bluuebunny/crossref_metadata_2025_split huggingface dataset:
DBSecSys 2.0: a database of Burkholderia mallei and Burkholderia pseudomallei secretion systems
Authors: Memišević Vesna , Kumar Kamal , Zavaljevski Nela , DeShazer David , Wallqvist Anders , Reifman Jaques 
Published: September 2016

Abstract
Background
Burkholderia mallei and B. pseudomallei are the causative agents of glanders and melioidosis, respectively, diseases with high morbidity and mortality rates. B. mallei and B. pseudomallei are closely related genetically; B. mallei evolved from an ancestral strain of B. pseudomallei by genome reduction and adaptation to an obligate intracellular lifestyle. Although these two bacteria cause different diseases, they share multiple virulence factors, including bacterial secretion systems, which represent key components of bacterial pathogenicity. Despite recent progress, the secretion system proteins for B. mallei and B. pseudomallei, their pathogenic mechanisms of action, and host factors are not well characterized.

Results
We previously developed a manually curated database, DBSecSys, of bacterial secretion system proteins for B. mallei. Here, we report an expansion of the database with corresponding information about B. pseudomallei. DBSecSys 2.0 contains comprehensive literature-based and computationally derived information about B. mallei ATCC 23344 and literature-based and computationally derived information about B. pseudomallei K96243. The database contains updated information for 163 B. mallei proteins from the previous database and 61 additional B. mallei proteins, and new information for 281 B. pseudomallei proteins associated with 5 secretion systems, their 1,633 human- and murine-interacting targets, and 2,400 host-B. mallei interactions and 2,286 host-B. pseudomallei interactions. The database also includes information about 13 pathogenic mechanisms of action for B. mallei and B. pseudomallei secretion system proteins inferred from the available literature or computationally. Additionally, DBSecSys 2.0 provides details about 82 virulence attenuation experiments for 52 B. mallei secretion system proteins and 98 virulence attenuation experiments for 61 B. pseudomallei secretion system proteins. We updated the Web interface and data access layer to speed-up users’ search of detailed information for orthologous proteins related to secretion systems of the two pathogens.

Conclusions
The updates of DBSecSys 2.0 provide unique capabilities to access comprehensive information about secretion systems of B. mallei and B. pseudomallei. They enable studies and comparisons of corresponding proteins of these two closely related pathogens and their host-interacting partners.
The database is available at http://dbsecsys.bhsai.org.
Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway
Authors: Zhang Jieyuan , Liu Xiaolin , Li Haiyan , Chen Chunyuan , Hu Bin , Niu Xin , Li Qing , Zhao Bizeng , Xie Zongping , Wang Yang 
Published: September 2016

AbstractBackgroundRecently, accumulating evidence has shown that exosomes, the naturally secreted nanocarriers of cells, can exert therapeutic effects in various disease models in the absence of parent cells. However, application of exosomes in bone defect repair and regeneration has been rarely reported, and little is known regarding their underlying mechanisms.MethodsExosomes derived from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-Exos) were combined with tricalcium phosphate (β-TCP) to repair critical-sized calvarial bone defects, and the efficacy was assessed by histological examination. We evaluated the in vitro effects of hiPSC-MSC-Exos on the proliferation, migration, and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) by cell-counting, scratch assays, and qRT-PCR, respectively. Gene expression profiling and bioinformatics analyses were also used to identify the underlying mechanisms in the repair.ResultsWe found that the exosome/β-TCP combination scaffolds could enhance osteogenesis as compared to pure β-TCP scaffolds. In vitro assays showed that the exosomes could release from β-TCP and could be internalized by hBMSCs. In addition, the internalization of exosomes into hBMSCs could profoundly enhance the proliferation, migration, and osteogenic differentiation of hBMSCs. Furthermore, gene expression profiling and bioinformatics analyses demonstrated that exosome/β-TCP combination scaffolds significantly altered the expression of a network of genes involved in the PI3K/Akt signaling pathway. Functional studies further confirmed that the PI3K/Akt signaling pathway was the critical mediator during the exosome-induced osteogenic responses of hBMSCs.ConclusionsWe propose that the exosomes can enhance the osteoinductivity of β-TCP through activating the PI3K/Akt signaling pathway of hBMSCs, which means that the exosome/β-TCP combination scaffolds possess better osteogenesis activity than pure β-TCP scaffolds. These results indicate that naturally secreted nanocarriers-exosomes can be used as a bioactive material to improve the bioactivity of the biomaterials, and that hiPS-MSC-Exos combined with β-TCP scaffolds can be potentially used for repairing bone defects.
The mechanosensor of mesenchymal stem cells: mechanosensitive channel or cytoskeleton?
Authors: Xiao E. , Chen Chider , Zhang Yi 
Published: September 2016

AbstractMesenchymal stem cells (MSCs) are multipotent adult stem cells. MSCs and their potential for use in regenerative medicine have been investigated extensively. Recently, the mechanisms by which MSCs detect mechanical stimuli have been described in detail. As in other cell types, both mechanosensitive channels, such as transient receptor potential melastatin 7 (TRPM7), and the cytoskeleton, including actin and actomyosin, have been implicated in mechanosensation in MSCs. This review will focus on discussing the precise role of TRPM7 and the cytoskeleton in mechanosensation in MSCs.
Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation
Authors: Zucca Enrica , Corsini Emanuela , Galbiati Valentina , Lange-Consiglio Anna , Ferrucci Francesco 
Published: September 2016

AbstractBackgroundData obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lung inflammatory disorders such as recurrent airway obstruction (RAO) in horses. RAO shares many features with human asthma, including an increased number of cells expressing mRNA for interleukin (IL)-4 and IL-5 and a decreased expression of IFN-γ in bronchoalveolar lavage fluid (BALF) of affected horses.MethodsThe release of TNF-α, IL-6, and TGF-β1 at different time points (1, 24, 48, and 72 h) was measured in equine alveolar macrophages stimulated or not with LPS (10 and 100 ng/mL) in the presence or absence of 10 % CM or 50 × 106MVs/mL.Cytokines were measured using commercially available ELISA kits. For multiple comparisons, analysis of variance was used with Tukey post-hoc test. Differences were considered significant atp ≤ 0.05.ResultsSignificant modulatory effects of CM on LPS-induced TNF-α release at 24 h, and of both CM and MVs on TNF-α release at 48 h were observed. A trend toward a modulatory effect of both CM and MVs on the release of TGF-β and possibly IL-6 was visible over time.ConclusionsResults support the potential use of CM and MVs in lung regenerative medicine, especially in situations in which TGF-β may be detrimental, such as respiratory allergy. Further studies should evaluate the potential clinical applications of CM and MVs in equine lung diseases, such as RAO and other inflammatory disorders.
Hyaluronan induces odontoblastic differentiation of dental pulp stem cells via CD44
Authors: Umemura Naoki , Ohkoshi Emika , Tajima Masamichi , Kikuchi Hirotaka , Katayama Tadashi , Sakagami Hiroshi 
Published: September 2016

AbstractBackgroundDental pulp tissue contains many undifferentiated mesenchymal cells, which retain the ability to differentiate into mature cells. Induced pluripotent stem cells have been developed from various cell sources, including dental pulp-derived stem cells, and evaluated for potential application to regenerative therapy. Dental pulp tissues overexpress CD44, a cell-adhesion factor involved in the induction of mineralization. In this study, we investigated the effects of hyaluronan—a known CD44 ligand—on dental pulp stem cells (DPSCs).MethodsDPSC CD44 expression was analyzed using immunofluorescence staining, flow cytometry, and western blotting. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Effects of hyaluronan on the cell cycle were analyzed by flow cytometry. Alkaline phosphatase activity was employed as marker of mineralization and measured by fluorometric quantification and western blotting. Bone morphogenetic protein (BMP)-2, BMP-4, dentin sialophosphoprotein (DSPP), and dentin matrix acidic phosphoprotein 1 (DMP-1) levels were measured using real-time polymerase chain reaction. Odontoblastic differentiation and the close cell signaling examination of DPSC differentiation were determined using western blotting.ResultsHyaluronan induced expression of the odontoblastic differentiation markers DMP-1 and DSPP. Moreover, the odontoblastic differentiation induced by hyaluronan was mediated by CD44—but not by Akt, Smad1 or MAPK signaling.ConclusionsOur results indicate that hyaluronan induces odontoblastic differentiation of DPSCs via CD44. This suggests that hyaluronan plays a crucial role in the induction of odontoblastic differentiation from DPSCs. Our findings may aid the development of new, inexpensive, and effective conservative treatments for dental pulp repair.
Recent advances in animal and human pluripotent stem cell modeling of cardiac laminopathy
Authors: Lee Yee-Ki , Jiang Yu , Ran Xin-Ru , Lau Yee-Man , Ng Kwong-Man , Lai Wing-Hon Kevin , Siu Chung-Wah , Tse Hung-Fat 
Published: September 2016

AbstractLaminopathy is a disease closely related to deficiency of the nuclear matrix protein lamin A/C or failure in prelamin A processing, and leads to accumulation of the misfold protein causing progeria. The resultant disrupted lamin function is highly associated with abnormal nuclear architecture, cell senescence, apoptosis, and unstable genome integrity. To date, the effects of loss in nuclear integrity on the susceptible organ, striated muscle, have been commonly associated with muscular dystrophy, dilated cardiac myopathy (DCM), and conduction defeats, but have not been studied intensively. In this review, we aim to summarize recent breakthroughs in an in vivo laminopathy model and in vitro study using patient-specific human induced pluripotent stem cells (iPSCs) that reproduce the pathophysiological phenotype for further drug screening. We describe several in-vivo transgenic mouse models to elucidate the effects of Lmna H222P, N195K mutations, and LMNA knockout on cardiac function, in terms of hemodynamic and electrical signal propagation; certain strategies targeted on stress-related MAPK are mentioned. We will also discuss human iPSC cardiomyocytes serving as a platform to reveal the underlying mechanisms, such as the altered mechanical sensation in electrical coupling of the heart conduction system and ion channel alternation in relation to altered nuclear architecture, and furthermore to enable screening of drugs that can attenuate this cardiac premature aging phenotype by inhibition of prelamin misfolding and oxidative stress, and also enhancement of autophagy protein clearance and cardiac-protective microRNA.
Cold burn injuries in the UK: the 11-year experience of a tertiary burns centre
Authors: Nizamoglu Metin , Tan Alethea , Vickers Tobias , Segaren Nicholas , Barnes David , Dziewulski Peter 
Published: September 2016

Abstract

Background
Guidance for the management of thermal injuries has evolved with improved understanding of burn pathophysiology. Guidance for the management of cold burn injuries is not widely available. The management of these burns differs from the standard management of thermal injuries. This study aimed to review the etiology and management of all cold burns presenting to a large regional burn centre in the UK and to provide a simplified management pathway for cold burns.

Methods
An 11-year retrospective analysis (1 January 2003–31 December 2014) of all cold injuries presenting to a regional burns centre in the UK was conducted. Patient case notes were reviewed for injury mechanism, first aid administered, treatment outcomes and time to healing. An anonymized nationwide survey on aspects of management of cold burns was disseminated between 13 July 2015–5 October 2015 to British Association of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS) and Plastic Surgery Trainees Association (PLASTA) members in the UK. Electronic searches of MEDLINE, EMBASE and the Cochrane Library were performed to identify relevant literature to provide evidence for a management pathway for cold burn injuries.

Results
Twenty-three patients were identified. Age range was 8 months–69 years. Total body surface area (TBSA) burn ranged from 0.25 to 5 %. Twenty cases involved peripheral limbs. Seventeen (73.9 %)cases were accidental, with the remaining six (26.1 %) cases being deliberate self-inflicted injuries. Only eight patients received first aid. All except one patient were managed conservatively. One case required skin graft application due to delayed healing. We received 52 responses from a total of 200 questionaires. Ninety percent of responders think clearer guidelines should exist. We present a simplified management pathway based on evidence identified in our literature search.

Conclusions
Cold burns are uncommon in comparison to other types of burn injuries. In the UK, a disproportionate number of cold burn injuries are deliberately self-inflicted, especially in the younger patient population. Our findings reflect a gap in clinical knowledge and experience. We proposed a simplified management pathway for managing cold burn injuries, consisting of adequate first aid using warm water, oral prostaglandin inhibitors, deroofing of blisters and topical antithromboxane therapy.
Genetic Determinants of Cisplatin Resistance in Patients With Advanced Germ Cell Tumors
Authors: Bagrodia Aditya , Lee Byron H. , Lee William , Cha Eugene K. , Sfakianos John P. , Iyer Gopa , Pietzak Eugene J. , Gao Sizhi Paul , Zabor Emily C. , Ostrovnaya Irina , Kaffenberger Samuel D. , Syed Aijazuddin , Arcila Maria E. , Chaganti Raju S. , Kundra Ritika , Eng Jana , Hreiki Joseph , Vacic Vladimir , Arora Kanika , Oschwald Dayna M. , Berger Michael F. , Bajorin Dean F. , Bains Manjit S. , Schultz Nikolaus , Reuter Victor E. , Sheinfeld Joel , Bosl George J. , Al-Ahmadie Hikmat A. , Solit David B. , Feldman Darren R. 
Published: September 2016

Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture–based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic profiling of patients with advanced GCT could improve current risk stratification and identify novel therapeutic approaches for patients with cisplatin-resistant disease.
Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth
Authors: Goffredo Martina , Mass Kendra , Parks Elizabeth J. , Wagner David A. , McClure Emily Ann , Graf Joerg , Savoye Mary , Pierpont Bridget , Cline Gary , Santoro Nicola 
Published: September 2016

Objective:
We aimed at determining the relationship of the gut microbiota and short chain fatty acids with obesity and fat partitioning and at testing potential differences in the ability of gut microbiota to ferment equal amounts of carbohydrates (CHO) between lean and obese youth.

Research Design and Methods:
We analyzed the gut microbiota of 84 youth in whom body fat distribution was measured by fast-magnetic resonance imaging, de novo lipogenesis (DNL) quantitated using deuterated water, and the capability of gut flora to ferment CHO was assessed by 13C-fructose treatment in vitro.

Results:
A significant association was found between the Firmicutes to Bacteroidetes ratio, and the abundance of Bacteroidetes and Actinobacteria with body mass index, visceral and SC fat (all P &lt; .05). Plasma acetate, propionate, and butyrate were associated with body mass index and visceral and SC fat (all P &lt; .05) and with hepatic DNL (P = .01, P = .09, P = .04, respectively). Moreover, the rate of CHO fermentation from the gut flora was higher in obese than in lean subjects (P = .018).

Conclusions:
These data demonstrate that obese youth show a different gut flora composition than lean and that short chain fatty acids are associated with body fat partitioning and DNL. Also, the gut microbiota of obese youth have a higher capability than the gut flora of lean to oxidize CHO.
Thyroid Function and Cancer Risk: The Rotterdam Study
Authors: Khan Samer R. , Chaker Layal , Ruiter Rikje , Aerts Joachim G. J. V. , Hofman Albert , Dehghan Abbas , Franco Oscar H. , Stricker Bruno H. C. , Peeters Robin P. 
Published: September 2016

Context:
In vitro and in vivo experiments have assigned both oncosuppressive and oncogenic properties to thyroid hormones. Population-based studies have found inconclusive results.

Objective:
We aimed to prospectively assess the relation between thyroid function and incident cancer in a population-based setting.

Design, Setting, and Participants:
The current study is a prospective population-based cohort study including 10 318 participants for whom baseline measurements of free T4 (FT4) and/or TSH were available.

Main Outcome Measures:
Cox proportional hazards models were used to assess hazard ratios (HRs) of any solid non-skin cancer, as well as lung, breast, prostate, and gastrointestinal cancer specifically.

Results:
Higher FT4 levels were associated with a higher risk of any solid cancer (HR, 1.42; 95% confidence interval [CI], 1.12–1.79), lung cancer (HR, 2.33; 95% CI, 1.39–3.92) and breast (HR, 1.77; 95% CI, 1.10–2.84) cancer. The risk estimates were similar after exclusion of thyroid-altering medication, but the association lost significance for breast cancer. Compared with the lowest FT4 tertile, the highest tertile was associated with a 1.13-fold increased risk of any solid, 1.79-fold increased risk of lung, and 1.14-fold increased risk of breast cancer (P for trend &lt;.05 for all). For TSH levels we found no associations with cancer risk. There was no differential effect of sex or age on the association between thyroid function and cancer risk.

Conclusions:
Higher FT4 levels are significantly associated with an increased risk of any solid, lung, and breast cancer. Further research should elucidate the underlying pathophysiological mechanisms.
Antimicrobial stewardship: The appropriate use of antibiotics
Authors: Fleming Naomi 
Published: September 2016

Antimicrobial resistance is a global problem that will have significance for all of us in future. Naomi Fleming looks at how practice nurses can contribute to antimicrobial stewardship and support patients to use antibiotics appropriately Antibiotics have been vital to our survival, but antimicrobial resistance is threatening to make them ineffective. Resistance threatens modern medicine, including our ability to provide chemotherapy, transplants, splenectomy and surgery, as well as treat acute and chronic infections ( Department of Health (DH), 2013 ). Antimicrobial stewardship aims to ensure effective treatment of infections, while minimising collateral damage. This article examines how practice nurses can contribute to the antimicrobial stewardship agenda and support patients to use antibiotics appropriately, with a particular focus on respiratory tract infections.
Promoting healing in venous leg ulceration
Authors: Brown Annemarie 
Published: September 2016

Venous leg ulcers are commonly seen in primary care. Annemarie Brown outlines the problems a practice nurse may encounter when helping to heal a venous leg ulcer and advises on how to select products to promote healing Venous leg ulcers are commonly seen in primary care. Compression therapy in the form of bandages or hosiery is considered to be the most effective treatment to heal venous leg ulcers ( World Union of Wound Healing Societies (WUWHS), 2008 ). In a simple venous leg ulcer with no obvious barriers to healing, a simple non-adherent contact layer in combination with compression is usually sufficient to promote healing ( Moffatt et al, 2004 ). However, if the composition of the wound bed of the venous leg ulcer is more complex—critically colonised, infected and with slough or moderate exudate—the practitioner needs to assess the wound and choose a dressing which will remove these potential barriers to healing. This article will outline the most common wound problems and provide strategies practice nurses can use to promote healing.