bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly sensitive MLH1 methylation analysis in blood identifies a cancer patient with low-level mosaic MLH1 epimutation
Authors: Dámaso Estela , Canet-Hermida Júlia , Vargas-Parra Gardenia , Velasco Àngela , Marín Fátima , Darder Esther , del Valle Jesús , Fernández Anna , Izquierdo Àngel , Mateu Gemma , Oliveras Glòria , Escribano Carmen , Piñol Virgínia , Uchima Hugo-Ikuo , Soto José Luis , Hitchins Megan , Farrés Ramon , Lázaro Conxi , Queralt Bernat , Brunet Joan , Capellá Gabriel , Pineda Marta 
Published: November 2019

AbstractConstitutionalMLH1methylation (epimutation) is a rare cause of Lynch syndrome. Low-level methylation (≤ 10%) has occasionally been described. This study aimed to identify low-level constitutionalMLH1epimutations and determine its causal role in patients withMLH1-hypermethylated colorectal cancer.Eighteen patients withMLH1-hypermethylated colorectal tumors in whomMLH1methylation was previously undetected in blood by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were screened forMLH1methylation using highly sensitive MS-melting curve analysis (MS-MCA). Constitutional methylation was characterized by different approaches.MS-MCA identified one patient (5.6%) with low-levelMLH1methylation (~ 1%) in blood and other normal tissues, which was confirmed by clonal bisulfite sequencing in blood. The patient had developed three clonally related gastrointestinalMLH1-methylated tumor lesions at 22, 24, and 25 years of age. The methylated region in normal tissues overlapped with that reported for other carriers of constitutionalMLH1epimutations. Low-levelMLH1methylation and reduced allelic expression were linked to the same genetic haplotype, whereas the opposite allele was lost in patient’s tumors. Mutation screening ofMLH1and other hereditary cancer genes was negative.Herein, a highly sensitive MS-MCA-based approach has demonstrated its utility for the identification of low-level constitutionalMLH1epigenetic mosaicism. The eventual identification and characterization of additional cases will be critical to ascertain the cancer risks associated with constitutionalMLH1 epigenetic mosaicism.
DNA methylation associated with postpartum depressive symptoms overlaps findings from a genome-wide association meta-analysis of depression
Authors: Lapato Dana M. , Roberson-Nay Roxann , Kirkpatrick Robert M. , Webb Bradley T. , York Timothy P. , Kinser Patricia A. 
Published: November 2019

Abstract
Background
Perinatal depressive symptoms have been linked to adverse maternal and infant health outcomes. The etiology associated with perinatal depressive psychopathology is poorly understood, but accumulating evidence suggests that understanding inter-individual differences in DNA methylation (DNAm) patterning may provide insight regarding the genomic regions salient to the risk liability of perinatal depressive psychopathology.

Results
Genome-wide DNAm was measured in maternal peripheral blood using the Infinium MethylationEPIC microarray. Ninety-two participants (46% African-American) had DNAm samples that passed all quality control metrics, and all participants were within 7 months of delivery. Linear models were constructed to identify differentially methylated sites and regions, and permutation testing was utilized to assess significance. Differentially methylated regions (DMRs) were defined as genomic regions of consistent DNAm change with at least two probes within 1 kb of each other. Maternal age, current smoking status, estimated cell-type proportions, ancestry-relevant principal components, days since delivery, and chip position served as covariates to adjust for technical and biological factors. Current postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale. Ninety-eight DMRs were significant (false discovery rate < 5%) and overlapped 92 genes. Three of the regions overlap loci from the latest Psychiatric Genomics Consortium meta-analysis of depression.

Conclusions
Many of the genes identified in this analysis corroborate previous allelic, transcriptomic, and DNAm association results related to depressive phenotypes. Future work should integrate data from multi-omic platforms to understand the functional relevance of these DMRs and refine DNAm association results by limiting phenotypic heterogeneity and clarifying if DNAm differences relate to the timing of onset, severity, duration of perinatal mental health outcomes of the current pregnancy or to previous history of depressive psychopathology.
Cancer genome landscape: a radiologist’s guide to cancer genome medicine with imaging correlates
Authors: Alessandrino Francesco , Smith Daniel A. , Tirumani Sree Harsha , Ramaiya Nikhil H. 
Published: November 2019

AbstractThe introduction of high throughput sequence analysis in the past decade and the decrease in sequencing costs has made available an enormous amount of genomic data. These data have shaped the landscape of cancer genome, which encompasses mutations determining tumorigenesis, the signaling pathways involved in cancer growth, the tumor heterogeneity, and its role in development of metastases. Tumors develop acquiring a series of driver mutations over time. Of the many mutated genes present in cancer, only few specific mutations are responsible for invasiveness and metastatic potential, which, in many cases, have characteristic imaging appearance. Ten signaling pathways, each with targetable components, have been identified as responsible for cancer growth. Blockage of any of these pathways form the basis for molecular targeted therapies, which are associated with specific pattern of response and toxicities. Tumor heterogeneity, responsible for the different mutation pattern of metastases and primary tumor, has been classified in intratumoral, intermetastatic, intrametastatic, and interpatient heterogeneity, each with specific imaging correlates. The purpose of this article is to introduce the key components of the landscapes of cancer genome and their imaging counterparts, describing the types of mutations associated with tumorigenesis, the pathways of cancer growth, the genetic heterogeneity involved in metastatic disease, as well as the current challenges and opportunities for cancer genomics research.
Lumbar vertebral osteomyelitis and psoas abscess caused by Actinomyces israelii after an operation under general anesthesia in a patient with end-stage renal disease: a case report
Authors: Yamada Yutaka , Kinoshita Chiharu , Nakagawa Hirokazu 
Published: November 2019

Abstract
Background
Actinomycosis is a chronic, slowly progressive infection caused by the Actinomyces species. Lumbar vertebral involvement of Actinomyces israelii is extremely rare; this is the first case report of lumbar vertebral osteomyelitis and psoas abscess caused by Actinomyces israelii after an operation under general anesthesia.

Case presentation
A 66-year-old Japanese man with end-stage renal disease was admitted to our hospital for an operation for cervical canal stenosis. After the operation under general anesthesia, during which tracheal intubation and nasogastric tube insertion were performed, he developed low back pain. During a second hospitalization, computed tomography revealed osteolysis of the lumbar endplates of L2 and L3, swelling of the intervertebral disk of L2/L3, and swelling of the left psoas major muscle. Percutaneous drainage of the intervertebral disc was performed, and the culture of the aspirate grew Actinomyces israelii. Based on the susceptibility, ampicillin was administered but his condition did not improve. We changed the antibiotics to ampicillin-sulbactam for coverage of unidentified oral commensals, and his symptoms and signs finally improved.

Conclusion
Our patient’s long-term end-stage renal disease had made the oral and gastrointestinal mucosal barriers very fragile. Under these conditions, even mildly invasive procedures such as tracheal intubation and nasogastric tube insertion could be the cause of infectious complication by oral commensals, including Actinomyces.
Leptospirosis meningitis transmission from a pet mouse: a case report
Authors: Nordholm Anne Christine , Omland Lars Haukali , Villumsen Steen , Al-Subeihe Imad , Katzenstein Terese L. 
Published: November 2019

Abstract
Background
Leptospirosis is a reemerging zoonosis with a worldwide distribution and a wide range of clinical manifestations. We report a case of leptospirosis meningitis in a previously healthy woman infected by her pet mouse.

Case presentation
A 27-year-old Caucasian woman with pet mice presented to our institute with a 1 week history of fever, headache, myalgia, vomiting, diarrhea, and dark urine. Her admission examination revealed neck stiffness, conjunctivitis, and icteric sclera. Her liver enzymes, bilirubin, white blood cell count, and C-reactive protein were elevated. Her cerebrospinal fluid showed an elevated white blood cell count. Polymerase chain reactions using her cerebrospinal fluid, blood, and urine showed negative results for leptospirosis, but the result of her microagglutination test was positive for Leptospira interrogans serovar sejroe with a more than threefold increase in paired sera. The patient was treated with ceftriaxone for 1 week, and her condition steadily improved.

Conclusions
This case report raises awareness of pet rodents as sources of leptospirosis. Leptospirosis meningitis should be considered in patients with meningeal symptoms and pet rodents.
Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells
Authors: Yang Kun , Li Dong , Wang Meitian , Xu Zhiliang , Chen Xiao , Liu Qiao , Sun Wenjie , Li Jiangxia , Gong Yaoqin , Liu Duo , Shao Changshun , Liu Qiji , Li Xi 
Published: November 2019

Abstract
Background
The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration.

Methods
We used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2′-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models.

Results
We found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p.

Conclusions
Blue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p.

Graphical abstract
Functional proteins of mesenchymal stem cell-derived extracellular vesicles
Authors: Qiu Guanguan , Zheng Guoping , Ge Menghua , Wang Jiangmei , Huang Ruoqiong , Shu Qiang , Xu Jianguo 
Published: November 2019

AbstractExtracellular vesicles (EVs) contain proteins, microRNAs, mRNAs, long non-coding RNAs, and phospholipids, and are a novel mechanism of intercellular communication. It has been proposed that the immunomodulatory and regenerative effects of mesenchymal stem/stromal cells (MSCs) are mainly mediated by soluble paracrine factors and MSC-derived EVs (MSC-EVs). Recent studies suggest that MSC-EVs may serve as a novel and cell-free alternative to whole-cell therapies. The focus of this review is to discuss the functional proteins which facilitate the effects of MSC-EVs. The first section of the review discusses the general functions of EV proteins. Next, we describe the proteomics of MSC-EVs as compared with their parental cells. Then, the review presents the current knowledge that protein contents of MSC-EVs play an essential role in immunomodulation and treatment of various diseases. In summary, functional protein components are at least partially responsible for disease-modulating capacity of MSC-EVs.
Biodistribution and post-therapy dosimetric analysis of [177Lu]Lu-DOTAZOL in patients with osteoblastic metastases: first results
Authors: Khawar Ambreen , Eppard Elisabeth , Roesch Frank , Ahmadzadehfar Hojjat , Kürpig Stefan , Meisenheimer Michael , Gaertner Florian. C. , Essler Markus , Bundschuh Ralph. A. 
Published: November 2019

Abstract
Background
Preclinical biodistribution and dosimetric analysis of [177Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177Lu]Lu-DOTAZOL in patients with metastatic skeletal disease.

Method
Four patients with metastatic skeletal disease (age range, 64–83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177Lu]Lu-DOTAZOL. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier’s dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose.

Results
Qualitative biodistribution analysis revealed early and high uptake of [177Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177Lu]Lu-DOTAZOL are consistent with preclinical data.

Conclusion
[177Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177Lu]Lu-DOTAZOL in the clinical setting.
The antecedents and consequences of employees’ followership behavior in social network organizational context: a longitudinal study
Authors: Xu Sheng , Yang Tonghua , Guo Ruliang , Zhang Wenyuan 
Published: November 2019

AbstractThe social network is a social structure made up of individuals who are tied by social links. With the rapid development of information technology, online social networking services and microblogging service received a lot of attention. Social networks provide a comprehensive communication platform of interaction, knowledge sharing, information dissemination to people, etc. They also bring a significant impact on people’s working style and interpersonal communication. Drawing from trait theory, regulatory focus theory, followership theory, political skills, self-construal theory, and performance theory, this study systematically investigates the antecedents that induce the difference in followership behavior and the different consequences of behavior on job performance. We introduce a novel hybrid similarity measure, and the best matching based supervised learning process is conducted for training the time series. The events before the current timestamp can be adopted as a training set, and an early predictor will be generated by learning the rules from the training set. The newly coming events will be used for verifying the predictor, or assessing and tuning it. This paper clarifies the antecedents’ mechanism for differences in followership behavior and the consequence mechanism that followership behavior differently impacts job performance.
Particularities of data mining in medicine: lessons learned from patient medical time series data analysis
Authors: Aljawarneh Shadi , Anguera Aurea , Atwood John William , Lara Juan A. , Lizcano David 
Published: November 2019

AbstractNowadays, large amounts of data are generated in the medical domain. Various physiological signals generated from different organs can be recorded to extract interesting information about patients’ health. The analysis of physiological signals is a hard task that requires the use of specific approaches such as the Knowledge Discovery in Databases process. The application of such process in the domain of medicine has a series of implications and difficulties, especially regarding the application of data mining techniques to data, mainly time series, gathered from medical examinations of patients. The goal of this paper is to describe the lessons learned and the experience gathered by the authors applying data mining techniques to real medical patient data including time series. In this research, we carried out an exhaustive case study working on data from two medical fields: stabilometry (15 professional basketball players, 18 elite ice skaters) and electroencephalography (100 healthy patients, 100 epileptic patients). We applied a previously proposed knowledge discovery framework for classification purpose obtaining good results in terms of classification accuracy (greater than 99% in both fields). The good results obtained in our research are the groundwork for the lessons learned and recommendations made in this position paper that intends to be a guide for experts who have to face similar medical data mining projects.
Evaluation of the association between exosomal levels and female reproductive system and fertility outcome during aging: a systematic review protocol
Authors: Mobarak Halimeh , Rahbarghazi Reza , Lolicato Francesca , Heidarpour Mohammad , Pashazadeh Fariba , Nouri Mohammad , Mahdipour Mahdi 
Published: November 2019

Abstract
Background
Exosomes may have critical roles in the maternal-embryo cross-talk for the recognition and maintenance of pregnancy during maternal aging. Exosomes have the capability to carry developmental signaling molecules with the ability to modulate gene expressions and affect growth and regulation of embryo during pregnancy. Systematic review aims to evaluate age-related alterations in the exosomal content and functions that can influence the reproductive performance in human and animal models as conveyors of senescence signals.

Methods
A literature search of electronic databases including MEDLINE (PubMed), Embase, ProQuest, Scopus, Google Scholar, WHO, SID, MAGIRAN, and Barakat will be conducted. Following the online search, articles will be screened by two independent reviewers according to inclusion and exclusion criteria. Eligible studies will be critically appraised by reviewers at the study level for methodological quality using Joanna Briggs Institute’s standardized critical appraisal tools. The extracted data from selected studies will cover the study populations, methods, current evidence about the physiological role of extracellular vesicles and exosomes in reproductive system, relevant outcomes, and possible conclusions about the effectiveness of exposure.

Discussion
Regarding the role of exosomes and their cargoes in the function of reproductive tract, the possible beneficial or adverse effects following exosomal administration from younger women to older women will be evaluated in the systematic review. As a result, exosome therapy could be suggested as a novel therapeutic agent if the favorable results are identified.
Effectiveness of trauma centers verification: Protocol for a systematic review
Authors: Batomen Brice , Moore Lynne , Carabali Mabel , Tardif Pier-Alexandre , Champion Howard , Nandi Arijit 
Published: November 2019

Abstract
Background
The implementation of trauma systems in many high-income countries over the last 50 years has led to important reductions in injury mortality and disability in many healthcare jurisdictions. Injury organizations including the American College of Surgeons and the Trauma Association of Canada as well as the World Health Organization provide consensus-based recommendations on resources and processes for optimal injury care. Many hospitals treating trauma patients seek verification to demonstrate that they meet these recommendations. This process may be labeled differently across jurisdictions. In Canada for example, it is called accreditation, but it has the same objective and very similar modalities. The objective of the study described in this protocol is to systematically review evidence on the effectiveness of trauma center verification for improving clinical processes and patient outcomes in injury care.

Methods
We will perform a systematic review of studies evaluating the association between trauma center verification and hospital mortality (primary outcome), as well as morbidity, resource utilization, and processes of care (secondary outcomes). We will search CINAHL, EMBASE, HealthStar, MEDLINE, and ProQuest databases, as well as key injury organization websites for gray literature. We will assess the methodological quality of studies using the Risk Of Bias In Non-randomized Studies – of Interventions (ROBINS-I) assessment tool. We are planning to conduct a meta-analysis if feasible based on the number of included studies and their heterogeneity. We will evaluate the quality of cumulative evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group methodology.

Discussion
This review will provide a synthesis of the body of evidence on trauma center verification effectiveness. Results could reinforce current verification modalities and may suggest ways to optimize them. Results will be published in a peer-reviewed journal and presented at an international clinical conference.

Systematic review registration
PROSPERO CRD42018107083.
Second-order numerical methods for the tempered fractional diffusion equations
Authors: Qiu Zeshan , Cao Xuenian 
Published: November 2019

AbstractIn this paper, a class of second-order tempered difference operators for the left and right Riemann–Liouville tempered fractional derivatives is constructed. And a class of second-order numerical methods is presented for solving the space tempered fractional diffusion equations, where the space tempered fractional derivatives are evaluated by the proposed tempered difference operators, and in the time direction is discreted by the Crank–Nicolson method. Numerical schemes are proved to be unconditionally stable and convergent with order $O(h^{2}+\tau ^{2})$O(h2+τ2). Numerical experiments demonstrate the effectiveness of the numerical schemes.