bluuebunny/crossref_metadata_2025_split huggingface dataset:
Travel-associated neurological disease terminated in a postmortem diagnosed atypical HSV-1 encephalitis after high-dose steroid therapy – a case report
Authors: Osterman Andreas , Ruf Viktoria C. , Domingo Cristina , Nitsche Andreas , Eichhorn Peter , Zimmermann Hanna , Seelos Klaus , Zange Sabine , Dimitriadis Konstantinos , Pfister Hans-Walter , Thye Thorsten , Giese Armin , Tappe Dennis , Böhm Stephan 
Published: February 2020

Abstract
Background
Human encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid treatment.

Case presentation
A previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient’s condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21 days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante mortem.

Conclusions
This case shows that standard high-dose steroid therapy can contribute to or possibly even trigger fulminant cerebral HSV reactivation in a critically ill patient. Thus, even if extensive laboratory diagnostics including wide-ranging search for infectious pathogens has been performed before and remained without results, continuous re-evaluation of potential differential diagnoses especially regarding opportunistic infections or reactivation of latent infections is of utmost importance, particularly if new symptoms occur.
Semi-constrained posterior stabilized total knee arthroplasty reproduces natural deep knee bending kinematics
Authors: Sumino Takanobu , Tomita Tetsuya , Sugamoto Kazuomi , Yamazaki Takaharu , Okazaki Ken 
Published: February 2020

AbstractBackgroundThe Flexible Nichidai Knee Posterior Stabilized (FNK-PS) system was designed to provide relatively high varus-valgus stabilities without the stem extensions to patients with severe knee joint disorders. This is a combination of a large tibial post and high femoral cam adapted to a PS system. The aim of our study was to analyze the in vivo two-dimensional/three-dimensional registration kinematics of the FNK PS-total knee arthroplasty (TKA) system during deep knee bending.MethodsNineteen knees from 15 total knee arthroplasty (TKA) patients who were able to squat with enough knee flexion were selected. During deep knee bending under weight bearing (WB) and non-weight bearing (NWB) conditions, we quantified range of motion, axial rotation, femoral anteroposterior translation, and post-cam engagement angle.ResultsThe maximum-flexion was significantly different between the two conditions. The mean axial femoral external rotation was 4.8° and 6.2° under WB and NWB conditions, respectively, at 120° flexion. Anteroposterior translation based on bicondylar posterior roll-back patterns was noted with increasing knee flexion. Both the medial and lateral femoral aspects were significantly more posterior during early to mid-flexion. Initial post-cam engagement occurred significantly earlier during flexion under NWB than under WB conditions. Under WB, the timing of the post-cam engagement correlated with the maximum flexion .ConclusionsThe kinematics of the semi-constrained PS system reproducibly exhibited a mild external rotation with smooth posterior roll-back. This was assisted by the engagement of the large tibial post and high femoral cam during the early phase of flexion.
Measuring resilience prospectively as the speed of affect recovery in daily life: a complex systems perspective on mental health
Authors: Kuranova Anna , Booij Sanne H. , Menne-Lothmann Claudia , Decoster Jeroen , van Winkel Ruud , Delespaul Philippe , De Hert Marc , Derom Catherine , Thiery Evert , Rutten Bart P. F. , Jacobs Nele , van Os Jim , Wigman Johanna T. W. , Wichers Marieke 
Published: February 2020

Abstract
Introduction
There is growing evidence that mental disorders behave like complex dynamic systems. Complex dynamic systems theory states that a slower recovery from small perturbations indicates a loss of resilience of a system. This study is the first to test whether the speed of recovery of affect states from small daily life perturbations predicts changes in psychopathological symptoms over 1 year in a group of adolescents at increased risk for mental disorders.

Methods
We used data from 157 adolescents from the TWINSSCAN study. Course of psychopathology was operationalized as the 1-year change in the Symptom Checklist-90 sum score. Two groups were defined: one with stable and one with increasing symptom levels. Time-series data on momentary daily affect and daily unpleasant events were collected 10 times a day for 6 days at baseline.
We modeled the time-lagged effect of daily unpleasant events on negative and positive affect after each unpleasant event experienced, to examine at which time point the impact of the events is no longer detectable.

Results
There was a significant difference between groups in the effect of unpleasant events on negative affect 90 min after the events were reported. Stratified by group, in the Increase group, the effect of unpleasant events on both negative (B = 0.05, p < 0.01) and positive affect (B = − 0. 08, p < 0.01) was still detectable 90 min after the events, whereas in the Stable group this was not the case.

Conclusion
Findings cautiously suggest that adolescents who develop more symptoms in the following year may display a slower affect recovery from daily perturbations at baseline. This supports the notion that mental health may behave according to the laws of a complex dynamic system. Future research needs to examine whether these dynamic indicators of system resilience may prove valuable for personalized risk assessment in this field.
Circular RNA-CDR1as acts as the sponge of microRNA-641 to promote osteoarthritis progression
Authors: Zhang Wei , Zhang Chi , Hu Chengfang , Luo Congfeng , Zhong Biao , Yu Xiaowei 
Published: February 2020

Abstract
Background
The antisense cerebellar degenerative-related protein-1 (CDR1as) has been identified as a sponge for several microRNAs. MiR-641 has been shown to be downregulated in osteoarthritic human chondrocytes, but its regulation and function in osteoarthritis (OA) has not been reported.

Methods
OA cartilage samples were obtained from the knee joints of 12 patients (8 males and 4 females at age of 57–73 years old) who underwent total knee arthroplasty. Normal articular cartilage samples were obtained from the knee joints of 10 trauma patients at age of 29–65 years old (6 males and 4 females). The levels of circRNA-CDR1as mRNA and miR-641 were examined by qRT-PCR and the contents of type II collagen (Col II), IL-6, MMP13 and GAPDH in chondrocytes were examined by Western blot.

Results
In this study, we found that circRNA-CDR1as level was significantly upregulated in OA chondrocytes, and negatively related with that of miR-641. RNA pull down assay confirmed that circRNA-CDR1as directly targets to miR-641. Furthermore, downregulation of circRNA-CDR1as increased type II collagen level but reduced MMP13 and IL-6 contents, while these effects were partly reversed by down-regulation of miR-641.

Conclusion
Overall, our results indicate that circRNA-CDR1as plays a crucial role in regulating OA progression via modulating extracellular matrix metabolism and inflammation via sponging miR-641 and provide a novel regulatory role of circRNA-CDR1as in OA.
Governance of health research funding institutions: an integrated conceptual framework and actionable functions of governance
Authors: Smits Pernelle , Champagne François 
Published: February 2020

Abstract
Background
Health research has scientific, social and political impacts. To achieve such impacts, several institutions need to participate; however, health research funding institutions are seldom nominated in the literature as essential players. The attention they have received has so far focused mainly on their role in knowledge translation, informing policy-making and the need to organise health research systems. In this article, we will focus solely on the governance of national health research funding institutions. Our objectives are to identify the main functions of governance for such institutions and actionable governance functions. This research should be useful in several ways, including in highlighting, tracking and measuring the governance trends in a given funding institution, and to forestall low-level governance.

Methods
First, we reviewed existing frameworks in the grey literature, selecting seven relevant documents. Second, we developed an integrated framework for health research funding institution governance and management.
Third, we extracted actionable information for governance by selecting a mix of North American, European and Asian institutions that had documentation available in English (e.g. annual report, legal status, strategy).

Results
The framework contains 13 functions – 5 dedicated to governance (intelligence acquisition, resourcing and instrumentation, relationships management, accountability and performance, and strategy formulation), 3 dedicated to management (priority-setting, financing and knowledge transfer), and 5 dedicated to transversal logics that apply to both governance and management (ethics, transparency, capacity reinforcement, monitoring and evaluation, and public engagement).

Conclusions
Herein, we provide a conceptual contribution for scholars in the field of governance and health research as well as a practical contribution, with actionable functions for high-level managers in charge of the governance of health research funding institutions.
Is patient-centred care for women a priority for policy-makers? Content analysis of government policies
Authors: Gagliardi Anna R. , Dunn Sheila , Foster Angel M. , Grace Sherry L. , Khanlou Nazilla , Stewart Donna E. , Straus Sharon E. 
Published: February 2020

Abstract
Background
Considerable research shows that women experience gendered disparities in healthcare access and quality. Patient-centred care (PCC) could reduce inequities by addressing the patient’s clinical and personal needs. Healthcare policies can influence service delivery to optimise patient outcomes. This study assessed whether and how government policies recognise and promote PCC for women (PCCW).

Methods
We analysed the content of English-language policies published in Canada from 2010 to 2018 on depression and cardiac rehabilitation – conditions featuring known gendered inequities – that were identified on government websites. We extracted data and used summary statistics to enumerate mentions of PCC and women’s health.

Results
We included 30 policies (20 depression, 10 cardiac rehabilitation). Of those, 20 (66.7%) included any content related to PCC (median 1.0, range 0.0 to 5.0), most often exchanging information (14, 46.7%) and making decisions (13, 43.3%). Less frequent domains were enabling self-management (8, 26.7%), addressing emotions (6, 20.0%) and fostering the relationship (4, 13.3%). No policies included content for the domain of managing uncertainty. A higher proportion of cardiac rehabilitation guidelines included PCC content. Among the 30 policies, 7 (23.3%) included content related to at least one women’s health domain (median 0.0, range 0.0 to 3.0). Most frequently included were social determinants of health (4, 13.3%). Fewer policies mentioned any issues to consider for women (2, 28.6%), issues specific to subgroups of women (2, 28.6%) or distinguished care for women from men (2, 28.6%). No policies included mention of abuse or violence, or discrimination or stigma. The policies largely pertained to depression. Despite mention of PCC or women’s health, policies offered brief, vague guidance on how to achieve PCCW; for example, “Patients value being involved in decision-making” and “Women want care that is collaborative, woman- and family-centered, and culturally sensitive.”

Conclusions
Despite considerable evidence of need and international recommendations, most policies failed to recognise gendered disparities or promote PCC as a mitigating strategy. These identified gaps represent opportunities by which government policies could be developed or strengthened to support PCCW. Future research should investigate complementary strategies such as equipping policy-makers with the evidence and tools required to develop PCCW-informed policies.
Comprehensive pharmacogenomic characterization of gastric cancer
Authors: Sa Jason K. , Hong Jung Yong , Lee In-Kyoung , Kim Ju-sun , Sim Moon-Hee , Kim Ha Jung , An Ji Yeong , Sohn Tae Sung , Lee Joon Ho , Bae Jae Moon , Kim Sung , Kim Kyoung-Mee , Kim Seung Tae , Park Se Hoon , Park Joon Oh , Lim Ho Yeong , Kang Won Ki , Her Nam-Gu , Lee Yeri , Cho Hee Jin , Shin Yong Jae , Kim Misuk , Koo Harim , Kim Mirinae , Seo Yun Jee , Kim Ja Yeon , Choi Min-Gew , Nam Do-Hyun , Lee Jeeyun 
Published: February 2020

AbstractBackgroundGastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments.MethodsTo address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers.ResultsWe identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors inALK-mutant tumors, a significant association betweenPIK3CA-E542K mutation and AZD5363 response, and transcriptome expression ofRNF11as a potential predictor of response to gefitinib.ConclusionsCollectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.
CHD4/NuRD complex regulates complement gene expression and correlates with CD8 T cell infiltration in human hepatocellular carcinoma
Authors: Shao Simin , Cao Haowei , Wang Zhongkun , Zhou Dongmei , Wu Chaoshen , Wang Shu , Xia Dian , Zhang Daoyong 
Published: February 2020

Abstract
Backgrounds
The NuRD (Nucleosome Remodeling and Deacetylation) complex is a repressive complex in gene transcription by modulating chromatin accessibility of target genes to transcription factors and RNA polymerase II. Although individual subunits of the complex have been implicated in many other cancer types, the complex’s role in human hepatocellular carcinoma (HCC) is not fully understood. More importantly, the NuRD complex has not yet been investigated as a whole in cancers.

Methods
We analyzed the expression of the NuRD complex in HCC and evaluated the prognostic value of NuRD complex expression in HCC using the RNA-seq data obtained from the TCGA project. We examined the effect of CHD4 knockdown on HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition, colony-forming ability, and on complement gene expression. We also performed bioinformatic analyses to investigate the correlation between the NuRD complex expression and immune infiltration.

Results
We found that nine subunits, out of 14 subunits of the NuRD complex examined, were significantly overexpressed in HCC, and their expression levels were positively correlated with cancer progression. More importantly, our data also demonstrated that these subunits tended to be overexpressed as a whole in HCC. Subsequent studies demonstrated that knockdown of CHD4 in HCC cells inhibits cell proliferation, migration, invasion, and colony-forming ability and promotes apoptosis of HCC cells, indicating that the CHD4/NuRD complex plays oncogenic roles in HCC. Further analysis revealed that the CHD4/NuRD complex regulates complement gene expression in HCC. Intriguingly, we found that the CHD4/NuRD complex expression was inversely correlated with CD8 T cell infiltration in HCC.

Conclusions
Our data demonstrate that the CHD4/NuRD complex plays an oncogenic role in human HCC and regulates complement gene expression in HCC cells. The results of inverse correlation between the CHD4/NuRD complex and CD8 T cell and DC cell infiltration in HCC suggest that the CHD4/NuRD complex not only plays direct regulatory roles in HCC cells, but also has an impact on the immune microenvironment of HCC.
Age-, tumor-, and metastatic tissue-associated DNA hypermethylation of a T-box brain 1 locus in human kidney tissue
Authors: Serth Jürgen , Peters Inga , Dubrowinskaja Natalia , Reese Christel , Albrecht Knut , Klintschar Michael , Lafos Marcel , Grote Alexander , Becker Albert , Hennenlotter Jörg , Stenzl Arnulf , Tezval Hossein , Kuczyk Markus A. 
Published: February 2020

Abstract
Background
While a considerable number of tumor-specific hypermethylated loci have been identified in renal cell cancer (RCC), DNA methylation of loci showing successive increases in normal, tumoral, and metastatic tissues could point to genes with high relevance both for the process of tumor development and progression. Here, we report that DNA methylation of a locus in a genomic region corresponding to the 3′UTR of the transcription factor T-box brain 1 (TBR1) mRNA accumulates in normal renal tissues with age and possibly increased body mass index. Moreover, a further tissue-specific increase of methylation was observed for tumor and metastatic tissue samples.

Results
Biometric analyses of the TCGA KIRC methylation data revealed candidate loci for age-dependent and tumor-specific DNA methylation within the last exon and in a genomic region corresponding to the 3′UTR TBR1 mRNA. To evaluate whether methylation of TBR1 shows association with RCC carcinogenesis, we measured 15 tumor cell lines and 907 renal tissue samples including 355 normal tissues, 175 tissue pairs of normal tumor adjacent and corresponding tumor tissue as well 202 metastatic tissues samples of lung, bone, and brain metastases by the use of pyrosequencing. Statistical evaluation demonstrated age-dependent methylation in normal tissue (R = 0.72, p < 2 × 10−16), association with adiposity (P = 0.019) and tumor-specific hypermethylation (P = 6.1 × 10−19) for RCC tissues. Comparison of tumor and metastatic tissues revealed higher methylation in renal cancer metastases (P = 2.65 × 10−6).

Conclusions
Our analyses provide statistical evidence of association between methylation of TBR1 and RCC development and disease progression.
Conditioned medium derived from FGF-2-modified GMSCs enhances migration and angiogenesis of human umbilical vein endothelial cells
Authors: Jin Shanshan , Yang Chengzhe , Huang Jiahui , Liu Lianlian , Zhang Yu , Li Shutong , Zhang Liguo , Sun Qinfeng , Yang Pishan 
Published: February 2020

Abstract
Background
Angiogenesis plays an important role in tissue repair and regeneration, and conditioned medium (CM) derived from mesenchymal stem cells (MSC-CM) possesses pro-angiogenesis. Nevertheless, the profile and concentration of growth factors in MSC-CM remain to be optimized. Fibroblast growth factor-2 (FGF-2) has been proven to be an effective angiogenic factor. Thus, the aim of this study was to verify whether FGF-2 gene overexpression optimized CM from human gingival mesenchymal stem cells (hGMSCs) and whether such optimized CM possessed more favorable pro-angiogenesis effect.

Methods
First, FGF-2 gene-modified hGMSCs were constructed using lentiviral transfection technology (LV-FGF-2+-hGMSCs) and the concentration of angiogenesis-related factors in LV-FGF-2+-hGMSC-CM was determined by ELISA. Then, human umbilical vein endothelial cells (HUVECs) were co-cultured for 3 days with LV-FGF-2+-hGMSC-CM, and the expression level of placenta growth factor (PLGF), stem cell factor (SCF), vascular endothelial growth factor receptor 2 (VEGFR2) in HUVECs were determined by qRT-PCR, western blot, and cellular immunofluorescence techniques. The migration assay using transwell and in vitro tube formation experiments on matrigel matrix was conducted to determine the chemotaxis and angiogenesis enhanced by LV-FGF-2+-hGMSC-CM. Finally, NOD-SCID mice were injected with matrigel mixed LV-FGF-2+-hGMSC-CM, and the plug sections were analyzed by immunohistochemistry staining with anti-human CD31 antibody.

Results
LV-FGF-2+-hGMSC-CM contained significantly more FGF-2, vascular endothelial growth factor A (VEGF-A), and transforming growth factor β (TGF-β) than hGMSC-CM. HUVECs pretreated with LV-FGF-2+-hGMSC-CM expressed significantly more PLGF, SCF, and VEGFR2 at gene and protein level than hGMSC-CM pretreated HUVECs. Compared with hGMSC-CM, LV-FGF-2+-hGMSC-CM presented significantly stronger chemotaxis to HUVECs and significantly strengthened HUVECs mediated in vitro tube formation ability. In vivo, LV-FGF-2+-hGMSC-CM also possessed stronger promoting angiogenesis ability than hGMSC-CM.

Conclusions
Overexpression of FGF-2 gene promotes hGMSCs paracrine of angiogenesis-related growth factors, thereby obtaining an optimized conditioned medium for angiogenesis promotion.
A safety type of genetically engineered bacterium that degrades chemical pesticides
Authors: Li Qin , Li Jing , Kang Ke-Lai , Wu Yi-Jun 
Published: February 2020

AbstractChemical pesticides are used widely and their residues are found in the environment. Pesticide pollution has become a global problem. To find an economical, effective and safety way to degrade residues of pesticides in environment, we constructed a genetically engineered bacterium (GEB) having the ability to degrade pesticides, emit green fluorescence and has a containment system by using a dual plasmid expression system. One plasmid contains the genes of enhanced green fluorescent protein (EGFP) and carboxylesterase B1 (CarE B1), which were cloned downstream of lambda PL promoter and expressed constitutively. The gene of CarE B1 encodes an insect-detoxifying enzyme possessing the degradability to organochloride pesticides, organophosphorus pesticides, carbamates, and pyrethoid insecticides. The other is the conditional suicide plasmid for containment system, in which the lethal gene used was the nuclease gene of Serratia marcescens without the leader-coding sequence and was placed downstream of T7 promoter. The GEB has wide prospects of application on cleanup of pesticide residues with its degradability to several pesticides and containment system.