bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysing the effectiveness of topical bleeding care following tooth extraction in patients receiving dual antiplatelet therapy-retrospective observational study
Authors: Lewandowski Bogumił , Myszka Aleksander , Migut Małgorzata , Czenczek-Lewandowska Ewelina , Brodowski Robert 
Published: January 2021

AbstractBackgroundPatients using antiplatelet drugs following infarctions, acute coronary syndrome or stroke pose a significant clinical problem if it is necessary to perform surgery, including dental surgery, since they are at risk of prolonged or secondary post-extraction bleeding. Discontinuation of this therapy is associated with a high risk of serious thromboembolic complications. The purpose of this study was to assess the effectiveness of TachoSil fibrin-collagen patches in stopping and preventing of secondary post-extraction bleeding in patients undergoing chronic antiplatelet therapy.MethodsThe study was conducted through retrospective examination of the medical records of 153 patients using chronic antiplatelet therapy and those qualified for tooth extraction. The largest group comprised 74 patients using aspirin and clopidogrel as dual platelet antiaggregation therapy; in this group 75 tooth extractions were carried out. In all of the patients TachoSil fibrin-collagen patches and stiches were applied to the wounds resulting from tooth removal.ResultsFollowing tooth extraction, primary bleeding was stopped in all the patients and their wounds closed via coagulation within 20–30 min. In eight cases, accounting for 4.9% of the patients, secondary bleeding occurred and was successfully stopped only by applying a pressure dressing soaked in tranexamic acid. Secondary bleeding occurred in three patients on the second day and in five patients on the third day following tooth removal.ConclusionTopical application of TachoSil patches following tooth removal in patients using single or dual antiplatelet therapy effectively stopped bleeding and prevented secondary bleeding after tooth extraction.
Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p
Authors: Liu Jianhui , Zhu Shaoliang , Tang Wei , Huang Qinghua , Mei Yan , Yang Huawei 
Published: January 2021

Abstract
Background
Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM.

Methods
Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA.

Results
Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM.

Conclusions
Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.
Triple threat: pancreatic cystic lesion presenting with spontaneous hemorrhage is found to harbor three distinct neoplasms
Authors: Cha Da Eun , Horn Callie , Passeri Michael 
Published: January 2021

AbstractBackgroundPancreatic serous cystadenoma (SCA) is a benign, cystic lesion with an indolent growth pattern. Complications such as spontaneous hemorrhage or malignant transformation from SCA are extremely rare. Our case report describes an unusual presentation of a patient with a previously diagnosed SCA, made unique by the presence of three separate neoplasms in the final specimen.Case presentationA 74-year-old male with a previous diagnosis of SCA presented emergently with epigastric pain and non-bilious vomiting. Laboratory results were notable for a hemoglobin of 8.3 g/dl. CT scan of the abdomen demonstrated a complex, solid-cystic mass in the pancreatic head with a large hematoma and questionable focus of active hemorrhage. Surgical resection was recommended due to the risk of malignancy, possibility of re-bleeding, and symptoms of severe duodenal compression. Pancreaticoduodenectomy was performed, and final pathology demonstrated three separate neoplasms: serous cystadenoma, intraductal papillary mucinous neoplasm, and neuroendocrine tumor.ConclusionWhile pancreatic SCA are benign tumors that can be observed safely in the majority of cases, surgical intervention is often indicated in patients with large, symptomatic cysts or when diagnosis is unclear. When undergoing surveillance, it is crucial for both the patient and the care team to be aware of the possibility of rare, but life-threatening complications, such as hemorrhage. Likewise, the possibility of misdiagnosis or concurrent neoplasia should be considered.
Alteration of transthyretin and thyroxine-binding globulin in major depressive disorder: multiple reaction monitoring-based proteomic analysis
Authors: Woo Hye In , Park Jisook , Lim Shinn-Won , Kim Doh Kwan , Lee Soo-Youn 
Published: January 2021

AbstractBackgroundMajor depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.MethodsA total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine).ResultsAmong 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (P = 0.026). A few differences were observed in protein levels related to SSRIs treatment, although they were not statistically significant. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (P = 0.007).ConclusionsIn proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.
Validation of multiplex PCR sequencing assay of SIV
Authors: Moriarty Ryan V. , Fesser Nicolas , Sutton Matthew S. , Venturi Vanessa , Davenport Miles P. , Schlub Timothy , O’Connor Shelby L. 
Published: January 2021

Abstract
Background
The generation of accurate and reproducible viral sequence data is necessary to understand the diversity present in populations of RNA viruses isolated from clinical samples. While various sequencing methods are available, they often require high quality templates and high viral titer to ensure reliable data.

Methods
We modified a multiplex PCR and sequencing approach to characterize populations of simian immunodeficiency virus (SIV) isolated from nonhuman primates. We chose this approach with the aim of reducing the number of required input templates while maintaining fidelity and sensitivity. We conducted replicate sequencing experiments using different numbers of quantified viral RNA (vRNA) or viral cDNA as input material. We performed assays with clonal SIVmac239 to detect false positives, and we mixed SIVmac239 and a variant with 24 point mutations (SIVmac239-24X) to measure variant detection sensitivity.

Results
We found that utilizing a starting material of quantified viral cDNA templates had a lower rate of false positives and increased reproducibility when compared to that of quantified vRNA templates. This study identifies the importance of rigorously validating deep sequencing methods and including replicate samples when using a new method to characterize low frequency variants in a population with a small number of templates.

Conclusions
Because the need to generate reproducible and accurate sequencing data from diverse viruses from low titer samples, we modified a multiplex PCR and sequencing approach to characterize SIV from populations from non-human primates. We found that increasing starting template numbers increased the reproducibility and decreased the number of false positives identified, and this was further seen when cDNA was used as a starting material. Ultimately, we highlight the importance of vigorously validating methods to prevent overinterpretation of low frequency variants in a sample.
Real-world evidence on Kovaltry (81-8973) in children with moderate or severe hemophilia A in Europe: a nested cohort analysis
Authors: O’Hara Jamie , Hirst Ceri , Cabre Marquez Jose Francisco , Burke Tom 
Published: January 2021

Abstract
Background
Untreated hemophilia A patients may experience recurrent bleeding events leading to debilitating joint damages. While RCT and pharmacokinetic data support the value of Kovaltry [an unmodified full-length recombinant factor VIII (FVIII) product], real world evidence in children is lacking. This report describes a descriptive and multivariate analysis of the effectiveness of Kovaltry in children with hemophilia A in the real-world setting, using data from medical chart abstraction and cross-sectional surveys of physicians, patients, and caregivers.

Results
Male patients aged < 18 years with moderate or severe hemophilia A, residing in five European countries and treated with FVIII were studied. The co-primary endpoints were the annualized bleeding rate (ABR) and the annual FVIII utilization rate. Twenty nine patients treated with Kovaltry were included, of whom 93% had severe disease and 75% were on continuous prophylactic treatment. The mean ABR was 2.66 ± 2.06, with rates decreasing with age. The children received on average 2.45 infusions per week, consistent across age groups (median 3; range 1–3). There were no reports of inhibitor development or adverse events in the study (AEs), and all patients were satisfied or very satisfied with the treatment. An exploratory multivariate analysis suggests no significant difference in ABR or units utilized between Kovaltry and some extended half life products in children with severe hemophilia A, though characteristics of these patient cohorts were markedly different.

Conclusion
This analysis demonstrates the effectiveness and safety of Kovaltry in a pan-European pediatric population with severe hemophilia A.
Exome sequencing in paediatric patients with movement disorders
Authors: Kwong Anna Ka-Yee , Tsang Mandy Ho-Yin , Fung Jasmine Lee-Fong , Mak Christopher Chun-Yu , Chan Kate Lok-San , Rodenburg Richard J. T. , Lek Monkol , Huang Shushu , Pajusalu Sander , Yau Man-Mut , Tsoi Cheung , Fung Sharon , Liu Kam-Tim , Ma Che-Kwan , Wong Sheila , Yau Eric Kin-Cheong , Tai Shuk-Mui , Fung Eva Lai-Wah , Wu Nick Shun-Ping , Tsung Li-Yan , Smeitink Jan , Chung Brian Hon-Yin , Fung Cheuk-Wing 
Published: January 2021

Abstract
Background
Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis.

Results
We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation.

Conclusions
A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.
The identification of novel immunogenic antigens as potential Shigella vaccine components
Authors: de Alwis Ruklanthi , Liang Li , Taghavian Omid , Werner Emma , The Hao Chung , Thu Trang Nguyen Hoang , Duong Vu Thuy , Davies D. Huw , Felgner Philip L. , Baker Stephen 
Published: January 2021

Abstract
Background
Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella O-antigen.

Methods
Using a reverse vaccinology approach, where genomic analysis informed the Shigella immunome via an antigen microarray, we aimed to identify novel immunogenic Shigella antigens. A core genome analysis of Shigella species, pathogenic and non-pathogenic Escherichia coli, led to the selection of 234 predicted immunogenic Shigella antigens. These antigens were expressed and probed with acute and convalescent serum from microbiologically confirmed Shigella infections.

Results
Several Shigella antigens displayed IgG and IgA seroconversion, with no difference in sero-reactivity across by sex or age. IgG sero-reactivity to key Shigella antigens was observed at birth, indicating transplacental antibody transfer. Six antigens (FepA, EmrK, FhuA, MdtA, NlpB, and CjrA) were identified in in vivo testing as capable of producing binding IgG and complement-mediated bactericidal antibody.

Conclusions
These findings provide six novel immunogenic Shigella proteins that could serve as candidate vaccine antigens, species-specific carrier proteins, or targeted adjuvants.
Increased levels of YKL-40 in patients with diabetes mellitus: a systematic review and meta-analysis
Authors: Luo Wanwan , Zhang Lingmin , Sheng Lingling , Zhang Zhencheng , Yang Zaixing 
Published: January 2021

AbstractBackgroundDiabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN.MethodsPubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case–control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese. Finally, twenty-five studies were included in this meta-analysis.ResultsCompared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD = 1.62, 95% CI 1.08 to 2.25, P = 0.000; GDM: SMD = 2.85, 95% CI 1.01 to 4.70, P = 0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD = 1.58, 95% CI 0.59 to 2.56, P = 0.002; microalbuminuria: SMD = 2.57, 95% CI 0.92 to 4.22, P = 0.002; macroalbuminuria: SMD = 2.69, 95% CI 1.40 to 3.98, P = 0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD = 1.49, 95% CI 0.28 to 2.71, P = 0.016; macroalbuminuria vs microalbuminuria: SMD = 0.93, 95% CI 0.34 to 1.52, P = 0.002).ConclusionsOur current meta-analysis demonstrates that serum level of YKL-40 is increased in DM and positively associated with the severe degree of albuminuria. Therefore, we suggest that YKL-40 could be considered to be detected, along with other inflammatory markers, if DM, especially DN, is suspected.
Radiation-induced toxicity in rectal epithelial stem cell contributes to acute radiation injury in rectum
Authors: Tirado Felipe Rodriguez , Bhanja Payel , Castro-Nallar Eduardo , Olea Ximena Diaz , Salamanca Catalina , Saha Subhrajit 
Published: January 2021

Abstract
Background
Radiation-induced rectal epithelial damage is a very common side effect of pelvic radiotherapy and often compromise the life quality and treatment outcome in patients with pelvic malignancies. Unlike small bowel and colon, effect of radiation in rectal stem cells has not been explored extensively. Here we demonstrate that Lgr5-positive rectal stem cells are radiosensitive and organoid-based transplantation of rectal stem cells mitigates radiation damage in rectum.

Methods
C57Bl6 male mice (JAX) at 24 h were exposed to pelvic irradiation (PIR) to determine the radiation effect in pelvic epithelium. Effect of PIR on Lgr5-positive rectal stem cells (RSCs) was determined in Lgr5-EGFP-Cre-ERT2 mice exposed to PIR. Effect of PIR or clinically relevant fractionated PIR on regenerative response of Lgr5-positive RSCs was examined by lineage tracing assay using Lgr5-eGFP-IRES-CreERT2; Rosa26-CAG-tdTomato mice with tamoxifen administration to activate Cre recombinase and thereby marking the ISC and their respective progeny. Ex vivo three-dimensional organoid cultures were developed from Lgr5-EGFP-Cre-ERT2 mice. Organoid growth was determined by quantifying the budding crypt/total crypt ratio. Organoids from Lgr5-EGFP-ires-CreERT2-TdT mice were transplanted in C57Bl6 male mice exposed to PIR. Engraftment and repopulation of Lgr5-positive RSCs were determined after tamoxifen administration to activate Cre recombinase in recipient mice. Statistical analysis was performed using Log-rank (Mantel-Cox) test and paired two-tail t test.

Result
Exposure to pelvic irradiation significantly damaged rectal epithelium with the loss of Lgr5+ve rectal stem cells. Radiosensitivity of rectal epithelium was also observed with exposure to clinically relevant fractionated pelvic irradiation. Regenerative capacity of Lgr5+ve rectal stem cells was compromised in response to fractionated pelvic irradiation. Ex vivo organoid study demonstrated that Lgr5+ve rectal stem cells are sensitive to both single and fractionated radiation. Organoid-based transplantation of Lgr5+ve rectal stem cells promotes repair and regeneration of rectal epithelium.

Conclusion
Lgr5-positive rectal stem cells are radiosensitive and contribute to radiation-induced rectal epithelial toxicity. Transplantation of Lgr5-positive rectal stem cells mitigates radiation-induced rectal injury and promotes repair and regeneration process in rectum.
Utilization of the Public Health Ordinance to prevent nosocomial spread in a case of acute measles-associated psychosis
Authors: Stein-Zamir Chen , Abramson Nitza , Sonnenfeld-Alroey Hagit , Charnes Jacob , Eckstein Dana , Dienstag Aryeh , Wolf Dana , Moses Allon E. , Weiss Yoram G. 
Published: January 2021

AbstractMeasles is a highly contagious disease. A 24 years old patient, recently exposed to measles (unvaccinated), presented in the emergency department with severe agitation, compatible with an acute psychotic episode, during the measles epidemic which spread in Israel in 2018–2019. Upon hospital admission, strict isolation was instructed, yet, without compliance, probably due to the patient’s status. Measles diagnosis was promptly confirmed. As measles transmission was eminent, public health measures were employed through immediate implementation of the section 15 of the Public Health Ordinance, allowing for compulsory short-term isolation. The patient’s condition improved within a few days and the measures were no longer necessary. This measles case occurred in the pre-Coronavirus disease 2019 (COVID-19) epidemic when use of a Public Health Ordinance was considered an extreme measure. This is in contrast to the current global use of Public Health laws to enforce strict quarantine and isolation on persons infected or potentially exposed to COVID-19. Nevertheless, minimizing infectious diseases transmission is a core function of public health law. Utilizing legal enforcement in circumstances of immediate public health hazard, such as nosocomial measles transmission, necessitates careful consideration. The integrative clinical and public health approach and prompt measures employed in this exceptional case, led to prevention of further infection spread.
Expression pattern analysis of three R2R3-MYB transcription factors for the production of anthocyanin in different vegetative stages of Arabidopsis leaves
Authors: Koo Yeonjong , Poethig R. Scott 
Published: January 2021

AbstractAnthocyanin is a type of flavonoid that appears purple in plants. PAP1, PAP2, and MYB113 are the three major R2R3-MYB transcription factors that regulate flavonoid biosynthesis inArabidopsis thaliana. In this study, we found that the three MYB genes regulate anthocyanin accumulation in different leaf stages. Under limited nutrient conditions, PAP1 and PAP2 genes were highly induced in juvenile leaves. Conversely, MYB113 was expressed mainly in adult leaves. In addition, we investigated the role of trans-acting siRNA4 (TAS4) in the post-transcriptional regulation of anthocyanin expression in Arabidopsis leaves. In plant growth, the inhibition of PAP1 and PAP2 gene expression by TAS4 was observed only in juvenile leaves, and MYB113 inhibition was observed in adult leaves. In conclusion, we found that transcription and transcript repression of the three MYB genes is differentially regulated by TAS4 in leaf developmental stages. Our results improve the understanding of the regulation of plant anthocyanin production under stress conditions.