bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of adenosine A3 receptor inhibits inflammatory cytokine production in colonic mucosa of patients with ulcerative colitis by down‐regulating the nuclear factor‐kappa B signaling
Authors: Ren Tian Hua , Lv Min Min , An Xiao Meng , Leung Wai Keung , Seto Wai‐Kay 
Published: November 2019

ObjectivesThe activation of the adenosine A3 receptor (A3AR) can regulate inflammation, but the way that this regulates colonic mucosal inflammation in ulcerative colitis (UC) remains unclear. This study aimed at examining A3AR expression and investigating the effect of A3AR activation on ex vivo cytokine expression and nuclear factor‐kappa B (NF‐κB) signaling in colonic mucosa.MethodsColonic mucosal biopsied tissue from 18 patients with UC and 11 healthy controls was tested for A3AR expression by immunofluorescence, quantitative real‐time polymerase chain reaction and Western blot. Following treatment for 24 hours with or without 2‐Cl‐IB‐MECA, an A3AR agonist, TNF‐α and IL‐1β secreted by the cultured colonic mucosal tissue were quantified by ELISA. The colonic mucosal epithelia were dissected and treated with, or without 2‐Cl‐IB‐MECA for 24 hours. The NF‐κB p65 protein and its distribution in the cultured colonic epithelia were examined by immunofluorescence and Western blot.ResultsCompared with the controls, down‐regulated A3AR expression and up‐regulated TNF‐α and IL‐1β production and NF‐κB p65 protein were observed in the UC colonic mucosa. The activation of A3AR by 2‐Cl‐IB‐MECA significantly decreased TNF‐α and IL‐1β production and attenuated the NF‐κB p65 activation in colonic tissues from patients with UC.ConclusionsA3AR activation inhibited inflammation by mitigating pro‐inflammatory cytokine production and the NF‐κB signal activation in colonic mucosa of patients with UC. A3AR activation may play a role in the pathogenesis of UC.
Growth of the acetogenic bacterium Acetobacterium woodii by dismutation of acetaldehyde to acetate and ethanol
Authors: Trifunović Dragan , Berghaus Natalie , Müller Volker 
Published: November 2019

SummaryAcetogenic bacteria are a group of strictly anaerobic bacteria that may have been first life forms on Earth since they employ an ancient pathway for CO2 fixation into acetyl‐CoA that is coupled to the synthesis of ATP, the Wood–Ljungdahl pathway. Electrons for CO2 reduction are derived from oxidation of H2 or CO and thus, these bacteria can grow lithotrophically on gases present on early Earth. Among the organic molecules present on early Earth is acetaldehyde, a highly volatile C2 compound. Here, we demonstrate that the acetogenic model bacterium Acetobacterium woodii grows on acetaldehyde. Acetaldehyde is dismutated to ethanol and acetyl‐CoA, most likely by the bifunctional alcohol dehydrogenase AdhE. Acetyl‐CoA is converted to acetate by two subsequent enzymes, phosphotransacetylase and acetate kinase, accompanied by the synthesis of ATP by substrate‐level phosphorylation. Apparently, growth on acetaldehyde does not employ the Wood–Ljungdahl pathway. Our finding opens the possibility of a simple and ancient metabolic pathway with only three enzymes that allows for biomass (acetyl‐CoA) and ATP formation on early Earth.
Ultrasound as a replacement for physical examination in clinical staging of axillary lymph nodes in breast cancer patients
Authors: Chen Xue , Li Xiaoting , Fan Zhaoqing , Li Jinfeng , Xie Yuntao , Wang Tianfeng , Ouyang Tao 
Published: November 2019

BackgroundThe status of axillary lymph nodes (ALNs) is one of the important factors in decision‐making for breast cancer treatment. Physical examination (PE) has long been the main, or even the only, means of clinical staging for ALNs in breast cancer. However, the sensitivity and accuracy of PE remains unsatisfactory. The results from this study suggest that axillary ultrasonography (US) should replace PE as a standard method for the clinical staging of ALNs in breast cancer.MethodsConsecutive and nonselective breast cancer patients treated between September 2018 and November 2018 in our center were enrolled in the study. Comparisons of ALN results between PE/US and pathological results were conducted and the difference in sensitivity, specificity and accuracy between PE and US were tested by McNemar chi‐square test.ResultsA total of 123 patients were enrolled into the study. Their ages ranged from 28 to 76 years with a median age of 53 ± 10. There were 83 ALN positive cases and 40 ALN negative cases confirmed pathologically. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PE and US were 54.2%, 90.0%, 65.9%, 91.8%, 48.7% versus 86.8%, 72.5%, 82.1%, 86.8%, 72.5%, respectively. The sensitivity and accuracy of US was significantly higher than that of PE (P = 0.004 and P = 0.002).ConclusionThe results of this study demonstrated that US is superior in evaluating ALNs when compared with PE and that US should replace PE as the standard method for the clinical staging of ALNs in breast cancer.
Lysophosphatidic acid receptor LPA3 prevents oxidative stress and cellular senescence in Hutchinson–Gilford progeria syndrome
Authors: Chen Wei‐Min , Chiang Jui‐Chung , Lin Yueh‐Chien , Lin Yu‐Nung , Chuang Pei‐Yun , Chang Ya‐Chi , Chen Chien‐Chin , Wu Kao‐Yi , Hsieh Jung‐Chien , Chen Shih‐Kuo , Huang Wei‐Pang , Chen Benjamin P. C. , Lee Hsinyu 
Published: November 2019

AbstractHutchinson–Gilford progeria syndrome (HGPS) is a rare laminopathy that produces a mutant form of prelamin A, known as Progerin, resulting in premature aging. HGPS cells show morphological abnormalities of the nuclear membrane, reduced cell proliferation rates, accumulation of reactive oxygen species (ROS), and expression of senescence markers. Lysophosphatidic acid (LPA) is a growth factor‐like lipid mediator that regulates various physiological functions via activating multiple LPA G protein‐coupled receptors. Here, we study the roles of LPA and LPA receptors in premature aging. We report that the protein level of LPA3 was highly downregulated through internalization and the lysosomal degradation pathway in Progerin‐transfected HEK293 cells. By treating Progerin HEK293 cells with an LPA3 agonist (OMPT, 1‐Oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate) and performing shRNA knockdown of the Lpa3r transcript in these cells, we showed that LPA3 activation increased expression levels of antioxidant enzymes, consequently inhibiting ROS accumulation and ameliorating cell senescence. LPA3 was shown to be downregulated in HGPS patient fibroblasts through the lysosomal pathway, and it was shown to be crucial for ameliorating ROS accumulation and cell senescence in fibroblasts. Moreover, in a zebrafish model, LPA3 deficiency was sufficient to cause premature aging phenotypes in multiple organs, as well as a shorter lifespan. Taken together, these findings identify the decline of LPA3 as a key contributor to the premature aging phenotypes of HGPS cells and zebrafish.
Real‐world outcome with abiraterone acetate plus prednisone in Asian men with metastatic castrate‐resistant prostate cancer: The Singapore experience
Authors: Chan Johan , Yap Shi Yin , Fong Yian Ching , Lim Heng Chi , Toh Chee Keong , Ng Quan Sing , Rajasekaran Tanujaa , Chua Melvin , Lee Lui Shiong , Wong Alvin , Loh Ker Yun , Chow Marcus , Wong Siew Wei , Kanesvaran Ravindran 
Published: November 2019

AbstractIntroductionSeveral small studies have reviewed the efficacy of abiraterone acetate plus prednisolone (AAP) in clinical practice outside a trial setting. We report the largest cohort study of clinical outcomes in metastatic castrate‐resistant prostate cancer (mCRPC) patients treated with AAP in a multicenter multiracial clinical setting.MethodsA retrospective analysis on mCRPC patients treated at four tertiary hospitals in Singapore from 2012 to 2017 was conducted. Disease characteristics, treatment outcomes, and adverse events were retrieved from electronic medical records. Primary clinical end‐point was overall survival (OS). A subset analysis of patients with various variables and OS curves were generated using the Kaplan–Meier method and compared using the log‐rank test.ResultsOut of 200 patients with mCRPC treated with AAP, 163 (81.5%) patients were chemo‐naïve (CN) and 37 (18.5%) patients were postchemotherapy (PC), with the median age of 68 (34–87) and 65 (52–80) years, respectively. Median OS was 20.0 (95% CI, 18.3–22.9) and 10.5 months (95% CI, 1.1–40.5) for CN and PC cohorts, respectively. A subset analysis of 108 patients showed a significantly longer OS in patients who had prior ADT for more than 12 months in CN patients (P < 0.001). Incidences of G3/G4 events were around 6.6%; most common side effect being hypertension with an incidence of 2.4%.ConclusionsTreatment of CN and PC patients with AAP was associated with a comparable OS and progression‐free survival to the reported series. Patients who were responsive to prior ADT of 12 months or more were associated with an improved OS.
30 years of sublingual immunotherapy
Authors: Passalacqua Giovanni , Bagnasco Diego , Canonica Giorgio Walter 
Published: November 2019

AbstractAllergen Immunotherapy (AIT) was introduced in clinical practice on an empirical basis more than 100 years ago. Since the first attempts, AIT was administered subcutaneously. Indeed, other routes of administration were proposed and studied, in particular to improve the safety, but only the sublingual route (SLIT) achieved a credibility based on evidence and was then accepted as a viable “alternative” option to the subcutaneous route. SLIT was largely used in clinical trials and clinical practice in this last 30 years. Thus, a large amount of data is available, coming from either controlled trials and postmarketing surveillance studies. It is clear that SLIT is overall effective, but it is also clear that the efficacy is not “class‐related,” as derived from meta‐analyses, but restricted to each specific product. The 30‐year lasting use of SLIT allowed to clarify many clinical aspects, such as efficacy, safety, use in asthma, regimens of administration, and optimal doses. In parallel, the mechanisms of action of AIT were elucidated, and new indications were proposed (eg food allergy, atopic dermatitis). In addition, the introduction of molecular‐based diagnosis, allowed to better refine the prescription of SLIT, based on specific sensitization profiles. The present article will describe the origin and evolution of SLIT for respiratory allergy, taking into account the clinical context that suggested this form of treatment, the recently developed aspects, the future perspectives and unmet needs, This is not, therefore, a systematic review, rather a narrative historical description of the past history, and a look forward to the future opportunities.
The predictive capacity of uterine artery Doppler for preterm birth—A cohort study
Authors: van Zijl Maud D. , Koullali Bouchra , Mol Ben W. J. , Snijders Rosalinde J. , Kazemier Brenda M. , Pajkrt Eva 
Published: November 2019

AbstractIntroductionMid‐trimester uterine artery resistance measured with Doppler sonography is predictive for iatrogenic preterm birth. In view of the emerging association between hypertensive disease in pregnancy and spontaneous preterm birth, we hypothesized that uterine artery resistance could also predict spontaneous preterm birth.Material and methodsWe performed a cohort study of women with singleton pregnancies. Uterine artery resistance was routinely measured at the 18‐22 weeks anomaly scan. Pregnancies complicated by congenital anomalies or intrauterine fetal death were excluded. We analyzed if the waveform of the uterine artery (no notch, unilateral notch or bilateral notch) was predictive for spontaneous and iatrogenic preterm birth, defined as delivery before 37 weeks of gestation. Furthermore, we assessed whether the uterine artery pulsatility index was associated with the risk of preterm birth.ResultsBetween January 2009 and December 2016 we collected uterine Doppler indices and relevant outcome data in 4521 women. Mean gestational age at measurement was 19+6 weeks. There were 137 (3.0%) women with a bilateral and 213 (4.7%) with a unilateral notch. Mean gestational age at birth was 38+6 weeks. Spontaneous and iatrogenic preterm birth rates were 5.7% and 4.9%, respectively. Mean uterine artery resistance was 1.12 in the spontaneous preterm birth group compared with 1.04 in the term group (P = 0.004) The risk of preterm birth was increased with high uterine artery resistance (OR 2.9 per unit; 95% CI 2.4‐3.9). Prevalence of spontaneous preterm birth increased from 5.5% in women without a notch in the uterine arteries to 8.0% in women with a unilateral notch and 8.0% in women with a bilateral notch. For iatrogenic preterm birth, these rates were 3.9%, 13.6% and 23.4%, respectively. Likelihood ratios for the prediction of spontaneous preterm birth were 1.6 (95% CI 1.0‐2.6) and 1.9 (95% CI 1.0‐3.5) for unilateral and bilateral notches, respectively, and for iatrogenic preterm birth they were 3.6 (95% CI 2.5‐5.2) and 6.8 (95% CI 4.7‐9.9) for unilateral and bilateral notches, respectively. Of all women with bilateral notching, 31.4% delivered preterm.ConclusionsMid‐trimester uterine artery resistance measured at 18‐22 weeks of gestation is a weak predictor of spontaneous preterm birth.
Percutaneous left atrial appendage closure, a safe alternative to anticoagulation for patients with nonvalvular atrial fibrillation and end‐stage renal disease on hemodialysis: A single center experience
Authors: Xipell Marc , Flores‐Umanzor Eduardo , Ojeda Raquel , Arias Marta , Cepas‐Guillén Pedro L. , Regueiro Ander , Freixa Xavier , Cases Aleix , Maduell Francisco 
Published: November 2019

AbstractThe evidence about the effectiveness and safety of oral anticoagulation in patients on hemodialysis is conflicting and scarce. Percutaneous left atrial appendage occlusion (LAAO) has demonstrated to be a valid alternative therapeutic option for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study is to present the outcomes of percutaneous LAAO in patients with end‐stage renal disease (ESRD) on hemodialysis and NVAF in our center. We conducted a retrospective review of clinical records, demographics, LAAO procedure, complications, and outcomes of patients with NVAF and ESRD on hemodialysis who underwent a percutaneous LAAO in our center between January 2017 and January 2019. In the period of the study, eight patients with ESRD on hemodialysis underwent a percutaneous LAAO in our center. The overall mean age was 67.5 years (range 56‐81; SD ± 7.2). All patients had permanent NVAF. The total mean dialysis duration was 8.49 years (range 0.83‐14.8; SD ± 6.2). The mean CHA2DS2‐VASc and HAS‐BLED scores were high (4.75 [SD ± 1.16] and 4.62 [SD ± 0.91], respectively). All patients had history of a major hemorrhagic event (BARC Score ≥3). Most patients (n = 6) showed left ventricular hypertrophy, and the average LVEF was 54% (SD ± 6.5). All devices were implanted successfully. Postprocedural antithrombotic regimen prescribed was based on antiplatelet therapy. No deaths, cardioembolic events, or major bleeding (according to the BARC scale) were reported during a mean follow‐up of 14.24 months (SD ± 9.44). Percutaneous LAAO could be of particular interest in patients with NVAF and CKD in hemodialysis. Further studies will be necessary to confirm this hypothesis.
NOP receptor antagonism reduces alcohol drinking in male and female rats through mechanisms involving the central amygdala and ventral tegmental area
Authors: Borruto Anna Maria , Fotio Yannick , Stopponi Serena , Brunori Gloria , Petrella Michele , Caputi Francesca Felicia , Romualdi Patrizia , Candeletti Sanzio , Narendran Rajesh , Rorick‐Kehn Linda M. , Ubaldi Massimo , Weiss Friedbert , Ciccocioppo Roberto 
Published: November 2019

Background and PurposeNociceptin/orphanin FQ (N/OFQ) peptide and its cognate receptor (NOP) are widely expressed in mesolimbic brain regions where they play an important role in modulating reward and motivation. Early evidence suggested that NOP receptor activation attenuates the rewarding effects of drugs of abuse, including alcohol. However, emerging data indicate that NOP receptor blockade also effectively attenuates alcohol drinking and relapse. To advance our understanding of the role of the N/OFQ‐NOP receptor system in alcohol abuse, we examined the effect of NOP receptor blockade on voluntary alcohol drinking at the neurocircuitry level.Experimental ApproachUsing male and female genetically selected alcohol‐preferring Marchigian Sardinian (msP) rats, we initially evaluated the effects of the selective NOP receptor antagonist LY2817412 (3, 10, and 30 mg·kg−1, p.o.) on alcohol consumption in a two‐bottle free‐choice paradigm. We then microinjected LY2817412 (3 and 6 μg·μl−1 per rat) in the central nucleus of the amygdala (CeA), ventral tegmental area (VTA), and nucleus accumbens (NAc).Key ResultsPeripheral LY2817412 administration dose‐dependently and selectively reduced voluntary alcohol intake in male and female msP rats. Central injections of LY2817412 markedly attenuated voluntary alcohol intake in both sexes following administration in the CeA and VTA but not in the NAc.Conclusion and ImplicationsThe present results revealed that the CeA and VTA are neuroanatomical substrates that mediate the effects of NOP receptor antagonism on alcohol consumption. Overall, our findings support the potential of NOP receptor antagonism as a treatment strategy to attenuate alcohol use and addiction.
Topography of behavior problems among children with neurodevelopmental conditions: Profile differences and overlaps
Authors: Gardiner Emily , Miller Anton R. , Lach Lucyna M. 
Published: November 2019

AbstractBackgroundThis exploratory proof of principle study examined the extent to which behavior problems represent a functional characteristic that crosses diagnostic boundaries.MethodsThis cross‐sectional study pertains to 179 caregivers of children, aged 4–13 years (M = 8.27) with cerebral palsy (n = 77), autism spectrum disorder (n = 58), and global developmental delay/intellectual disability (n = 44). Caregivers completed the Strengths and Difficulties Questionnaire, which provides a measure of conduct problems, emotional symptoms, hyperactivity‐inattention, peer problems, as well as total difficulties.ResultsBehavior problem severity differed across diagnostic groups (p < .001). Visual examination of box plots indicated substantial overlap within Strengths and Difficulties Questionnaire subscales across children with autism spectrum disorder, cerebral palsy, and global developmental delay/intellectual disability. Children within each condition demonstrated matching profile topographies, such that hyperactivity‐inattention difficulties were most severe. Repeated measures analysis of variances confirmed that children within each group received significantly higher ratings on the hyperactivity‐inattention subscale (all p < .001).ConclusionsThe approach adopted to examine the data and findings have the potential to inform how we conceptualize and study behavior problems among children with neurodevelopmental conditions. Importantly, children with particular conditions did not demonstrate unique constellations of difficulties. Clinicians must therefore be attuned to the possibility of commonality in behavior problems across children with disparate diagnoses, irrespective of syndrome‐specific expectations.
Efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia due to 21‐hydroxylase deficiency: A systematic review and meta‐analysis
Authors: Xu Lizhen , Lin Wei , Cai Liangchun , Huang Huibin , Liang Jixing , Li Liantao , Zong Liyao , Wang Nengying , Wen Junping , Chen Gang 
Published: November 2019

AbstractObjectiveTo assess the efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia.MethodsMEDLINE, EMBASE, the Cochrane Library, the clinicaltrials.gov website databases were systematically searched from inception through March 2019. WMD and SMD with 95%CIs were calculated using random or fixed effects models.ResultsThere was a significant reduction in virilization in the DEX‐treated group (WMD: −2.39, 95%CI: −3.31,‐1.47). No significant differences were found in newborn physical outcomes for birth weight (WMD: 0.09, 95%CI: −0.09, 0.27) and birth length (WMD = 0.27, 95%CI: −0.68, 1.21). Concerning cognitive functions, no significant differences in the domains of psychometric intelligence (SMD: 0.05, 95%CI: −0.74, 0.83), verbal memory (SMD: −0.17, 95%CI: −0.58, 0.23), visual memory (SMD: 0.10, 95%CI: −0.14, 0.34), learning (SMD: −0.02, 95%CI: −0.27, 0.22) and verbal processing (SMD: −0.38, 95%CI: −0.93, 0.17). Regarding behavioural problems, no significant differences in the domains of internalizing problems (SMD: 0.16, 95%CI: −0.49, 0.81), externalizing problems (SMD: 0.07, 95%CI: −0.30, 0.43) and total problems (SMD: 0.14, 95%CI: −0.23, 0.51). With respect to temperament, no significant differences in the domains of emotionality (SMD: 0.13, 95%CI: −0.79, 1.05), activity (SMD: 0.04, 95%CI: −0.32, 0.39), shyness (SMD: 0.25, 95%CI: −0.70, 1.20) and sociability (SMD: −0.23, 95%CI: −0.90, 0.44).ConclusionsPrenatal DEX treatment reduced virilization with no significant differences in newborn physical outcomes, cognitive functions, behavioural problems and temperament. The results need to be interpreted cautiously due to the existence of limitations.
Distortion of inferences and undue exaggeration of study limitations: Response to Shrotriya et al.
Authors: Majgaonkar Iravatee , Vaidyanathan Srinivas , Srivathsa Arjun , Shivakumar Shweta , Limaye Sunil , Athreya Vidya 
Published: November 2019

AbstractOur study titled “Land sharing potential of large carnivores in human‐modified landscapes of western India” used an occupancy framework to provide baseline information on patterns and determinants of large carnivore presence in human‐use landscapes. In their letter, Shrotriya et al. raise concerns about our survey design, distort our inferences, and present unwarranted exaggeration of our study limitations. Here, we provide detailed responses to key the issues raised by the authors while reiterating the accurate interpretations of our findings.