bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic tool for fate mapping of Oct4 (Pou5f1)-expressing cells and their progeny past the pluripotency stage
Authors: Kuzmin Andrey A. , Ermakova Veronika V. , Sinenko Sergey A. , Ponomartsev Sergey V. , Starkova Tatiana Y. , Skvortsova Elena V. , Cherepanova Olga , Tomilin Alexey N. 
Published: December 2019

Abstract
Background
Methods based on site-specific recombinases are widely used in studying gene activities in vivo and in vitro. In these studies, constitutively active or inducible variants of these recombinases are expressed under the control of either lineage-specific or ubiquitous promoters. However, there is a need for more advanced schemes that combine these features with possibilities to choose a time point from which lineage tracing starts in an autonomous fashion. For example, the key mammalian germline gatekeeper gene Oct4 (Pou5f1) is expressed in the peri-implantation epiblast which gives rise to all cells within embryos. Thus the above techniques are hardly applicable to Oct4 tracing past the epiblast stage, and the establishment of genetic tools addressing such a limitation is a highly relevant pursuit.

Methods
The CRISPR/Cas9 tool was used to manipulate the genome of mouse embryonic stem cells (ESCs), and various cell culture technics—to maintain and differentiate ESCs to neural cell, lentivirus-based reprogramming technique—to generate induced pluripotent stem cells (iPSCs).

Results
In this paper, we have developed a two-component genetic system (referred to as O4S) that allows tracing Oct4 gene activity past the epiblast stage of development. The first component represents a knock-in of an ubiquitous promoter-driven inducible Cre, serving as a stop signal for downstream tdTomato. Upon activation of Cre activity with 4-hydroxytamoxifen (4-OHT) at any given time point, the recombinase excises a stop signal and poses the second component of the system—the FlpO recombinase, knocked into 3’UTR of Oct4, to be expressed upon activation of the latter gene. Oct4-driven expression of FlpO, in turn, triggers the tdTomato expression and thus, permanently marks Oct4+ cells and their progeny. We have validated the O4S system in cultured ESCs and shown that it is capable, for example, to timely capture an activation of Oct4 gene during the reprogramming of somatic cells into iPSCs.

Conclusions
The developed O4S system can be used to detect Oct4 activation event, both permanent and transient, in somatic cell types outside the germline. The approach can be equally adjusted to other genes, provided the first component of the system is placed under transcriptional control of these genes, thus, making it a valuable tool for cell fate mapping in mice.
Activation of type I interferon antiviral response in human neural stem cells
Authors: Lin Jhao-Yin , Kuo Rei-Lin , Huang Hsing-I 
Published: December 2019

AbstractBackgroundNeural stem cells (NSCs) residing in the central nervous system play an important role in neurogenesis. Several viruses can infect these neural progenitors and cause severe neurological diseases. The innate immune responses against the neurotropic viruses in these tissue-specific stem cells remain unclear.MethodsHuman NSCs were transfected with viral RNA mimics or infected with neurotropic virus for detecting the expression of antiviral interferons (IFNs) and downstream IFN-stimulated antiviral genes.ResultsNSCs are able to produce interferon-β (IFN-β) (type I) and λ1 (type III) after transfection with poly(I:C) and that downstream IFN-stimulated antiviral genes, such as ISG56 and MxA, and the viral RNA sensors RIG-I, MDA5, and TLR3, can be expressed in NSCs under poly(I:C) or IFN-β stimulation. In addition, our results show that the pattern recognition receptors RIG-I and MDA5, as well as the endosomal pathogen recognition receptor TLR3, but not TLR7 and TLR8, are involved in the activation of IFN-β transcription in NSCs. Furthermore, NSCs infected with the neurotropic viruses, Zika and Japanese encephalitis viruses, are able to induce RIG-I-mediated IFN-β expression.ConclusionHuman NSCs have the ability to activate IFN signals against neurotropic viral pathogens.
Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice
Authors: Che Chen , Dudick Kayla , Shoemaker Robin 
Published: December 2019

AbstractBackgroundOver a third of reproductive-age women in the USA are obese, and the prevalence of cardiovascular disease (CVD) is rising in premenopausal women. Cardiac hypertrophy is an independent predictor of CVD. In contrast to pregnancy, where transiently increased left ventricular (LV) mass is not associated with cardiac damage, obesity-mediated cardiac hypertrophy is pathological. There is a paucity of data describing the effect of obesity during pregnancy on maternal cardiovascular health. The purpose of this study was to determine the long-term effect of obesity during pregnancy on cardiac function and structure in mice.MethodsFemale C57BL/6 J mice were fed a high-fat (HF) or a low-fat (LF) diet for 20 weeks. After 4 weeks, LF- and HF-fed female mice were either crossed with males to become pregnant or remained non-pregnant controls. Following delivery, pups were euthanized, and females maintained on respective diets. After 20 weeks of diet feeding, cardiac function was quantified by echocardiography, and plasma leptin and adiponectin concentrations quantified in LF- and HF-fed postpartum and nulliparous females. mRNA abundance of genes regulating cardiac hypertrophy and remodeling was quantified from left ventricles using the NanoString nCounter Analysis System. Cardiac fibrosis was assessed from picrosirius red staining of left ventricles.ResultsHF-fed postpartum mice had markedly greater weight gain and fat mass expansion with obesity, associated with significantly increased LV mass, cardiac output, and stroke volume compared with HF-fed nulliparous mice. Plasma leptin, but not adiponectin, concentrations were correlated with LV mass in HF-fed females. HF feeding increased LV posterior wall thickness; however, LV chamber diameter was only increased in HF-fed postpartum females. Despite the marked increase in LV mass in HF-fed postpartum mice, mRNA abundance of genes regulating fibrosis and interstitial collagen content was similar between HF-fed nulliparous and postpartum mice. In contrast, only HF-fed postpartum mice exhibited altered expression of genes regulating the extracellular matrix.ConclusionsThese results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.
Learning important features from multi-view data to predict drug side effects
Authors: Liang Xujun , Zhang Pengfei , Li Jun , Fu Ying , Qu Lingzhi , Chen Yongheng , Chen Zhuchu 
Published: December 2019

AbstractThe problem of drug side effects is one of the most crucial issues in pharmacological development. As there are many limitations in current experimental and clinical methods for detecting side effects, a lot of computational algorithms have been developed to predict side effects with different types of drug information. However, there is still a lack of methods which could integrate heterogeneous data to predict side effects and select important features at the same time. Here, we propose a novel computational framework based on multi-view and multi-label learning for side effect prediction. Four different types of drug features are collected and graph model is constructed from each feature profile. After that, all the single view graphs are combined to regularize the linear regression functions which describe the relationships between drug features and side effect labels. L1 penalties are imposed on the regression coefficient matrices in order to select features relevant to side effects. Additionally, the correlations between side effect labels are also incorporated into the model by graph Laplacian regularization. The experimental results show that the proposed method could not only provide more accurate prediction for side effects but also select drug features related to side effects from heterogeneous data. Some case studies are also supplied to illustrate the utility of our method for prediction of drug side effects.
Role of F-18 FDG PET/CT in non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas
Authors:   On behalf of Catholic University Lymphoma Group, Park Hye Lim , O Joo Hyun , Park Sonya Youngju , Jung Seung-Eun , Park Gyeongsin , Choi Byung-Ock , Kim Sung Hoon , Jeon Young-Woo , Cho Seok-Goo , Yang Suk-Woo 
Published: December 2019

Abstract
Background
Despite the widespread use of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in the diagnosis and response assessment of patients with lymphoma, few studies have assessed its value in ocular adnexal lymphomas. The purpose of this study was to evaluate the role of FDG PET/CT in staging of non-conjunctival origin ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphomas (OAML). In addition, the diagnostic sensitivity of FDG PET/CT was compared with magnetic resonance imaging (MRI). FDG PET/CT of 123 consecutive patients with pathologically proven OAML between January 2009 and February 2016 were retrospectively reviewed. The patients with MALT lymphoma originating from conjunctiva were excluded. A total 50 patients with non-conjunctival origin OAML were assessed. Maximum standardized uptake value (SUVmax) and additional PET parameters were measured for all lesions. Sensitivity for primary tumor detection was compared with MRI.

Results
Ten patients had bilateral OAML and total 60 OAML lesions were analyzed. MRI was missing in one patient. The tumor locations were as follows: eyelid, 9; lacrimal gland, 18; orbit, 33. Fifty lesions (83.3%) were FDG-avid tumors with mean ± SD SUVmax 4.8 ± 2.4 (range 2.0~11.1). The mean SUVmax according to tumor location were as follows: eyelid, 3.7 ± 1.1 (2.8~5.3); lacrimal gland, 3.6 ± 1.4 (2.1~6.4); orbit, 5.7 ± 2.6 (2.0~11.1). Mean SUVmax among the 3 locations were statistically different (P = 0.010). The sensitivity was calculated as 83.1% (49/59) for FDG PET/CT and 89.8% (53/59) for MRI, which were statistically comparable (P = 0.219 by McNemar’s test). Seven of 50 patients (14%) were upstaged by detection of extraocular lesions by FDG PET/CT (1 kidney and lung, 1 tonsil, 4 cervical LNs, 1 sacral foramen).

Conclusion
83.3% of the non-conjunctival origin OAML were FDG-avid tumors, with FDG PET/CT showing comparable sensitivity to that of MRI. FDG PET/CT detected unsuspected extraocular lymphoma involvement in 14% of the patients. FDG PET/CT performed for staging of non-conjunctival origin OAML may thus guide therapeutic management.
Multimodal image-guided surgery of HER2-positive breast cancer using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast tumor model
Authors: Deken Marion M. , Bos Desirée L. , Tummers Willemieke S. F. J. , March Taryn L. , van de Velde Cornelis J. H. , Rijpkema Mark , Vahrmeijer Alexander L. 
Published: December 2019

AbstractBackgroundCombining modalities using dual-labeled antibodies may allow preoperative and intraoperative tumor localization and could be used in image-guided surgery to improve complete tumor resection. Trastuzumab is a monoclonal antibody against the human epidermal growth factor-2 (HER2) receptor and dual-labeled trastuzumab with both a fluorophore (IRDye800CW) and a radioactive label (111In) can be used for multimodal imaging of HER2-positive breast cancer. The aim of this study was to demonstrate the feasibility of HER2-targeted multimodal imaging using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast cancer model.MethodsTrastuzumab was conjugated withp-isothiocyanatobenzyl (ITC)-diethylenetriaminepentaacetic acid (DTPA) and IRDye800CW-NHS ester and subsequently labeled with111In. In a dose escalation study, the biodistribution of 10, 30, and 100 μg [111In]In-DTPA-trastuzumab-IRDye800CW was determined 48 h after injection in BALB/c nude mice with orthotopic high HER2-expressing tumors. Also, a biodistribution study was performed in a low HER2-expressing breast cancer model. In addition, multimodal image-guided surgery was performed in each group. Autoradiography, fluorescence microscopy, and immunohistochemically stained slices of the tumors were compared for co-localization of tumor tissue, HER2 expression, fluorescence, and radiosignal.ResultsBased on the biodistribution data, a 30 μg dose of dual-labeled trastuzumab (tumor-to-blood ratio 13 ± 2) was chosen for all subsequent studies. [111In]In-DTPA-trastuzumab-IRDye800CW specifically accumulated in orthotopic HER2-positive BT474 tumors (101 ± 7 %IA/g), whereas uptake in orthotopic low HER2-expressing MCF7 tumor was significantly lower (1.2 ± 0.2 %IA/g,p= 0.007). BT474 tumors could clearly be visualized with both micro-SPECT/CT, fluorescence imaging and subsequently, image-guided resection was performed. Immunohistochemical analyses of BT474 tumors demonstrated correspondence in fluorescence, radiosignal, and high HER2 expression.ConclusionsDual-labeled trastuzumab showed specific accumulation in orthotopic HER2-positive BT474 breast tumors with micro-SPECT/CT and fluorescence imaging and enabled image-guided tumor resection. In the clinical setting, [111In]In-DTPA-trastuzumab-IRDye800CW could be valuable for preoperative detection of (metastatic) tumors by SPECT/CT imaging, and intraoperative localization by using a gamma probe and fluorescence image-guided surgery to improve radical resection of tumor tissue in patients with HER2-positive tumors.
Impact of a multidisciplinary care bundle for necrotizing skin and soft tissue infections: a retrospective cohort study
Authors:   the Henri Mondor Hospital Necrotizing Fasciitis group, Urbina Tomas , Hua Camille , Sbidian Emilie , Bosc Romain , Tomberli Françoise , Lepeule Raphael , Decousser Jean-Winoc , Mekontso Dessap Armand , Chosidow Olivier , de Prost Nicolas 
Published: December 2019

Abstract

Background
Necrotizing skin and soft tissue infections (NSTIs) require both prompt medical and surgical treatment. The coordination of multiple urgent interventions by care bundles has improved outcome in other settings. This study aimed to assess the impact of a multidisciplinary care bundle on management and outcome of patients with NSTIs.

Methods
Patients with NSTIs admitted between 2006 and 2017 were compared according to admission before or after bundle implementation (2012–2013). This bundle consisted mainly in (1) the creation of a multidisciplinary task force; (2) management guidelines on empirical antibiotics, intensive care unit admission criteria, a triage algorithm to accelerate operating room access; and (3) an active communication policy. Patient recruitment and management were compared between pre- and post-implementation periods. Main outcome was day 60-censored hospital survival.

Results
Overall, 224 patients were admitted: 60 before, 35 during, and 129 after bundle implementation. Admission after implementation was associated with increased yearly admissions (10 [8–13] vs 30 [24–43] patients/year, p = 0.014) and decreased mortality (30 vs 15%, HR = 0.49 [0.26–0.92]; p = 0.026) but was no longer a protective factor for mortality after adjustment on confounding factors (adjusted HR = 0.90 [0.43–1.88], p = 0.780). There was no significant difference regarding time to surgery (0 [0–1] vs 0 [0–1] days, p = 0.192) or rate of antibiotic treatment within 24 h (98% vs 99%, p > 0.99).

Conclusions
Implementation of a multidisciplinary care bundle for NSTIs was feasible, but in a retrospective study from an already experienced center was not associated with significantly increased survival after adjustment.
How to detect a positive response to a fluid bolus when cardiac output is not measured?
Authors: Ait-Hamou Zakaria , Teboul Jean-Louis , Anguel Nadia , Monnet Xavier 
Published: December 2019

Abstract
Background
Volume expansion is aimed at increasing cardiac output (CO), but this variable is not always directly measured. We assessed the ability of changes in arterial pressure, pulse pressure variation (PPV) and heart rate (HR) or of a combination of them to detect a positive response of cardiac output (CO) to fluid administration.

Methods
We retrospectively included 491 patients with circulatory failure. Before and after a 500-mL normal saline infusion, we measured CO (PiCCO device), HR, systolic (SAP), diastolic (DAP), mean (MAP) and pulse (PP) arterial pressure, PPV, shock index (HR/SAP) and the PP/HR ratio.

Results
The fluid-induced changes in HR were not correlated with the fluid-induced changes in CO. The area under the receiver operating characteristic curve (AUROC) for changes in HR as detectors of a positive fluid response (CO increase ≥ 15%) was not different from 0.5. The fluid-induced changes in SAP, MAP, PP, PPV, shock index (HR/SAP) and the PP/HR ratio were correlated with the fluid-induced changes in CO, but with r < 0.4. The best detection was provided by increases in PP, but it was rough (AUROC = 0.719 ± 0.023, best threshold: increase ≥ 10%, sensitivity = 72 [66–77]%, specificity = 64 [57–70]%). Neither the decrease in shock index nor the changes in other indices combining changes in HR, shock index, PPV and PP provided a better detection of a positive fluid response than changes in PP.

Conclusion
A positive response to fluid was roughly detected by changes in PP and not detected by changes in HR. Changes in combined indices including the shock index and the PP/HR ratio did not provide a better diagnostic accuracy.
Associations between microRNA (miR-25, miR-32, miR-125, and miR-222) polymorphisms and recurrent implantation failure in Korean women
Authors: Lee Jeong Yong , Ahn Eun Hee , Kim Jung Oh , Park Han Sung , Ryu Chang Soo , Kim Ji Hyang , Kim Young Ran , Lee Woo Sik , Kim Nam Keun 
Published: December 2019

Abstract
Background
Recurrent implantation failure (RIF) is the failure of embryos to implant more than two times in a given individual. There is debate about a precise definition for RIF, but we consider more than two implantation failures for individuals who undergo in vitro fertilization-embryo transfer (IVF-ET) to constitute RIF. There are many potential reasons for RIF, including embryonic factors, immunological factors, uterine factors, coagulate factors, and genetic factors. Genetic variation has been suggested as one of the contributing factors leading to RIF, and a number of single-nucleotide polymorphisms (SNPs) have been reported to be associated with RIF. The recent elucidation of miRNA functions has provided new insight into the regulation of gene expression.

Methods
We investigated associations between polymorphisms in four miRNAs and RIF in 346 Korean women: 118 patients with RIF and 228 controls. We determined the genotypes of the miRNAs in the study participants by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis. We analyzed the effects of genotypes, allele combinations, and environmental and clinical factors on the risk of RIF.

Results
The miR-25 T/miR-125aT/miR-222G (odds ratio (OR), 0.528; 95% confidence interval (CI), 0.282–0.990; P = 0.044) and miR-25 T/miR-125aT allele combinations were associated with a reduced risk of RIF. The miR-25 T/miR-32C/miR-125aC/miR-222 T allele combination was associated with an increased risk of RIF. The miR-222GT+TT genotypes interacted with high prothrombin time (≥ 12 s) to increase the risk of RIF.

Conclusions
MicroRNA polymorphisms are significantly different between patients that experience RIF and healthy controls. Combinations of microRNA polymorphisms were associated with the risk of RIF. Interactions between environmental factors and genotypes increased the risk of RIF in Korean women.
Parental opinions regarding consent for observational research of no or minimal risk in the pediatric intensive care unit
Authors: Hodson Jessica , Garros Christiana , Jensen Jodie , Duff Jonathan P. , Garcia Guerra Gonzalo , Joffe Ari R. 
Published: December 2019

Abstract
Background
The aim of the study was to determine opinions and knowledge regarding the process of obtaining informed consent to participate in observational research in pediatric intensive care.

Methods
Survey 1 asked decision makers what model(s) of consent was acceptable for each type of observational research both before and after background information. Survey 2 asked decision makers about the experience of being asked for consent to observational research, and knowledge regarding the consent process both before and after background information.

Results
Cooperation rate was 100/117 (85%). The proportion in favor of any of the offered alternatives to signed informed consent for observational research, after receiving all the background information, was 74-80%, lowest for observational prospective research with a minimal risk intervention 37/50 (74%; 95% CI 60–84%). The proportion who agreed they felt overwhelmed by being approached for consent to observational research was 26 (52%; 95% CI 39-65%). Most respondents (from 60 to 74%) felt they understood the concepts regarding observational research; however, after reading background information, most (from 60 to 74%) felt their understanding had improved “a great deal”.

Conclusion
Understanding of risk, practical difficulties, consent bias, and Research Ethics Board safeguards was poor. Future study is needed to confirm our finding that most agreed with alternative methods of consent for observational research.
Laparoscopic treatment in a patient with median arcuate ligament syndrome identified at the onset of superior mesenteric artery dissection: a case report
Authors: Okada Haruhiko , Ehara Kazuhisa , Ro Hisashi , Yamada Masaki , Saito Tetsuya , Negami Naoki , Ishido Yasunori , Sato Masahiko 
Published: December 2019

Abstract
Background
Median arcuate ligament syndrome (MALS) is a rare clinical entity caused mainly by extrinsic compression of the celiac axis by the median arcuate ligament (MAL). Severe celiac artery stenosis can lead to the development of collateral circulation, aneurysms, and, rarely, superior mesenteric artery (SMA) dissection. The treatment of MALS involves the surgical release of the MAL. However, a standard procedure with the use of laparoscopy has not been established, and intraoperative complications can lead to severe vascular injury.

Case presentation
The patient was a 43-year-old man with MALS identified at the onset of SMA dissection. After treatment for the SMA dissection, he underwent laparoscopic MAL release. Using the technique of laparoscopic gastrectomy within the surgical field, we performed laparoscopic MAL release and ganglionectomy safely with a good view. Immediate symptomatic improvement was acquired, and no recurrence was observed at the 20-month follow-up.

Conclusion
We reported a rare case of MALS and SMA dissection. A horizontal 3D laparoscopic approach of the celiac axis allows for safe, meticulous, and radical MAL release and ganglionectomy.