also found that E. multilocularis had higher percentage of sequences containing signal peptides (17/19, 89.47%) than that of E. granulosuss.s. (14/23, 60.87%). Transcript analysis showed all the E. granulosuss.s. KDPI genes were expressed differentially in four developmental stages of the worm. Transcription analysis showed that 9 KDPIs (including EG_07244,EGR_08716 and EGR_10096) were highly upregulated in adult worm, and 2 KDPIs (EG_09268 and EG_09490) were highly expressed in the cyst germinal membrane. Quantitative gene expression analysis(qPCR) of four genes confirmed the expression of these genes. EGR_08716 and its homologous gene (EmuJ_001137000) were highly and specifically expressed in adult worms of the two worms.

Conclusions
A total 19 and 23 KDPIs were identified in the genomes of E. multilocularis and E. granulosus s.s. , respectively. The differential expression of these KDPIs in different stages may indicate their different roles in the different hosts. The difference in characterization of KDPIs may be associated with the different pathology of metacestode stage of these two parasites.
Design and performance of a bovine 200 k SNP chip developed for endangered German Black Pied cattle (DSN)
Authors: Neumann Guilherme B. , Korkuć Paula , Arends Danny , Wolf Manuel J. , May Katharina , Reißmann Monika , Elzaki Salma , König Sven , Brockmann Gudrun A. 
Published: December 2021

Abstract
Background
German Black Pied cattle (DSN) are an endangered dual-purpose breed which was largely replaced by Holstein cattle due to their lower milk yield. DSN cattle are kept as a genetic reserve with a current herd size of around 2500 animals. The ability to track sequence variants specific to DSN could help to support the conservation of DSN’s genetic diversity and to provide avenues for genetic improvement.

Results
Whole-genome sequencing data of 304 DSN cattle were used to design a customized DSN200k SNP chip harboring 182,154 variants (173,569 SNPs and 8585 indels) based on ten selection categories. We included variants of interest to DSN such as DSN unique variants and variants from previous association studies in DSN, but also variants of general interest such as variants with predicted consequences of high, moderate, or low impact on the transcripts and SNPs from the Illumina BovineSNP50 BeadChip. Further, the selection of variants based on haplotype blocks ensured that the whole-genome was uniformly covered with an average variant distance of 14.4 kb on autosomes. Using 300 DSN and 162 animals from other cattle breeds including Holstein, endangered local cattle populations, and also a Bos indicus breed, performance of the SNP chip was evaluated. Altogether, 171,978 (94.31%) of the variants were successfully called in at least one of the analyzed breeds. In DSN, the number of successfully called variants was 166,563 (91.44%) while 156,684 (86.02%) were segregating at a minor allele frequency > 1%. The concordance rate between technical replicates was 99.83 ± 0.19%.

Conclusion
The DSN200k SNP chip was proved useful for DSN and other Bos taurus as well as one Bos indicus breed. It is suitable for genetic diversity management and marker-assisted selection of DSN animals. Moreover, variants that were segregating in other breeds can be used for the design of breed-specific customized SNP chips. This will be of great value in the application of conservation programs for endangered local populations in the future.
Comparison of novel rapid diagnostic of blood culture identification and antimicrobial susceptibility testing by Accelerate Pheno system and BioFire FilmArray Blood Culture Identification and BioFire FilmArray Blood Culture Identification 2 panels
Authors: Sze Dorothy T. T. , Lau Candy C. Y. , Chan Tsz-Ming , Ma Edmond S. K. , Tang Bone S. F. 
Published: December 2021

AbstractBackgroundConventional turnaround time (TAT) for positive blood culture (PBC) identification (ID) and antimicrobial susceptibility testing (AST) is 2–3 days. We evaluated the TAT and ID/AST performance using clinical and seeded samples directly from PBC bottles with different commercial approaches: (1) Accelerate Pheno® system (Pheno) for ID/AST; (2) BioFire® FilmArray® Blood Culture Identification (BCID) Panel and/ or BCID2 for ID; (3) direct AST by VITEK® 2 (direct AST); and (4) overnight culture using VITEK® 2 colony AST.ResultsA total of 141 PBC samples were included in this evaluation. Using MALDI-TOF (Bruker MALDI Biotyper) as the reference method for ID, the overall monomicrobial ID sensitivity/specificity are as follows: Pheno 97.9/99.9%; BCID 100/100%; and BCID2 100/100%, respectively. For AST performance, broth microdilution (BMD) was used as the reference method. For gram-negatives, overall categorical and essential agreements (CA/EA) for each method were: Pheno 90.3/93.2%; direct AST 92.6/88.5%; colony AST 94.4/89.5%, respectively. For gram-positives, the overall CA/EAs were as follows: Pheno 97.2/98.89%; direct AST 97.2/100%; colony AST 97.2/100%, respectively. The BCID/BCID2 and direct AST TATs were around 9–20 h (1/9-19 h for ID with resistance markers/AST), with 15 min/sample hands-on time. In comparison, Pheno TATs were around 8–10 h (1.5/7 h for ID/AST) with 2 min/sample hands-on time, maintains a clinically relevant fast report of antibiotic minimal inhibitory concentration (MIC) and allows for less TAT and hands-on time.ConclusionIn conclusion, to the best of our knowledge, this is the first study conducted as such in Asia; all studied approaches achieved satisfactory performance, factors such as TAT, panel of antibiotics choices and hands-on time should be considered for the selection of appropriate rapid ID and AST of PBC methods in different laboratory settings.
Seed development in Paeonia ostii (Paeoniaceae), with particular reference to embryogeny
Authors: Zhang Keliang , Cao Weizhang , Baskin Jerry M. , Baskin Carol C. , Sun Jing , Yao Linjun , Tao Jun 
Published: December 2021

Abstract
Background
Seeds of Paeonia ostii have been proposed as a source of raw material for the production of edible oil; however, lack of information about the developmental biology of the seeds hampers our ability to use them. Our aim was to investigate development of the seed coat, endosperm and embryo of P. ostii in relation to timing of accumulation of nutrient reserves from pollination to seed maturity. Ovules and developing seeds of P. ostii were collected at various stages of development from zygote to maturity. Seed fresh mass, dry mass, germination, moisture, soluble sugars, starch, protein and oil content were determined. Ontogeny of seeds including embryo, endosperm and seed coat were analyzed histologically.

Results
The ovule of P. ostii is anatropous, crassinucellate and bitegmic. The zygote begins to divide at about 5 days after pollination (DAP), and the division is not accompanied by cell wall formation. By 25 DAP, the proembryo begins to cellularize. Thereafter, several embryo primordia appear at the surface of the cellularized proembryo, but only one matures. Endosperm development follows the typical nuclear type. The seed coat is derived from the outer integument. During seed development, soluble sugars, starch and crude fat content increased and then decreased, with maximum contents at 60, 80 and 100 DAP, respectively. Protein content was relatively low compared with soluble sugars and crude fat, but it increased throughout seed development.

Conclusions
During seed development in P. ostii, the seed coat acts as a temporary storage tissue. Embryo development of P. ostii can be divided into two stages: a coenocytic proembryo from zygote (n + n) that degenerates and a somatic embryo from peripheral cells of the proembryo (2n → 2n). This pattern of embryogeny differs from that of all other angiosperms, but it is similar to that of gymnosperms.
Transcatheter closure of ventricular septal rupture with prolonged support of intra-aortic balloon pump after primary PCI: a case report
Authors: Yang Chuan , Sun Yong , Zou Deling , Sun Zhaoqing , Zhang Xinzhong , Su Guangsheng , Qi Jing , Pang Wenyue 
Published: December 2021

Abstract
Background
Ventricular septal rupture (VSR) is a rare but severe complication of acute myocardial infarction (AMI). For such cases, surgical repair is recommended by major guidelines, but not always possible for such cases.

Case presentation
A 72-year-old man presented to the emergency room. ECG showed the ST-segment was elevated by 2–3 mm in lead II, III, and aVF, with Q-waves. Coronary angiography (CAG) showed multi-vessel disease with a total occlusion of the right coronary artery (RCA) and severe stenosis of the left anterior descending artery (LAD). A diagnosis of acute inferior myocardial infarction was made. VSR occurred immediately after percutaneous coronary intervention (a 2.5 × 20 mm drug-eluting stent implanted in RCA), and the patient developed cardiogenic shock. An intra-aortic balloon pump (IABP) was used to stabilize the hemodynamics. Transthoracic echocardiography (TTE) revealed an 11.4-mm left-to-right shunt in the interventricular septum. An attempt was made to reduce the IABP augmentation ratio for weaning on day 12 but failed. Transcatheter closure was conducted using a 24-mm double-umbrella occluder on day 28. The patient was weaned from IABP on day 31 and underwent secondary PCI for LAD lesions on day 35. The patient was discharged on day 41. Upon the last follow-up 6 years later, CAG and TTE revealed no in-stent restenosis, no left-to-right shunt, and 51% left ventricular ejection fraction.

Conclusions
Prolonged implementation of IABP can be a viable option to allow deferred closure of VSR in AMI patients, and transcatheter closure may be considered as a second choice for the selected senior and vulnerable patients, but the risk is still high.
Prognostic value of diagnostic scales in community-acquired sepsis mortality at an emergency service. Prognosis in community-adquired sepsis
Authors: Clar Jorge , Oltra María Rosa , Benavent Raquel , Pinto Carolina , Ruiz Adrian , Sanchez Maria Teresa , Noceda Jose , Redon Josep , Forner Maria Jose 
Published: December 2021

Abstract
Objectives
To asses the prognostic value of diagnostic scales in mortality of community-adquired sepsis and added value of additional parameters.

Methods
Prospective observational study of patients with community-adquired sepsis in the Emergency Room of University Hospital. The study population were patients presented in the Emergency Room with confirmed infection and practicians sepsis diagnosis. Demographics, triage vital signs, inhaled oxygen fraction, inflammatory markers, biochemistry, all-cause mortality during hospitalization and three months after were recorded. Prognostic value of qSOFA, NEWS, SOFA, SIRS, and amplified scales were calculated by using logistic regression and ROC curves.

Results
201 patients, 54% male, average age 77±11,2 years were included. Sixty-three (31.5%) died during hospitalization and 24 (12%) three months after discharge. At the time of admission vital signs related with in-hospital mortality were Glasgow Coma Scale <13, respiratory rate ≥22 bpm, temperature, oxygen desaturation, high flow oxygen therapy and heart rate. Patients dead in-hospital had lower PaCO2, higher lactate, glucose and creatinine. Greater predictive capacity of the scales, from higher to lower, was: qSOFA, NEWS2, SOFA and SIRS. Amplified scales with lactate >2mg/dl, glucose, blood level >190mg/dl and PaCO2 <35mmHg improved predictive value.

Conclusion
Amplified-qSOFA and amplified-NEWS2 scales at Emergency Department may offer a better prognostic of septic patients mortality.