bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Values, ceRNA Network, and Immune Regulation Function of SDPR in KRAS-mutant Lung Cancer
Authors: Luo Xiaoqing , Peng Shunli , Ding Sijie , Zeng Qin , Wang Rong , Ma Yueyun , Chen Shiyu , Wang Yanxia , Wang Wei 
Published: August 2020

Abstract
Background: SDPR plays an important role in formation of pulmonary alveoli. However, the function and values of SDPR remain unknown in lung cancer. We explored prognostic values, expression pattern and biological function of SDPR in NSCLC and KRAS-mutant lung cancers.Methods: SDPR expression were evaluated by RT-qPCR, IHC, Western blotting based on human NSCLC cells, lung adenocarcinoma tissues array, KRAS-mutant transgenetic mice, TCGA and GEO datasets. The prognosis values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. The bioinformatics implication of SDPR including SDPR-combinated TFs and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules and tumor infiltration models were illustrated.Results: SDPR expression was downregulated among tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients in both lung cancer and KRAS-mutant subgroup. Meanwhile, ceRNA network to clarify the regulatory and biological functions of SDPR was constructed. Negative correlations were found between SDPR and immune checkpiont moluculars (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns.Conclusions: This study elucidates regulation network of SDPR in KRAS-mutant NSCLC, and illustrates correlations between low SDPR expression and suppressed immune systems, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.
Network-Based Drug Discovery Identifies Statins as a Repurposing Agent to Improve Activity of Current Therapies in Chronic Lymphocytic Leukemia.
Authors: Gimenez Neus , Tripathi Rupal , Giró Ariadna , Rosich Laia , López-Guerra Mònica , Lopez-Oreja Irene , Playa-Albinyana Heribert , Arenas Fabian , Mas José Manuel , Perez-Galan Patricia , Delgado Julio , Campo Elias , Farrés Judith , Colomer Dolors 
Published: August 2020

Abstract
Background: Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. The present study aimed to identify drugs targeting key proteins described to have a role in the microenvironment.Methods: We used a platform for drug discovery based on systems biology and artificial intelligence. Bioactive compounds have been screened in silico and selected compounds were evaluated in CLL cell lines in the presence of stromal cells to mimic the microenvironment and validated the best candidates in primary CLL cells. Results: Our results showed that the commercial drug simvastatin was the most effective and selective out of the tested compounds. Simvastatin decreased CLL cell survival and proliferation as well as cell adhesion. Importantly, this drug enhanced the antitumor effect of venetoclax and ibrutinib. Conclusions: We proposed that systems biology approaches combined with pharmacology screening could help to find new drugs for CLL treatment and to predict new combinations with current therapies. Our results highlight the possibility of repurposing widely used drugs such as statins to target the microenvironment and to improve the efficacy of ibrutinib or venetoclax in CLL cells.
RNA N6-Methyladenosine Reader IGF2BP3 Regulates Cell Cycle and Angiogenesis in Colon Cancer
Authors: Yang Zhou , Wang Tingfeng , Wu Dejun , Min Zhijun , Tan Jingyun , Yu Bo 
Published: August 2020

Abstract
Background: N6-Methyladenosine (m6A) modification has been implicated in multiple processes for colon cancer development. IGF2BP3 was a newly reported m6A reader, whereas its role in colon cancer remains unclear. Methods: The expression of m6A associated enzymes and total m6A level were measured by Western Blotting analysis and m6A RNA Methylation Quantification Kit respectively. Cell cycle was analyzed by flowcytometry. The interaction of IGF2BP3 and related targets was analyzed by RNA immunoprecipitation (RIP) and m6A RNA immunoprecipitation (MeRIP) assays.Results: We investigated all m6A regulated enzymes in colon cancer and found only the overexpression of IGF2BP3 was associated with cancer progression and survival based on The Cancer Genome Atlas (TCGA) databases. Additionally, we also demonstrated IGF2BP3 was associated with DNA replication in the cell cycle. Knockdown of IGF2BP3 significantly repressed percentage of S phase of cell cycle as well as cell proliferation. Further research demonstrated IGF2BP3 binds to the mRNA of Cyclin D1 (checkpoint of G1/S phase of cell cycle) and reduced its mRNA stability via reading m6A modification in the CDS region. Overexpression of Cyclin D1 in IGF2BP3 down-regulated cells completely rescued the inhibited percentage of S phase in cell cycle as well as cell proliferation. Additionally, we also demonstrated a similar role of IGF2BP3 at VEGF. IGF2BP3 binds to the mRNA of VEGF and reads m6A modification, thus regulated both expression and stability of VEGF mRNA. Knockdown of IGF2BP3 repressed angiogenesis in colon cancer via regulating VEGF. Conclusion: Knockdown of IGF2BP3 repressed DNA replication in the S phase of cell cycle and angiogenesis via reading m6A modification of Cyclin D1 and VEGF respectively. IGF2BP3 was a possible prognosis marker and potential therapeutic target of colon cancer.
The medial thalamus plays an important role in the cognitive and emotional modulation of orofacial pain: a functional magnetic resonance imaging-based study
Authors: Jin Yu , Yang Hong , Zhang Feifei , Wang Jue , Liu He , Yang Xin , Long Hu , Li Fei , Gong Qiyong , Lai Wenli 
Published: August 2020

Abstract
Background The thalamus plays a critical role in the perception of orofacial pain. We investigated the neural mechanisms of orofacial pain by exploring the intrinsic functional alterations of the thalamus and assessing the changes in functional connectivity (FC) between the thalamic subregions with significant functional alterations and other brain regions in orofacial pain using the seed-based FC approach. Methods The study comprised 49 participants in the orofacial pain group and 49 healthy controls. Orofacial pain was caused by orthodontic separators. The resting-state functional magnetic resonance imaging data of the two groups were analyzed to obtain the fractional amplitude of low-frequency fluctuations (fALFFs) of the thalamus, and the thalamic subregions with significant fALFF abnormalities were used as seeds for FC analysis. Student’s t-tests were used to perform comparisons. Pearson’s correlation analysis was performed using SPM software. Results Forty-four participants with orofacial pain (mean age, 21.0±0.9 years; 24 women) and 49 age- and sex-matched healthy controls (mean age, 21.0±2.6 years; 27 women) were finally included. Compared with the control group, the orofacial pain group demonstrated (1) increased function in the dorsal thalamus and decreased function in the medial thalamus; (2) decreased FC between the medial thalamus and 12 brain regions (p<0.05, family-wise error corrected, voxel>100); and (3) potential positive and negative correlations between the medial thalamus-seeded FC and visual analog scale score changes (p<0.05, AlphaSim corrected). Conclusions The findings show that the medial and dorsal thalamus play important roles in orofacial pain perception and that the medial thalamus likely plays an important role in the cognitive and emotional modulation of orofacial pain.
Test for Covid-19 seasonality and the risk of second waves
Authors: Engelbrecht Francois A. , Scholes Robert J. 
Published: August 2020

Abstract
Eight months into the Covid-19 pandemic it remains unclear whether transmission of SARS-CoV-2 is affected by climate factors. Using a dynamic epidemiological model with Covid-19 climate sensitivity in the likely range, we demonstrate why attempts to detect a climate signal in Covid-19 have thus far been inconclusive. Then we formulate a novel methodology and related criteria that can be used to test for seasonal climate sensitivity in observed Covid-19 infection data. We show that if the disease does have a substantial seasonal dependence, and herd immunity is not established during the first peak season of the outbreak (or a vaccine does not become available), there is likely to be a seasonality-sensitive second wave of infections about one year after the initial outbreak. In regions where non-pharmaceutical control has contained the disease in the first year of outbreak and thus kept a large portion of the population susceptible, the second wave may be substantially larger in amplitude than the first if control measures are relaxed. This is simply because it develops under the favorable conditions of a full autumn to winter period and from a larger pool of infected individuals.
In Silico Molecular Docking and Ab initio DFT Studies as a Tool for a Quick Screening on Drug Inhibitors for SARS-Cov-2 RNA-Dependent Polymerase
Authors: Vlasiou Manos C. , Ioannou Kyriakos I. , Pafiti Kyriaki S. 
Published: August 2020

Abstract
In silico molecular docking took place in order to evaluate already FDA approved drugs for several diseases, as inhibitors for SARSCov-2 RNA- dependent polymerase. The best candidates with the highest binding affinities, evaluated for their energy determined by their electron density. Remdesivir and Saquinavir seemed to be good candidates for clinical trials but their predicted toxicity based on their calculated structures revealed that these two substances should evaluated more for their side effects
Sociological Modeling of Smart City with the implementation of UN Sustainable Development Goals
Authors: Kolesnichenko Olga , Mazelis Lev , Sotnik Alexander , Yakovleva Dariya , Amelkin Sergey , Grigorevsky Ivan , Kolesnichenko Yuriy 
Published: August 2020

Abstract
The COVID-19 pandemic before mass vaccination can be restrained only by the limitation of contacts between people, which makes the digital economy a key condition for survival. More than half of the world’s population lives in urban areas, and many cities have already transformed into “smart” digital / virtual habs. Digital services make city life safe without an economy lockout and unemployment. Urban society strives to be safe, sustainable, well-being, and healthy. We set the task to construct a hybrid sociological and technological concept of a smart city with matched solutions, complementary to each other. Our modeling with the elaborated digital architectures and with the bionic solution for ensuring sufficient data governance clearly showed that smart city in comparison with the traditional city is tightly interconnected inside like social “organism”. We have entered a decisive decade during which the world will change by moving closer towards SDGs targets 2030 as well as by the transformation of cities and their digital infrastructures. It is important to recognize the large vector of sociological transformation as smart cities are just a transition phase to human-centered personal space or smart home. The “atomization” of the world urban population raises the gap problem in achieving SDGs because of different approaches to constructing digital architectures for smart cities or smart homes in countries. The strategy of creating smart cities should bring each citizen closer to SDGs at the individual level, laying in the personal space the principles of sustainable development and wellness of personality.
The impact of the COVID-19 lockdown on disordered eating behaviors in youths with type 1 diabetes: Analysis of cross-sectional survey data.
Authors: Troncone Alda , Chianese Antonietta , Zanfardino Angela , Cascella Crescenzo , Piscopo Alessia , Borriello Anna , Rollato Serena , Casaburo Francesca , Testa Veronica , Iafusco Dario 
Published: August 2020

Abstract
Background: Recent research indicates that patients with type 1 diabetes (T1D) are at higher risk for disordered eating behaviors (DEBs) than their peers without diabetes. The present study aimed at examining the impact of the COVID-19 lockdown on DEBs in a sample of Italian children and adolescents with T1D and in matched-pair healthy controls.Methods: 138 children and adolescents with T1D (aged 8.01-19.11 years, 65 boys) attending a Southern Italian diabetic service and 276 age- and gender-matched healthy peers voluntarily completed a cross-sectional online survey of eating behaviors (ChEAT and Eat-26), anthropometric characteristics, and clinical characteristics. Results: 8.69% (N=12) of participants with T1D and 13.4% (N=37) of controls had ChEAT/EAT-26 scores indicating presence of DEBs, with no differences between patients—whether children (total ChEAT score F(1, 157)=.104, p=.748) or adolescents (total EAT-26 score F(1, 255)=.135, p=.731)—and healthy peers. zBMI values were lower than those measured in the latest diabetes visit (p<.0001), while HbA1c values remained unchanged (p=.110). In both groups, adolescents had lower Oral Control scores than children (T1D: F(1, 138)= 20.411, p<.0001, η2 =.132, controls: F(1, 276)=18.271, p<.0001, η2 =.063); additionally, gender (female) and age were found to be significant predictors of several ChEAT/EAT-26 scores.Discussion: Psychological conditions in relation to DEB symptoms of children and adolescents with T1D were not aggravated by lockdown conditions. Results indicated DEBs as more of a female adolescent developmental issue rather than as a result of the challenges of living with a chronic illness aggravated by outbreak. Possible effects of parental pressure on their children’s eating behaviors in the context of home confinement and of using a non-diabetes-specific measure to assess DEBs are discussed.
Frequency and severity of Covid-19 in patients treated with biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) for inflammatory rheumatic disease. A case-control study
Authors: LOHSE Anne , BOSSERT Marie , BOZGAN Ana-Maria , BOURGOIN Charlotte , CHARPENTIER Aline , GUILLOCHON Cerise , KESSLER Julie , BALBLANC Jean-Charles , CONROZIER Thierry 
Published: August 2020

Abstract
The aim of the study was to assess the impact (frequency and severity) of Covid-19 on patients treated with biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) for inflammatory rheumatic disease and to compare it to a control group consisting of patients with musculoskeletal conditions not treated with bDMARDs.Patients and methods:A case control study in 200 outpatients with musculoskeletal conditions. 100 consecutive patients who have been treated with bDMARDs and 100 other consecutive patients who did not take bDMARDs were asked to complete a 15-item standardized questionnaire regarding demographic data. The following information was recorded: gender, age, weight, height, body mass index, professional activity, family status, total number of children and number of children under 18, rheumatic disease diagnosis, current treatment for rheumatism, type of containment, close contact with Covid-19 patients, Covid-19 symptoms, Covid-19 test result and hospitalization for Covid-19.Results:bDMARD patients mostly suffered from rheumatoid arthritis, or RA, (47%) and ankylosing spondylitis (42%). The most prescribed bDMARDs were TNFα inhibitors (57%), IL-6 blockers (12%) and JAK inhibitors (11%). The mean duration of the current biological treatment was 38.6 months. Patients from the control group were suffering chiefly from osteoarthritis (45%) and RA (21%). Compared to the control group, patients treated with bDMARDs were 10 years younger (p<0.001), fewer were retired (56% versus 31%) and more were on sick or incapacity leave (6% versus 18%). During lockdown, they were more likely to be working from home or working short term (27% versus 9%). 18 patients from the bDMARDs group stopped biological treatment: one because of Covid-19 evidenced by PCR, 11 because of symptoms suggesting Covid- 19 and only six from fear of contracting the disease. 12 patients, including the one Sars-CoV-2 +, resumed their treatment after a few weeks of interruption. There was no severe Covid-19 infection in the bDMARDs group. Among the three patients from the control group who had contracted Covid-19, one developed a very severe disease.Conclusion :This case-control study did not show an increase in the frequency or severity of Covid-19 in subjects suffering from chronic inflammatory rheumatism treated with biotherapies. Larger-scale studies are necessary before affirming that biologics do not expose patients to an increased risk of disease and complications.
Mitigating Arrhythmia Risk in Hydroxychloroquine and Azithromycin Treated COVID-19 Patients using Arrhythmia Risk Management Plan
Authors: Maneikis Kazimieras , Ringeleviciute Ugne , Bacevicius Justinas , Dieninyte-Misiune Egle , Burokaite Emilija , Kazbaraite Gintare , Janusaite Marta Monika , Dapkeviciute Austeja , Zucenka Andrius , M.D. Valdas Peceliunas , Kryzauskaite Lina , M.D. Vytautas Kasiulevicius , M.D. Donata Ringaitiene , M.D. Birute Zablockiene , Zvirblis Tadas , M.D. Germanas Marinskis , M.D. Ligita Jancoriene , M.D. Laimonas Griskevicius 
Published: August 2020

Abstract
Background: Hydroxychloroquine and Azithromycin use is associated with QT interval prolongation and arrhythmias. Despite ongoing multiple clinical trials for treatment of COVID19 infection, no definite cardiac safety protocols were proposed. The aim of our study was to assess cardiac safety in COVID-19 patients treated with the combination of Hydroxychloroquine and Azithromycin using close monitoring and arrhythmia risk management plan.Methods and results: We retrospectively examined arrhythmia safety of treatment with Hydroxychloroquine and Azithromycin in the setting of pre-defined cardiac arrhythmia risk management plan. 81 patients were included from March 23rd to May 10th 2020. The median age was 59 years, 58.0% were female. The majority of the study population (82.7%) had comorbidities, 98.8% had radiological signs of pneumonia. 7 patients (8.6%) had QTc prolongation of ≥500 ms. The treatment was discontinued in 4 patients (4.9%). 14 patients (17.3%) experienced QTc≥480 ms and 16 patients (19.8%) had an increase of QTc≥60 ms. None of the patients developed ventricular tachycardia. The risk factors significantly associated with QTc≥500 ms were hypokalemia (p = 0.032) and use of diuretics during the treatment (p = 0.020). Three patients had a lethal outcome; none of them associated with ventricular arrhythmias.Conclusion: We recorded a low incidence of QTc prolongation ≥500 ms and no ventricular tachycardia events in COVID-19 patients treated with Hydroxychloroquine and Azithromycin using cardiac arrhythmia risk management plan.
The relationship between DBT family training and perceived criticism: a pre-post study
Authors: Leeuwen Hanneke van , Bosch Wies van den , Ossewaarde Lindsey , Egger Jos 
Published: August 2020

Abstract
Background: Dysregulating emotional and behavioural phenomena of patients with Borderline Personality Disorder (BPD), such as repeated non-suicidal self-injury, are strongly affecting patients’ family members or partners. In addition, critical disapproval of this emotional and behavioural phenomena by family members and reconciling understanding, affects the patients’ sensitivity for rejection. As a result, individuals with BPD appear to have less satisfying social support. This negative spiral possibly elicits further challenging behaviour. Therapy programs for BPD might therefore benefit from the inclusion of family members or partners in the treatment. One of the programs that includes family members is the network training of Dialectical Behaviour Therapy (DBT). This study examines the impact of the DBT network training on the perceived criticism of both patients and network members. Method: This study follows a pre-post design where a DBT network training is given to 33 patients (mean age 25 years) and 61 relatives during 8 group sessions. The degree of perceived criticism is measured by using a self-report questionnaire. Results: Results show that the overall scores of the perceived criticism scale decrease significantly for both patients and relatives after following the DBT network training. More specific, item scores of both patients and relatives concerning how critical they looked towards the other and how critical they thought the other looked at them also decreased significantly after following the DBT network training. Conclusion: Findings suggest that a DBT network training may be instrumental in decreasing levels of perceived criticism. Further research may focus on the putative mechanisms of behaviour such as improved perspective taking, behavioural change, and the evaluation of social cues.
Development and Psychometric Analysis of Supportive Care Needs scale for Pulmonary Tuberculosis Patients
Authors: Ren Jing , Han Dongfang , Zhang Jingjun , Wang Yingli , Huang Qiaoqiao , Tian Tian , Li Xiaomei 
Published: August 2020

Abstract
Background

Providing integrated patient-centred care based on the patient’s needs has emerged as the first pillar of tuberculosis prevention and control strategies. However, a reliable and valid instrument is still lacking. Hence, the aim of this study was to develop and psychometrically test a new scale for assessing the supportive care needs of patients with pulmonary tuberculosis.
Methods

A methodological study involving item generation and psychometric evaluation was used. Based on the Supportive Care Needs Framework, the item-pool was drafted from a systematic review of the literature, expert consultations and feedback from a pilot study. A convenience sample of 518 patients was recruited from four hospitals in Shaan’xi Province from September 10, 2019, to January 20, 2020. Item reduction and scale validation were assessed for content validity, construct validity, Cronbach’s alpha coefficient, half-split reliability, and test-retest reliability.
Results

The final scale encompasses 25 items in five domains: practical, psycho-emotional, social, information and physical. The item level content validity index ranged from 0.80 to 1.00, and the scale level content validity was 0.925. Five factors that explained 80% of the total variance were also identified in exploratory factor analysis and confirmed in confirmatory factor analysis. The CFA model fit indices were x2/df = 2.229 (p < 0.001), GFI = 0.853, AGFI = 0.820, RMSEA = 0.069. All items had acceptable convergent and discriminant validity. Cronbach’s α coefficient, the split-half reliability coefficient and the test-retest reliability coefficient were 0.884, 0.883 and 0.854, respectively.
Conclusions

This newly developed scale demonstrated acceptable reliability and validity, and it could be used to assess the supportive care needs of pulmonary tuberculosis patients in clinical settings.