bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-107 affects cartilage matrix degradation in the pathogenesis of knee osteoarthritis by regulating caspase-1
Authors: Qian Jiatian , Fu Peiliang , Li Shiao , Li Xiang , Chen Yancheng , Lin Zhenen 
Published: January 2021

AbstractBackgroundKnee osteoarthritis (KOA) seriously affects the quality of life of KOA patients. This study aimed to investigate whether miR-107 could regulate KOA through pyroptosis to affect collagen protein secreted by chondrocytes through IL-1β.MethodsThe proliferation of chondrocytes was detected by CCK-8 assay. RT-qPCR analysis was used to identify miR-107 expression and transfection effects. The expression of Col II, IL-1β, IL-18, and MMP13 in supernatant of chondrocytes or chondrocytes was detected by ELISA assay and western blot analysis. The pyroptosis of chondrocytes was analyzed by TUNEL assay and the expression of pyroptosis-related proteins was analyzed by western blot. Luciferase reporter assay confirmed the relation of miR-107 to caspase-1.ResultsThe proliferation of chondrocytes was decreased after LPS induction and further decreased by treatment of ATP. Single LPS treatment for chondrocytes downregulated the Col II expression while upregulated the expression of IL-1β, IL-18, and MMP-13, which was further changed by ATP treatment. miR-107 expression was decreased in chondrocytes induced by LPS and further decreased in chondrocytes induced by LPS and ATP. In addition, miR-107 overexpression increased the proliferation and decreased the pyroptosis of chondrocytes induced by LPS and ATP. miR-107 overexpression upregulated the Col II expression while down-regulated the expression of IL-1β, IL-18, and MMP-13 in supernatant of chondrocytes or chondrocytes induced by LPS and ATP. miR-107 overexpression down-regulated the expression of caspase-1, c-caspase-1, GSDMD-N, and TLR4 in chondrocytes induced by LPS and ATP. Furthermore, miR-107 directly targeted caspase-1.ConclusionsmiR-107 can protect against KOA by downregulating caspase-1 to decrease pyroptosis, thereby promoting collagen protein secreted by chondrocytes by down-regulating IL-1β.
A biomechanics study on ligamentous injury in anterior-posterior compression type II pelvic injury
Authors: Kong Jianzhong , Chu Yupeng , Zhou Chengwei , Sun Shuaibo , Bao Guodong , Xu Yu , Guo Xiaoshan , Shui Xiaolong 
Published: January 2021

Abstract
Background
Anterior-posterior compression (APC) type II pelvis fracture is caused by the destruction of pelvic ligaments. This study aims to explore ligaments injury in APC type II pelvic injury.

Method
Fourteen human cadaveric pelvis samples with sacrospinous ligament (SPL), sacrotuberous ligament (SBL), anterior sacroiliac ligament (ASL), and partial bone retaining unilaterally were acquired for this study. They were randomly divided into hemipelvis restricted and unrestricted groups. We recorded the separation distance of the pubic symphysis and anterior sacroiliac joint, external rotation angle, and force when ASL ruptured. We observed the external rotation damage to the pelvic bone and ligaments.

Result
When ASL failed, there was no significant difference in pubic symphysis separation (28.6 ± 8.4 mm to 23.6 ± 8.2 mm, P = 0.11) and anterior sacroiliac joint separation (11.4 ± 3.8 mm to 9.7 ± 3.9 mm, P = 0.30) between restricted and unrestricted groups. The external rotation angle (33.9 ± 5.5° to 48.9 ± 5.2°, P < 0.01) and force (553.9 ± 82.6 N to 756.6 ± 41.4 N, P < 0.01) were significantly different. Pubic symphysis separation between two groups ranged from 14 to 40 mm. In the restricted group, both SBL and SPL were injured. SPL ruptured first, and then SBL and the interosseous sacroiliac ligament were damaged while the posterior ligament remained unharmed. In the unrestricted group, interosseous sacroiliac ligament and posterior sacroiliac ligaments were damaged, while SBL and SPL were not. When the ASL, SBL, and SPL all failed, pubic symphysis and anterior sacroiliac joint separation between two groups increased significantly (from 28.6 ± 8.4 to 42.0 ± 7.6 mm, 11.4 ± 3.8 to 16.7 ± 4.2 mm respectively, all P < 0.05).

Conclusion
Pelvic external rotation injury is either hemipelvic restricted or unrestricted, which can result in different outcomes. When the ASL ruptures, the unrestricted group needs greater external rotation angle and force, without SBL or SPL injury, while both SBL and SPL were injured in another group. When ASL fails in two groups, pubic symphysis separation fluctuates considerably. Finally, when the ASL ruptures, SBL and SPL may be undamaged.
The patient journey toward a diagnosis of hereditary transthyretin (ATTRv) amyloidosis
Authors: Vera-Llonch Montserrat , Reddy Sheila R. , Chang Eunice , Tarbox Marian H. , Pollock Michael 
Published: January 2021

Abstract
Background
Despite emerging treatments for hereditary transthyretin (ATTRv) amyloidosis, the disease is often misdiagnosed, with reported diagnostic delays of up to several years. Knowledge of the patient journey leading up to diagnosis may help to promote earlier intervention. The study’s objective was to examine patient clinical characteristics and healthcare utilization prior to ATTRv amyloidosis diagnosis.

Methods
Patients ≥ 18 years and newly diagnosed with ATTRv amyloidosis identified in IBM® MarketScan® Commercial and Medicare Supplemental data using a claims-based algorithm as follows: diagnosis required ≥ 1 medical claim with relevant amyloidosis diagnosis code (ICD-10-CM: E85.0-.4, E85.89, E85.9; excludes light chain and wild type) during identification (ID) period (1/1/2016–12/31/2017), and ≥ 1 occurrence of qualifying criteria during 2011–2017: ≥ 15 days diflunisal use without > 30-day gap, liver transplant, or claim with specific codes E85.1 or E85.2. The index date was defined as the date of first claim with amyloidosis diagnosis code in ID period. Patients had continuous enrollment ≥ 5 years pre-index date (look-back period). Occurrence of selected comorbid conditions and symptoms and healthcare utilization (testing, emergency department visits and hospitalization) measured during the look-back period; demographics, physician specialty, and Charlson comorbidity index (CCI) measured 1 year pre-index. Patients with an ICD-9/10 amyloidosis code during the look-back period were excluded. An ATTRv-free reference cohort was created from a random sample of enrollees who lacked any diagnosis of amyloidosis and matched 3:1 to ATTRv patients on age, gender, and region to provide reference values; same index and enrollment requirement as match.

Results
For the 141 qualifying patients with ATTRv and 423 matched controls, mean (standard deviation) age was 62.5 (14.2) years and 53.9% were female. Mean CCI for ATTRv cohort was 2.7 (3.0) versus 1.1 (1.9) among controls. Selected comorbidities, testing, visits, and hospitalization were common among patients with ATTRv during the look-back period with higher rates versus controls.

Conclusions
Patients with ATTRv amyloidosis experience multiple neurological, cardiovascular, and other clinical manifestations, testing, and hospitalization prior to diagnosis. Occurrence of potential markers of illness is most common in the year before diagnosis.
Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients
Authors: Sklar Michael Chaim , Madotto Fabiana , Jonkman Annemijn , Rauseo Michela , Soliman Ibrahim , Damiani L. Felipe , Telias Irene , Dubo Sebastian , Chen Lu , Rittayamai Nuttapol , Chen Guang-Qiang , Goligher Ewan C. , Dres Martin , Coudroy Remi , Pham Tai , Artigas Ricard M. , Friedrich Jan O. , Sinderby Christer , Heunks Leo , Brochard Laurent 
Published: January 2021

AbstractBackgroundIn patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity.MethodsProspective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering.ResultsSeventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0–50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering.ConclusionLow levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity.Trial RegistrationClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.
Uncovering deeply conserved motif combinations in rapidly evolving noncoding sequences
Authors: Ross Caroline Jane , Rom Aviv , Spinrad Amit , Gelbard-Solodkin Dikla , Degani Neta , Ulitsky Igor 
Published: January 2021

Abstract
Background
Animal genomes contain thousands of long noncoding RNA (lncRNA) genes, a growing subset of which are thought to be functionally important. This functionality is often mediated by short sequence elements scattered throughout the RNA sequence that correspond to binding sites for small RNAs and RNA binding proteins. Throughout vertebrate evolution, the sequences of lncRNA genes changed extensively, so that it is often impossible to obtain significant alignments between sequences of lncRNAs from evolutionary distant species, even when synteny is evident. This often prohibits identifying conserved lncRNAs that are likely to be functional or prioritizing constrained regions for experimental interrogation.

Results
We introduce here LncLOOM, a novel algorithmic framework for the discovery and evaluation of syntenic combinations of short motifs. LncLOOM is based on a graph representation of the input sequences and uses integer linear programming to efficiently compare dozens of sequences that have thousands of bases each and to evaluate the significance of the recovered motifs. We show that LncLOOM is capable of identifying specific, biologically relevant motifs which are conserved throughout vertebrates and beyond in lncRNAs and 3′UTRs, including novel functional RNA elements in the CHASERR lncRNA that are required for regulation of CHD2 expression.

Conclusions
We expect that LncLOOM will become a broadly used approach for the discovery of functionally relevant elements in the noncoding genome.
A rapid thioacidolysis method for biomass lignin composition and tricin analysis
Authors: Chen Fang , Zhuo Chunliu , Xiao Xirong , Pendergast Thomas H. , Devos Katrien M. 
Published: January 2021

AbstractBackgroundBiomass composition varies from plant to plant and greatly affects biomass utilization. Lignin is a heterogeneous phenolic polymer derived mainly fromp-coumaryl, coniferyl, and sinapyl alcohols and makes up to 10–25% of lignocellulosic biomass. Recently, tricin, anO-methylated flavone, was identified as a lignin monomer in many grass species. Tricin may function as a nucleation site for lignification and is advocated as a novel target for lignin engineering to reduce lignin content and improve biomass digestibility in grasses. Thioacidolysis is an analytical method that can be adapted to analyze both lignin monomeric composition and tricin content in the lignin polymer. However, the original thioacidolysis procedure is complex, laborious, and time consuming, making it difficult to be adopted for large-scale screening in biomass research. In this study, a modified, rapid higher throughput thioacidolysis method was developed.ResultsIn combination with gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS), the modified thioacidolysis method can be used to simultaneously characterize the lignin composition and tricin content using 2–5 mg of dry samples. The modified method eliminates the solvent extraction and drastically improves the throughput; 80 samples can be processed in one day per person. Our results indicate that there is no significant difference in the determination of lignin S/G ratio and tricin content between the original and modified methods.ConclusionsA modified thioacidolysis protocol was established. The results demonstrate that the modified method can be used for rapid, high-throughput, and reliable lignin composition and tricin content analyses for screening transgenic plants for cell wall modifications or in large-scale genome-wide association studies (GWAS).
Potential vectors of Leishmania spp. in an Atlantic Forest conservation unit in northeastern Brazil under anthropic pressure
Authors: Pinheiro Marcos Paulo Gomes , Silva-Inacio Cássio Lázaro , Silva Marcel Miranda de Medeiros , Araújo Paulo Sérgio Fagundes de , Ximenes Maria de Fátima Freire de Melo 
Published: January 2021

AbstractBackgroundPhlebotomines are a group of insects which include vectors of theLeishmaniaparasites that cause visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL), diseases primarily affecting populations of low socioeconomic status. VL in Brazil is caused byLeishmania infantum, with transmission mainly attributed toLutzomyia longipalpis, a species complex of sand fly, and is concentrated mainly in the northeastern part of the country. CL is distributed worldwide and occurs in five regions of Brazil, at a higher incidence in the north and northeast regions, with etiological agents, vectors, reservoirs and epidemiological patterns that differ from VL. The aim of this study was to determine the composition, distribution and ecological relationships of phlebotomine species in an Atlantic Forest conservation unit and nearby residential area in northeastern Brazil.MethodsCenters for Disease Control and Shannon traps were used for collections, the former at six points inside the forest and in the peridomestic environment of surrounding residences, three times per month for 36 months, and the latter in a forest area, once a month for 3 months. The phlebotomines identified were compared with climate data using simple linear correlation, Pearson’s correlation coefficient and cross-correlation. The estimate of ecological parameters was calculated according to the Shannon-Wiener diversity index, standardized index of species abundance and the dominance index.ResultsA total of 75,499 phlebotomines belonging to 11 species were captured in the CDC traps, the most abundant beingEvandromyia walkeri,Psychodopygus wellcomeiandLu. longipalpis.Evandromyia walkeriabundance was most influenced by temperature at collection time and during the months preceding collection and rainfall during the months preceding collection.Psychodopygus wellcomeiabundance was most affected by rainfall and relative humidity during the collection month and the month immediately preceding collection time.Lutzomyia longipalpisabundance showed a correlation with temperature and the rainfall during the months preceding collection time. The Shannon trap contained a total of 3914 phlebotomines from these different species.Psychodopygus wellcomei, accounting for 91.93% of the total, was anthropophilic and active mainly at night.ConclusionsMost of the species collected in the traps were seasonal and exhibited changes in their composition and population dynamics associated with local adaptions. The presence of vectorsPs. wellcomeiandLu. longipalpisunderscore the epidemiological importance of these phlebotomines in the conservation unit and surrounding anthropized areas. Neighboring residential areas should be permanently monitored to prevent VL or CL transmission and outbreaks.Graphical Abstract
Analysis of an Ebola virus disease survivor whose host and viral markers were predictive of death indicates the effectiveness of medical countermeasures and supportive care
Authors: Bosworth Andrew , Rickett Natasha Y. , Dong Xiaofeng , Ng Lisa F. P. , García-Dorival Isabel , Matthews David A. , Fletcher Tom , Jacobs Michael , Thomson Emma C. , Carroll Miles W. , Hiscox Julian A. 
Published: January 2021

Abstract
Background
Ebola virus disease (EVD) is an often-fatal infection where the effectiveness of medical countermeasures is uncertain. During the West African outbreak (2013–2016), several patients were treated with different types of anti-viral therapies including monoclonal antibody-based cocktails that had the potential to neutralise Ebola virus (EBOV). However, at the time, the efficacy of these therapies was uncertain. Given the scale of the outbreak, several clinical phenotypes came to the forefront including the ability of the same virus to cause recrudescence in the same patient—perhaps through persisting in immune privileged sites. Several key questions remained including establishing if monoclonal antibody therapy was effective in humans with severe EVD, whether virus escape mutants were selected during treatment, and what is the potential mechanism(s) of persistence. This was made possible through longitudinal samples taken from a UK patient with EVD.

Methods
Several different sample types, plasma and cerebrospinal fluid, were collected and sequenced using Illumina-based RNAseq. Sequence reads were mapped both to EBOV and the human genome and differential gene expression analysis used to identify changes in the abundance of gene transcripts as infection progressed. Digital Cell Quantitation analysis was used to predict the immune phenotype in samples derived from blood.

Results
The findings were compared to equivalent data from West African patients. The study found that both virus and host markers were predictive of a fatal outcome. This suggested that the extensive supportive care, and most likely the application of the medical countermeasure ZMab (a monoclonal antibody cocktail), contributed to survival of the UK patient. The switch from progression to a ‘fatal’ outcome to a ‘survival’ outcome could be seen in both the viral and host markers. The UK patient also suffered a recrudescence infection 10 months after the initial infection. Analysis of the sequencing data indicated that the virus entered a period of reduced or minimal replication, rather than other potential mechanisms of persistence—such as defective interfering genomes.

Conclusions
The data showed that comprehensive supportive care and the application of medical countermeasures are worth pursuing despite an initial unfavourable prognosis.
Association study between immune-related miRNAs and mixed connective tissue disease
Authors: Stypińska Barbara , Lewandowska Aleksandra , Felis-Giemza Anna , Olesińska Marzena , Paradowska-Gorycka Agnieszka 
Published: January 2021

Abstract
Background
Mixed connective tissue disease (MCTD) is a rare condition that is distinguished by the presence of specific U1-RNP antibodies. Information about its etiopathology and diagnostics is still unclear. miRNAs such as miR-146, miR-155, and miR-143 emerged as key regulators of the immune system, known to be involved in the development of autoimmune diseases and cancers. We performed an association study between immune-related miRNAs and MCTD severity and susceptibility.

Methods
A total of 169 MCTD patients and 575 healthy subjects were recruited to the case–control study. The miRNA polymorphisms were genotyped using TaqMan SNP genotyping assay. TNF-α, IL-6, and IFN-γ levels in serum were determined using ELISA. qRT-PCR of TRAF6, IRAK1, and microRNAs was performed using Taqman miRNA assays and TaqMan Gene Expression Assays.

Results
miR-146a rs2910164 G allele and GG genotype as well as miR-143 rs713147 A allele were more frequent in healthy subjects than in MCTD patients. miR-146a rs2910164 CC genotype and miR-143 T-rs353299*T-rs353291*T-rs713147*G-rs353298 and C-rs353299*C-rs353291*T-rs713147*A-rs353298 haplotypes were associated with MCTD susceptibility. miR-146a rs2910164 C/T was associated with scleroderma and lymphadenopathy. miR-143 rs353299 C/T was associated with swollen fingers or hands, the presence of enlarged lymph nodes, and pericarditis/pleuritis. miR-143 rs353298 A/G was associated with the occurrence of pericarditis/pleuritis and scleroderma. miR-143 rs353291 T/C showed association with pericarditis/pleuritis. The serum TNF-α, IFN-γ, and IL-6 levels were significantly higher in MCTD patients compared to healthy subjects. miR-143 SNPs were associated with higher proinflammatory cytokine concentration in serum only in healthy controls. IRAK1 and TRAF6 expression were higher in the MCTD patients compared to controls.

Conclusions
The results of our case–control study indicate the possible significance of miR-146a and miR-143/145 in the susceptibility and clinical picture of MCTD.
MicroRNA-320a: an important regulator in the fibrotic process in interstitial lung disease of systemic sclerosis
Authors: Li Yiqun , Huang Jing , Hu Chaojun , Zhou Jiaxin , Xu Dong , Hou Yong , Wu Chanyuan , Zhao Jiuliang , Li Mengtao , Zeng Xiaofeng , Liu Changzheng , Wang Qian , Zhao Yan 
Published: January 2021

Abstract
Background
Systemic sclerosis (SSc) is an acquired autoimmune disorder characterized by excessive accumulation of collagen and progressive tissue fibrosis. Although interstitial lung disease (ILD) complicates the majority of SSc patients and is the leading cause of death, its pathogenesis remains largely unclear. In the current study, we aimed to evaluate the role of microRNAs in SSc-ILD.

Methods
miRNA expression patterns were assessed by miRNA array and real-time PCR from serum and PBMCs of SSc-ILD patients and healthy controls. Bleomycin-induced SSc-ILD mouse model was used to verify the miRNA expression in the lung tissue. The function of miRNAs in pulmonary fibroblasts was assessed using miRNA inhibitors, and mimics.

Results
miR-320a was significantly downregulated in both SSc-ILD patients and mouse models. The inhibition or overexpression of miR-320a in human pulmonary fibroblasts significantly affected the protein expression of type I collagen. Luciferase reporter assay, RT-PCR, and western blot analysis identified TGFBR2 and IGF1R as direct targets of miR-320a. Upon TGF-β stimulation, the expression of miR-320a and collagen genes were significantly upregulated.

Conclusion
miR-320a, together with its target genes, TGFBR2 and IGF1R, constituted a complex regulatory network, and played an important role in the fibrotic process of SSc-ILD. Investigation of more detailed mechanisms of miR-320a-mediated regulation of collagen expression may provide new therapeutic strategies for SSc-ILD.