bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mature and immature β-cells both contribute to islet function and insulin release
Authors: Nasteska Daniela , Fine Nicholas , Ashford Fiona , Cuozzo Federica , Viloria Katrina , Smith Gabrielle , Dahir Aisha , Dawson Peter , Lai Yu-Chiang , Bastidas-Ponce Aimée , Bakhti Mostafa , Rutter Guy , Fiancette Remi , Nano Rita , Piemonti Lorenzo , Lickert Heiko , Zhou Qiao , Akerman Ildem , Hodson David 
Published: July 2020

Abstract
Transcriptionally mature and immature β-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that differences in β-cell maturity, defined using PDX1 and MAFA expression, are required for proper islet operation. Functional mapping of rodent and human islets containing proportionally more mature β-cells revealed defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of mature β-cells led to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, the islet signalling network was found to contribute to differences in maturity across β-cells. During metabolic stress, islet function could be restored by redressing the balance between immature and mature β-cells. Thus, preserving a balance between immature and mature β-cells might be important for islet engineering efforts and more broadly the treatment of type 1 and type 2 diabetes.
Generating Real-World Evidence from Unstructured Clinical Notes to Examine Clinical Utility of Genetic Tests: Use Case in BRCAness
Authors: ZHAO Yiqing , Weroha Saravut J , Goode Ellen , Liu Hongfang , Wang Chen 
Published: July 2020

Abstract
Background: Next-generation sequencing provides comprehensive information about individuals’ genetic makeup and is commonplace in oncology clinical practice. However, the utility of genetic information in clinical decision-making process has not been examined extensively from a real-world, data-driven perspective. Through mining real-world data (RWD) from clinical notes, we could extract patients’ genetic information and further associate treatment decisions with genetic information.Methods: We proposed a real-world evidence (RWE) study framework that incorporates context-based natural language processing (NLP) methods and data quality examination before final association analysis. The framework was demonstrated on a Foundation-tested women cancer cohort (N=196). Upon retrieval of patients’ genetic information using NLP system, we assessed completeness of genetic data captured in unstructured clinical notes according a genetic data-model. We examined the distribution of different topics regarding BRCA1/2 throughout patients’ treatment process, and then analyzed the association between BRCA1/2 mutation status and the discussion/prescription of targeted therapy. Results: We identified seven topics in clinical context of genetic mentions including: Information, Evaluation, Insurance, Order, Negative, Positive, and Variants of unknown significance (VUS). Our rule-based system achieved a precision of 0.87, recall of 0.93 and F-measure of 0.91. Our machine learning system achieved a precision of 0.901, recall of 0.899 and F-measure of 0.9 for four-topic classification and a precision of 0.833, recall of 0.823 and F-measure of 0.82 for seven-topic classification. We found in result-containing sentences, capture of BRCA1/2 mutation information was 75%, but detailed variant information (e.g. variant types) is largely missing. Using cleaned RWD, significant associations were found between BRCA1/2 positive mutation and targeted therapies.Conclusions: In conclusion, we demonstrated a framework to generate RWE using RWD from different clinical sources. Rule-based NLP system achieved the best performance for resolving contextual variability when extracting RWD from unstructured clinical notes. Data quality issue such as incompleteness and discrepancies exist thus manual data cleaning is needed before further analysis can be performed. Finally, we were able to use cleaned RWD to evaluate real-world utility of genetic information to initiate prescription of targeted therapy.
Functional spreading of hyperexcitability induced by human and synthetic intracellular Aβ oligomers
Authors: Fernandez-Perez Eduardo Javier , Muñoz Braulio , Bascuñan Denisse Andrea , Peters Christian , Riffo-Lepe Nicolas Osiel , Espinoza María Paz , Morgan Peter James , Filippi Caroline , Bourboulou Romain , Sengupta Urmi , Kayed Rakez , Epsztein Jerome , Aguayo Luis 
Published: July 2020

Abstract
Background: Intracellular amyloid-beta oligomers (iAβo) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimer’s disease (AD). However, to date, no mechanism linking them has been reported. Methods: Here, the effects of human AD brain-derived (h-iAβo) and synthetic (iAβo) peptides on synaptic currents and action potential (AP) firing were investigated in hippocampal neurons in vitro , ex vivo and in vivo. Results: Starting from 500 pM, iAβo rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-related fluorescence changes indicated that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iAβo, indicating that iAβo can increase network excitability at a distance. Current-clamp recordings suggested that iAβo increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties. Conclusion: These results strongly indicate that iAβo causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offer an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.
Acute Pulmonary Embolism in Coronavirus Disease 2019
Authors: Guo Yanan , Sun Wenwu , Liu Yanli , Lv Yanling , Zhao Su , Chen Liangkai , Liu Zhengqing , Yu Li 
Published: July 2020

Abstract
Background Pulmonary embolism is a severe condition prone to misdiagnosis given its nonspecific signs and symptoms. Previous studies on the pneumonia outbreak caused by coronavirus disease 2019 (COVID-19) showed a number of patients with elevated d-dimer, whether those patients combined with pulmonary embolism got our attention. Methods Data on clinical manifestations, laboratory and radiological findings, treatment, and disease progression of 19 patients with laboratory-confirmed COVID-19 pneumonia,who completed computed tomographic pulmonary angiography (CTPA) during hospitalization in the Central Hospital of Wuhan from January 2 to March 26, 2020, were reviewed. Results Of the 19 suspected pulmonary embolism and subjected to CTPA patients, six were diagnosed with pulmonary embolism. The Wells’ score of the six patients with pulmonary embolism was 0–1, which suggested a low risk of pulmonary embolism. The median level of d-dimers collected at the day before or on the day of CTPA completion in the patients with pulmonary embolism was 18.36 (interquartile range [IQR]: 6.69–61.46) µg/mL, which was much higher than that in the patients without pulmonary embolism (median 9.47 [IQR: 4.22–28.02] µg/mL). Of the 6 patients diagnosed with pulmonary embolism, all patients received anticoagulant therapy, 5 of which survived and were discharged and 1 died. Conclusion A potential causal relationship exists between COVID-19 infection and pulmonary embolism, but whether this phenomenon is common remains uncertain. The clinical manifestations of COVID-19 patients who developed pulmonary embolism are similar to those of patients with increased d-dimer alone, prompting a significant challenge on differential diagnoses.
Improving knowledge, attitude, and practices of complementary feeding using practical intervention training for parents living in stunting villages in Central Lombok, Indonesia: A community-based study
Authors: Tengkawan Jeslyn , Septisari Ayu Anandhika , Ihyauddin Zulfikar , Karuniawaty Titi Pambudi , Nurbaiti Lina , Dewi Nurhandini Eka , Sekartini Rini 
Published: July 2020

Abstract
BackgroundStunting is one of the major child public health concerns in Indonesia. West Nusa Tenggara (WNT) province, specifically, is still struggling to reduce its stunting prevalence as it is still higher than the average national prevalence, accounted for 31.4% in 2018. Ensuring knowledge, attitude, and practices (KAP) of complementary feeding among parents is relevant to succeeding in the implementation of stunting reduction programs. This study aimed to assess the effectiveness of interventions in the form of seminar and workshop on preparing complementary feeding in stunting villages in Central Lombok, Indonesia.MethodsThis is a quasi-experimental community-based study, held in three stunting villages of Central Lombok, WNT, from June until August 2019. Three villages were chosen randomly from ten stunting-villages in Central Lombok District and divided into three groups, i.e., control group, seminar group and seminar and workshop group. We assessed KAP before and after intervention with a four-week interval.ResultsA total of 205 participants were enrolled in this study, consisting of 67, 70, and 68 participants for the control group, the first intervention group, and the second intervention group, respectively. Most participants had poor knowledge (75.1%) of complementary feeding in the baseline assessment. We found an insignificant change in knowledge, but notable alterations in attitudes and practices after intervention. Seminar intervention could increase practice, while complete intervention (seminar and workshop) could increase both practices and attitudes significantly (p = 0.015 dan p = 0.014). We found that complete intervention was more effective in increasing attitudes compared to the control group (p = 0.039). In contrast, practices in both seminar and complete intervention was increased effectively than controls (p = 0.006 vs. p = 0.008), and no differences between seminar and complete intervention group (p = 0.943).ConclusionsComplementary feeding KAP among parents in stunting villages in Central Lombok was inadequate. Our study showed that the combination of seminar and workshop increased parents’ attitudes and practices, while the seminar only increased parents’ practices. We suggest further prospective study to assess how long the effectivity of such interventions could impact and last; and obtain any cultural concerns.Trial registration: 376/UN18.8/ETIK/2018
Serum miRNA Profile in Diabetic Patients with Ischemic Heart Disease as a Promising non-invasive Biomarker
Authors: Bielska Agnieszka , Bauer Witold , Szalkowska Anna , Sidorkiewicz Iwona , Skwarska Anna , Raczkowska Justyna , Ostrowski Damian , Gugala Kamil , Dobrzycki Slawomir , Niemira Magdalena , Kretowski Adam 
Published: July 2020

Abstract
Background

The increasing morbidity and mortality of type 2 diabetic mellitus (T2DM) patients with ischemic heart disease (IHD) highlights an urgent need to identify early biomarkers, which would help to predict individual risk of development of IHD. Here, we postulate that circulating serum-derived miRNAs may serve as potential biomarkers for early IHD diagnosis and help to identify diabetic individuals with a predisposition to undergo IHD.
Methods

We obtained serum samples from T2DM patients either with IHD or IHD-free and analysed the expression levels of 798 miRNAs using the NanoString nCounter Technology Platform. The prediction of the putative miRNAs targets was performed using the Ingenuity Pathway Analysis (IPA) software. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs.
Results

Our data showed that 9 miRNAs (miR-1224-5p, miR-1303, miR-3147, miR-4455, miR-498, miR-548b-3p, miR-548d-3p, miR-615-3p, miR-651-5p) were significantly upregulated in T2DM IHD patients compared to T2DM patients without IHD. In patients with upregulated miRNA, functional enrichment analysis of target genes by IPA indicated networks and canonical pathways involved in the pathology of the cardiovascular system. All tested miRNAs showed high diagnostic value (AUC > 0.8).
Conclusions

Taken together, our findings suggest that circulating miRNAs might have a crucial role in the development of IHD in diabetic patients and may be used as a potential biomarker for early diagnosis.
Comparative Cost Analysis of Cervical Cancer Screening Programme Based on Molecular Detection of Hpv In Spain
Authors: Ibáñez Raquel , Mareque María , Granados Rosario , Andía Daniel , García-Rojo Marcial , Quílez Jose C , Oyagüez Itziar 
Published: July 2020

Abstract
Background
HPV cervical cancer screening (CCS) must use validated HPV tests based on the molecular detection of either viral mRNA (Aptima HPV Assay – AHPV) or DNA. AHPV has demonstrated the same cross-sectional and longitudinal sensitivity for the detection of HSIL/CIN2 + lesions but with greater specificity than HPV-DNA tests. The study aimed to estimate the total costs of a CCS with a primary HPV test based on the detection of mRNA compared to DNA in women aged 35–65 years for the National Health System.
Methods
A decision-tree-based model to estimate the cost of the CCS until the first colposcopy was designed based on Spanish CCS guidelines. The total cost (€,2019) for CCS with AHPV or DNA tests (HC2 and Cobas) was calculated, including HPV test, liquid-based cytology (LBC) and colposcopy, for a population of 7,263,529 women aged 35–65 years (assuming 70% coverage). Clinical inputs derived from a literature review were validated by a multidisciplinary expert panel. Data from head-to-head studies between different HPV tests were selected. The HPV prevalence used in women aged 35–64 was 7.5% for AHPV, 11.5% for HC2 and 12.4% for Cobas.
Results
The use of AHPV avoided 151,699 (-47%) and 151,165 (-47%) colposcopies and 290,541 (-35%) and 355,913 (-40%) LBC vs HC2 and Cobas, respectively; and allows saving €-39,839,711 vs HC2 and €-41,866,613 vs Cobas.
Conclusions
Assuming that 70% of women from 35–65 years attend the CCS programme, the cost of screening up to the first colposcopy using AHPV would provide cost savings of up to €41.9 million vs DNA tests in Spain.
Pediatric Tuina for the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Preschool Children: Study Protocol for a Pilot Randomized Controlled Trial
Authors: Chen Shu Cheng , Yu Juan , Suen Lorna Kwai-Ping , Sun Yan , Pang Ya Zheng , Wang Dong Dong , Zhao Wen Xia , Yeung Jerry Wing Fai 
Published: July 2020

Abstract
Background: Medication and behavior therapy are the conventional treatments for attention deficit hyperactivity disorder (ADHD), but they have limitations for preschool children. Evidence suggests that pediatric tuina might have beneficial effects on this condition. Therefore, we aim to preliminarily assess the effects and feasibility of parent-administered pediatric tuina for ADHD symptoms in preschoolers.Methods: It is a single-center, two-arm, parallel, open-label, pilot randomized controlled trial. Sixty children with pre-specified ADHD symptoms (hyperactivity, anxiety, and sleep disturbance) together with one of their parents will be recruited and randomized into two groups at a 1: 1 ratio. Parents in the parent-administered tuina group (intervention group, n=30) will attend an online training program to learn pediatric tuina skills for ADHD symptoms and conduct this treatment on their children at home. Parents in the parent-child interaction group (comparison group, n=30) will attend an online training about progressive muscle relaxation exercise and do this exercise with their children at home. Additional teaching materials will be provided to the participants in both groups. Both interventions should be carried out every other day during a 2-month treatment period, with each time around 20 minutes. Assessment will be performed at baseline, week4, and week 8. The primary outcome measure is the Swanson, Nolan and Pelham Parent Scale; the secondary outcomes include Preschool Anxiety Scale, Children's Sleep Habits Questionnaire, and Parental Stress Scale. A process evaluation embedded within the outcome evaluation will be performed. Differences in the scale scores and test parameters between groups will be examined using a linear mixed-effects model. Qualitative data will be analyzed using thematic content analysis, facilitated by QSR NVivo.Discussion: This study will provide evidence on the acceptability and feasibility of pediatric tuina for ADHD in preschool children. The process evaluation will help to better understand the facilitators and barriers of the intervention functioning.Trial registration: The study was registered at ClinicalTrials.gov (Identifier: NCT04237259) on 14 February 2020. Protocol version: 2, date June 23, 2020
Factors Contributing to Psychological Distress in the Working Population, With A Special Reference to Gender Difference - A Population-Based Study
Authors: Viertiö Satu , Kiviruusu Olli , Piirtola Maarit , Kaprio Jaakko , Korhonen Tellervo , Marttunen Mauri , Suvisaari Jaana 
Published: July 2020

Abstract
BackgroundPsychological distress refers to non-specific symptoms of stress, anxiety and depression, and it is more common in women. Our aim was to investigate factors contributing to psychological distress in the working population, with a special reference to gender differences. Methods We used questionnaire data from the nationally representative Finnish Regional Health and Well-being Study (ATH) collected in the years 2012–2016 (target population participants aged 20 +, n=96 668, response rate 53%), restricting the current analysis to those persons who were working full-time and under 65 of age (n=34 468). Psychological distress was assessed using the Mental Health Inventory-5 (MHI-5) (cut-off value <=52). We studied the following factors potentially associated with psychological distress: sociodemographic factors, living alone, having children under 18 years of age, lifestyle-related factors, social support, helping others outside of the home and work-related factors. We used logistic regression analysis to examine association between having work-family conflict with the likelihood for psychological distress. We first performed the models separately for men and women. Then interaction by gender was tested in the combined data for those independent variables where gender differences appeared probable in the analyses conducted separately for men and women.Results Women reported more psychological distress than men (11.0% vs. 8.8%, respectively, p<0.0001). Loneliness, job dissatisfaction and family-work conflict were associated with the largest risk of psychological distress. Having children, active participation, being able to successfully combine work and family roles, and social support were found to be protective factors. A significant interaction with gender was found in only two variables: ignoring family due to being absorbed in one’s work was associated with distress in women (OR 1.30 (95% CI 1.00–1.70), and mental strain of work in men (OR 2.71 (95% CI 1.66–4.41).Conclusions Satisfying work, family life and being able to successfully combine the two are important sources of psychological well-being for both genders in the working population.
Removal of a Missing Intrauterine Contraceptive Device After Location Through an Ultrasound: A Case Report Within a Rural Setting and Review of Literature
Authors: Argaw Mesele Damte , Abawollo Hailemariam Segni , Desta Binyam Fekadu , Tsegaye Zergu Taffesse , Belete Dejene Mengistu , Abebe Melkamu Getu 
Published: July 2020

Abstract
Background: In the last decade, (2000- 2019), the modern contraceptive prevalence among married women of reproductive age (14-49 years), has increased by only 2.1%. The slow progress was due to limited access to services and myths surrounding methods held by both users and providers. This case report was identified, diagnosed and managed by a midwife working in rural health center in low resource setting. However, literature is scare on the management of missing Intra-Uterine Contraceptive Device (IUCD) thread removal services of confirmed diagnosis using Vscan or limited ultrasound services in rural health centers. The aim of reporting this case report was developed to enhance easy access to intra-uterine contraceptive method removals, which may address myths associated with difficulties of undergoing the services in rural set-up.A 26 year-old married woman, Gravida 1 and Para 1, attended Mekoy Health Center for IUCD removal service after seven years of protection and internally referred to limited obstetric ultrasound service room due to non- visualization of IUCD thread with Vaginal Speculum examination. An ultrasonography scan however, showed a centrally located copper-T 380A IUCD in the endometrial cavity. As a result, after dilatation of the cervix, a successful removal of the Copper-T 308A was conducted. The client received followed up care for two hours post-procedure and was then discharged.Conclusions: This case highlights the importance of availing diagnostic and removal services in rural set ups to mitigate myths in the community. The availability of limited obstetric ultrasound scanning services can improve the diagnoses and management of conditions in clients. The reported case shows that although, the basic infrastructure was limited, ultrasound scanning and Long Acting Reversible Contraception (LARC) trained midwives can ensure the provision of safe IUCD removal services in rural areas.
Secreted Frizzled-Related Protein 5 (SFRP5) protects ATDC5 cells against LPS-induced inflammation and apoptosis via inhibiting Wnt5a/JNK pathway
Authors: Sun Minghui , Wang Weijun , Min Lingtian , Chen Cheng , Li Qing , Weng Wenjie 
Published: July 2020

Abstract
Background
Secreted frizzled–related protein 5 (SFRP5) is an endogenous inhibitor of Wnt5a (wingless-type family member 5a), which has been implicated in anti-inflammatory response. In this study, we aimed to investigate whether SFRP5 could protect chondrocytes against LPS-induced inflammation and apoptosis.
Methods
ATDC5 cells that overexpressed with SFRP5 or not were challenged with LPS to observe the effects of SFRP5 overexpression on LPS-triggered inflammation and apoptosis as well as Wnt5a/JNK activation. Wnt5a was elevated in ATDC5 cells in the presence of SFRP5 overexpression, to determine whether Wnt5a/JNK signaling was involved in the actions of SFRP5.
Results
The mRNA and protein levels of SFRP5 was significantly reduced by LPS in a concentration-dependent manner. Overexpression of SFRP5 in ATDC5 cells inhibited LPS-induced inflammation and apoptosis, as evidenced by decreased production of TNF-α, IL-1β, IL-6 and ROS, together with a reduced ratio of TUNEL-positive cells, a lower expression of Bax and cleaved caspase 3, but a higher expression of Bcl-2. Meanwhile, SFRP5 overexpression also repress Wnt5a and phosphorylated JNK expression. However, the overexpression of Wnt5a considerably weakened the inhibitory effect of SFRP5 on LPS-triggered inflammation and apoptosis. Besides, the level of Wnt5a and JNK phosphorylation, which was inhibited by SFRP5 overexpression, was also partially recovered by Wnt5a overexpression.
Conclusion
SFRP5 could alleviate LPS-induced ATDC5 cells inflammation and apoptosis, this actions may rely on repressing Wnt5a/JNK activation.