bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel synonymous ABCA3 variant identified in a Chinese family with lethal neonatal respiratory failure
Authors: Zhang Weifeng , Liu Zhiyong , Lin Yiming , Wang Ruiquan , Xu Jinglin , He Ying , Zhang Fengfeng , Wu Lianqiang , Chen Dongmei 
Published: October 2021

AbstractBackgroundLethal respiratory failure is primarily caused by a deficiency of pulmonary surfactant, and is the main cause of neonatal death among preterm infants. Pulmonary surfactant metabolism dysfunction caused by variants in theABCA3gene is a rare disease with very poor prognosis. Currently, the mechanisms associated with someABCA3variants have been determined, including protein mistrafficking and impaired phospholipid transport. However, some novel variants and their underlying pathogenesis has not been fully elucidated yet. In this study we aimed to identify the genetic features in a family with lethal respiratory failure.MethodsWe studied members of two generations of a Chinese family, including a female proband, her parents, her monozygotic twin sister, and her older sister. Trio whole exome sequencing (WES) were used on the proband and her parents to identify theABCA3variants. Sanger sequencing and real-time quantitative polymerase chain reaction (PCR) were used on the monozygotic twin sister of proband to validate theABCA3synonymous variant and exon deletion, respectively. The potential pathogenicity of the identified synonymous variant was predicted using the splice site algorithms dbscSNV11_AdaBoost, dbscSNV11_RandomForest, and Human Splicing Finder (HSF).ResultsAll patients showed severe respiratory distress, which could not be relieved by mechanical ventilation, supplementation of surfactant, or steroid therapy, and died at an early age. WES analysis revealed that the proband had compound heterozygousABCA3variants, including a novel synonymous variant c.G873A (p.Lys291Lys) in exon 8 inherited from the mother, and a heterozygous deletion of exons 4–7 inherited from the father. The synonymous variant was consistently predicted to be a cryptic splice donor site that may lead to aberrant splicing of the pre-mRNA by three different splice site algorithms. The deletion of exons 4–7 of theABCA3gene was determined to be a likely pathogenic variant. The variants were confirmed in the monozygotic twin sister of proband by Sanger sequencing and qPCR respectively. The older sister of proband was not available to determine if she also carried bothABCA3variants, but it is highly likely based on her clinical course.ConclusionsWe identified a novel synonymous variant and a deletion in theABCA3gene that may be responsible for the pathogenesis in patients in this family. These results add to the known mutational spectrum of theABCA3gene. The study ofABCA3variants may be helpful for the implementation of patient-specific therapies.
A novel missense mutation of FOXC1 in an Axenfeld–Rieger syndrome patient with a congenital atrial septal defect and sublingual cyst: a case report and literature review
Authors: Li Kaiming , Tang Min , Xu Manhua , Yu Yinggui 
Published: October 2021

Abstract
Background
Axenfeld–Rieger syndrome (ARS) is a rare autosomal dominant hereditary disease characterized primarily by maldevelopment of the anterior segment of both eyes, accompanied by developmental glaucoma, and other congenital anomalies. FOXC1 and PITX2 genes play important roles in the development of ARS.

Case presentation
The present report describes a 7-year-old boy with iris dysplasia, displaced pupils, and congenital glaucoma in both eyes. The patient presented with a congenital atrial septal defect and sublingual cyst. The patient’s family has no clinical manifestations. Next generation sequencing identified a pathogenic heterozygous missense variant in FOXC1 gene (NM_001453:c. 246C>A, p. S82R) in the patient. Sanger sequencing confirmed this result, and this mutation was not detected in the other three family members.

Conclusion
To the best of our knowledge, the results of our study reveal a novel mutation in the FOXC1 gene associated with ARS.
Plasmodium malariae infections as a cause of febrile disease in an area of high Plasmodium falciparum transmission intensity in Eastern Uganda
Authors: Ayo Daniel , Odongo Bakar , Omara Joseph , Andolina Chiara , Mulder Ole , Staedke Sarah G. , Bousema Teun 
Published: October 2021

AbstractBackgroundPlasmodium falciparumis responsible for the vast majority of (severe) clinical malaria cases in most African settings. OtherPlasmodiumspecies often go undiagnosed but may still have clinical consequences.Case presentationHere, five cases ofPlasmodium malariaeinfections from Eastern Uganda (aged 2–39 years) are presented. These infections were all initially mistaken forP. falciparum,butPlasmodiumschizonts (up to 2080/µL) were identified by microscopy. Clinical signs included history of fever and mild anaemia.ConclusionThese findings highlight the importance of considering non-falciparum species as the cause of clinical malaria. In areas of intenseP. falciparumtransmission, where rapid diagnostic tests that detect onlyP. falciparumantigens are commonly used, non-falciparum malaria cases may be missed.
The prognostic value of arginase-1 and glypican-3 expression levels in patients after surgical intrahepatic cholangiocarcinoma resection
Authors: Qiang Zeyuan , Zhang Haofeng , Jin Shuai , Yan Cao , Li Zhen , Tao Lianyuan , Yu Haibo 
Published: October 2021

Abstract
Background
The aim of this study was to investigate the prognostic value of arginase-1 (Arg-1) and glypican-3 (GPC-3) in patients with intrahepatic cholangiocarcinoma (ICC).

Methods
Two hundred and thirty-seven patients with ICC were included in this study. All patients had undergone radical surgery and had complete clinical information. Immunohistochemistry was used to assess the levels of Arg-1 and GPC-3 in ICC tissues. Univariate and multivariate analyses were conducted to identify independent risk factors in ICC. The relationship between Arg-1 and GPC-3 levels and patient survival was determined using the Kaplan-Meier method.

Results
High Arg-1 and GPC-3 expression levels were associated with poor prognosis in patients with ICC, and they could be as new prognostic biomarkers in ICC.

Conclusion
Arg-1 and GPC-3 can serve as independent prognostic biomarkers in ICC.
Avenues of research in dietary interventions to target tumor metabolism in osteosarcoma
Authors: Leite Taiana Campos , Watters Rebecca Jean , Weiss Kurt Richard , Intini Giuseppe 
Published: October 2021

AbstractOsteosarcoma (OS) is the most frequent primary bone cancer, affecting mostly children and adolescents. Although much progress has been made throughout the years towards treating primary OS, the 5-year survival rate for metastatic OS has remained at only 20% for the last 30 years. Therefore, more efficient treatments are needed. Recent studies have shown that tumor metabolism displays a unique behavior, and plays important roles in tumor growth and metastasis, making it an attractive potential target for novel therapies. While normal cells typically fuel the oxidative phosphorylation (OXPHOS) pathway with the products of glycolysis, cancer cells acquire a plastic metabolism, uncoupling these two pathways. This allows them to obtain building blocks for proliferation from glycolytic intermediates and ATP from OXPHOS. One way to target the metabolism of cancer cells is through dietary interventions. However, while some diets have shown anticancer effects against certain tumor types in preclinical studies, as of yet none have been tested to treat OS. Here we review the features of tumor metabolism, in general and about OS, and propose avenues of research in dietary intervention, discussing strategies that could potentially be effective to target OS metabolism.
A scoping review on the measurement of transnationalism in migrant health research in high-income countries
Authors: Kim Ye Na , Urquia Marcelo , Villadsen Sarah Fredsted , Merry Lisa 
Published: October 2021

Abstract
Background
Migrants commonly maintain transnational ties as they relocate and settle in a new country. There is a growing body of research examining transnationalism and health. We sought to identify how transnationalism has been defined and operationalized in migrant health research in high income countries and to document which populations and health and well-being outcomes have been studied in relation to this concept.

Methods
We conducted a scoping review using the methodology recommended by the Joanna Briggs Institute (JBI). We searched nine electronic databases; no time restrictions were applied. Studies published in English or French in peer-reviewed journals were considered. Studies were eligible if they included a measure of transnationalism (or one of its dimensions; social, cultural, economic, political and identity ties and/or healthcare use) and examined health or well-being.

Results
Forty-seven studies, mainly cross-sectional designs (81%), were included; almost half were conducted in the United States. The majority studied immigrants, broadly defined; 23% included refugees and/or asylum-seekers while 36% included undocumented migrants. Definitions of transnationalism varied according to the focus of the study and just over half provided explicit definitions. Most often, transnationalism was defined in terms of social connections to the home country. Studies and measures mainly focused on contacts and visits with family and remittance sending, and only about one third of studies examined and measured more than two dimensions of transnationalism. The operationalization of transnationalism was not consistent and reliability and validity data, and details on language translation, were limited. Almost half of the studies examined mental health outcomes, such as emotional well-being, or symptoms of depression. Other commonly studied outcomes included self-rated health, life satisfaction and perceived discrimination.

Conclusion
To enhance comparability in this field, researchers should provide a clear, explicit definition of transnationalism based on the scope of their study, and for its measurement, they should draw from validated items/questions and be consistent in its operationalization across studies. To enhance the quality of findings, more complex approaches for operationalizing transnationalism (e.g., latent variable modelling) and longitudinal designs should be used. Further research examining a range of transnationalism dimensions and health and well-being outcomes, and with a diversity of migrant populations, is also warranted.
A potential misdiagnosis in the COVID-19 pandemic era: a case report of superimposed thrombosis or tumor recurrence
Authors: Zoroufian Arezou , Mohseni-Badalabadi Reza , Mahalleh Mehrdad , Ghorashi Seyyed Mojtaba , Momtahen Sharam , Omidi Negar 
Published: October 2021

Abstract
Background
The clinical manifestations of coronavirus disease 2019 (COVID-19) overlap with those of other disorders, especially cardiovascular disease.

Case presentation
We herein describe a 58-year-old woman who presented with syncopal episodes and dyspnea on exertion with a left atrial (LA) mass, scheduled for surgical removal and mitral valve replacement. Nearly 3 months later, the patient developed dyspnea, fever, and a sore throat, resulting in hospital admission with suspected COVID-19. During the diagnostic evaluation, a larger LA mass was detected. The mass seemed to be a COVID-19–induced organized thrombus with prosthetic mitral valve malfunction. Resection was, therefore, planned. An immunohistochemistry study revealed a liposarcoma.

Conclusions
The unusual early recurrence of liposarcomas and the misdiagnosis with COVID-19–induced thrombosis are the hallmark of the present case.
RaDiCo, the French national research program on rare disease cohorts
Authors: Amselem Serge , Gueguen Sonia , Weinbach Jérôme , Clement Annick , Landais Paul ,   for the RaDiCo Program
Published: October 2021

Abstract
Background
Rare diseases (RDs) affect nearly 3 million people in France and at least 26–30 million people in Europe. These diseases, which represent a major medical concern, are mainly of genetic origin, often chronic, progressive, degenerative, life threatening and disabling, accounting for more than one third of all deaths occurring during infancy. In this context, there are needs for coordinated information on RDs at national/international levels, based on high quality, interoperable and sharable data. The main objective of the RaDiCo (Rare Disease Cohorts) program, coordinated by Inserm, was the development of RD e-cohorts via a national platform. The cohort projects were selected through a national call in 2014. The e-cohorts are supported by an interoperable platform, equivalent to an infrastructure, constructed on the "cloud computing" principle and in compliance with the European General Data Protection Regulation. It is dedicated to allow a continuous monitoring of data quality and consistency, in line with the French Health Data Hub.

Results
Depending on cohorts, the objectives are to describe the natural history of the studied RD(s), identify the underlying disease genes, establish phenotype-genotype correlations, decipher their pathophysiology, assess their societal and medico-economic impact, and/or identify patients eligible for new therapeutic approaches. Inclusion of prevalent and incident cases started at the end of 2016. As of April 2021, 5558 patients have been included within 13 RD e-cohorts covering 67 diseases integrated in 10 European Reference Networks and contributing to the European Joint Program on RDs. Several original results have been obtained in relation with the secondary objectives of the RaDiCo cohorts. They deal with discovery of new disease genes, assessment of treatment management, deciphering the underlying pathophysiological mechanisms, diagnostic approaches, genotype–phenotype relationships, development and validation of questionnaires relative to disease burden, or methodological aspects.

Conclusion
RaDiCo currently hosts 13 RD e-cohorts on a sharable and interoperable platform constructed on the “cloud computing” principle. New RD e-cohorts at the European and international levels are targeted.
Determining oncogenic patterns and cancer predisposition through the transcriptomic profile in Mitchell–Riley syndrome with heterotopic gastric mucosa and duodenal atresia: a case report
Authors: Calcaterra Valeria , Chiricosta Luigi , Mazzon Emanuela , Gugnandolo Agnese , Alberti Daniele , Maestri Luciano , Meroni Milena , Vestri Elettra , Verduci Elvira , Dilillo Dario , Zuccotti Gianvincenzo , Pelizzo Gloria 
Published: October 2021

Abstract
Background
Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell–Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia.

Results
We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including “Evading apoptosis” (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), “Proliferation” (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), “Sustained angiogenesis” (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), “Genomic instability” (BAD, BBC3) and “Insensitivity to anti-growth signals” (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as “PI3K signaling”, “ERK signaling”, “JAK-STAT signaling”, “Calcium signaling”, “Other RAS signaling”, “WNT signaling”.

Conclusions
In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed.
Immunoprofiling of early, untreated rheumatoid arthritis using mass cytometry reveals an activated basophil subset inversely linked to ACPA status
Authors: Koppejan H. , Hameetman M. , Beyrend G. , van Unen V. , Kwekkeboom J. C. , van der Helm-van Mil A. H. , Toes R. E. M. , van Gaalen F. A. 
Published: October 2021

Abstract
Background
Autoantibody production is a hallmark of rheumatoid arthritis (RA). Anti-citrullinated protein antibodies (ACPA) are highly disease-specific, and their presence is associated with more severe disease and poor prognosis compared to ACPA-negative patients. However, the immune cell composition associated with antibody-positive/negative disease is incompletely defined. Mass cytometry (MC) is a high-dimensional technique offering new possibilities in the determination of the immune cell composition in rheumatic diseases. Here, we set up a broad phenotyping panel to study the immune cell profile of early untreated RA to investigate if specific immune cell subsets are associated with ACPA+ versus ACPA− RA.

Methods
Freshly obtained PBMCs of early, untreated RA patients (8 ACPA+ and 7 ACPA−) were analysed using a 36-marker MC panel, including markers related to various immune lineages. Data were processed using Cytosplore for dimensional reduction (HSNE) and clustering. Groups were compared using Cytofast. A second validation cohort of cryopreserved PBMCs obtained from early RA patients (27 ACPA+ and 20 ACPA−) was used to confirm MC data by flow cytometry (FC). FC data were processed and analysed using both an unsupervised analysis pipeline and through manual gating.

Results
MC indicated no differences when comparing major immune lineages (i.e. monocytes, T and B cells), but highlighted two innate subsets: CD62L+ basophils (p = 0.33) and a subset of CD16− NK cells (p = 0.063). Although the NK cell subset did not replicate by FC, FC replication confirmed the difference in CD62L+ basophil frequency when comparing ACPA+ to ACPA− patients (mean 0.32% vs. 0.13%; p = 0.01).

Conclusions
Although no differences in major lineages were found between early ACPA+ and ACPA− RA, this study identified the reduced presence of activated basophils in ACPA-negative disease as compared to ACPA-positive disease and thereby provides the first evidence for a connection between activated basophils and ACPA status.
Treatments and outcomes in Chinese patients with serologically active clinically quiescent systemic lupus erythematosus: a retrospective observational study
Authors: Huang Hong , Mu Lin , Zhang Zhuoli , Gao Dai , Hao Yanjie , Zhou Wei 
Published: October 2021

Abstract
Objective
To clarify the frequency and outcome of patients with systemic lupus erythematosus (SLE) who achieved the clinical state as serologically active clinically quiescent (SACQ) and to identify factors associated with the flare of disease.

Methods
Clinical data of patients diagnosed as SLE and followed in Peking University First Hospital from 2009 to 2015 were retrospectively reviewed. Six hundred eighty-two patients who were followed up for more than 6 months were analyzed. SACQ was defined as an at least a 6-month period with persistent serologic activity and without clinical activity and daily dose of prednisone or equivalent were less than 7.5 mg. Serologically quiescent clinically quiescent (SQCQ) patients served as control groups. Data including demographics, initial symptoms, duration to SACQ, treatments before and after SACQ, and characteristics of the patients suffered from flare were analyzed.

Results
Among the 682 patients, 170 patients were SACQ (24.9%) and 187 patients were SQCQ. SQCQ patients (38.61 ± 15.08 years old) were older at baseline than SACQ patients (38.61 ± 15.08 years vs. 32.09 ± 14.35 years, p < 0.001). Of 170 SACQ patients, 32.9% experienced flare that was significantly higher than 15.5% of SQCQ patients (29/187). Corticosteroids (OR 1.323, 95% CI 1.129 to 1.550; p = 0.001) was an independent risk factor for flare, while antimalarials (OR 0.045, 95% CI 0.004 to 0.474; p = 0.010) and immunosuppressants (OR 0.332, 95% CI 0.156 to 0.706; p = 0.004) were protective factors in SACQ patients; however, only antimalarials was protective factors in SQCQ patients (OR 0.028, 95% CI 0.001 to 0.743; p = 0.033).

Conclusion
About one third of SLE patients with SACQ experience flare, significantly more frequent than that of patients with SQCQ. Thus, approach to prevent flare in SACQ patient is required. Maintenance therapy of hydroxychloroquine and immunosuppressant agents may be protective and beneficial treatment strategy in these patients.
Dysregulation of RNA interference components in COVID-19 patients
Authors: Mousavi Seyyed Reza , Sajjadi Maryam Sadat , Khosravian Farinaz , Feizbakhshan Sara , Salmanizadeh Sharareh , Esfahani Zahra Taherian , Beni Faeze Ahmadi , Arab Ameneh , Kazemi Mohammad , Shahzamani Kiana , Sami Ramin , Hosseinzadeh Majid , Salehi Mansoor , Lotfi Hajie 
Published: October 2021

Abstract
Objective
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus causing severe respiratory illness (COVID-19). This virus was initially identified in Wuhan city, a populated area of the Hubei province in China, and still remains one of the major global health challenges. RNA interference (RNAi) is a mechanism of post-transcriptional gene silencing that plays a crucial role in innate viral defense mechanisms by inhibiting the virus replication as well as expression of various viral proteins. Dicer, Drosha, Ago2, and DGCR8 are essential components of the RNAi system, which is supposed to be dysregulated in COVID-19 patients. This study aimed to assess the expression level of the mentioned mRNAs in COVID-19patients compared to healthy individuals.

Results
Our findings demonstrated that the expression of Dicer, Drosha, and Ago2 was statistically altered in COVID-19 patients compared to healthy subjects. Ultimately, the RNA interference mechanism as a crucial antiviral defense system was suggested to be dysregulated in COVID-19 patients.
Characterization of the non-homogenous Dirac-harmonic equation
Authors: Shi Guannan , Ding Shusen , Liu Bing 
Published: October 2021

AbstractWe introduce the non-homogeneous Dirac-harmonic equation for differential forms and characterize the basic properties of solutions to this new type of differential equations, including the norm estimates and the convergency of sequences of the solutions. As applications, we prove the existence and uniqueness of the solutions to a special non-homogeneous Dirac-harmonic equation and its corresponding reverse Hölder inequality.
Factorization of Cesàro operator and related inequalities
Authors: Roopaei Hadi 
Published: October 2021

AbstractIn this paper, we introduce two factorizations for the Cesàro matrix of order n based on Cesàro and gamma matrices. The results of these factorizations are new inequalities, one of which is a generalized version of the well-known Hardy’s inequality. Moreover, we obtain the norm of Cesàro operator of order n on Cesàro and gamma matrix domains.