bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy for uterus weighing ≥ 1kg
Authors: Wang Xiaojuan , LI Junwei , Hua Keqin , Chen Yisong 
Published: September 2020

Abstract
Background: The transvaginal natural orifice transluminal endoscopic surgery (vNOTES) applied in gynecology has been developed recent years and been evolving. In this study, we aimed to evaluate the feasibility and effect of the vNOTES hysterectomy for uterus ≥ 1 kilogram (kg).Methods: From January 2019 to March 2020, patients with benign indications in cases of uterus weighing ≥ 1kg, underwent vNOTES hysterectomy were studied retrospectively. The patients’ demographics, indications for surgery, operation outcomes and follow-up details were recorded. Results: 39 patients were performed vNOTES hysterectomy for large uterus (mean weight 1141.8 gram, range from 1000 to 1720), indications for surgery included bulky uterine myomas or adenomysosis. The mean age was 48 years (range 42-66) and mean BMI was 24 kg/m2 (range 18.4-38). Mean operating time was 123.3 minutes (rang 40-400) and the mean estimated blood loss was 206.7 milliliters (range 10-1300). The mean pain assessment was 2.1 (range 0-5). The mean length of stay was 2.4 nights (1-11). 1 patient experienced ureteral injury and was performed ureteral anastomosis. 3 patients were converted to vaginal-assisted trans-umbilicus single-port laparoscopy. The learning curve was analyzed to show that 20 cases were needed to achieve proficiency in vNOTES hysterectomy for large uterus ≥ 1 kg.Conclusion: Our preliminary experience suggested that vNOTES hysterectomy for large uterus weighing ≥ 1kg was feasible and safe, meanwhile this procedure had the advantages of all the minimal invasive approach such as fast recovery and aesthetic advantage.
A novel sequential treatment of palbociclib enhances the effect of cisplatin in RB-proficient triple-negative breast cancer
Authors: Huang Yajing , Wu Hao , Li Xingrui 
Published: September 2020

Abstract
Background: Triple-negative breast cancer (TNBC) is a highly aggressive malignancy lack of sensitivity to chemo-, endocrine and targeted therapy. CDK4/6 inhibitors, combined with endocrine therapy, have been proven to be effective in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. So we investigated that whether CDK4/6 inhibitor palbociclib (PD) could enhance effects of cisplatin (CDDP) on TNBC.Methods: The effects of different drug regimens of PD and CDDP on MDA-MB-231 and RB-knockdown MDA-MB-231 (sh-MDA-MB-231) cells were assessed in vitro and vivo. MDA-MB-468 and RB-overexpression MDA-MB-468 cells were used to assess the effect of PD-CDDP regimen in vitro. Immunoblotting illustrated cyclin D1/RB/E2F axis signaling pathway.Results: PD induced G1 phase cell cycle arrest in MDA-MB-231 cell line. However, synchronous treatment with PD and CDDP for 24h, PD used for 24h and then followed by CDDP or CDDP used for 24h and then followed by PD all had no influence on cell apoptosis of MDA-MB-231 cells. We further investigated the effect of PD or CDDP withdrawal on sequential treatment and found that PD used for 48h and then withdrawn for 48h followed by CDDP (PD-CDDP) could significantly increase apoptosis, inhibit cell viability and colony formation of MDA-MB-231 cells, while in other regimens PD and CDDP represented additive or antagonistic response. Preferential use of PD could increase DNA damage by CDDP as measured through γH2AX. These findings above were negative in sh-MDA-MB-231 cells and cell function experiments of MDA-MB-468 and RB-overexpression MDA-MB-468 cells could draw similar conclusions, which indicated that PD enhanced the sensitivity of TNBC cells to CDDP in a RB dependent manner. In vivo, this combination treatment inhibited tumor growth and Ki-67 expression compared with single drug treatments in MDA-MB-231 xenograft models. Western blotting analysis presented that PD enhanced sensitivity to CDDP through CDK4/6-cyclin D-RB-E2F pathway. Conclusions: Pre-treatment with PD synchronized tumor cell cycle through CDK4/6-cyclin D1-RB-E2F pathway, which could increase anti-tumor effect of CDDP. PD-CDDP might be an effective treatment for RB-proficient TNBC patients.
The apelin-13 peptide protects the heart against apoptosis through the ERK/MAPK and PI3K/AKT signaling pathways.
Authors: Wang Xuejun , Zhang Li , Feng Mengwen , Zhang Hao , Xu Jia , Cheng Zijie , Qian Lingmei 
Published: September 2020

Abstract
Background: It has been acknowledged that endocrine activity is associated with the function of multiple systems in vivo. The apelin-13 peptide has been demonstrated to play a crucial role in physiological and pathological processes. However, the function of apelin-13 peptide in doxorubicin (DOX)-induced cardiotoxicity is unknown. Methods: We explored the function and mechanism of apelin-13 peptide in apoptosis and oxidative stress by cell counting kit-8 (CCK-8) assay, trypan blue staining, TUNEL, lactate dehydrogenase (LDH), mitochondrial membrane potential assay kit with JC-1 (JC-1) and western blot in vitro. Then we verified the effect of apelin-13 in vivo by detecting serum apelin-13, CKMB, LDH, cardiac troponin I (cTnI) and cardiac troponin T (cTnT). EF, FS and LVEDs were used to identify the structural modification by echocardiography. Sirius red staining and HE staining assay were used to detecting the myocardial fibers alteration under apelin-13 treatment.Results: Treatment with apelin-13 peptide significantly enhanced cell viability, mitochondrial membrane potential, but reduced LDH release, rate of apoptotic cells and activation of caspase-3 in vitro. In mice, apelin-13 alleviated the heart dysfunction induced by DOX. 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) inhibited the effect of extracellular signal-related kinases (ERK), phosphatidylinositol 3 kinases (PI3K) and protein kinase B (AKT) proteins phosphorylation expression compared with DOX.Conclusion: The apelin-13 and apelin receptor (APJ) interaction on the cell membrane inhibits apoptosis through the ERK/mitogen-activated protein kinase (MAPK) and PI3K/AKT signaling pathways. Our research gives a first glimpse on the biological function and mechanism of apelin-13 on cardiotoxicity.
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: September 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, which is a modality of traditional Chinese medicine, 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
Splenic Infarction and Infectious Diseases in Korea
Authors: Im Jae Hyoung , Chung Moon-Hyun , Lee Hye-Jin , Kwon Hea Yoon , Baek JiHyeon , Jang Ji-Hun , Lee Jin-Soo 
Published: September 2020

Abstract
BackgroundThe spleen contains immune cells and exhibits a pattern of infarction different from other organs; as such, splenic infarction (SI) may provide important clues to infection. However, the nature of the relationship between SI and infectious disease(s) is not well understood. Accordingly, this retrospective study investigated the relationship between SI and infection. MethodsHospital records of patients with SI, who visited Inha University Hospital (Incheon, Republic of Korea) between January 2008 and December 2018, were reviewed. Patient data regarding clinical presentation, causative pathogens, risk factors, and radiological findings were collected and analyzed.ResultsOf 353 patients with SI, 101 with infectious conditions were enrolled in this study, and their data were analyzed to identify associations between SI and infection. Ten patients were diagnosed with infective endocarditis (IE), and 26 exhibited bacteremia without IE. Twenty-seven patients experienced systemic infection due to miscellaneous causes (negative result on conventional automated blood culture), including the following intracellular organisms: parasites (malaria [n =12], babesiosis [n =1]); bacteria (scrub typhus [n =5]); viruses (Epstein–Barr [n =1], cytomegalovirus [n =1]); and unidentified pathogen[s] (n =7). Splenomegaly was more common among patients with miscellaneous systemic infection; infarction involving other organs was rare. Thirty-eight patients had localized infections (e.g., respiratory, intra-abdominal, or skin and soft tissue infection), and most (35 of 38) had other risk factors for SI. ConclusionsIn this study, various infectious conditions were found to be associated with SI, and intracellular organisms were the most common causative pathogens. Further studies are needed to examine other possible etiologies and the underlying pathophysiological mechanisms.
Melphalan induces cardiotoxicity through oxidative stress in cardiomyocytes derived from human induced pluripotent stem cells
Authors: Liu Rui , Li Dong , Sun Fangxu , Rampoldi Antonio , Maxwell Joshua , Wu Ronghu , Fischbach Peter , Castellino Sharon , Du Yuhong , Fu Haian , Mandawat Anant , Xu Chunhui 
Published: September 2020

Abstract
Background. Treatment-induced cardiotoxicity is a leading noncancer-related cause of acute and late onset morbidity and mortality in cancer patients on antineoplastic drugs such as melphalan—increasing clinical case reports have documented that it could induce cardiotoxicity including severe arrhythmias and heart failure. As the mechanism by which melphalan impairs cardiac cells remains poorly understood, here we aimed to use cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) to investigate the cellular and molecular mechanisms of melphalan-induced cardiotoxicity and to explore potential targeted therapeutics.Methods. hiPSC-CMs were generated and treated with clinically relevant doses of melphalan. In order to characterize melphalan-induced cardiotoxicity, cell viability and apoptosis were quantified at various treatment durations. Ca2+ transient and contractility analyses were used to examine the alterations of hiPSC-CM function. Proteomic analysis, reactive oxygen species detection, and RNA-Sequencing were conducted to investigate underlying mechanisms. Results. Melphalan treatment of hiPSC-CMs induced oxidative stress, caused Ca2+-handling defects and dysfunctional contractility, altered global transcriptomic and proteomic profiles, and resulted in apoptosis and cell death. The antioxidant N-acetyl-L-cysteine attenuated these genomic, cellular and functional alterations. In addition, several other signaling pathways including the p53 and transforming growth factor-β signaling pathways were also implicated in melphalan-induced cardiotoxicity according to the proteomic and transcriptomic analyses.Conclusions. Melphalan induces cardiotoxicity through the oxidative stress pathway. This study provides a unique resource of the global transcriptomic and proteomic datasets for melphalan-induced cardiotoxicity and can potentially open up new clinical mechanism-based targets to prevent and treat melphalan-induced cardiotoxicity.
Increasing use of linezolid in a tertiary NICU during a 10-year period: reasons and concerns for the future
Authors: Matrat Lucie , Plaisant Frank , Barreto Christine , Claris Olivier , Butin Marine 
Published: September 2020

Abstract
Background: Linezolid has been increasingly used in tertiary NICUs. The objectives of this study were to explore the indications of these linezolid prescriptions, to analyze a possible misuse and to provide solutions to avoid such misuse.Methods: A monocentric retrospective cohort study included all neonates hospitalized in one tertiary NICU between January 1st, 2010 and December 31st, 2019 and who received at least one administration of linezolid. These data were confronted to epidemiological and antibiotic use data from the same NICU. Two independent pediatricians secondarily classified linezolid uses as adequate or not.Results: During the study period, 66 infections in 57 patients led to linezolid use. Most patients were pre-term and 21 patients (37%) died. Infections were mainly related to methicillin-resistant coagulase negative staphylococci and were frequently either pneumoniae (35%) or isolated bacteremia (48%), including 25 persistent bacteremia (64% of the 39 bacteremia). Need for a better tissue distribution or first-line treatment failure were the main reasons to initiate linezolid. Linezolid was administered for a median duration of 7 [3;10] days. No side effects were reported. Twenty-two (33%) of the 66 linezolid prescriptions were retrospectively classified as inadequate. Conclusions: A rapid increase in linezolid prescriptions has been observed in our tertiary NICU, from 2014 to 2019, with 33% inadequate uses. This worrisome trend should lead to search for therapeutic alternatives and to work on antibiotic stewardship to prevent the emergence of new antimicrobial bacterial resistance.
Navigate: A study protocol for a randomized controlled trial of an online treatment decision aid for men with low risk prostate cancer and their partners
Authors: Schofield Penelope , Gough Karla , Hyatt Amelia , White Alan , Frydenberg Mark , Chambers Suzanne , Gordon Louisa , Gardiner Robert , Murphy Declan , Cavedon Lawrence , Richards Natalie , Murphy Barbara , Quinn Stephen , Juraskova Ilona 
Published: September 2020

Abstract
Background
Active surveillance (AS) is the disease management option of choice for low risk prostate cancer. Despite this, men with low risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on: uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol.
Methods
304 men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects; and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia’s peak national body for prostate cancer. Eligible patients will be men within three months of being diagnosed with LRPC, aged 18 years or older and who are yet to make a treatment decision and who are deemed eligible for AS by their treating clinician, and who have internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS one month after consent will be determined through patient self-report. Men and their partners will complete study outcome measures before randomisation, and one, three and six months after study consent.
Discussion
The Navigate online decision aid has the potential to increase the choice of AS in LRPC, avoiding or delaying unnecessary radical treatments and associated side effects. In addition, Navigate is likely to reduce patients’ and partners’ confusion and distress in management decision-making, and increase their quality of life.
Incidence and predictors of diabetic ketoacidosis among children with diabetes in west and east gojjam zone referral hospitals north west Ethiopia, 2019.
Authors: assefa birtukan , Zeleke Haymanot , Murugan Rajalakshmi , Wondwossen Kalkidan 
Published: September 2020

Abstract
Background: Recurrent diabetic ketoacidosis in patients with already diagnosed diabetic mellitus remains a relevant problem in pediatric with an incidence of 1–10% per patient. Children may die due to cerebral edema and had significant mortality (24%) and morbidity (35%).Objective: We assess the incidence and predictors of diabetic ketoacidosis among diabetic children at East and West Gojjam zone referral hospitals, North West Ethiopia, 2019.Methods: An institution-based retrospective follow up study was conducted on children who were registered from January 1, 2014, to January 1, 2019. Epi data version 3.1 & Stata 14 were used for data entering and analysis respectively.Result: A total of 354 children were included from this 207(58.5%) had diabetic ketoacidosis. The overall incidence rate of diabetic ketoacidosis was 2.27/100 children/month of observation. Age <5 years (AHR: 3.52, 95% CI (2.25, 5.49), non-adherence (AHR: 1.54, 95% CI (1.11, 2.14), inappropriate insulin storage (AHR: 1.36, 95% CI (1.008, 1.85), presence of upper respiratory tract infections during diabetic ketoacidosis diagnose (AHR: 2.22, 95% CI (1.11, 4.45) and preceding gastroenteritis (AHR: 2.18, 95% CI (1.07, 4.44) were significant predictors. Conclusion: age <5 years old, non-adherence, inappropriate insulin placement at home, Preceding gastroenteritis, and presence of upper respiratory tract infections at the time of diabetic ketoacidosis development were significant predictors. Hence, assessing and close monitoring as well as strengthened diabetic education should be given for the above predictors.
Neuromedin B Promotes Chondrocyte Differentiation of Mesenchymal Stromal Cells via Calcineurin and Calcium Signaling
Authors: Maumus Marie , Fonteneau Guillaume , Ruiz Maxime , Assou Said , Boukhaddaoui Hassan , Pastoureau Philippe , De Ceuninck Frédéric , Jorgensen Christian , Noël Danièle 
Published: September 2020

Abstract
Background: Articular cartilage is a complex tissue with poor healing capacities. Current approaches for cartilage repair based on mesenchymal stromal cells (MSCs) are often disappointing because of the lack of relevant differentiation factors that could drive MSC differentiation towards a stable mature chondrocyte phenotype. Methods: We used a large-scale transcriptomic approach to identify genes that are modulated at early stages of chondrogenic differentiation using the reference cartilage micropellet model. Results: We identified several modulated genes and selected neuromedin B (NMB) as one of the early and transiently modulated genes. We found that the timely regulated increase of NMB was specific for chondrogenesis and not observed during osteogenesis or adipogenesis. Furthermore, NMB expression levels correlated with the differentiation capacity of MSCs and its inhibition resulted in impaired chondrogenic differentiation indicating that NMB is required for chondrogenesis. We further showed that NMB activated the calcineurin activity through a Ca++-dependent signaling pathway. Conclusion: NMB is a newly described chondroinductive bioactive factor that upregulates the key chondrogenic transcription factor Sox9 through the modulation of Ca2+ signaling pathway and calcineurin activity.
Quantifying nanodiamonds biodistribution in whole cells with correlative iono-nanoscopy
Authors: Mi Zhaohong , Tan Hong Qi , Chen Ce-Belle , Dou Yanxin , Yang Chengyuan , Turaga Shuvan Prashant , Watt Frank , Bettiol Andrew 
Published: September 2020

Abstract
Correlative imaging and quantification of intracellular nanoparticles with the underlying ultrastructure is crucial for understanding cell-nanoparticle interactions in biological research. However, correlative nanoscale imaging of whole cells still remains a daunting challenge. Here, we report a straightforward nanoscopic approach for whole-cell correlative imaging, by simultaneous ionoluminescence and ultrastructure mapping implemented with a highly focused beam of alpha particles. We demonstrate that fluorescent nanodiamonds exhibit fast, ultrabright and stable emission upon excitation by alpha particles. Thus, by using fluorescent nanodiamonds as imaging probes, our approach enables quantification and correlative localization of single nanodiamonds within a whole cell at sub-40 nm resolution. As an application example, we show that our approach, together with Monte Carlo simulations, can be employed to provide unique insights into the mechanisms of nanodiamond radiosensitization at the single whole-cell level. These findings may benefit clinical studies of radio-enhancement effects by nanoparticles in charged-particle cancer therapy.