bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bactericidal Activity of Serum By Brucella Abortus RB51 Outer Membrane Protein’s Combined By Brucella Abortus S99 Lipopolysaccharide Induction
Authors: Attar Adeleh , Afkhami Hamed , Khaledi Mansoor , S.Sadati Mahdi 
Published: February 2021

Abstract
Brucellosis vaccines are designed to induce the cellular immunity. An effective brucellosis vaccine is one that could induce both cellular and humoral immunity. Serum Bactericidal Assay(SBA) is an important method for the determination of vaccine humoral immunity. This study is the first to observe humoral immunity in brucellosis by SBA. Extracted B.abortus LPS and OMP’s were injected to rabbits. Group1 injected by 25µg of LPS, Group2 injected by 50µg of OMP ‘s and Group3 injected by 1ml of combined vaccine, 3 times every 2 weeks. The Groups were challenged with B.abortus 544 in the second injection. Sera were separated 2 weeks after the last injection. SBA was performed, each well was streak cultured into a plate of Brucella Agar. Colony count was done for each plate. Results have shown, the third injection of the combined vaccine, had the highest titer of 1/64, and the efficacy of the vaccine was %87.71.
Multi-scale Observation and Data-driven Modeling of Magnetic Reconnection in Flaring Chromospheric Plasmas on the Sun
Authors: Yan Xiaoli , Xue Zhike , Jiang Chaowei , Priest Eric , Kliem Bernhard , Yang Liheng , Wang Jincheng , Kong Defang , Song Yongliang , Feng Xueshang , Liu Zhong 
Published: February 2021

Abstract
Magnetic reconnection is a multi-faceted process of energy conversion in astrophysical, space and laboratory plasmas that operates at microscopic scales but has macroscopic drivers and consequences. Solar flares present a key laboratory for its study, leaving imprints of the microscopic physics in radiation spectra and allowing the macroscopic evolution to be imaged, yet a full observational characterization remains elusive. Here we combine high resolution imaging and spectral observations of a solar flare at multiple wavelengths with data-driven magnetohydrodynamic modeling to study the dynamics of the involved plasma from the current sheet to the plasmoid scale. The flare resulted from the interaction of a twisted filament and chromospheric fibrils. By inferring the reconnection to be fast and mediated by plasmoids, the relevance of this reconnection mode is found to extend beyond hot flare plasmas to such cool structures in the chromosphere, which have many analogs in astrophysical objects.
Molecular Analysis Revealed that Namibian Cheetahs (Acinonyx Jubatus) are definitive hosts of a so far undescribed Besnoitia species
Authors: Schares Gereon , Joeres Maike , Rachel Franziska , Tuschy Mareen , Czirják Gábor Á. , Maksimov Pavlo , Conraths Franz J. , Wachter Bettina 
Published: February 2021

Abstract
Background: Besnoitia darlingi, B. neotomofelis and B. oryctofelisi are closely related coccidian parasites with felids as definitive hosts. These parasites use a variety of animal species as intermediate hosts. North American opossums (Didelphis virginiana), North American southern plains woodrats (Neotoma micropus) and South American domestic rabbits (Oryctolagus cuniculus) are intermediate hosts of B. darlingi, B. neotomofelis and B. oryctofelisi, respectively. Based on conserved regions in the Internal Transcribed Spacer-1 (ITS-1) sequence of the ribosomal DNA (rDNA), a real-time PCR for a sensitive detection of these Besnoitia spp. in tissues of intermediate hosts and faeces of definitive hosts has recently been established. Available sequence data suggest that species such as B. akodoni and B. jellisoni are also covered by this real-time PCR. It has been hypothesised that additional Besnoitia spp. exist worldwide, which are closely related to B. darlingi or B. darlingi-like parasites (B. neotomofelis, B. oryctofelisi, B. akodoni or B. jellisoni). Related but not closely related to these species is B. besnoiti, the cause of bovine besnoitiosis.Methods: Faecal samples from two free-ranging cheetahs (Acinonyx jubatus) from Namibia that had previously tested positive for coccidian parasites by coproscopy, were used for this study. A conventional PCR verified the presence of coccidian parasite DNA. To clarify the identity of these coccidia, the faecal DNA samples were further characterised by species-specific PCRs and Sanger sequencing.Results: One of the samples tested positive for B. darlingi or B. darlingi-like parasites by real-time PCR, while no other coccidian parasites including Toxoplasma gondii, Hammondia hammondi, H. heydorni, B. besnoiti, and Neospora caninum were detected in the two samples. The rDNA of the B. darlingi-like parasite was amplified and partially sequenced. Comparison with existing sequences in GenBank revealed a close relationship to other Besnoitia spp., but showed also clear divergences. Conclusions: Our results suggest that a so far unknown Besnoitia species exists in Namibian wildlife, which is closely related to B. darlingi, B. neotomofelis, B. oryctofelisi, B. akodoni or B. jellisoni. The cheetah appears to be the definitive host of this newly discovered parasite, while a prey species of the cheetah may act as intermediate hosts.
Breast Cancer Incidence and Early Diagnosis in a Family History Risk and Prevention Clinic: 33-Year Experience in 14,311 Women
Authors: Evans D. Gareth R. , Howell Sacha J , Gandhi Ashu , Veen Elke M van , Woodward Emma R , Harvey James , Barr Lester , Wallace Andrew , Lalloo Fiona , Wilson Mary , Hurley Emma , Lim Yit , Maxwell Anthony J , Harkness Elaine F. , Howell Anthony 
Published: February 2021

Abstract
Purpose:Women at increased familial breast cancer risk have been offered screening starting at an earlier age and increased frequency than national Screening Programmes for over 30years. There are limited data on longer-term largescale implementation of this approach on cancer diagnosis.Methods:Women at our institution at ≥17% lifetime breast cancer risk have been offered enhanced screening with annual mammography starting at age 35 or 5-years younger than youngest affected relative, with upper age limit 50 for moderate and 60 for high-risk. Breast cancer pathology, stage and receptor status were assessed as well as survival from cancer diagnosis by Kaplan-Meier analysis.Results:Overall 14,311 women were seen and assessed for breast cancer risk, with 649 breast cancers occurring in 129,119.5 years follow up (post-prevalent annual incidence=4.55/1,000). Of 323/394 invasive breast cancers occurring whilst on enhanced screening, most were LN negative (72.9%), T1 (≤20mm,73.2%) and stage-1 (61.4%). Ten-year breast cancer specific survival was 91.3%(95%CI=87.4–94.0) significantly better than the 75.9%(95%CI=74.9-77.0) published for England in 2013-2017. As expected, survival was significantly better for women with screen detected cancers(p<0.001). Ten-year survival was particularly good for those with diagnosed ≤40 at 93.8% (n=75;95%CI=84.2–97.6). Women with lobular breast cancers had worse 10-year survival at 85.9% (95%CI=66.7–94.5). Breast cancer specific survival was good for 119 BRCA1/2 carriers with 20-year survival in BRCA1:91.2%(95%CI=77.8-96.6) and 83.8% (62.6-–93.5) for BRCA2Conclusions:Targeted breast screening in women aged 30-60 years at increased familial risk is associated with good long-term survival that is substantially better than expected from population data.
Identification of an Oligosaccharide Dehydrogenase from Pycnoporus Cinnabarinus Provides Insights into Fungal Breakdown of Lignocellulose
Authors: Cerutti Gabriele , Gugole Elena , Montemiglio Linda Celeste , Turbé-Doan Annick , Chena Dehbia , Navarro David , Lomascolo Anne , Piumi François , Exertier Cécile , Freda Ida , Vallone Beatrice , Record Eric , Savino Carmelinda , sciara giuliano 
Published: February 2021

Abstract
Background: Fungal glucose dehydrogenases (GDHs) are FAD-dependent enzymes belonging to the glucose-methanol-choline oxidoreductase superfamily. These enzymes are classified in the “Auxiliary Activity” family 3 (AA3) of the Carbohydrate-Active enZymes database, and more specifically in subfamily AA3_2, that also includes the closely related flavoenzymes aryl-alcohol oxidase and glucose 1-oxidase. Based on sequence similarity to known fungal GDHs, an AA3_2 enzyme active on glucose was identified in the genome of Pycnoporus cinnabarinus, a model Basidiomycete able to completely degrade lignin.Results: In our work, substrate screening and functional characterization showed an unexpected preferential activity of this enzyme toward oligosaccharides containing a b(1à3) glycosidic bond, with the highest efficiency observed for the disaccharide laminaribiose. Despite its sequence similarity to GDHs, we defined a novel enzymatic activity, namely oligosaccharide dehydrogenase (ODH), for this enzyme. The crystallographic structures of ODH in the sugar-free form and in complex with glucose and laminaribiose unveiled a peculiar saccharide recognition mechanism which is not shared with previously characterized AA3 oxidoreductases and accounts for ODH preferential activity toward oligosaccharides. The sugar molecules in the active site of ODH are mainly stabilized through CH-p interactions with aromatic residues rather than through hydrogen bonds with highly conserved residues, as observed instead for the fungal glucose dehydrogenases and oxidases characterized to date. Finally, three sugar-binding sites were identified on ODH external surface, which were not previously observed and might be of importance in the physiological scenario.Conclusions: Structure-function analysis of ODH is consistent with its role as an auxiliary enzyme in lignocellulose degradation and unveils yet another enzymatic function within the AA3 family of the Carbohydrate-Active enZymes database. Our findings allow deciphering the molecular determinants of substrate binding and provide insight into the physiological role of ODH, opening new perspectives to exploit biodiversity for lignocellulose transformation into fuels and chemicals.
Janus Kinase Inhibition Ameliorates Cerebral Ischemic Injury and Neuroinflammation through Reducing NLRP3 Inflammasome Activation via JAK2/STAT3 Pathway Inhibition
Authors: Zhu Hua , Zhong Yi , Jian Zhihong , Ye Yingze , Zhang Yonggang , Pu Bei , Hu Xinyao , Xu Qingxue , Xiong Xiaoxing , Gu Lijuan 
Published: February 2021

Abstract
BackgroundEvidence shows that inflammatory responses play multiphasic roles in stroke pathogenesis. Ruxolitinib (Rux), a selective oral JAK 1/2 inhibitor, is efficacious in COVID-19 by reducing inflammation via the JAK2/STAT3 pathway. MethodsHere, we investigated whether JAK2 inhibition has neuroprotective effects against ischemic stroke (IS) in MCAO mice in vivo and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model, and explored the potential molecular mechanisms. Rux was applied to MCAO mice. Immunofluorescence staining, RT-qPCR, and western blots were used to measure the expression of NLRP3 inflammation components and proinflammatory cytokines as well as JAK2/STAT3 pathway. Local STAT3 deficiency in brain tissue was established to investigate the interplay between NLRP3 and STAT3 signaling.ResultsRux treatment obviously improved neurological scores, decreased the infarct size and ameliorated cerebral edema 3 days after stroke. In addition, immunofluorescence staining and western blots showed that Rux application inhibited the expression of NLRP3 inflammasome components, proteins related to the NLRP3 inflammasome and phosphorylated STAT3 (p-STAT3) in neurons. Furthermore, Rux administration inhibited the expression of proinflammatory cytokines, including TNF-α, IFN-γ, HMBG1, IL-1β, IL-2, and IL-6 in middle cerebral artery occlusion (MCAO) model mice, suggesting that Rux may alleviate IS injury by inhibiting proinflammatory reactions via JAK2/STAT3 signaling pathway regulation. Local STAT3 deficiency decreased histone H3 and H4 acetylation on the NLRP3 promoter and the NLRP3 inflammasome component expression, indicating that the NLRP3 inflammasome may be directly regulated by STAT3 signaling. Finally, the effect of Rux on the NLRP3 inflammasome was further assessed in a HT22 cell OGD/R model in vitro. Rux application markedly suppressed lipopolysaccharide (LPS)-induced NLRP3 inflammasome secretion and JAK2/STAT3 pathway activation in vitro the in OGD/R HT22 cell model.ConclusionJAK2 inhibition by Rux in MCAO mice decreased STAT3 phosphorylation, thus inhibiting downstream proinflammatory cytokines and H3 and H4 acetylation on the NLRP3 promoter, resulting in downregulation of NLRP3 inflammasome component expression.
The APOBEC3A deaminase drives episodic mutagenesis in cancer cells
Authors: Maciejowski John , Petljak Mia , Chu Kevan , Dananberg Alexandra , Bergstrom Erik , von Morgen Patrick , Alexandrov Ludmil , Stratton Michael 
Published: February 2021

Abstract
The APOBEC3 family of cytidine deaminases is widely speculated to be a major source of somatic mutations in cancer1–3. However, causal links between APOBEC3 enzymes and mutations in human cancer cells have not been established. The identity of the APOBEC3 paralog(s) that may act as prime drivers of mutagenesis and the mechanisms underlying different APOBEC3-associated mutational signatures are unknown. To directly investigate the roles of APOBEC3 enzymes in cancer mutagenesis, candidate APOBEC3 genes were deleted from cancer cell lines recently found to naturally generate APOBEC3-associated mutations in episodic bursts4. Deletion of the APOBEC3A paralog severely diminished the acquisition of mutations of speculative APOBEC3 origins in breast cancer and lymphoma cell lines. APOBEC3 mutational burdens were undiminished in APOBEC3B knockout cell lines. APOBEC3A deletion reduced the appearance of the clustered mutation types kataegis and omikli, which are frequently found in cancer genomes. The uracil glycosylase UNG and the translesion polymerase REV1 were found to play critical roles in the generation of mutations induced by APOBEC3A. These data represent the first evidence for a long-postulated hypothesis that APOBEC3 deaminases generate prevalent clustered and non-clustered mutational signatures in human cancer cells, identify APOBEC3A as a driver of episodic mutational bursts, and dissect the roles of the relevant enzymes in generating the associated mutations in breast cancer and B cell lymphoma cell lines.
Spatial patterns of tumour growth impact clonal diversification: computational modelling and evidence in the TRACERx Renal study
Authors: Fu Xiao , Zhao Yue , Lopez Jose , Rowan Andrew , Au Lewis , Fendler Annika , Hazell Steve , Xu Hang , Horswell Stuart , Shepherd Scott , Spain Lavinia , Byrne Fiona , Stamp Gordon , O'Brien Tim , Nicol David , Augustine Marcellus , Chandra Ashish , Rudman Sarah , Toncheva Antonia , Furness Andrew , Pickering Lisa , Orton Matthew , Doran Simon , Koh Dow-Mu , Messiou Christina , Dafydd Derfel ap , Kumar Santosh , Larkin James , Swanton Charles , Sahai Erik , Litchfield Kevin , Turajlic Samra , Bates Paul 
Published: February 2021

Abstract
Intra-tumour genetic heterogeneity (ITH) fuels cancer evolution. The role of clonal diversity and genetic complexity in the progression of clear-cell renal cell carcinomas (ccRCCs) has been characterised, but the ability to predict clinically relevant evolutionary trajectories remains limited. Here, towards enhancing this ability, we investigated spatial features of clonal diversification through a combined computational modelling and experimental analysis in the TRACERx Renal study. We observe through modelling that spatial patterns of tumour growth impact the extent and trajectory of subclonal diversification. Moreover, subpopulations with high clonal diversity, and parallel evolution events, are frequently observed near the tumour margin. In-silico time-course studies further showed that budding structures on the tumour surface could indicate future steps of subclonal evolution. Such structures were evident radiologically in 15 early-stage ccRCCs, raising the possibility that spatially resolved sampling of these regions, when combined with sequencing, may enable identification of evolutionary potential in early-stage tumours.
Comparing Death or Neurodevelopmental Outcomes of Haemodynamically Significant Patent Ductus Arteriosus in Very Low Birth Weight Preterm Infants
Authors: Wu Jia-Ying Jania , Niduvaje Krishnamoorthy , Lee Le Ye , Amin Zubair 
Published: February 2021

Abstract
BackgroundOptimal management of haemodynamically significant patent ductus arteriosus (HsPDA) remains controversial for premature infants. Treatment options include conservative treatment with fluid restriction and diuretics, medical treatment with cyclo-oxygenase (COX) inhibitors or surgical ligation. Our primary objective is to compare the death and/or adverse neurodevelopmental outcomes among very low birth weight (VLBW) infants with HsPDA who were managed with conservative, medical and/or surgical treatment. The secondary objectives are to examine antenatal factors predisposing to surgical treatment and the neonatal short-term morbidities between three groups.MethodsThis was a retrospective, gestational age-stratified study of VLBW infants born in National University Hospital (NUH) in Singapore and admitted to the intensive care unit from 2007–2016.. Perinatal variables, short-term neonatal outcomes and neurodevelopmental outcomes were studied. Statistical analysis were performed with chi square and t-test.. Results124 infants were included. 17 VLBW infants managed conservatively [C] were identified and compared with 83 VLBW infants managed medically [M] and 24 VLBW infants managed surgically [S]. The main group analysis compared outcomes between infants managed [C] and those who received either medical or surgical treatment [M+S]. The subgroup analysis compared outcomes between infants managed [C] vs [M] and [C] vs [S]. The main group analysis found group M+S infants had a higher incidence of chronic lung disease (CLD) (p=0.005) than group C. The odds ratio (OR) of group M+S developing CLD was significant (OR 6.83). They were significantly shorter (p=0.017) and had a smaller head circumference (p=0.039) at discharge. Group S infants were older at discharge, due to a longer NICU stay , and were lighter , shorter and had a smaller head circumference (p<0.05). No significant differences in death, composite outcome of death and global development delay and neurological outcomes such as hearing loss, cerebral palsy (CP) and speech delay were found. Conclusions: Comparing the management, infants requiring surgical treatment for hsPDA were more likely to have short-term complications such as CLD, longer hospitalization, and poorer growth. Despite a more turbulent postnatal course, death and/or adverse neurodevelopmental outcomes were not worse in these infants. Further randomized control studies will be useful to verify these findings.
Investigation of the Motor Skills Assessments of Typically Developing Preschool Children in China
Authors: Song Huiqi , Wang Jing Jing , Lau Patrick WC 
Published: February 2021

Abstract
Background: The assessment of perschoolers’ motor skills is essential to know young children’s motor development and evaluate the intervention effects of promotion in children’s sport activities. The purpose of this study was to review the motor skills assessment tools in Chinese preschool-aged children, compare them in the international context, and provide guidelines to find appropriate motor skill assessment tool in China. Methods: The comprehensive literature search was carried out in WANGFAGN, CNKI, VIP, ERIC, EMBASE, MEDLINE, Ovid PsycINFO, SPORTDiscus and BIOSIS previews databases. Relevant articles published between January 2000 and May 2020 were retrieved. Studies that described the discriminative and evaluative measures of motor skills among the population aged 3-6 years in China were included. Results: A total of 17 studies were included in this review describing 7 tools including 4 self-developed tools and 3 international tools used in China. TGMD-2 appeared in a large proportion of studies, international tools used in China were incomplete in terms of translation, verification of reliability and validity, item selection and the implementation. Regarding the self-constructed tools, the CDCC was the most utilized self-developed tool, but it was mainly applied in intellectual development assessment. Through the comparison between Chinese self-constructed and international tools, the construction of the CDCC and the Gross Motor Development Assessment Scale contained relatively complete development steps. The test content, validity and reliability, implementation instruction, and generalizability of self-constructed tools are still lacking. Conclusions: Both international and self-developed motor skills assessment tools have been rarely applied in China, available tools lack enough validation and appropriate adjustments. Cultural differences in motor development between Chinese and Western populations should be considered when constructing a Chinese localized MSAT.
Congenital Bilateral and Multifocal Mesenchymal hamartoma of the chest wall: A Case in a Neonate and Differential Diagnosis
Authors: li jiwei , Zhang Tie song , Li li , Wang Meifen , shen lan 
Published: February 2021

Abstract
Background:Mesenchymal hamartoma of the chest wall(MHCW) is a rare benign extrapleural lesion that arises from rib or spine of neonates or early infancy, and commonly presents as a unilateral mass. Here, we describe a rare case of bilateral and multifocal MHCW in the right 5th rib and the left 11-12th thoracic and 1st lumbar vertebrae.Case presentation:A male neonate of 3700g weight transferred to our hospital with mild respiratory distress and an asymptomatic, progressively enlarging intra-thoracic mass. Computed tomography scan(CT) and magnetic resonance imaging(MRI) indicated a large well-circumscribed, heterogeneous enhancing mass, arising from the posterior-medial aspect of the right chest wall, involving 3-5th posterior ribs. Other smaller sizes lesions observed in vertebral arch and transverse process of the left 11-12th thoracic and 1st lumbar vertebrae. The thoracotomy with en bloc resection of the mass and the 5th rib was performed. Microscopically, the lesion was cystic and solid, consisted of hyaline cartilages, mesenchymal cells, and various-sized hemorrhagic spaces. Immunohistochemically, the cartilages and mesenchymal cells were positive for S-100, Smooth Muscle Actin(SMA), CD163 and CD68. The epithelium cells of aneurysmal bone cyst(ABC)-like were negative for CD34. Ki-67 estimated at 5%-10%. Fluorescence in situ hybridization(FISH) was negative for USP6 gene break-apart probe, which ruled out primary ABC. At 8-month follow-up postoperatively, the right chest walls with no sign of recurrence and the lesions of left vertebral arch and transverse process were stable, no increased in size.Conclusion:The bilateral and multifocal MHCW is considerably rare and related clinical research is limited. Fortunately, we clearly observed the tumor’s origin, growth process from the earlier pregnancy to delivery, different effects during the fetal periods, and differential diagnosis. This report may raise awareness regarding the MHCW.