bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidrug-resistant surgical site infections in a humanitarian surgery project
Authors: MURPHY R. A. , OKOLI O. , ESSIEN I. , TEICHER C. , ELDER G. , PENA J. , RONAT J.-B. , BERNABÉ K. J. 
Published: August 2016

SUMMARYThe epidemiology of surgical site infections (SSIs) in surgical programmes in sub-Saharan Africa is inadequately described. We reviewed deep and organ-space SSIs occurring within a trauma project that had a high-quality microbiology partnership and active follow-up. Included patients underwent orthopaedic surgery in Teme Hospital (Port Harcourt, Nigeria) for trauma and subsequently developed a SSI requiring debridement and microbiological sampling. Data were collected from structured chart reviews and programmatic databases for 103 patients with suspected SSI [79% male, median age 30 years, interquartile range (IQR) 24–37]. SSIs were commonly detected post-discharge with 58% presenting >28 days after surgery. The most common pathogens were: Staphylococcus aureus (34%), Pseudomonas aeruginosa (16%) and Enterobacter cloacae (11%). Thirty-three (32%) of infections were caused by a multidrug-resistant (MDR) pathogen, including 15 patients with methicillin-resistant S. aureus. Antibiotics were initiated empirically for 43% of patients and after culture and sensitivity report in 32%. The median number of additional surgeries performed in patients with SSI was 5 (IQR 2–6), one patient died (1%), and amputation was performed or recommended in three patients. Our findings suggest the need for active long-term monitoring of SSIs, particularly those associated with MDR organisms, resulting in increased costs for readmission surgery and treatment with late-generation antibiotics.
Glial degeneration with oxidative damage drives neuronal demise in MPSII disease
Authors: Zalfa Cristina , Verpelli Chiara , D'Avanzo Francesca , Tomanin Rosella , Vicidomini Cinzia , Cajola Laura , Manara Renzo , Sala Carlo , Scarpa Maurizio , Vescovi Angelo Luigi , De Filippis Lidia 
Published: August 2016

AbstractMucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.
Projected increase in amyotrophic lateral sclerosis from 2015 to 2040
Authors: Arthur Karissa C. , Calvo Andrea , Price T. Ryan , Geiger Joshua T. , Chiò Adriano , Traynor Bryan J. 
Published: August 2016

AbstractAlthough amyotrophic lateral sclerosis (ALS) is relatively rare, the socioeconomic significance of the disease is extensive. It is therefore vital to project the epidemiologic trend of ALS. To date, there have been few published studies attempting to estimate the number and distribution of ALS cases in the upcoming years. Here we show that the number of ALS cases across the globe will increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of 69%. This increase is predominantly due to ageing of the population, particularly among developing nations. This projection is likely an underestimate due to improving healthcare and economic conditions. The results should be used to inform healthcare policy to more efficiently allocate healthcare resources.
Increasing flash droughts over China during the recent global warming hiatus
Authors: Wang Linying , Yuan Xing , Xie Zhenghui , Wu Peili , Li Yaohui 
Published: August 2016

AbstractThe recent global warming slowdown or hiatus after the big El Niño event in 1997/98 raises the questions of whether terrestrial hydrological cycle is being decelerated and how do the hydrological extremes respond to the hiatus. However, the rapidly developing drought events that are termed as “flash droughts” accompanied by extreme heat, low soil moisture and high evapotranspiration (ET), occurred frequently around the world, and caused devastating impacts on crop yields and water supply. Here, we investigate the long-term trend and variability of flash droughts over China. Flash droughts are most likely to occur over humid and semi-humid regions, such as southern and northeastern China. Flash drought averaged over China increased by 109% from 1979 to 2010, and the increase was mainly due to a long term warming of temperature (50%), followed by the contributions from decreasing soil moisture and increasing ET. There was a slight drop in temperature after 1997, but the increasing trend of flash droughts was tripled. Further results indicate that the decreasing temperature was compensated by the accelerated drying trends of soil moisture and enhanced ET, leading to an acceleration of flash droughts during the warming hiatus. The anthropogenic warming in the next few decades may exacerbate future flash drought conditions in China.
TRPV4 regulates calcium homeostasis, cytoskeletal remodeling, conventional outflow and intraocular pressure in the mammalian eye
Authors: Ryskamp Daniel A. , Frye Amber M. , Phuong Tam T. T. , Yarishkin Oleg , Jo Andrew O. , Xu Yong , Lakk Monika , Iuso Anthony , Redmon Sarah N. , Ambati Balamurali , Hageman Gregory , Prestwich Glenn D. , Torrejon Karen Y. , Križaj David 
Published: August 2016

AbstractAn intractable challenge in glaucoma treatment has been to identify druggable targets within the conventional aqueous humor outflow pathway, which is thought to be regulated/dysregulated by elusive mechanosensitive protein(s). Here, biochemical and functional analyses localized the putative mechanosensitive cation channel TRPV4 to the plasma membrane of primary and immortalized human TM (hTM) cells, and to human and mouse TM tissue. Selective TRPV4 agonists and substrate stretch evoked TRPV4-dependent cation/Ca2+ influx, thickening of F-actin stress fibers and reinforcement of focal adhesion contacts. TRPV4 inhibition enhanced the outflow facility and lowered perfusate pressure in biomimetic TM scaffolds populated with primary hTM cells. Systemic delivery, intraocular injection or topical application of putative TRPV4 antagonist prodrug analogs lowered IOP in glaucomatous mouse eyes and protected retinal neurons from IOP-induced death. Together, these findings indicate that TRPV4 channels function as a critical component of mechanosensitive, Ca2+-signaling machinery within the TM, and that TRPV4-dependent cytoskeletal remodeling regulates TM stiffness and outflow. Thus, TRPV4 is a potential IOP sensor within the conventional outflow pathway and a novel target for treating ocular hypertension.
Natural product derivative BIO promotes recovery after myocardial infarction via unique modulation of the cardiac microenvironment
Authors: Kim Yong Sook , Jeong Hye-yun , Kim Ah Ra , Kim Woong-Hee , Cho Haaglim , Um JungIn , Seo Youngha , Kang Wan Seok , Jin Suk-Won , Kim Min Chul , Kim Yong-Chul , Jung Da-Woon , Williams Darren R. , Ahn Youngkeun 
Published: August 2016

AbstractThe cardiac microenvironment includes cardiomyocytes, fibroblasts and macrophages, which regulate remodeling after myocardial infarction (MI). Targeting this microenvironment is a novel therapeutic approach for MI. We found that the natural compound derivative, BIO ((2′Z,3′E)-6-Bromoindirubin-3′-oxime) modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using a series of co-culture studies, BIO induced proliferation in cardiomyocytes and inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti-fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the expression of pro-inflammatory factors. Significantly, BIO modulated the molecular crosstalk between cardiac fibroblasts and differentiating macrophages to induce polarization to the anti-inflammatory M2 phenotype. In the optically transparent zebrafish-based heart failure model, BIO induced cardiomyocyte proliferation and completely recovered survival rate. BIO is a known glycogen synthase kinase-3β inhibitor, but these effects could not be recapitulated using the classical inhibitor, lithium chloride; indicating novel therapeutic effects of BIO. We identified the mechanism of BIO as differential modulation of p27 protein expression and potent induction of anti-inflammatory interleukin-10. In a rat MI model, BIO reduced fibrosis and improved cardiac performance. Histological analysis revealed modulation of the cardiac microenvironment by BIO, with increased presence of anti-inflammatory M2 macrophages. Our results demonstrate that BIO produces unique effects in the cardiac microenvironment to promote recovery post-MI.
Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of non-syndromic orofacial cleft
Authors: Li Dandan , Zhang Hongchuang , Ma Lan , Han Yue , Xu Min , Wang Zhendong , Jiang Hongbing , Zhang Weibing , Wang Lin , Pan Yongchu 
Published: August 2016

AbstractWe hypothesized that microRNA binding site single nucleotide polymorphisms (SNPs) in fibroblast growth factors (FGFs) and their receptor genes (FGFRs) may affect microRNA and mRNA interactions and are thereby associated with susceptibility of non-syndromic orofacial cleft (NSOC). Ten SNPs among the FGF and FGFR genes were selected and their associations with NSOC susceptibility were investigated in a case-control study of 602 patients with NSOC and 605 healthy controls. FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 showed suggestive association with NSOC susceptibility. In the combination analysis, the observed odds ratios (ORs) decreased with the number of protective alleles (rs1048201-T, rs3733336-G and rs546782-T) but were not statistically significant beyond the first comparison. Hsa-miRNA-496, hsa-miRNA-145 and hsa-miRNA-187 were predicted to be miRNAs with binding sites within/near these SNPs and were expressed in lip tissues. Decreased FGF2, FGF5 and FGF9 expression was observed in three cell lines transfected with the corresponding miRNAs. Moreover, the three SNPs could contribute to differential binding efficacy between hsa-miRNA-496 and FGF2, hsa-miRNA-145 and FGF5, hsa-miRNA-187 and FGF9 in luciferase assay. The results suggest that FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 are associated with the risk of NSOC and that these miRNA-FGF interactions may affect NSOC development.
VHLdb: A database of von Hippel-Lindau protein interactors and mutations
Authors: Tabaro Francesco , Minervini Giovanni , Sundus Faiza , Quaglia Federica , Leonardi Emanuela , Piovesan Damiano , Tosatto Silvio C. E. 
Published: August 2016

AbstractMutations in von Hippel-Lindau tumor suppressor protein (pVHL) predispose to develop tumors affecting specific target organs, such as the retina, epididymis, adrenal glands, pancreas and kidneys. Currently, more than 400 pVHL interacting proteins are either described in the literature or predicted in public databases. This data is scattered among several different sources, slowing down the comprehension of pVHL’s biological role. Here we present VHLdb, a novel database collecting available interaction and mutation data on pVHL to provide novel integrated annotations. In VHLdb, pVHL interactors are organized according to two annotation levels, manual and automatic. Mutation data are easily accessible and a novel visualization tool has been implemented. A user-friendly feedback function to improve database content through community-driven curation is also provided. VHLdb presently contains 478 interactors, of which 117 have been manually curated, and 1,074 mutations. This makes it the largest available database for pVHL-related information. VHLdb is available from URL: http://vhldb.bio.unipd.it/.
Fibroproliferative response to urothelial failure obliterates the ureter lumen in a mouse model of prenatal congenital obstructive nephropathy
Authors: Lee Amanda J. , Polgar Noemi , Napoli Josephine A. , Lui Vanessa H. , Tamashiro Kadee-Kalia , Fujimoto Brent A. , Thompson Karen S. , Fogelgren Ben 
Published: August 2016

AbstractCongenital obstructive nephropathy (CON) is the most prevalent cause of pediatric chronic kidney disease and end-stage renal disease. The ureteropelvic junction (UPJ) region, where the renal pelvis transitions to the ureter, is the most commonly obstructed site in CON. The underlying causes of congenital UPJ obstructions remain poorly understood, especially when they occur in utero, in part due to the lack of genetic animal models. We previously showed that conditional inactivation of Sec10, a central subunit of the exocyst complex, in the epithelial cells of the ureter and renal collecting system resulted in late gestational bilateral UPJ obstructions with neonatal anuria and death. In this study, we show that without Sec10, the urothelial progenitor cells that line the ureter fail to differentiate into superficial cells, which are responsible for producing uroplakin plaques on the luminal surface. These Sec10-knockout urothelial cells undergo cell death by E17.5 and the urothelial barrier becomes leaky to luminal fluid. Also at E17.5, we measured increased expression of TGFβ1 and genes associated with myofibroblast activation, with evidence of stromal remodeling. Our findings support the model that a defective urothelial barrier allows urine to induce a fibrotic wound healing mechanism, which may contribute to human prenatal UPJ obstructions.
Dysregulated immune system networks in war veterans with PTSD is an outcome of altered miRNA expression and DNA methylation
Authors: Bam Marpe , Yang Xiaoming , Zumbrun Elizabeth E. , Zhong Yin , Zhou Juhua , Ginsberg Jay P. , Leyden Quinne , Zhang Jiajia , Nagarkatti Prakash S. , Nagarkatti Mitzi 
Published: August 2016

AbstractPost-traumatic stress disorder patients experience chronic systemic inflammation. However, the molecular pathways involved and mechanisms regulating the expression of genes involved in inflammatory pathways in PTSD are reported inadequately. Through RNA sequencing and miRNA microarray, we identified 326 genes and 190 miRNAs that were significantly different in their expression levels in the PBMCs of PTSD patients. Expression pairing of the differentially expressed genes and miRNAs indicated an inverse relationship in their expression. Functional analysis of the differentially expressed genes indicated their involvement in the canonical pathways specific to immune system biology. DNA methylation analysis of differentially expressed genes also showed a gradual trend towards differences between control and PTSD patients, again indicating a possible role of this epigenetic mechanism in PTSD inflammation. Overall, combining data from the three techniques provided a holistic view of several pathways in which the differentially expressed genes were impacted through epigenetic mechanisms, in PTSD. Thus, analysis combining data from RNA-Seq, miRNA array and DNA methylation, can provide key evidence about dysregulated pathways and the controlling mechanism in PTSD. Most importantly, the present study provides further evidence that inflammation in PTSD could be epigenetically regulated.
Emotional Modulation of Conflict Processing in the Affective Domain: Evidence from Event-related Potentials and Event-related Spectral Perturbation Analysis
Authors: Ma Jianling , Liu Chang , Chen Xu 
Published: August 2016

AbstractPrevious studies have revealed the impact of emotion on conflict processing. The present study was conducted to investigate whether cognitive control in the affective domain is also affected by emotion. Emotional face-word and body-word Stroop tasks were explored and contrasted and both behavioural and electrophysiological measures were recorded. Behavioural results showed that both tasks replicated previous robust interference effects. At the physiological level, the two tasks showed dissociable neural activity in the early attention and perception stages. It was also found that the face-word task evoked more pronounced N1 and P2 amplitudes than the body-word task. However, the two tasks evoked comparable N450 amplitudes. At later processing stages, positive slow potentials were modulated by target emotion and congruency. In addition, time-frequency analyses also revealed that the face-word task induced enhanced theta activity compared to the body-word task at both early and later stages of processing. The present findings provide support for the dual competition framework and suggest the dynamic modulation of emotion on cognitive control in the affective domain.
Lung Microtissue Array to Screen the Fibrogenic Potential of Carbon Nanotubes
Authors: Chen Zhaowei , Wang Qixin , Asmani Mohammadnabi , Li Yan , Liu Chang , Li Changning , Lippmann Julian M. , Wu Yun , Zhao Ruogang 
Published: August 2016

AbstractDue to their excellent physical and chemical characteristics, multi-wall carbon nanotubes (MWCNT) have the potential to be used in structural composites, conductive materials, sensors, drug delivery and medical imaging. However, because of their small-size and light-weight, the applications of MWCNT also raise health concerns. In vivo animal studies have shown that MWCNT cause biomechanical and genetic alterations in the lung tissue which lead to lung fibrosis. To screen the fibrogenic risk factor of specific types of MWCNT, we developed a human lung microtissue array device that allows real-time and in-situ readout of the biomechanical properties of the engineered lung microtissue upon MWCNT insult. We showed that the higher the MWCNT concentration, the more severe cytotoxicity was observed. More importantly, short type MWCNT at low concentration of 50 ng/ml stimulated microtissue formation and contraction force generation, and caused substantial increase in the fibrogenic marker miR-21 expression, indicating the high fibrogenic potential of this specific carbon nanotube type and concentration. The presented microtissue array system provides a powerful tool for high-throughput examination of the therapeutic and toxicological effects of target compounds in realistic tissue environment.
Retrieval-Based Model Accounts for Striking Profile of Episodic Memory and Generalization
Authors: Banino Andrea , Koster Raphael , Hassabis Demis , Kumaran Dharshan 
Published: August 2016

AbstractA fundamental theoretical tension exists between the role of the hippocampus in generalizing across a set of related episodes, and in supporting memory for individual episodes. Whilst the former requires an appreciation of the commonalities across episodes, the latter emphasizes the representation of the specifics of individual experiences. We developed a novel version of the hippocampal-dependent paired associate inference (PAI) paradigm, which afforded us the unique opportunity to investigate the relationship between episodic memory and generalization in parallel. Across four experiments, we provide surprising evidence that the overlap between object pairs in the PAI paradigm results in a marked loss of episodic memory. Critically, however, we demonstrate that superior generalization ability was associated with stronger episodic memory. Through computational simulations we show that this striking profile of behavioral findings is best accounted for by a mechanism by which generalization occurs at the point of retrieval, through the recombination of related episodes on the fly. Taken together, our study offers new insights into the intricate relationship between episodic memory and generalization, and constrains theories of the mechanisms by which the hippocampus supports generalization.
A Retrospective Study of thrombolysis with 0.6 mg/kg Recombinant Tissue Plasminogen Activator (rt-PA) in Mild Stroke
Authors: Yang Jie , Yu Fei , Liu Hong , An Hedi , Xiong Ran , Huang Dongya 
Published: August 2016

AbstractWe sought to assess the safety, effectiveness and cost of 0.6 mg/kg rt-PA treatment for patients with acute mild stroke and to compare that with 0.9 mg/kg. We retrospectively analyzed consecutive acute ischemic stroke patients who had a NIHSS score ≤5 at admission and who were treated with rt-PA within 4.5 hours of symptom onset. The demographic data, clinical outcomes and hospitalization cost were analyzed. A total of 108 patients were included. Forty six patients (42.6%) received a 0.6 mg/kg dosage of rt-PA. The baseline characteristics of the two groups were well matched (p > 0.05). Regarding the safety and effectiveness, the 0.6 mg/kg dosage group had a comparable proportion of symptomatic intracranial hemorrhage (sICH) (0.6 mg/kg, 4.3% vs 0.9 mg/kg, 4.8%; p > 0.05), early neurological deterioration (END) (19.6% vs 17.7%; p > 0.05), in-hospital mortality (4.3% vs 1.6%; p > 0.05), and a similar rate of favorable functional outcome (mRS score 0–1) at 3 months (73.9% vs 71.0%; p > 0.05) to those who received the standard dosage. However, the hospital cost was markedly lower in the 0.6 mg/kg group (0.6 mg/kg, 3,401.7 USD vs 0.9 mg/kg, 4,157.4 USD; p < 0.01). Our study suggest that 0.6 mg/kg rt-PA shared similar effectiveness and safety profile compared with that of 0.9 mg/kg in treating mild stroke, but cost less.
Stratification of responders towards eculizumab using a structural epitope mapping strategy
Authors: Volk Anna-Luisa , Hu Francis Jingxin , Berglund Magnus M. , Nordling Erik , Strömberg Patrik , Uhlen Mathias , Rockberg Johan 
Published: August 2016

AbstractThe complement component 5 (C5)-binding antibody eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). As recently reported there is a need for a precise classification of eculizumab responsive patients to allow for a safe and cost-effective treatment. To allow for such stratification, knowledge of the precise binding site of the drug on its target is crucial. Using a structural epitope mapping strategy based on bacterial surface display, flow cytometric sorting and validation via haemolytic activity testing, we identified six residues essential for binding of eculizumab to C5. This epitope co-localizes with the contact area recently identified by crystallography and includes positions in C5 mutated in non-responders. The identified epitope also includes residue W917, which is unique for human C5 and explains the observed lack of cross-reactivity for eculizumab with other primates. We could demonstrate that Ornithodorus moubata complement inhibitor (OmCI), in contrast to eculizumab, maintained anti-haemolytic function for mutations in any of the six epitope residues, thus representing a possible alternative treatment for patients non-responsive to eculizumab. The method for stratification of patients described here allows for precision medicine and should be applicable to several other diseases and therapeutics.