bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cutaneous neurofibromas: patients’ medical burden, current management and therapeutic expectations: results from an online European patient community survey
Authors: Guiraud Marlene , Bouroubi Athmane , Beauchamp Roxane , Bocquet Arnaud , Grégoire Jean-Marc , Rauly-Lestienne Isabelle , Blanco Ignacio , Wolkenstein Pierre , Schmitt Anne-Marie 
Published: December 2019

Abstract
Background
Neurofibromatosis type 1 is an inherited condition with variable phenotypic expression and a high medical and social burden.
The objectives of this patient survey were to better understand the real-world experiences of patients living with cutaneous neurofibromas (cNF), to perceive their satisfaction and feelings about cNF current management (only laser and surgery are currently available), and to highlight their expectations of new therapeutic modalities.

Results
One hundred seventy patients from 4 European countries took part in the study, 65% (n = 110) were women and mean age was 39 years old. 96% (n = 164) of respondents have cNF on visible parts of the body and the survey confirmed that total number of cNF and visibility increase with age.
Patients reported that cNF mainly impacts everyday mood, general daily life and social life. The visibility of cNF had a higher impact than their number.
92% (n = 156) of patients have a regular and multidisciplinary medical follow-up. The dermatologist is one of the most consulted healthcare professionals.
76% (n = 130) of respondents have treated their cNF: 65% (n = 111) had surgery and 38% (n = 64) had multiple laser sessions. Frequency of operations and regrowth of cNF were the two most unsatisfactory aspects with both treatments for patients. Indeed, after removal, new cNF appear in more than 75% (n = 128) of cases.
As a future treatment, patients expected a topical (30%, n = 51) or oral medication (29%, n = 50). Around 2 out of 3 patients would agree to take it at least once a day or more for life but they would like a well-tolerated treatment.
According to patients, the most important effectiveness criteria of a new treatment are to block cNF growth and reduce their number. 70% (n = 119) of patients would consider a future treatment moderately effective to very effective if it could clear 30% of cNF.

Conclusions
This first cNF European patient community survey confirmed that the visible stigma and unaesthetic aspect of cNF have an important impact on patients’ quality of life. The survey highlighted that patients were not entirely satisfied with the actual surgery and laser treatments and revealed their clear and realistic expectations for future treatment of cNF.
Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for Alzheimer’s disease
Authors: Jia Lin , Piña-Crespo Juan , Li Yonghe 
Published: December 2019

AbstractAlzheimer’s disease (AD) is an aging-related neurological disorder characterized by synaptic loss and dementia. Wnt/β-catenin signaling is an essential signal transduction pathway that regulates numerous cellular processes including cell survival. In brain, Wnt/β-catenin signaling is not only crucial for neuronal survival and neurogenesis, but it plays important roles in regulating synaptic plasticity and blood-brain barrier integrity and function. Moreover, activation of Wnt/β-catenin signaling inhibits amyloid-β production and tau protein hyperphosphorylation in the brain. Critically, Wnt/β-catenin signaling is greatly suppressed in AD brain via multiple pathogenic mechanisms. As such, restoring Wnt/β-catenin signaling represents a unique opportunity for the rational design of novel AD therapies.
RT2 PCR array screening reveals distinct perturbations in DNA damage response signaling in FUS-associated motor neuron disease
Authors: Wang Haibo , Rangaswamy Suganya , Kodavati Manohar , Mitra Joy , Guo Wenting , Guerrero Erika N. , Van Den Bosch Ludo , Hegde Muralidhar L. 
Published: December 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that has been linked to defective DNA repair. Many familial ALS patients harbor autosomal dominant mutations in the gene encoding the RNA/DNA binding protein ‘fused in sarcoma’ (FUS) commonly inducing its cytoplasmic mislocalization. Recent reports from our group and others demonstrate a role of FUS in maintaining genome integrity and the DNA damage response (DDR). FUS interacts with many DDR proteins and may regulate their recruitment at damage sites. Given the role of FUS in RNA transactions, here we explore whether FUS also regulates the expression of DDR factors. We performed RT2 PCR arrays for DNA repair and DDR signaling pathways in CRISPR/Cas9 FUS knockout (KO) and shRNA mediated FUS knockdown (KD) cells, which revealed significant (> 2-fold) downregulation of BRCA1, DNA ligase 4, MSH complex and RAD23B. Importantly, similar perturbations in these factors were also consistent in motor neurons differentiated from an ALS patient-derived induced pluripotent stem cell (iPSC) line with a FUS-P525L mutation, as well as in postmortem spinal cord tissue of sporadic ALS patients with FUS pathology. BRCA1 depletion has been linked to neuronal DNA double-strand breaks (DSBs) accumulation and cognitive defects. The ubiquitin receptor RAD23 functions both in nucleotide excision repair and proteasomal protein clearance pathway and is thus linked to neurodegeneration. Together, our study suggests that the FUS pathology perturbs DDR signaling via both its direct role and the effect on the expression of DDR genes. This underscors an intricate connections between FUS, genome instability, and neurodegeneration.
LSD1/KDM1A inhibitors in clinical trials: advances and prospects
Authors: Fang Yuan , Liao Guochao , Yu Bin 
Published: December 2019

AbstractHistone demethylase LSD1 plays key roles during carcinogenesis, targeting LSD1 is becoming an emerging option for the treatment of cancers. Numerous LSD1 inhibitors have been reported to date, some of them such as TCP, ORY-1001, GSK-2879552, IMG-7289, INCB059872, CC-90011, and ORY-2001 currently undergo clinical assessment for cancer therapy, particularly for small lung cancer cells (SCLC) and acute myeloid leukemia (AML). This review is to provide a comprehensive overview of LSD1 inhibitors in clinical trials including molecular mechanistic studies, clinical efficacy, adverse drug reactions, and PD/PK studies and offer prospects in this field.
Clinical correlates of blood-derived circulating tumor DNA in pancreatic cancer
Authors: Patel Hitendra , Okamura Ryosuke , Fanta Paul , Patel Charmi , Lanman Richard B. , Raymond Victoria M. , Kato Shumei , Kurzrock Razelle 
Published: December 2019

Abstract
Background
Treatment outcomes for patients with advanced pancreatic ductal adenocarcinoma (PDAC) remain dismal. There are unmet needs for understanding the biologic basis of this malignancy using novel next-generation sequencing technologies. Herein, we investigated the clinical utility of circulating tumor DNA (ctDNA) (the liquid biopsy) in this malignancy.

Methods
ctDNA was analyzed in 112 patients with PDAC (54–73 genes) and tissue DNA in 66 patients (315 genes) (both clinical-grade next-generation sequencing). Number of alterations, %ctDNA, concordance between ctDNA and tissue DNA, and correlation of ctDNA results with survival were assessed.

Results
The most common genes altered in ctDNA were TP53 (46% of patients, N = 51) and KRAS (44%, N = 49). Median number of characterized ctDNA alterations per patient was 1 (range, 0–6), but patients with advanced PDAC had significantly higher numbers of ctDNA alterations than those with surgically resectable disease (median, 2 versus 0.5, P = 0.04). Overall, 75% (70/94) of advanced tumors had ≥ 1 ctDNA alteration. Concordance rate between ctDNA and tissue DNA alterations was 61% for TP53 and 52% for KRAS. Concordance for KRAS alterations between ctDNA and tissue DNA from metastatic sites was significantly higher than between ctDNA and primary tumor DNA (72% vs 39%, P = 0.01). Importantly, higher levels of total %ctDNA were an independent prognostic factor for worse survival (hazard ratio, 4.35; 95% confidence interval, 1.85–10.24 [multivariate, P = 0.001]). A patient with three ctDNA alterations affecting the MEK pathway (GNAS, KRAS, and NF1) attained a response to trametinib monotherapy ongoing at 6 months.

Conclusions
Our findings showed that ctDNA often harbored unique alterations some of which may be targetable and that significantly greater numbers of ctDNA alterations occur in advanced versus resectable disease. Furthermore, higher ctDNA levels were a poor prognostic factor for survival.
Italian guidelines for the prevention and management of dental trauma in children
Authors: Cagetti Maria Grazia , Marcoli Piero Alessandro , Berengo Mario , Cascone Piero , Cordone Livio , Defabianis Patrizia , De Giglio Osvalda , Esposito Nicola , Federici Antonio , Laino Alberto , Majorana Alessandra , Nardone Michele , Pinchi Vilma , Pizzi Silvia , Polimeni Antonella , Privitera Maria Grazia , Talarico Valentina , Zampogna Stefania 
Published: December 2019

AbstractDental trauma is a frequent occurrence in children and adolescent and a correct diagnosis and treatment are essential for a favourable long-term prognosis. The present Guidelines aim to formulate evidence-based recommendations to assist dentists, paediatricians, surgeons, teachers, school and sport staff, parents in the prevention and first aid of dental trauma in children and to provide a careful assessment of the medico-legal implications, reviewing the first draft of the guidelines published in 2012. A multidisciplinary panel on the behalf of the Italian Ministry of Health and in collaboration with the WHO Collaborating Centre for Epidemiology and Community Dentistry of Milan, developed this document. The following four queries were postulated: 1) Which kind of precautions the health personnel, parents, sports and educational personnel must activate in order to prevent the dental trauma damage? 2) How an orofacial trauma in paediatric patients should be managed either in the Emergency Care Unit and/or in private dental office? 3) What criteria should be adopted by a dentist private practitioner to fill in a certificate in cases of dental and/or tempomandibular joint trauma occurring in children and adolescents? 4) What are the elements that should lead clinicians to suspect a non-accidental dental trauma? A systematic review and analysis of the scientific literature published in English, Italian and French from 2007 to 2017 regarding dental trauma in children and adolescents aged 0–18 years was performed, and about 100 papers were analysed and included. The following four domains were analysed and discussed: Dental Trauma Prevention Strategies and Health Education, First aid in orofacial and dental trauma, Certificate of the dental trauma, Oral and dental signs of child abuse and neglect. Twenty-eight recommendations were draw up and codified by the panel according to the Methodological handbook, produced by the Istituto Superiore di Sanità, in order to guide physicians in the prevention and first aid of dental trauma in children and adolescents. In addition, a careful assessment of the medico-legal implications is reported in this document.
Association of a novel circulating tumor DNA next-generating sequencing platform with circulating tumor cells (CTCs) and CTC clusters in metastatic breast cancer
Authors: Davis Andrew A. , Zhang Qiang , Gerratana Lorenzo , Shah Ami N. , Zhan Youbin , Qiang Wenan , Finkelman Brian S. , Flaum Lisa , Behdad Amir , Gradishar William J. , Platanias Leonidas C. , Cristofanilli Massimo 
Published: December 2019

Abstract
Purpose
Liquid biopsies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), can be used to understand disease prognosis, tumor heterogeneity, and dynamic response to treatment in metastatic breast cancer (MBC). We explored a novel, 180-gene ctDNA panel and the association of this platform with CTCs and CTC clusters.

Methods
A total of 40 samples from 22 patients with MBC were included in the study. For the primary analysis, all patients had ctDNA sequencing using the PredicinePLUS™ platform. CTCs and CTC clusters were examined using the CellSearch™ System. Clinical and pathological variables were reported using descriptive analyses. Associations between CTC count and specific genomic alterations were tested using the Mann-Whitney U test.

Results
Of 43 sequenced patients, 40 (93%) had at least one detectable genomic alteration with a median of 6 (range 1–22). Fifty-seven different genes were altered, and the landscape of genomic alterations was representative of MBC, including the commonly encountered alterations TP53, PTEN, PIK3CA, ATM, BRCA1, CCND1, ESR1, and MYC. In patients with predominantly hormone-receptor-positive MBC, the number of CTCs was significantly associated with alterations in ESR1 (P < 0.005), GATA3 (P < 0.05), CDH1 (P < 0.0005), and CCND1 (P < 0.05) (Mann-Whitney U test). Thirty-six percent of patients had CTC clusters, which were associated with alterations in CDH1, CCND1, and BRCA1 (all P < 0.05, Mann-Whitney U test). In an independent validation cohort, CTC enumeration confirmed significant associations with ESR1 and GATA3, while CTC clusters were significantly associated with CDH1.

Conclusions
We report on a novel ctDNA platform that detected genomic alterations in the vast majority of tested patients, further indicating potential clinical utility for capturing disease heterogeneity and for disease monitoring. Detection of CTCs and CTC clusters was associated with particular genomic profiles.
Secukinumab efficacy on resolution of enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies
Authors: Coates Laura C. , Wallman Johan K. , McGonagle Dennis , Schett Georg A. , McInnes Iain B. , Mease Philip J. , Rasouliyan Lawrence , Quebe-Fehling Erhard , Asquith Darren L. , Fasth Andreas E. R. , Pricop Luminita , Gaillez Corine 
Published: December 2019

AbstractBackgroundEnthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies.MethodAssessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3–6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment.ResultsA total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3–6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg.ConclusionSecukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis.Trial registrationFUTURE 2:ClinicalTrials.gov,NCT01752634(date of study registration: December 19, 2012), and EudraCT,2012-004439-22(date of study registration: December 12, 2012)FUTURE 3:ClinicalTrials.gov,NCT01989468(date of study registration: November 21, 2013), and EudraCT,2013-004002-25(date of study registration: December 17, 2013)
Survey of knowledge for diagnosing and managing prediabetes in Latin-America: cross-sectional study
Authors: Garay Jennifer , Camacho Paul A. , Lopez-Lopez Jose , Alvernia Juliana , Garcia Marcela , Cohen Daniel D. , Calderon Carlos , Lopez-Jaramillo Patricio 
Published: December 2019

Abstract
Background
Prediabetes has been proposed as a risk factor for the development of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). Despite the clinical importance of prediabetes, little is known about the level of knowledge, beliefs and barriers to screening and treating prediabetes amongst care health providers in Latin America. The aim of the present survey was to evaluate the knowledge and beliefs about prediabetes amongst in Latin American health care providers.

Methodology
In a cross-sectional study, we adapted the written survey designed by the Johns Hopkins University group, and applied it to health care providers across Latin America during three meetings, in 2017, and with physicians from primary care centers in Bucaramanga, Colombia convened in 2017. The survey consisted of questions under four headings, diabetes screening, management of prediabetes, pharmacological treatment—metformin use, and demographic information. We perform a descriptive analysis to determine the differences in responses between different medical specialties.

Results
The majority of the care providers that answered the survey were Colombian physicians, 54.5% of respondents had 10 years or more since completing their training and more women responded. Only 9.5% identified the 12 prediabetes risk factors described in the literature. The most common risk factor identified was a family history of diabetes, followed by overweight, a sedentary lifestyle and dyslipidemia, while ethnicity was the risk factor least commonly. 47.1% answered that laboratory tests to detect prediabetes are fasting glucose and HbA1C, 82.5% correctly identified fasting plasma glucose as the best test, 35.9% correctly responded that to the recommended weight loss goal is 5 to 7% and 49.1% that 150 min is considered the minimum level of physical activity per week. 78% agreed that the identification and treatment of prediabetes is important. 56% believed that patients with prediabetes progress more rapidly to diabetes and 40.6% considered that metformin could reduce the risk of diabetes in patients already diagnosed with prediabetes.

Conclusion
These results demonstrate that there are important gaps in the knowledge of the diagnosis, clinical implications and management of prediabetes amongst Latin America health providers.
Gene expression analysis of membrane progesterone receptors in women with recurrent spontaneous abortion: a case control study
Authors: Rahnama Reyhane , Rafiee Mitra , Fouladi Saloomeh , Akbari-Fakhrabadi Maryam , Mehrabian Ferdos , Rezaei Abbas 
Published: December 2019

AbstractObjectiveRecurrent spontaneous abortion (RSA) is a condition which is defined as three consecutive pregnancy losses prior to 20 weeks from the last menstrual period. Progesterone is a steroid hormone that has an essential role in the implantation and maintenance of pregnancy. The progesterone signaling is performed by nuclear progesterone receptors (NPRs) and membrane progesterone receptors (mPR). The aim of this study was to analyze gene expression ofmPR-α,mPR-βand NPR in the endometrium of patients with a history of RSA compared to normal fertile women.ResultsIn this study, endometrial samples were obtained from 10 women with a history of RSA and 10 fertile women during days 10–14 of menstrual cycle. Relative expression ofmPR-α,mPR-βandNPRgenes were studied by a quantitative real time polymerase chain reaction (qRT-PCR) and compared between the two groups. The mean relative expression ofmPR-βgene was significantly lower in the case group compared to the fertile women (p < 0.05). However, the gene expression ofmPR-αandNPRshowed no significant difference between two groups. The findings suggest a reduction of endometrial gene expression ofmPR-βin RSA patients may play an important role in pathogenesis of RSA.
Use of ecological momentary assessment to detect variability in mood, sleep and stress in bipolar disorder
Authors: Li Han , Mukherjee Dahlia , Krishnamurthy Venkatesh Basappa , Millett Caitlin , Ryan Kelly A. , Zhang Lijun , Saunders Erika F. H. , Wang Ming 
Published: December 2019

Abstract
Objective
Our aim was to study within-person variability in mood, cognition, energy, and impulsivity measured in an Ecological Momentary Assessment paradigm in bipolar disorder by using modern statistical techniques. Exploratory analyses tested the relationship between bipolar disorder symptoms and hours of sleep, and levels of pain, social and task-based stress. We report an analysis of data from a two-arm, parallel group study (bipolar disorder group N = 10 and healthy control group N = 10, with 70% completion rate of 14-day surveys). Surveys of bipolar disorder symptoms, social stressors and sleep hours were completed on a smartphone at unexpected times in an Ecological Momentary Assessment paradigm twice a day. Multi-level models adjusted for potential subject heterogeneity were adopted to test the difference between the bipolar disorder and health control groups.

Results
Within-person variability of mood, energy, speed of thoughts, impulsivity, pain and perception of skill of tasks was significantly higher in the bipolar disorder group compared to health controls. Elevated bipolar disorder symptom domains in the evening were associated with reduced sleep time that night. Stressors were associated with worsening of bipolar disorder symptoms. Detection of symptoms when an individual is experiencing difficulty allows personalized, focused interventions.
Reconstruction of the pelvis after traumatically induced bilateral partial hemipelvectomy: a case report
Authors: Kamitomo Ayako , Hayashi Minoru , Tokunaka Ryohei , Yoshida Yuki , Tatsuta Sayo , Sasaki Yoshie 
Published: December 2019

Abstract
Background
Traumatic hemipelvectomy is a catastrophic fracture of the pelvis as a result of high-energy trauma, such as in a car accident. There have been few case reports of traumatic hemipelvectomy because many of these patients die before they are transferred to a hospital. However, an increasing number of patients are being saved and admitted to hospital due to improvements in resuscitation and the emergency response system. Accordingly, there has been a growing body of reports on the management and reconstruction of traumatic hemipelvectomy.

Case presentation
A healthy 20-year-old Japanese man was trapped beneath a 3-ton steel frame while working on a crane. We describe here a very challenging case of traumatically induced bilateral partial hemipelvectomy with successful reconstruction of our patient’s pelvis using a unilateral anterolateral thigh flap.

Conclusion
To the best of our knowledge, there have been few reports of bilateral hemipelvectomy and our case is the first to be successfully treated with a unilateral anterolateral thigh flap.