bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular lesions in hereditary hemorrhagic telangiectasia: genetics and clinical characteristics
Authors: Gómez-Acebo Inés , Prado Sara Rodríguez , De La Mora Ángel , Puente Roberto Zarrabeitia , de la Roza Varela Beatriz , Dierssen-Sotos Trinidad , Llorca Javier 
Published: June 2020

Abstract
Background
The aim of our study is to study the association between eye lesions in Hereditary Hemorrhagic Telangiectasia (HHT) and other signs of the disease, as well as to characterize its genetics.

Methods
A cross-sectional study was conducted of a cohort of 206 patients studied in the HHT Unit of Hospital de Sierrallana, a reference centre for Spanish patients with HHT. Odds ratios for several symptoms or characteristics of HHT and ocular lesions were estimated using logistic regression adjusting for age and sex.

Results
The ocular involvement was associated with being a carrier of a mutation for the ENG gene, that is, suffering from a type 1 HHT involvement (OR = 2.09; 95% CI [1.17–3.72]). p = 0.012). In contrast, patients with ocular lesions have less frequently mutated ACVRL1/ALK1 gene (OR = 0.52; 95% CI [0.30–3.88], p = 0.022).

Conclusions
In conclusion, half of the patients with HHT in our study have ocular involvement. These eye lesions are associated with mutations in the ENG gene and ACVRL1/ALK1 gene. Thus, the ENG gene increases the risk of ocular lesions, while being a carrier of the mutated ACVRL1/ALK1 gene decreases said risk.
Identifying novel genetic alterations in pediatric acute lymphoblastic leukemia based on copy number analysis
Authors: Batista-Gomes Jéssica Almeida , Mello Fernando Augusto Rodrigues , de Oliveira Edivaldo Herculano Corrêa , de Souza Michel Platini Caldas , Wanderley Alayde Vieira , da Costa Pantoja Laudreisa , dos Santos Ney Pereira Carneiro , Khayat Bruna Cláudia Meireles , Khayat André Salim 
Published: June 2020

AbstractCopy number variations (CNVs) analysis may reveal molecular biomarkers and provide information on the pathogenesis of acute lymphoblastic leukemia (ALL). We investigated the gene copy number in childhood ALL by microarray and select three new recurrent CNVs to evaluate by real-time PCR assay: DMBT1, KIAA0125 and PRDM16 were selected due to high frequency of CNVs in ALL samples and based on their potential biological functions in carcinogenesis described in the literature. DBMT1 deletion was associated with patients with chromosomal translocations and is a potential tumor suppressor; KIAA0125 and PRDM16 may act as an oncogene despite having a paradoxical behavior in carcinogenesis. This study reinforces that microarrays/aCGH is it is a powerful tool for detection of genomic aberrations, which may be used in the risk stratification.
VISTA: an immune regulatory protein checking tumor and immune cells in cancer immunotherapy
Authors: Huang Xing , Zhang Xiaozhen , Li Enliang , Zhang Gang , Wang Xun , Tang Tianyu , Bai Xueli , Liang Tingbo 
Published: June 2020

AbstractVISTA (V-domain immunoglobulin suppressor of T cell activation) is a well-established immune regulatory receptor. However, pre-clinical investigations indicated more complicated influences of VISTA on cancer immunity than previously recognized. Here, we review the current knowledge on the therapeutic phenotypes and molecular mechanisms that underlie the contradictory roles of VISTA in checking anti-cancer immune responses. Furthermore, we highlight the potential indeterminacy of VISTA-targeted strategies in cancer immunotherapy, with in silico analyses. In fact, VISTA functions like a homeostatic regulator that actively normalizes immune responses. Thus, the regulatory role of VISTA in anti-cancer immunity remains to be fully elucidated.
SRSF10 inhibits biogenesis of circ-ATXN1 to regulate glioma angiogenesis via miR-526b-3p/MMP2 pathway
Authors: Liu Xiaobai , Shen Shuyuan , Zhu Lu , Su Rui , Zheng Jian , Ruan Xuelei , Shao Lianqi , Wang Di , Yang Chunqing , Liu Yunhui 
Published: June 2020

Abstract
Background
Angiogenesis plays an important role in the progress of glioma. RNA-binding proteins (RBPs) and circular RNAs (circRNAs), dysregulated in various tumors, have been verified to mediate diverse biological behaviors including angiogenesis.

Methods
Quantitative real-time PCR (qRT-PCR) and western blot were performed to detect the expression of SRSF10, circ-ATXN1, miR-526b-3p, and MMP2/VEGFA. The potential function of SRSF10/circ-ATXN1/miR-526b-3p axis in glioma-associated endothelial cells (GECs) angiogenesis was further studied.

Results
SRSF10 and circ-ATXN1 were significantly upregulated in GECs compared with astrocyte-associated endothelial cells (AECs). Knockdown of SRSF10 or circ-ATXN1 significantly inhibited cell viability, migration and tube formation of GECs where knockdown of SRSF10 exerted its function by inhibiting the formation of circ-ATXN1. Moreover, the combined knockdown of SRSF10 and circ-ATXN1 significantly enhanced the inhibitory effects on cell viability, migration and tube formation of GECs, compared with knockdown of SRSF10 and circ-ATXN1, respectively. MiR-526b-3p was downregulated in GECs. Circ-ATXN1 functionally targeted miR-526b-3p in an RNA-induced silencing complex. Up-regulation of miR-526b-3p inhibited cell viability, migration and tube formation of GECs. Furthermore, miR-526b-3p affected the angiogenesis of GECs via negatively regulating the expression of MMP2/VEGFA.

Conclusion
SRSF10/circ-ATXN1/miR-526b-3p axis played a crucial role in regulating the angiogenesis of GECs. The above findings provided new targets for anti-angiogenic therapy in glioma.
A child with a novel DDX3X variant mimicking cerebral palsy: a case report
Authors: Hu Liqin , Xin Xiaoqin , Lin Shaobin , Luo Min , Chen Junkun , Qiu Hongsheng , Ma Li , Huang Jungao 
Published: June 2020

Abstract
Background
Cerebral palsy (CP) is a non-progressive disorder of movement and posture due to a static insult to the brain. In CP, the depth of investigation is guided by the patients’ medical history and their clinical examination. Magnetic resonance imaging (MRI) has a high yield and is widely used for investigation in CP.

Case presentation
In this paper, we report a novel DDX3X variant in a girl afflicted with the X-linked mental retardation-102 (MRX102). The girl had been misdiagnosed with CP in her early life based on a comprehensive clinical evaluation and associated clinical features, such as developmental delay, reduced activities of the arms and legs, and abnormal brain MRI. Subsequently, whole-exome sequencing was applied to better distinguish between CP and actual MRX102 with similar characteristics.

Conclusions
We report on a de novo heterozygous DDX3X variant mimicking cerebral palsy and suggest a thorough and conscientious review during diagnosis of CP.
Advances in paediatrics in 2019: current practices and challenges in allergy, endocrinology, gastroenterology, public health, neonatology, nutrition, nephrology, neurology, respiratory diseases and rheumatic diseases
Authors: Caffarelli Carlo , Santamaria Francesca , Mirra Virginia , Bacchini Ermanno , Santoro Angelica , Bernasconi Sergio , Corsello Giovanni 
Published: June 2020

AbstractWe highlight the main developments that have been published during the first semester of the last year in the Italian Journal of Pediatrics. We have carefully chosen information from numerous exciting progresses issued in the Journal in the field of allergy, endocrinology, gastroenterology, neonatology, nutrition, nephrology, neurology, public health, respiratory diseases and rheumatic diseases. The impact on the care of patients has been placed in the broader context of studies that appeared in other journals. We think that many observations can be used directly to upgrade management of patients.
Computational inference of cancer-specific vulnerabilities in clinical samples
Authors: Jang Kiwon , Park Min Ji , Park Jae Soon , Hwangbo Haeun , Sung Min Kyung , Kim Sinae , Jung Jaeyun , Lee Jong Won , Ahn Sei-Hyun , Chang Suhwan , Choi Jung Kyoon 
Published: June 2020

Abstract
Background
Systematic in vitro loss-of-function screens provide valuable resources that can facilitate the discovery of drugs targeting cancer vulnerabilities.

Results
We develop a deep learning-based method to predict tumor-specific vulnerabilities in patient samples by leveraging a wealth of in vitro screening data. Acquired dependencies of tumors are inferred in cases in which one allele is disrupted by inactivating mutations or in association with oncogenic mutations. Nucleocytoplasmic transport by Ran GTPase is identified as a common vulnerability in Her2-positive breast cancers. Vulnerability to loss of Ku70/80 is predicted for tumors that are defective in homologous recombination and rely on nonhomologous end joining for DNA repair. Our experimental validation for Ran, Ku70/80, and a proteasome subunit using patient-derived cells shows that they can be targeted specifically in particular tumors that are predicted to be dependent on them.

Conclusion
This approach can be applied to facilitate the development of precision therapeutic targets for different tumors.
Therapeutic pulmonary telerehabilitation protocol for patients affected by COVID-19, confined to their homes: study protocol for a randomized controlled trial
Authors: Gonzalez-Gerez Juan Jose , Bernal-Utrera Carlos , Anarte-Lazo Ernesto , Garcia-Vidal Jose Antonio , Botella-Rico Jose Martin , Rodriguez-Blanco Cleofas 
Published: June 2020

Abstract
Background
In December 2019, 27 cases of pneumonia, of unknown cause, were identified in the province of Hubei (China). The WHO declared the situation as a Public Health Emergency of International Concern, and it was finally declared a global pandemic on March 11, 2020. The Spanish Government obliges the entire population to remain confined to their homes, with the exception of essential basic services, to stop the spread of COVID-19. Home isolation implies a notable physical deconditioning. Telerehabilitation methods have reported positive experiences, and we propose to study in affected patients of COVID-19, due to the general house confinement of the entire Spanish population.

Methods
Patients will be recruited in the regions of Andalusia, Murcia, and Valencia (Spain). Patients will remain confined to their homes, and there, they will carry out their assigned exercise program, which will be controlled telematically. Evaluators will attend to carry out all measurements at the beginning, during, and end of the study, telematically controlled. The patients will be randomly divided into three groups, two of them will perform a home exercise program (breathing exercises or non-specific exercises for muscle toning) and the third group will perform sedentary activities, using mental activation techniques, and will act as a sham group. We will evaluate respiratory variables and other variables of the physical state through physical tests, effort, and perceived fatigue. The data will be statistically analyzed, and the hypotheses will be tested between the groups, using the SPSS software, v.24, considering a 95% confidence interval.

Discussion
We will analyze the results, in terms of the level of fatigue and perceived exertion, physical health, and maintenance of respiratory activity of two types of exercise programs, toning and respiratory, applied in patients affected by COVID-19 during the period of home confinement. We intend to investigate a field not previously studied, such as the repercussion of carrying out a toning and respiratory exercise program in these patients, in historical circumstances that no one had previously observed in Spain, since the general population has never been forced to remain confined in their homes, due to a pandemic infection, by a coronavirus (COVID-19). Observing the effects that these two home exercise programs could produce in patients infected with COVID-19, we will try to better analyze and understand the mechanisms that are associated with the worsening of breathing in this type of patient.

Trial registration
Brazilian Clinical Trial Registry RBR-6m69fc. Registered on March 31, 2020.
The ProBio trial: molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer
Authors: Crippa Alessio , De Laere Bram , Discacciati Andrea , Larsson Berit , Connor Jason T. , Gabriel Erin E. , Thellenberg Camilla , Jänes Elin , Enblad Gunilla , Ullen Anders , Hjälm-Eriksson Marie , Oldenburg Jan , Ost Piet , Lindberg Johan , Eklund Martin , Grönberg Henrik 
Published: June 2020

Abstract
Background
Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis.

Methods
The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC.

Discussion
Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study.

Conclusions
The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.

Trial registration
ClinicalTrials.gov Identifier NCT03903835. Date of registration: April 4, 2019. Status: Recruiting.
A new knockdown resistance (kdr) mutation, F1534L, in the voltage-gated sodium channel of Aedes aegypti, co-occurring with F1534C, S989P and V1016G
Authors: Kushwah Raja Babu S. , Kaur Taranjeet , Dykes Cherry L. , Ravi Kumar H. , Kapoor Neera , Singh Om P. 
Published: June 2020

Abstract
Background
Aedes aegypti is a primary vector of dengue, chikungunya and Zika infections in India. In the absence of specific drugs or safe and effective vaccines for these infections, their control relies mainly on vector control measures. The emergence of insecticide resistance in vectors, especially against pyrethroids, is a serious threat to the insecticide-based vector control programme. This study reports the presence of multiple knockdown resistance (kdr) mutations present in an Ae. aegypti population from Bengaluru (India), including a new mutation F1534L.

Methods
Aedes aegypti collected from Bengaluru were subjected to insecticide susceptibility tests with DDT, deltamethrin and permethrin. The DNA sequencing of partial domain II, III and IV of the voltage-gated sodium channel (VGSC) was performed to screen kdr mutations present in the population and PCR-based assays were developed for their detection. Genotyping of kdr mutations was done using PCR-based assays, allelic frequencies were determined, and tests of genetic association of kdr mutations with the insecticide resistance phenotype were performed.

Results
The Ae. aegypti population was resistant to DDT, deltamethrin and permethrin. The DNA sequencing of the VGSC revealed the presence of four kdr mutations, i.e. S989P and V1016G in domain II and two alternative kdr mutations F1534C and F1534L in domain III. Allele-specific PCR assays (ASPCR) were developed for the detection of kdr mutations S989P and V1016G and an existing PCR-RFLP based strategy was modified for the genotyping of all three known kdr mutations in domain III (F1534L, F1534C and T1520I). Genotyping of Ae. aegypti samples revealed a moderate frequency of S989P/V1016G (18.27%) and F1534L (17.48%), a relatively high frequency of F1534C (50.61%) and absence of T1520I in the population. Mutations S989P and V1016G were in complete linkage disequilibrium in this population while they were in linkage equilibrium with kdr mutations F1534C and F1534L. The alleles F1534C and F1534L are genetically associated with permethrin resistance.

Conclusions
A new kdr mutation, F1534L, was found in an Ae. aegypti population from Bengaluru (India), co-occurring with the other three mutations S989P, V1016G and F1534C. The findings of a new mutation have implications for insecticide resistance management.
Repeated assessment of work-related exhaustion: the temporal stability of ratings in the Lund University Checklist for Incipient Exhaustion
Authors: Persson Roger , Österberg Kai 
Published: June 2020

Abstract
Objective
Screening inventories are important tools in clinical settings and research but may be sensitive to temporary fluctuations. Therefore, we revisited data from a longitudinal study with the Lund University Checklist for Incipient Exhaustion (LUCIE) that comprised occupationally active individuals (n = 1355; 27–52 years; 57% women) and one initial paper and pencil survey and 10 subsequent equally spaced online surveys. In the present study we examine to what extent the LUCIE scores changed across 3 years (11 assessments) and whether episodes of temporary elevated LUCIE scores (LTE) coincided with reports of negative or positive changes at work or in private life.

Results
In the total sample, the prevalence rates for the four LUCIE classifications of signs of increasing exhaustion (from no exhaustion to possible exhaustion disorder) ranged from 65.4–73.0%, 16.6–20.9%, 6.2–9.6%, and 3.4–5.0%. Of 732 individuals screened for LTE episodes, 16% had an LTE episode. The LTE episodes typically coincided with reports of adverse changes at work or, to a lesser extent, in private life. Thus, LUCIE classifications appear reliable and lend themselves to repeated use on the same individuals, or group of individuals. Even single episodes of elevated LUCIE scores seem appropriately to indicate adverse reactions to the work situation.
Prevalence and susceptibility to antibiotics from Campylobacter jejuni and Campylobacter coli isolated from chicken meat in southern Benin, West Africa
Authors: Kouglenou Sylvain Daton , Agbankpe Alidehou Jerrold , Dougnon Victorien , Djeuda Armando Djiyou , Deguenon Esther , Hidjo Marie , Baba-Moussa Lamine , Bankole Honore 
Published: June 2020

Abstract
Objective
Poultry is commonly considered to be the primary vehicle for Campylobacter infection in humans. The aim of this study is to assess the risk of Campylobacteriosis in chicken meat consumers in southern Benin by assessing the prevalence and resistance profile of Campylobacter coli and Campylobacter jejuni isolated from chicken thigh in Southern Benin.

Results
The contamination rate of Campylobacter in the samples was 32.8%. From this percentage, 59.5% were local chicken thighs and 40.5% of imported chicken thighs (p = 0.045). After molecular identification, on the 256 samples analyzed, the prevalence of C. jejuni was 23.4% and 7.8% for C. coli, with a concordance of 0.693 (Kappa coefficient of concordance) with the results from phenotypic identification. Seventy-two-point seven percent of Campylobacter strains were resistant to Ciprofloxacin, 71.4% were resistant to Ampicillin and Tetracycline. 55.8% of the strains were multi-drug resistant.
Incidence of malignancy in patients with common variable immunodeficiency according to therapeutic delay: an Italian retrospective, monocentric cohort study
Authors: Pedini Veronica , Verga Jacopo Umberto , Terrenato Irene , Menghini Denise , Mezzanotte Cristina , Danieli Maria Giovanna 
Published: June 2020

Abstract
Background
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency and has a broad spectrum of clinical manifestations. Among non-infectious complications, an increased incidence of malignancies may have a special relevance for survival, but little is known about treatment efficacy on malignant complications.

Methods
This was a monocenter retrospective study on CVID patients, designed to provide preliminary data for the investigation of the possible link between therapeutic delay and tumor incidence.

Results
A total of 67 CVID subjects were included. The median diagnostic delay was 7.5 years (range: 0–63 years), and the median therapeutic delay was 8.5 years (range: 0–67 years). Malignancies were diagnosed in 18 (27%) patients. Eight out of 18 (44%) patients with a malignancy had lymphoma. Patients who developed a malignancy showed a longer therapeutic delay in comparison to patients with no malignancy, although no statistical significance was achieved (11 years vs 8 years, respectively, p = 0.424). We observed a lower frequency of malignancy in CVID patients with reduced therapeutic delay compared with patients with therapeutic delay ≥ 10 years. With a therapeutic delay of > 1 year, 74% had no tumor, and 25% had a tumor; with a therapeutic delay of > 10 years, 65% had no tumor and 35% had a malignancy. Among patients who had no malignancy, 64% had a therapeutic delay of < 10 years, and 36% had a therapeutic delay of ≥ 10 years. Among patients with malignancy, 47% of subjects had a therapeutic delay < 10 years, and 53% a therapeutic delay ≥ 10 years.

Conclusions
The observation of clinical characteristics of our patients with CVID may suggest that an early institution of IgG replacement therapy could be of benefit for the prevention of malignant complications.
Name of the registry: Comitato Etico Regionale delle Marche. Trial registration number: 1505. Date of registration: 27/10/2016, Retrospectively registered URL of trial registry record: http://www.ospedaliriuniti.marche.it/portale/archivio13_cerm-ancona_0_446_1.html. The trial was not registered before the first participant was enrolled
Atypical parkinsonism and intrathecal anti-glutamic acid decarboxylase antibodies – an unusual association: a case report
Authors: Stefanoni Giovanni , Formenti Anna , Tremolizzo Lucio , Stabile Andrea , Appollonio Ildebrando , Ferrarese Carlo 
Published: June 2020

Abstract
Background
Immunological causes of parkinsonism are very rare and usually characterized by early presentation, poor response to levodopa, and additional clinical features.

Case presentation
We describe a 58-year-old white man who presented with a 1-year history of gait disturbance with disequilibrium leading to falls. We report an association between parkinsonism and presence of anti-glutamic acid decarboxylase antibodies in his cerebrospinal fluid, discussing clinical presentation and follow-up.

Conclusions
Besides the possibility of a casual association, this case allows us to hypothesize an alternative pathophysiological mechanism of parkinsonism implying interference with glutamic acid decarboxylase and gamma-aminobutyric acid functions, eventually resulting in basal ganglia circuit dysregulation.