bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of LIN28B polymorphisms with chronic hepatitis B virus infection
Authors: Han Qunying , Sang Jiao , Fan Xiude , Wang Xiaoyun , Zeng Lu , Zhang Xiaoge , Zhang Kun , Li Na , Lv Yi , Liu Zhengwen 
Published: June 2020

Abstract
Background
LIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown.

Methods
This study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated.

Results
LIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491–0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561–0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439–0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503–0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445–0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019).

Conclusions
These results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.
Outcomes in patients with lacrimal gland carcinoma treated with definitive radiotherapy or eye-sparing surgery followed by adjuvant radiotherapy
Authors: Lin Yun-Hsuan , Huang Shih-Ming , Yap Wing-Keen , Yang Ju-Wen , Yeung Ling , Tsan Din-Li , Chang Joseph Tung-Chieh , Chen Lung-Chien 
Published: June 2020

Abstract
Background
The optimal treatment for lacrimal gland cancer remains unclear. Eye-preserving surgery, as opposed to exenteration, followed by adjuvant radiotherapy (RT), has recently been reported to deliver satisfactory outcomes, but evidence is sparse. The aim of the present study was to evaluate outcomes in patients with lacrimal gland cancer treated at two tertiary medical centers.

Methods
We retrospectively examined data from patients with lacrimal gland cancer who had received eye-preserving surgical treatment followed by adjuvant RT with or without chemotherapy, or (if the tumor was inoperable) needle biopsy with definitive RT with or without chemotherapy. Baseline clinical and pathological characteristics were considered. Outcomes of interest included post-treatment complications, overall survival (OS), locoregional progression-free survival (LPFS), and distant metastasis-free survival (DMFS).

Results
Eighteen patients were included. Two-year OS, LPFS, and DMFS rates were 69.0, 76.7, and 71.4%, respectively. Patients with early-stage (T1–T2) lacrimal gland cancer had significantly better outcomes than those with advanced-stage disease (T3–T4). Two-year OS, LPFS, and DMFS rates were each 100% in patients with disease stages T1–T2, and 37.5, 50, and 37.5%, respectively, in those with disease stages T3–T4 (P < 0.05). Orbital complications were well tolerated.

Conclusions
Eye-sparing surgery with adjuvant RT can achieve satisfactory results in patients with T1–T2 lacrimal gland carcinoma. Disease stage T3 and above was associated with poor outcomes even with post-operative RT, likely due to distant metastasis. Adding neoadjuvant chemotherapy or adjuvant chemotherapy to current treatment strategies might be a suitable choice for this group of patients.
The utility of 18F-FDG PET and PET/CT in the diagnosis and staging of chondrosarcoma: a meta-analysis
Authors: Zhang Qingyu , Xi Yongming , Li Dong , Yuan Zenong , Dong Jun 
Published: June 2020

Abstract
Objective
Chondrosarcoma is the second most common primary bone sarcoma; however, unlike other tumors, the biopsy cannot easily make a definite diagnosis or predict the histological grade. This meta-analysis was performed to evaluate the utility of 18F-FDG PET and PET/CT to differentiate chondrosarcoma from benign cartilaginous lesions and to predict the histopathological grade of chondrosarcoma.

Material and methods
A comprehensive search was performed in three electronic databases including Medline/PubMed, the Cochrane Library and Embase to retrieve diagnostic studies evaluating the role of 18F-FDG PET or PET/CT for appraising the status of chondrosarcoma. Reference lists of related articles were also scrutinized manually. Useful data were extracted to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the summary receiver operating characteristic curve (sROC), and the area under the curve (AUC) of 18F-FDG PET or PET/CT in diagnosing chondrosarcoma, and pooled weighted mean differences (WMD) of maximum standardized uptake value (SUVmax) between different entities of cartilaginous neoplasms by using Stata 19.0.

Results
A total of twelve studies provided sufficient data for the quantitative analysis. For the diagnosis of chondrosarcoma, the pooled sensitivity, specificity, and DOR of 18F-FDG PET were 0.84 (95% confidence interval [CI] 0.46 to 0.97), 0.82 (95% CI 0.55 to 0.94), and 24.244 (95% CI 1.985 to 96.148), respectively while those of 18F-FDG PET/CT were 0.94 (95% CI 0.86 to 0.97), 0.89 (95% CI 0.82 to 0.93), and 112.999 (95% CI 41.341 to 308.866), respectively. The pooled WMD of SUVmax were − 0.89 (95% CI −1.67 to −0.10) between benign cartilaginous lesions and grade 1 (G1) chondrosarcoma, −1.94 (95% CI −2.76 to −1.12) between G1 and grade 2 (G2) chondrosarcoma, and − 2.37 (95% CI −5.79 to 1.05) between G2 and grade 3 (G3) chondrosarcoma.

Conclusions
In a word, 18F-FDG PET/CT revealed excellent accuracy in the diagnosis of chondrosarcoma and might assist in clinical decision-making. Meanwhile, although SUVmax alone showed restricted ability to differentiate benign cartilaginous lesions and G1 chondrosarcoma, as well as between G2 and G3 chondrosarcoma, it can identify intermediate/high-grade chondrosarcoma from low-grade ones.

Level of evidence
Level I evidence, a summary of meta-analysis
Fetal aortic valvuloplasty: first report of two cases from Saudi Arabia
Authors: Atiyah Merna , Kurdi Ahmed , Al Tuwaijry Osama , Al Sahari Atif , Al Rakaf Maha , Babic Inas , Al Habshan Fahad , Alhalees Zohair , Al Najashi Khalid 
Published: June 2020

Abstract
Background
Fetal aortic stenosis may progress to hypoplastic left heart syndrome (HLHS), which carries a poor prognosis. We report two infants with fetal aortic stenosis successfully treated with fetal aortic valvuloplasty (FAV) using balloon dilatation.

Case presentation
Of five fetuses with aortic stenosis fulfilling the FAV criteria of severe aortic stenosis with a left ventricular length Z-score of ≥ − 2, retrograde flow in the transverse aortic arch, left-to-right flow across the foramen ovale, monophasic mitral inflow, and significant left ventricular dysfunction, we obtained permission for FAV in two fetuses. FAV was performed successfully under echocardiographic guidance using balloon dilatation. Both fetuses survived to birth. During FAV, mild pericardial effusion developed when introducing the stylet needle in the second fetus, and this resolved within 48 h. No intraprocedural complications occurred in the first patient, and no maternal complications occurred. The first infant underwent the Ross procedure after birth and is currently 7 years old and doing well. The second patient underwent aortic and mitral valve repair with endocardial fibroelastosis resection approximately 2 weeks after birth, which temporarily addressed the mitral valve stenosis; high doses of inotropes were subsequently required. The infant died of sepsis at 2 months of age.

Conclusion
FAV using balloon dilatation to treat fetal aortic stenosis was successful in our two patients, with subsequent neonatal biventricular repair resulting in long-term survival in one patient and death secondary to sepsis in the second patient.
Pathologic substrate of gastropathy in Anderson-Fabry disease
Authors: Di Toro Alessandro , Narula Nupoor , Giuliani Lorenzo , Concardi Monica , Smirnova Alexandra , Favalli Valentina , Urtis Mario , Alvisi Costanza , Antoniazzi Elena , Arbustini Eloisa 
Published: June 2020

AbstractIn both classic and late-onset AFD, mutations of the GLA gene cause deficient activity of the alpha-galactosidase enzyme resulting in intracellular accumulation of the undigested substrate. Gastrointestinal symptoms (GI) are common but non-specific and imputed to the AFD, irrespective of the demonstration of substrate accumulation in GI cells. We demonstrate substrate accumulation in gastric epithelial, vascular, and nerve cells of patients with classic AFD and, vice versa, absence of accumulation in late-onset AFD and controls.
Novel MNX1 mutations and genotype–phenotype analysis of patients with Currarino syndrome
Authors: Han Lu , Zhang Zhen , Wang Hui , Song Hui , Gao Qing , Yan Yuchun , Tao Ran , Xiao Ping , Li Long , Jiang Qian , Li Qi 
Published: June 2020

AbstractBackgroundCurrarino syndrome (CS) is a specific complex of congenital caudal anomalies, including anorectal malformations, presacral mass and sacral anomalies. Mutations in theMNX1gene are closely related to CS and occur in almost all familial cases and less than half of sporadic patients. We investigated the spectrum ofMNX1pathogenic variants and associated clinical features in Chinese patients with CS.ResultsSeventeen index patients from 16 families were recruited from 2015 to 2018. All patients were diagnosed with CS and treated at the Capital Institute of Pediatrics Affiliated Children’s Hospital. Genetic testing was applied to identify mutations in CS patients and their relatives by whole-exome sequencing and Sanger sequencing. Functional verification was performed for a recurrent noncanonical splice site variant inMNX1with a minigene splicing assay. In 17 CS patients, 14 were complete CS and 3 were mild CS. Nine variants inMNX1were identified in 11 patients, and these included two frameshift mutations (p.Leu223Leufs*61, p.X402Serfs*70), four nonsense mutations (p.Gly42X, p.Cys88X, p.Gln24X, p.Cys241X), one missense mutation (p.Trp288Leu), one splice region variant (c.691 + 3G > T) and one polyalanine polymorphism (p.Ala135insAlaAla). Seven of these nine variants have never been reported. PathogenicMNX1mutations were found in 100% (4/4) of familial and 46% (6/13) of sporadic patients.ConclusionOur study expanded the mutation spectrum ofMNX1and provided clinical and genetic analyses of seventeen CS patients from mainland China.
Inherited duplication of the pseudoautosomal region Xq28 in a subject with Gilles de la Tourette syndrome and intellectual disability: a case report
Authors: Maccarini Stefania , Cipani Annamaria , Bertini Valeria , Skripac Jelena , Salvi Alessandro , Borsani Giuseppe , Marchina Eleonora 
Published: June 2020

Abstract
Background
Tourette syndrome (TS) is a complex neurodevelopmental disorder (NDD) characterized by multiple chronic involuntary motor and vocal tics with onset during childhood or adolescence. Most TS patients present with additional comorbidities, typically attention deficit hyperactivity disorder (ADHD), obsessive- compulsive disorder (OCD), autism spectrum disorder (ASD) and intellectual disability (ID). Both TS and ID are genetically complex disorders that likely occur as a result of the effects of multiple genes interacting with other environmental factors. In addition to single gene mutations and chromosomal disorders, copy number variations (CNVs) are implicated across many NDDs and ID and contribute to their shared genetic etiology. Screening of CNVs using microarray-based Comparative Genomic Hybridization (aCGH) is now routinely performed in all subjects with NDD and ID.

Case presentation
We report a case of a 12-year-old girl diagnosed with Gilles de la Tourette Syndrome associated to behavior disorders and intellectual disability in particular with regard to language. Array-CGH analysis showed a CNV of a subtelomeric region Xq28 (gain of 260 kb) inherited from the healthy father. The duplication contains two genes, VAMP7 and SPRY3 of the PAR2 pseudoautosomal region. FISH analysis revealed that the duplicated segment is located on the short arm of a chromosome 13, resulting in a trisomy of the region. In the proband the expression levels of the genes evaluated in the peripheral blood sample are comparable both those of the mother and to those of female control subjects.

Conclusions
Although the trisomy of the 260 kb region from Xq28 identified in proband is also shared by the healthy father, it is tantalizing to speculate that, together with genetic risk factors inherited from the mother, it may play a role in the development of a form of Tourette syndrome with intellectual disability. This hypothesis is also supported by the fact that both genes present in the duplicated region (VAMP7 and SPRY3) are expressed in the CNS and are implicated in neurotransmission and neurite growth and branching. In addition, similar CNVs have been identified in individuals whose phenotype is associated with autism spectrum disorders or intellectual disability.
Differential expression of Cdk5-phosphorylated CRMP2 following a spared nerve injury
Authors: Moutal Aubin , Ji Yingshi , Bellampalli Shreya Sai , Khanna Rajesh 
Published: June 2020

AbstractEffective treatment of high-impact pain patients is one of the major stated goals of the National Pain Strategy in the United States. Identification of new targets and mechanisms underlying neuropathic pain will be critical in developing new target-specific medications for better neuropathic pain management. We recently discovered that peripheral nerve injury-induced upregulation of an axonal guidance phosphoprotein collapsin response mediator protein 2 (CRMP2) and the N-type voltage-gated calcium (CaV2.2) as well as the NaV1.7 voltage-gated sodium channel, correlates with the development of neuropathic pain. In our previous studies, we found that interfering with the phosphorylation status of CRMP2 is sufficient to confer protection from chronic pain. Here we examined the expression of CRMP2 and CRMP2 phosphorylated by cyclin-dependent kinase 5 (Cdk5, on serine residue 522 (S522)) in sciatic nerve, nerve terminals of the glabrous skin, and in select subpopulations of DRG neurons in the SNI model of neuropathic pain. By enhancing our understanding of the phosphoregulatory status of CRMP2 within DRG subpopulations, we may be in a better position to design novel pharmacological interventions for chronic pain.
Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients
Authors: Spakowicz Daniel , Lou Shaoke , Barron Brian , Gomez Jose L. , Li Tianxiao , Liu Qing , Grant Nicole , Yan Xiting , Hoyd Rebecca , Weinstock George , Chupp Geoffrey L. , Gerstein Mark 
Published: June 2020

AbstractSputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes.
The PRINTEMPS study: protocol of a cluster-randomized controlled trial of the local promotion of a smartphone application and associated website for the prevention of suicidal behaviors in the adult general population in France
Authors: Gandré Coralie , Le Jeannic Anaïs , Vinet Marie-Amélie , Turmaine Kathleen , Courtet Philippe , Roelandt Jean-Luc , Vaiva Guillaume , Giraudeau Bruno , Alberti Corinne , Chevreul Karine 
Published: June 2020

Abstract
Background
Suicide constitutes a cause of death which could be prevented by e-health programs accessible to the general population. Effective promotion has the potential to maximize the uptake of such programs. However, few e-health programs have been combined with promotion campaigns. The primary objective of this trial is to assess the effectiveness of a tailored promotion, at a local level, of a mobile application and website offering evidence-based content for suicide prevention (the StopBlues program), and to compare the effectiveness of two types of local promotion in terms of their impact on suicidal acts. Secondary objectives focus on the effectiveness of the promotion in terms of the intensity of utilization of the StopBlues program, help-seeking behaviors and the level of psychological impairment of program users.

Methods/design
This is a three-arm, parallel-group, cluster-randomized controlled trial, with before-and-after observation. Thirty-four clusters, corresponding to geographical areas sharing a common local authority in France, will be included. They will be randomly assigned to one of the following arms with a ratio of 1:1:1: a control group; a basic promotion group in which promotion of the StopBlues program will be done by local authorities; and an intensified promotion group in which basic promotion will be supplemented by an additional one in a general practitioner’s waiting room. The primary outcome measure will be the number of suicidal acts within each cluster over a 12-month period following the launch of the intervention. Baseline data will be collected for each cluster over the 12-month period prior to the trial. Secondary outcomes will include length of use of the StopBlues program, measures of help-seeking behaviors and level of psychological distress among users of the program, as well as the cost-effectiveness and budgetary impact of its promotion. A more sustained promotion by local authorities will also be implemented after 12 months in the control group and assessed using the same outcome measures.

Discussion
This research should contribute to the sparse evidence base regarding the promotion of e-health programs and will support the wider delivery of the intervention evaluated if proven effective.

Trial registration
ClinicalTrials.gov, ID: NCT03565562. Registered on 11 June 2018
Clinical efficacy of ceramic versus resin-based composite endocrowns in Chinese adults: study protocol for a randomized controlled trial
Authors: Wang Jilei , Ling Zhiting , Zheng Ziting , Zheng Chunqing , Gai Yawen , Zeng Yuting , Zhu Xiaoxia , Chen Liya , Wu Buling , Yan Wenjuan 
Published: June 2020

Abstract
Background
Endocrown restoration is widely used to restore endodontically treated teeth. However, the clinical effects of different computer-aided design/computer-aided manufacturing (CAD/CAM) materials for endocrown restoration are not clear. The primary objective of this trial is to compare the clinical efficacy of resin-based bloc and ceramic endocrowns for restoring endodontically treated teeth.

Methods
The proposed resin-based bloc and ceramic endocrown assessment trial is a parallel group-designed randomized controlled trial. We will recruit 156 adults between 18 and 75 years old with a minimum of one such molar. The inclusion criteria were good oral hygiene habits, root apex of molar without evident damage, receipt of standard endodontic treatment, need for endocrown restoration, and only one endocrown restoration performed per patient. Patients participating in another study or those with systemic diseases, disabilities, or known allergies to used materials will be excluded. All patients will be randomized and restored with resin-based bloc and ceramic endocrown according to a random number table. Clinical evaluations will be performed at baseline and after treatment at 6, 12, and 24 months, in accordance with the modified Federation Dentaire Internationale (FDI) criteria, by two independent evaluators. The primary outcome is marginal adaptation; secondary outcomes include wear, tooth integrity, fracture of material and retention, marginal staining, and patient view. All data will be analyzed by an independent statistician. Signed rank-sum tests will be used for intragroup comparisons. Wilcoxon rank-sum tests will be used for intergroup comparisons. Hierarchical logistic regression will be used to adjust the baseline and other important indicators.

Discussion
This study will investigate endocrowns of two CAD/CAM materials for endodontically treated molars. The results may help clinicians choose the better CAD/CAM material option and explain to patients the advantages and disadvantages of these two materials with evidence-based support. For patients, the results may lead to improvement in long-term restoration.

Trial registration
ClinicalTrials.gov NCT04033380. Registered on 24 July 2019
Identification of novel genes associated with dysregulation of B cells in patients with primary Sjögren’s syndrome
Authors: Inamo Jun , Suzuki Katsuya , Takeshita Masaru , Kassai Yoshiaki , Takiguchi Maiko , Kurisu Rina , Okuzono Yuumi , Tasaki Shinya , Yoshimura Akihiko , Takeuchi Tsutomu 
Published: June 2020

Abstract
Background
The aim of this study was to identify the molecular mechanism of dysregulation of B cell subpopulations of primary Sjögren’s syndrome (pSS) at the transcriptome level.

Methods
We enrolled patients with pSS (n = 6) and healthy controls (HCs) (n = 6) in the discovery cohort using microarray and pSS (n = 14) and HCs (n = 12) in the validation cohort using quantitative PCR (qPCR). Peripheral B cells acquired from these subjects were separated by cell sorting into four subsets: CD38−IgD+ (Bm1), CD38+IgD+ (naive B cells), CD38highIgD+ (pre-germinal centre B cells) and CD38±IgD− (memory B cells). We performed differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA).

Results
Expression of the long non-coding RNA LINC00487 was significantly upregulated in all B cell subsets, as was that of HLA and interferon (IFN) signature genes. Moreover, the normalized intensity value of LINC00487 significantly correlated with the disease activity score of all pSS B cell subsets. Studies of human B cell lines revealed that the expression of LINC00487 was strongly induced by IFNα. WGCNA revealed six gene clusters associated with the B cell subpopulation of pSS. Further, SOX4 was identified as an inter-module hub gene.

Conclusion
Our transcriptome analysis revealed key genes involved in the dysregulation of B cell subpopulations associated with pSS.

Trial registration
Not required.