bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMPK Prevents Palmitic Acid‐Induced Apoptosis and Lipid Accumulation in Cardiomyocytes
Authors: Adrian Lucas , Lenski Matthias , Tödter Klaus , Heeren Jörg , Böhm Michael , Laufs Ulrich 
Published: August 2017

AbstractPalmitic acid, a main fatty acid (FA) in human nutrition, can induce apoptosis of cardiomyocytes. However, a specific combination of palmitic, myristic and palmitoleic acid (CoFA) has been reported to promote beneficial cardiac growth. The aim of this study was to investigate the relevance of CoFA for cardiac growth and to delineate the underlying signaling pathways of CoFA and palmitic acid treatment. CoFA treatment of C57Bl/6 mice increased FA serum concentrations. However, morphologic and echocardiographic analysis did not show myocardial hypertrophy. Cell culture studies using rat ventricular cardiomyocytes revealed an increased phosphorylation of AMP activated protein kinase α (AMPKα) to 155 ± 19% and its target acetyl‐CoA‐carboxylase to 177 ± 23% by CoFA. Treatment with myristic acid also increased AMPKα phosphorylation to 189 ± 32%. Palmitic acid did not activate AMPKα but increased expression of the FA translocase CD36 (FAT/CD36) to 163 ± 23% and adipose‐differentiation‐related‐protein (ADRP), a sensitive marker of lipid accumulation, to 168 ± 42%. This was associated with an increased phosphorylation of the stress‐activated‐protein‐kinase/Jun‐amino‐terminal‐kinase (SAPK/JNK) to 173 ± 27%. In CoFA‐treated cells, phosphorylation of SAPK/JNK was unaltered. FACS analysis revealed increased apoptosis to 159 ± 5% by palmitic acid but not by CoFA. AMPK activator AICAR (5‐aminoimidazole‐4‐carboxamide ribonucleotide) prevented up‐regulation of ADRP and increased apoptosis by palmitic acid. Confirming these findings, inhibition of AMPK by compound C in CoFA‐treated cardiomyocytes resulted in an increased expression of ADRP to 154 ± 27%, FAT/CD36 to 167 ± 28% and apoptosis to 183 ± 12%. These data reveal that AMPK activation plays an important role in prevention of palmitic acid‐induced apoptosis and lipid accumulation in cardiomyocytes.
MatriDerm Decreases Donor Site Morbidity After Radial Forearm Free Flap Harvest in Transgender Surgery
Authors: Watfa William , di Summa Pietro G. , Meuli Joaquim , Raffoul Wassim , Bauquis Olivier 
Published: August 2017

Abstract

Background
Phalloplasty with the radial forearm free flap is associated with a large donor site defect.

Aim
To compare two methods of donor site closure for functional and cosmetic long-term results: full-thickness skin grafting vs split-thickness skin grafting with MatriDerm.

Methods
Thirty-seven transgender patients had a neophallus created from a radial forearm free flap, and all were operated on by the same senior surgeon. Eight patients had their donor site defect closed by total skin grafting and 29 patients, operated on after 2009, received a split-thickness skin graft with MatriDerm closure. All 37 patients were evaluated by questionnaire and by careful clinical examination. Pressure perception was assessed with the Semmes-Weinstein monofilament test. Sensory recovery, skin quality, and cosmetic result also were compared. The contralateral arm was used as the control.

Outcomes
Pressure perception values showed better sensory return in the MatriDerm group. Split-thickness skin grafting with MatriDerm achieved superior results in skin sensibility, superficial radial nerve recovery, and cosmetic aspect.

Results
Our findings support the hypothesis that MatriDerm can be used to preserve sensory function and decrease morbidity of the donor site.

Clinical Implications
The use of a dermal substitute decreases the morbidity of the forearm free flap donor site.

Strengths and Limitations
The strength of this study is its retrospective nature conducted of a prospectively maintained database of 37 consecutive radial forearm free flaps with superimposable dimensions and location performed by the same surgeon, thus limiting biases. A limitation is its small sample (particularly for the control group).

Conclusion
Our experience showed that the combination of a split-thickness skin graft with MatriDerm substantially decreases postoperative complications at the donor site defect on the forearm of transgender patients.
Targeting cytokines for treatment of neuropathic pain
Authors: Hung Alice L. , Lim Michael , Doshi Tina L. 
Published: August 2017

Abstract

Background
Neuropathic pain is a challenging condition often refractory to existing therapies. An increasing number of studies have indicated that the immune system plays a crucial role in the mediation of neuropathic pain. Exploration of the various functions of individual cytokines in neuropathic pain will provide greater insight into the mechanisms of neuropathic pain and suggest potential opportunities to expand the repertoire of treatment options.

Methods
A literature review was performed to assess the role of pro-inflammatory and antiinflammatory cytokines in the development of neuropathic pain. Both direct and indirect therapeutic approaches that target various cytokines for pain were reviewed. The current understanding based on preclinical and clinical studies is summarized.

Results and conclusions
In both human and animal studies, neuropathic pain has been associated with a pro-inflammatory state. Analgesic therapies involving direct manipulation of various cytokines and indirect methods to alter the balance of the immune system have been explored, although there have been few large-scale clinical trials evaluating the efficacy of immune modulators in the treatment of neuropathic pain. TNF-α is perhaps the widely studied pro-inflammatory cytokine in the context of neuropathic pain, but other pro-inflammatory (IL-1β, IL-6, and IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β) signaling molecules are garnering increased interest. With better appreciation and understanding of the interaction between the immune system and neuropathic pain, novel therapies may be developed to target this condition.
Cannabinoid hyperemesis syndrome presentation to the emergency department: A two-year multicentre retrospective chart review in a major urban area
Authors: Hernandez Jeremy M. , Paty Jared , Price Ira M. 
Published: August 2017

AbstractObjectiveCannabinoid hyperemesis syndrome (CHS) is a paradoxical side effect of cannabis use. Patients with CHS often present multiple times to the emergency department (ED) with cyclical nausea, vomiting, and abdominal pain, and are discharged with various misdiagnoses. CHS studies to date are limited to case series. The objective was to examine the epidemiology of CHS cases presenting to two major urban tertiary care centre EDs and one urgent care centre over a 2-year period.MethodsUsing explicit variables, trained abstractors, and standardized abstraction forms, we abstracted data for all adults (ages 18 to 55 years) with a presenting complaint of vomiting and/or a discharge diagnosis of vomiting and/or cyclical vomiting, during a 2-year period. The inter-rater agreement was measured using a kappa statistic.ResultsWe identified 494 cases: mean age 31 (+/-11) years; 36% male; and 19.4% of charts specifically reported cannabis use. Among the regular cannabis users (>three times per week), 43% had repeat ED visits for similar complaints. Moreover, of these patients, 92% had bloodwork done in the ED, 92% received intravenous fluids, 89% received antiemetics, 27% received opiates, 19% underwent imaging, 8% were admitted to hospital, and 8% were referred to the gastroenterology service. The inter-rater reliability for data abstraction was kappa=1.ConclusionsThis study suggests that CHS may be an overlooked diagnosis for nausea and vomiting, a factor that can possibly contribute to unnecessary investigations and treatment in the ED. Additionally, this indicates a lack of screening for CHS on ED history, especially in quantifying cannabis use and eliciting associated symptoms of CHS.
THE EU–US UNEMPLOYMENT PUZZLE REVISITED: INSTITUTIONS, DEMOGRAPHY, AND CAPITAL FLOWS
Authors: Marchiori Luca , Pierrard Olivier , Sneessens Henri R. 
Published: August 2017

AbstractThe historical evolution of the EU–US unemployment-rate gap is often explained in the literature in terms of asymmetric changes in labor-market institutions. There may well also be asymmetries in population aging, which may generate international capital flows and have substantial impacts on relative unemployment rates. In this paper, we ask whether the combination of institutions, aging, and capital flows explains the rise in the unemployment gap between 1960 and 2010. To this end, we set up a two-region OLG model with search unemployment in which we introduce the historical and projected changes in labor-market institutions and demographics. We show that asymmetric institutional changes alone can reproduce a large part of the historical rise in the unemployment gap. However, this result no longer holds once we add asymmetric aging in closed economies. We find this initial result again, and in an even stronger form, when we allow for international capital mobility.
Geospatial Distribution of Local Health Department Tweets and Online Searches About Ebola During the 2014 Ebola Outbreak
Authors: Wong Roger , Harris Jenine K. 
Published: August 2017

AbstractObjectiveThis study compared the geospatial distribution of Ebola tweets from local health departments (LHDs) to online searches about Ebola across the United States during the 2014 Ebola outbreak.MethodsBetween September and November 2014, we collected all tweets sent by 287 LHDs known to be using Twitter. Coordinates for each Ebola tweet were imported into ArcGIS 10.2.2 to display the distribution of tweets. Online searches with the search term “Ebola” were obtained from Google Trends. A Pearson’s correlation test was performed to assess the relationship between online search activity and per capita number of LHD Ebola tweets by state.ResultsEbola tweets from LHDs were concentrated in cities across the northeast states, including Philadelphia and New York City. In contrast, states with the highest online search queries for Ebola were primarily in the south, particularly Oklahoma and Texas. A weak, negative, non-significant correlation (r=−0.03, P=0.83, 95% CI: −0.30, 0.25) was observed between online search activity and per capita number of LHD Ebola tweets by state.ConclusionsWe recommend that LHDs consider using social media to communicate possible disease outbreaks in a timely manner, and that they consider using online search data to tailor their messages to align with the public health interests of their constituents. (Disaster Med Public Health Preparedness. 2018; 12: 287–290)
Reproduction biotechnologies in germplasm banking of livestock species: a review
Authors: Morrell J.M. , Mayer I. 
Published: August 2017

SummaryMany biotechnologies are currently used in livestock breeding with the aim of improving reproductive efficiency and increasing the rate of genetic progress in production animals. Semen cryopreservation is the most widely used cryobiotechnology, although vitrification techniques now allow embryos and oocytes to be banked in ever-increasing numbers. Cryopreservation of other types of germplasm (reproductive tissue in general) is also possible, although the techniques are still in the early stages of development for use in livestock species. Although still in their infancy, these techniques are increasingly being used in aquaculture. Germplasm conservation enables reproductive tissues from both animals and fish to be preserved to generate offspring in the future without having to maintain large numbers of living populations of these species. However, such measures need careful planning and coordination. This review explains why the preservation of genetic diversity is needed for livestock and fish, and describes some of the issues involved in germplasm banking. Furthermore, some recent developments in semen handling leading to improved semen cryopreservation and biosecurity measures are also discussed.
Finite model reasoning over existential rules
Authors: AMENDOLA GIOVANNI , LEONE NICOLA , MANNA MARCO 
Published: August 2017

AbstractOntology-based query answering asks whether a Boolean conjunctive query is satisfied by all models of a logical theory consisting of a relational database paired with an ontology. The introduction of existential rules (i.e., Datalog rules extended with existential quantifiers in rule heads) as a means to specify the ontology gave birth to Datalog+/-, a framework that has received increasing attention in the last decade, with focus also on decidability and finite controllability to support effective reasoning. Five basic decidable fragments have been singled out: linear, weakly acyclic, guarded, sticky, and shy. Moreover, for all these fragments, except shy, the important property of finite controllability has been proved, ensuring that a query is satisfied by all models of the theory iff it is satisfied by all its finite models. In this paper, we complete the picture by demonstrating that finite controllability of ontology-based query answering holds also for shy ontologies, and it therefore applies to all basic decidable Datalog+/- classes. To make the demonstration, we devise a general technique to facilitate the process of (dis)proving finite controllability of an arbitrary ontological fragment.
Role of PD-L1 expression as a biomarker for GEP neuroendocrine neoplasm grading
Authors: Cavalcanti Elisabetta , Armentano Raffaele , Valentini Anna Maria , Chieppa Marcello , Caruso Maria Lucia 
Published: August 2017

AbstractNeuroendocrine neoplasms (NENs) are rare, heterogeneous and ubiquitous tumors commonly localized in the gastrointestinal tract, lung, and pancreas. The clinical behavior of NEN is highly unpredictable; in fact, low-grade cases can unexpectedly be associated with metastases. Currently, the 2010 WHO NEN classification employs histological differentiation and the proliferation index for grading tumors but fails to provide reliable prognostic and therapeutic indications. Therefore, there is an urgent need for a better characterization of G2/G3 NENs. Similar to several other tumors, NENs possess immune-escape mechanisms, but very little has yet been done to characterize this crucial aspect. There are no available data describing PD-L1 expression in these tumors. Here we provide, for the first time, evidence of PD-L1 tissue expression in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). PD-L1 expression was significantly associated with a high-grade WHO classification (G3) (P<0.001) but not with gender, primary site, or lymph node status. The PD-L1 positivity rate and signal intensity are directly correlated (P<0.001) with a grade increase from G1 to G3. In particular in G3 cases, we observed a dichotomy between the morphology (WD- and PD-NENs) and Ki67. Moreover, our study demonstrated a significant association with the grade and PD-L1 expression levels in immune-infiltrating cells (P<0.001). In particular, G3 tumors are characterized by strong PD-L1 expression in both the tumor and infiltrating immune cells (P<0.001), reflecting an unfavorable environment for T-cell-mediated tumor aggression. These findings suggest that NENs might acquire resistance to immune surveillance by upregulating PD-L1 and inhibiting peritumoral and intratumoral infiltrating lymphocytes. Here we demonstrate that PD-L1 is currently the best-known biomarker for G3 NENs, becoming the new gold standard for G3 NEN discrimination. Furthermore, pharmacological approaches using anti-PD-1 antibodies may become the logical choice for the treatment of G3 cases with a poor prognosis.
Cardioprotective effects of fibroblast growth factor 21 against doxorubicin-induced toxicity via the SIRT1/LKB1/AMPK pathway
Authors: Wang Shudong , Wang Yonggang , Zhang Zhiguo , Liu Quan , Gu Junlian 
Published: August 2017

AbstractDoxorubicin (DOX) is a highly effective antineoplastic anthracycline drug; however, the adverse effect of the cardiotoxicity has limited its widespread application. Fibroblast growth factor 21 (FGF21), as a well-known regulator of glucose and lipid metabolism, was recently shown to exert cardioprotective effects. The aim of this study was to investigate the possible protective effects of FGF21 against DOX-induced cardiomyopathy. We preliminarily established DOX-induced cardiotoxicity models in H9c2 cells, adult mouse cardiomyocytes, and 129S1/SyImJ mice, which clearly showed cardiac dysfunction and myocardial collagen accumulation accompanying by inflammatory, oxidative stress, and apoptotic damage. Treatment with FGF21 obviously attenuated the DOX-induced cardiac dysfunction and pathological changes. Its effective anti-inflammatory activity was revealed by downregulation of inflammatory factors (tumor necrosis factor-α and interleukin-6) via the IKK/IκBα/nuclear factor-κB pathway. The anti-oxidative stress activity of FGF21 was achieved via reduced generation of reactive oxygen species through regulation of nuclear transcription factor erythroid 2-related factor 2 transcription. Its anti-apoptotic activity was shown by reductions in the number of TUNEL-positive cells and DNA fragments along with a decreased ratio of Bax/Bcl-2 expression. In a further mechanistic study, FGF21 enhanced sirtuin 1 (SIRT1) binding to liver kinase B1 (LKB1) and then decreased LKB1 acetylation, subsequently inducing AMP-activated protein kinase (AMPK) activation, which improved the cardiac inflammation, oxidative stress, and apoptosis. These alterations were significantly prohibited by SIRT1 RNAi. The present work demonstrates for the first time that FGF21 obviously prevented DOX-induced cardiotoxicity via the suppression of oxidative stress, inflammation, and apoptosis through the SIRT1/LKB1/AMPK signaling pathway.
Lysosomotropism depends on glucose: a chloroquine resistance mechanism
Authors: Gallagher Laura E , Radhi Ohood A , Abdullah Mahmud O , McCluskey Anthony G , Boyd Marie , Chan Edmond Y W 
Published: August 2017

AbstractThere has been long-standing interest in targeting pro-survival autophagy as a combinational cancer therapeutic strategy. Clinical trials are in progress testing chloroquine (CQ) or its derivatives in combination with chemo- or radiotherapy for solid and haematological cancers. Although CQ has shown efficacy in preclinical models, its mechanism of action remains equivocal. Here, we tested how effectively CQ sensitises metastatic breast cancer cells to further stress conditions such as ionising irradiation, doxorubicin, PI3K-Akt inhibition and serum withdrawal. Contrary to the conventional model, the cytotoxic effects of CQ were found to be autophagy-independent, as genetic targeting of ATG7 or the ULK1/2 complex could not sensitise cells, like CQ, to serum depletion. Interestingly, although CQ combined with serum starvation was robustly cytotoxic, further glucose starvation under these conditions led to a full rescue of cell viability. Inhibition of hexokinase using 2-deoxyglucose (2DG) similarly led to CQ resistance. As this form of cell death did not resemble classical caspase-dependent apoptosis, we hypothesised that CQ-mediated cytotoxicity was primarily via a lysosome-dependent mechanism. Indeed, CQ treatment led to marked lysosomal swelling and recruitment of Galectin3 to sites of membrane damage. Strikingly, glucose starvation or 2DG prevented CQ from inducing lysosomal damage and subsequent cell death. Importantly, we found that the related compound, amodiaquine, was more potent than CQ for cell killing and not susceptible to interference from glucose starvation. Taken together, our data indicate that CQ effectively targets the lysosome to sensitise towards cell death but is prone to a glucose-dependent resistance mechanism, thus providing rationale for the related compound amodiaquine (currently used in humans) as a better therapeutic option for cancer.
Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma
Authors: Liu Kuisheng , Ren Tingting , Huang Yi , Sun Kunkun , Bao Xing , Wang Shidong , Zheng Bingxin , Guo Wei 
Published: August 2017

AbstractThe cure rate of osteosarcoma has not improved in the past 30 years. The search for new treatments and drugs is urgently needed. Apatinib is a high selectivity inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2) tyrosine kinase, exerting promising antitumoral effect in various tumors. The antitumor effect of Apatinib in human osteosarcoma has never been reported. We investigated the effects of Apatinib in osteosarcoma in vitro and in vivo. Osteosarcoma patients with high levels of VEGFR2 have poor prognosis. Apatinib can inhibit cell growth of osteosarcoma cells. In addition to cycle arrest and apoptosis, Apatinib induces autophagy. Interestingly, inhibition of autophagy increased Apatinib-induced apoptosis in osteosarcoma cells. Immunoprecipitation confirmed direct binding between VEGFR2 and signal transducer and activator of transcription 3 (STAT3). Downregulation of VEGFR2 by siRNA resulted in STAT3 inhibition in KHOS cells. VEGFR2 and STAT3 are inhibited by Apatinib in KHOS cells, and STAT3 act downstream of VEGFR2. STAT3 and BCL-2 were downregulated by Apatinib. STAT3 knockdown by siRNA reinforced autophagy and apoptosis induced by Apatinib. BCL-2 inhibits autophagy and was apoptosis restrained by Apatinib too. Overexpression of BCL-2 decreased Apatinib-induced apoptosis and autophagy. Apatinib repressed the expression of STAT3 and BCL-2 and suppressed the growth of osteosarcoma in vivo. To sum up, deactivation of VEGFR2/STAT3/BCL-2 signal pathway leads to Apatinib-induced growth inhibition of osteosarcoma.
SMARCD1 regulates senescence-associated lipid accumulation in hepatocytes
Authors: Inoue Chisato , Zhao Chong , Tsuduki Yumi , Udono Miyako , Wang Lixiang , Nomura Masatoshi , Katakura Yoshinori 
Published: August 2017

AbstractPreviously, we have identified 16 senescence-associated genes by a subtractive proteomic analysis using presenescent and senescent human fibroblast cells, TIG-1. The aim of this study was to clarify the role of SMARCD1, one of the identified genes, also known as BAF60a, in hepatic senescence. SMARCD1 is a member of the SWI/SNF chromatin remodeling complex family, and regulates the transcription of target genes through the alterations of chromatin structure. We demonstrated that the reduced expression of SMARCD1 triggers cellular senescence and induces the accumulation of lipids, suggesting that SMARCD1 acts as a mediator in these processes. Furthermore, palmitic acid treatment and high-fat diet led to a significant reduction of SMARCD1 expression, and consequently induced cellular senescence and lipid accumulation in HepG2 cells and mouse liver, respectively. The results obtained here suggest that dietary nutrient-associated impaired expression of SMARCD1 triggers cellular senescence and lipid accumulation, indicating a potential application of SMARCD1 in the prevention of lifestyle-related diseases.