bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induced pluripotent stem cell‐derived conditional medium promotes Leydig cell anti‐apoptosis and proliferation via autophagy and Wnt/β‐catenin pathway
Authors: Guo Xiaoling , Chen Yong , Hong Tingting , Chen Xianwu , Duan Yue , Li Chao , Ge Renshan 
Published: April 2018

AbstractLeydig cell transplantation is a better alternative in the treatment of androgen‐deficient males. The main purpose of this study was to investigate the effects of induced pluripotent stem cell‐derived conditioned medium (iPS‐CM) on the anti‐apoptosis, proliferation and function of immature Leydig cells (ILCs), and illuminate the underlying mechanisms. ILCs were exposed to 200 μmol/L hydrogen peroxide (H2O2) for 24 hours with or without iPS‐CM treatments. Cell apoptosis was detected by flow cytometric analysis. Cell proliferation was assessed using cell cycle assays and EdU staining. The steroidogenic enzyme expressions were quantified with Western blotting. The results showed that iPS‐CM significantly reduced H2O2‐induced ILC apoptosis through down‐regulation of autophagic and apoptotic proteins LC3‐I/II, Beclin‐1, P62, P53 and BAX as well as up‐regulation of BCL‐2, which could be inhibited by LY294002 (25 μmol/L). iPS‐CM could also promote ILC proliferation through up‐regulation of β‐catenin and its target proteins cyclin D1, c‐Myc and survivin, but was inhibited by XAV939 (10 μmol/L). The level of bFGF in iPS‐CM was higher than that of DMEM‐LG. Exogenous bFGF (20 ng/mL) or Wnt signalling agonist lithium chloride (LiCl) (20 mmol/L) added into DMEM‐LG could achieve the similar effects of iPS‐CM. Meanwhile, iPS‐CM could improve the medium testosterone levels and up‐regulation of LHCGR, SCARB1, STAR, CYP11A1, HSD3B1, CYP17A1, HSD17B3 and SF‐1 in H2O2‐induced ILCs. In conclusion, iPS‐CM could reduce H2O2‐induced ILC apoptosis through the activation of autophagy, promote proliferation through up‐regulation of Wnt/β‐catenin pathway and enhance testosterone production through increasing steroidogenic enzyme expressions, which might be used in regenerative medicine for future.
Menstrual and reproductive factors and type 2 diabetes risk: The Japan Public Health Center‐based Prospective Study
Authors: Nanri Akiko , Mizoue Tetsuya , Noda Mitsuhiko , Goto Atsushi , Sawada Norie , Tsugane Shoichiro ,   the Japan Public Health Center‐based Prospective Study (JPHC Study) Group
Published: April 2018

AbstractAims/IntroductionMenstrual and reproductive factors, including age at menarche, parity and breast‐feeding, have been linked to type 2 diabetes risk. We prospectively investigated the association between these factors and type 2 diabetes risk in a large Japanese cohort.Materials and MethodsParticipants were 37,511 women aged 45–75 years who participated in the baseline (1990–1993), second (1995–1998) and third surveys (2000–2003) of the Japan Public Health Center‐based Prospective Study, and who had no history of diabetes at the second survey. Menstrual and reproductive history was ascertained using questionnaires at the baseline and second surveys. Odds ratios of self‐reported, physician‐diagnosed type 2 diabetes over the 5‐year period from the second survey were estimated using logistic regression.ResultsAt the third survey, 513 new cases of type 2 diabetes were self‐reported. The odds ratios of type 2 diabetes tended to increase with the number of parity, after adjustment for covariates other than body mass index (P for trend = 0.029). The multivariable‐adjusted odds ratios of type 2 diabetes for women with three or more births was 1.56 (95% confidence interval 0.96–2.53) compared with those who were nulliparous. The association between parity and type 2 diabetes risk was attenuated after additional adjustment for body mass index (P for trend = 0.12). No factors other than parity were significantly associated with type 2 diabetes risk.ConclusionsHigher parity might be associated with an increased risk of type 2 diabetes among Japanese women, partly through increasing bodyweight.
Coevolution of virulence and immunosuppression in multiple infections
Authors: Kamiya Tsukushi , Mideo Nicole , Alizon Samuel 
Published: April 2018

AbstractMany components of host–parasite interactions have been shown to affect the way virulence (i.e. parasite‐induced harm to the host) evolves. However, coevolution of multiple parasite traits is often neglected. We explore how an immunosuppressive adaptation of parasites affects and coevolves with virulence in multiple infections. Applying the adaptive dynamics framework to epidemiological models with coinfection, we show that immunosuppression is a double‐edged sword for the evolution of virulence. On one hand, it amplifies the adaptive benefit of virulence by increasing the abundance of coinfections through epidemiological feedbacks. On the other hand, immunosuppression hinders host recovery, prolonging the duration of infection and elevating the cost of killing the host (as more opportunities for transmission will be forgone if the host dies). The balance between the cost and benefit of immunosuppression varies across different background mortality rates of hosts. In addition, we find that immunosuppression evolution is influenced considerably by the precise trade‐off shape determining the effect of immunosuppression on host recovery and susceptibility to further infection. These results demonstrate that the evolution of virulence is shaped by immunosuppression while highlighting that the evolution of immune evasion mechanisms deserves further research attention.
Managerial turnover and entrenchment
Authors: Wu Zenan , Weng Xi 
Published: April 2018

AbstractWe consider a two‐period model in which the success of the firm depends on the effort of a first‐period manager (the incumbent) as well as the effort and ability of a second‐period manager. At the end of the first period, the board receives a noisy signal of the incumbent manager's ability and decides whether to retain or replace the incumbent manager. We show that severance pay can be utilized in the optimal contract to provide a credible commitment to a lenient second‐period equilibrium replacement policy, mitigating the first‐period moral hazard problem. Unlike existing models that aim to rationalize managerial entrenchment, we identify conditions on the information structure under which both entrenchment and anti‐entrenchment emerge in the optimal contract. Specifically, our model predicts that it is optimal for the board to design a contract to induce entrenchment (respectively, anti‐entrenchment) if the signal regarding the incumbent manager's ability becomes sufficiently uninformative (respectively, informative).
Clinical differences between elderly‐onset ulcerative colitis and non‐elderly‐onset ulcerative colitis: A nationwide survey data in Japan
Authors: Komoto Shunsuke , Higashiyama Masaaki , Watanabe Chikako , Suzuki Yasuo , Watanabe Mamoru , Hibi Toshifumi , Takebayashi Toru , Asakura Keiko , Nishiwaki Yuji , Miura Soichiro , Hokari Ryota 
Published: April 2018

AbstractBackground and AimStudies on the characteristics of elderly‐onset ulcerative colitis (EOUC) and non‐elderly‐onset ulcerative colitis (NEOUC) have reported conflicting findings. The aim of this study was to compare disease characteristics of EOUC and NEOUC by analyzing the database of the Japanese nationwide inflammatory bowel disease (IBD) registry.MethodsWe analyzed the age of disease onset, sex, disease severity, and disease extent in patients with ulcerative colitis that were newly diagnosed and registered within 1 year between 2004 and 2009 (n = 28 179). We also analyzed the medical treatment, rate of IBD‐related surgery, and postoperative complications. We compared them between younger than 65 years old (NEOUC group) and 65 years old or older (EOUC group) patients.ResultsA total of 25 401 (90.1%) and 2778 (9.9%) patients were included in the NEOUC and EOUC groups, respectively. In the EOUC group, disease activity was significantly higher, and extent of pathological changes in the colon more extended significantly. Laboratory findings showed that inflammatory markers were elevated significantly in the EOUC group. The proportion of those with IBD‐related hospitalization was significantly higher in the EOUC group (54.2% vs 35.7%, P < 0.001). The proportion of patients who were treated with corticosteroids was significantly higher in the EOUC group (36.7% vs 30.8%, P < 0.001). Significantly more number of patients underwent IBD‐related surgery in the EOUC group (0.68% vs 0.27%, P < 0.001).ConclusionElderly patients show higher disease activity, with a higher proportion requiring IBD‐related hospitalization and IBD‐related surgery, according to the nationwide registry in Japan.
Insights into the regulation of C‐repeat binding factors in plant cold signaling
Authors: Liu Jingyan , Shi Yiting , Yang Shuhua 
Published: April 2018

AbstractCold temperatures, a major abiotic stress, threaten the growth and development of plants, worldwide. To cope with this adverse environmental cue, plants from temperate climates have evolved an array of sophisticated mechanisms to acclimate to cold periods, increasing their ability to tolerate freezing stress. Over the last decade, significant progress has been made in determining the molecular mechanisms underpinning cold acclimation, including following the identification of several pivotal components, including candidates for cold sensors, protein kinases, and transcription factors. With these developments, we have a better understanding of the CBF‐dependent cold‐signaling pathway. In this review, we summarize recent progress made in elucidating the cold‐signaling pathways, especially the C‐repeat binding factor‐dependent pathway, and describe the regulatory function of the crucial components of plant cold signaling. We also discuss the unsolved questions that should be the focus of future work.
Relationships between executive function, working memory, and decision‐making on the Iowa Gambling Task: Evidence from ventromedial patients, dorsolateral patients, and normal subjects
Authors: Ouerchefani Riadh , Ouerchefani Naoufel , Allain Philippe , Ben Rejeb Mohamed Riadh , Le Gall Didier 
Published: April 2018

The results of previous studies are inconsistent in regard to the relationship between the Iowa Gambling Task (IGT), working‐memory (WM), and executive tasks, and whether these cognitive processes could be considered as mechanisms underlying a decision‐making deficit. Moreover, the relationship between theIGTand executive measures is examined based on a limited number of executive tasks, within different populations showing diffuse damage. In addition, there are fewer studies carried out within control participants, with those studies also being inconclusive. It is also suggested that the association of theIGTperformance with executive tasks depends on whether theIGTwas running under ambiguity or under risk. In this work, all of these issues are studied. Results showed that both patients with ventromedial (VMPFC,N = 10) and dorsolateral (DLPFC,N = 10) prefrontal cortex lesions are significantly impaired on almost all executive tasks,WMtasks, and theIGT. Furthermore, when theIGTis run under risk, there are significant correlations between executive measures and theIGTfor theDLPFCpatients and the control participants (N = 34) but not theVMPFCpatients. No correlation was found betweenWMtasks and theIGTfor both frontal subgroups and control participants. These findings suggested that the mechanisms underlying theIGTdeficit differ according to the lesion locations.
Homologs from sulfur oxidation (Sox) and methanol dehydrogenation (Xox) enzyme systems collaborate to give rise to a novel pathway of chemolithotrophic tetrathionate oxidation
Authors: Pyne Prosenjit , Alam Masrure , Rameez Moidu Jameela , Mandal Subhrangshu , Sar Abhijit , Mondal Nibendu , Debnath Utsab , Mathew Boby , Misra Anup Kumar , Mandal Amit Kumar , Ghosh Wriddhiman 
Published: April 2018

SummaryThe SoxXAYZB(CD)2‐mediated pathway of bacterial sulfur‐chemolithotrophy explains the oxidation of thiosulfate, sulfide, sulfur and sulfite but not tetrathionate. Advenella kashmirensis, which oxidizes tetrathionate to sulfate, besides forming it as an intermediate during thiosulfate oxidation, possesses a soxCDYZAXOB operon. Knock‐out mutations proved that only SoxBCD is involved in A. kashmirensis tetrathionate oxidation, whereas thiosulfate‐to‐tetrathionate conversion is Sox independent. Expression of two glutathione metabolism‐related proteins increased under chemolithotrophic conditions, as compared to the chemoorganotrophic one. Substrate‐dependent oxygen consumption pattern of whole cells, and sulfur‐oxidizing enzyme activities of cell‐free extracts, measured in the presence/absence of thiol inhibitors/glutathione, corroborated glutathione involvement in tetrathionate oxidation. Furthermore, proteome analyses detected a sulfite:acceptor oxidoreductase (SorAB) exclusively under chemolithotrophic conditions, while expression of a methanol dehydrogenase (XoxF) homolog, subsequently named thiol dehydrotransferase (ThdT), was found to increase 3‐ and 10‐fold during thiosulfate‐to‐tetrathionate conversion and tetrathionate oxidation respectively. A thdT knock‐out mutant did not oxidize tetrathionate but converted half of the supplied 40 mM S‐thiosulfate to tetrathionate. Knock‐out of another thiosulfate dehydrogenase (tsdA) gene proved that both ThdT and TsdA individually converted ∼ 20 mM S‐thiosulfate to tetrathionate. The overexpressed and isolated ThdT protein exhibited PQQ‐dependent thiosulfate dehydrogenation, whereas its PQQ‐independent thiol transfer activity involving tetrathionate and glutathione potentially produced a glutathione:sulfodisulfane adduct and sulfite. SoxBCD and SorAB were hypothesized to oxidize the aforesaid adduct and sulfite respectively.
The Secret Dynamism of Divine Simplicity
Authors: Mazzocco Mariel 
Published: April 2018

AbstractWhile it was a centerpiece of medieval theology, the thesis of God's simplicity is often perceived by contemporary thinkers as enigmatic or even incoherent. After having presented the recent debate on divine simplicity from a historical perspective, this paper questions the attribute of simplicity from the perspective of the fourteenth‐century German preacher Meister Eckhart and shows that the so‐called speculative mystical thought of the Middle Ages is able to suggest new perspectives regarding God's simplicity, and to enrich discussions on this difficult aspect of the divine nature.
Effects of BMP‐2 on the osteogenic differentiation of bone marrow stem cells in fibrous dysplasia
Authors: Um S , Kim HY , Seo B‐M 
Published: April 2018

ObjectivesThe purpose of this study was to evaluate the effects of BMP‐2 on bone‐grafting procedures for the treatment of fibrous dysplasia based on in vitro and in vivo experiments.Subjects and MethodsProliferation of stem cells was determined by colony‐forming assay, CCK‐8 assay and BrdU staining. OCT4 and NANOG expression was analysed by flow cytometry and immunocytochemistry. Osteogenic differentiation was assessed by measuring ALP activity, Alizarin red S staining and in vivo transplantation. Gene expression of the osteogenic markers, osteocalcin and type 1 collagen, was determined by RT‐PCR.ResultsFD‐BMSCs showed few calcium deposits and low ALP activity. Bone formation by transplanted FD‐BMSCs was also suppressed relative to that of normal BMSCs. However, BMP‐2 treatment enhanced osteogenic differentiation of FD‐BMSCs mixed with normal BMSCs in vitro and in vivo. Overall, BMP‐2 treatment promoted osteogenic differentiation of FD‐BMSCs mixed with normal BMSCs.ConclusionsIn patients with FD, stem cells in affected bone are influenced by the mutation, resulting in weak bone formation with the proliferation of immature osteogenic cells. Current treatment of FD involves surgical removal of excess bulk lesions, which can cause facial disfigurement. Our results suggest that BMP‐2 application is a good adjunctive modality to the surgical treatment of patients with FD.
The use of cardiac‐CT alone to exclude left atrial thrombus before atrial fibrillation ablation: Efficiency, safety, and cost analysis
Authors: Mosleh Wassim , Sheikh Ali , Said Zaid , Ahmed Mohamed Abdel‐Aal , Gadde Siri , Shah Tanvi , Wilson Michael F. , Beck Hiroko , Kim Chee , Sharma Umesh C. 
Published: April 2018

AbstractBackgroundAtrial fibrillation (AF) is a growing financial burden on the healthcare system. Cardiac computed tomographic angiography (CCTA) is needed for pulmonary vein mapping before AF ablation (AFA). CCTA has shown to be an alternative to transesophageal echocardiogram (TEE) to rule out left atrial appendage thrombus (LAAT) pre‐AFA. We aim to examine the safety, cost‐effectiveness, and time‐efficiency of utilizing CCTA alone to rule out LAAT before AFA.MethodsWe prospectively screened patients with paroxysmal AF undergoing cryoablation. CCTA with delayed enhancement was performed within 72 hours of AFA. Once LAAT was ruled out, patients were enrolled and planned TEE was cancelled. A retrospective control cohort that had both CCTA and TEE prior to AFA was identified. Direct cost data, electrophysiology laboratory utilization time, and 30‐day stroke outcomes were collected from the EMR, follow‐up phone calls, or clinic visits, and comparative analyses were performed.ResultsSeventy patients met the inclusion criteria in the prospective CCTA‐only cohort, and 71 for the retrospective CCTA+TEE cohort. Baseline characteristics were similar between the two groups. There was a nonsignificant reduction in overall cost ($15,870 ± 1,710 vs $16,557 ± 2,508, P = 0.06) in CCTA‐only cohort, whereas the electrophysiology laboratory utilization time was significantly reduced (241.6 ± 41.7 vs 181.3 ±36.4 minutes, P < 0.001). There were no strokes reported on 30‐day follow‐up in the CCTA‐only group.ConclusionsIn low‐to‐intermediate stroke risk patients with paroxysmal AF undergoing cryoablation, eliminating TEE and employing CCTA‐only strategy to rule‐out LAAT improves electrophysiology laboratory efficiency without influencing periprocedural cost or increasing postprocedural stroke risk.
Early repolarization is involved in ventricular fibrillation in patients with variant angina
Authors: Shinohara Tetsuji , Kondo Hidekazu , Fukui Akira , Akioka Hidefumi , Teshima Yasushi , Yufu Kunio , Nakagawa Mikiko , Takahashi Naohiko 
Published: April 2018

AbstractBackgroundVariant angina (VA) is caused by reversible coronary artery spasm, which is characterized by chest pain with ST segment elevations on a standard 12‐lead electrocardiogram (ECG) at rest. VA attack often causes lethal ventricular arrhythmia. The early repolarization (ER) pattern is associated with ventricular fibrillation (VF). However, whether the ER pattern is involved in VF in patients with VA is not known. We investigated the association between the ER pattern and VF in patients with VA.MethodsFifty patients underwent induction of ST elevation on 12‐lead ECGs with total or nearly total occlusion by provocation test (VA patients). Twelve of these patients underwent induction of VF or had documented VF before hospital admission (VF occurrence group). The J‐wave morphology was characterized as exhibiting notching or slurring. The amplitude of each J wave was measured manually with amplified waveforms.ResultsER patterns were observed significantly more often in the VF occurrence group than in the non‐VF occurrence group (P = 0.007). The J‐wave amplitude was significantly higher in the VF occurrence group compared with the non‐VF occurrence group (P = 0.02). Univariate analyses suggested that age, smoking, and ER patterns were associated with VF. Upon multivariate analyses, age (odds ratio [OR] = 0.880; 95% confidence interval [CI]: 0.794–0.975; P = 0.014) and ER patterns (OR = 8.937; 95% CI:1.661–48.06; P = 0.011) predicted VF independently.ConclusionsThese data suggest that an ER pattern in VA patients is a risk factor for VF. The ER pattern may be one of the useful factors for adaptation of implantation of implantable cardioverter‐defibrillator in patients with coronary spasm‐induced VF.
The puzzle of hyper‐change
Authors: Law Andrew 
Published: April 2018

AbstractIf there is a second dimension of time – a so‐called ‘hypertime’ – is it logically possible for the past to change? Some have said yes; others have said no. I say yesprovidedthat one has the appropriate ontological view of hypertime. So far, the ontology of hypertime has seldom been discussed. As such, this paper not only defends the logical possibility of a changing past, but aims to start a discussion on what ontological commitments are required to make sense of a changing past.
Intending, believing, and supposing at will
Authors: Shepherd Joshua 
Published: April 2018

AbstractIn this paper I consider an argument for the possibility of intending at will, and its relationship to an argument about the possibility of believing at will. I argue that although we have good reason to think we sometimes intend at will, we lack good reason to think this in the case of believing. Instead of believing at will, agents like us often suppose at will.
UC‐1V150, a potent TLR7 agonist capable of activating macrophages and potentiating mAb‐mediated target cell deletion
Authors: Dahal L. N. , Gadd A. , Edwards A. D. , Cragg M. S. , Beers S. A. 
Published: April 2018

AbstractToll‐like receptors (TLR) are critical mediators of the immune system with their activation linked to infection, inflammation and the pathogenesis of immune diseases including autoimmunity and cancer. For this reason, over the last 2 decades, TLR and their associated signalling pathways have been targeted therapeutically to enhance innate and adaptive immunity. Several TLR ligands, both endogenous and synthetic are at various phases of clinical testing, and new ligands are continually emerging. Agonists of TLR7 are known immune response modifiers, simultaneously stimulating several cell types, resulting in immune cell activation and cytokine and chemokine release. The immune stimulating properties of the TLR7 agonist Imiquimod has also been exploited for use in the treatment of malignant superficial tumours of the skin. Here, we investigated a novel TLR7 agonist UC‐1V150 and demonstrate it activates both human and mouse myeloid cells in vitro and in vivo, to deliver potent FcγR‐mediated engulfment of opsonized target cells.