bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study
Authors: McClung Michael R , Brown Jacques P , Diez-Perez Adolfo , Resch Heinrich , Caminis John , Meisner Paul , Bolognese Michael A , Goemaere Stefan , Bone Henry G , Zanchetta Jose R , Maddox Judy , Bray Sarah , Grauer Andreas 
Published: April 2018

ABSTRACT

Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score ≤–2.0 and ≥–3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker β-CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and β-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
Evaluation of 4‐bp insertion/deletion polymorphism within the 3′UTR of SGSM3 in bladder cancer using mismatch PCR‐RFLP method: A preliminary report
Authors: Hashemi Mohammad , Bahari Gholamreza , Bizhani Fatemeh , Danesh Hiva , Sarhadi Shamim , Ziaee Seyed Amir Mohsen , Basiri Abbas , Narouie Behzad , Taheri Mohsen , Ghavami Saeid 
Published: April 2018

AbstractThe small G protein signaling modulator 3 (SGSM3) has been shown to be associated with small G‐protein‐coupled receptor signaling. There is little data regarding the impact of SGSM3 polymorphisms on cancer risk. In the present study, we aimed to evaluate the impact of 4‐bp insertion/deletion (rs56228771) polymorphism in the 3′UTR of SGSM3 and susceptibility to bladder cancer in a sample of the Iranian population. This case‐control study included 143 pathologically confirmed bladder cancer patients and 144 healthy subjects. The SGSM3 4‐bp ins/del (rs56228771) variant was determined by mismatch PCR‐RFLP. The findings showed that ins/del genotype and ins allele of SGSM3 4‐bp ins/del polymorphism significantly increased the risk of bladder cancer (OR = 3.11, 95%CI = 1.70‐5.71, P < 0.0001 and OR = 2.11, 95%CI = 1.27‐3.52, P = 0.004, respectively). Our findings support an association between 4‐bp ins/del polymorphism in the 3′UTR of SGSM3 and the risk of bladder cancer in an Iranian population. Additional studies with larger sample sizes and diverse ethnicities are warranted to establish if such an association exists in general.
Protein phosphatase 2A mediates JS‐K‐induced apoptosis by affecting Bcl‐2 family proteins in human hepatocellular carcinoma HepG2 cells
Authors: Liu Ling , Huang Zile , Chen Jingjing , Wang Jiangang , Wang Shuying 
Published: April 2018

AbstractProtein phosphatase 2A (PP2A) is an important enzyme within various signal transduction pathways. The present study was investigated PP2A mediates JS‐K‐induced apoptosis by affecting Bcl‐2 family protein. JS‐K showed diverse inhibitory effects in five HCC cell lines, especially HepG2 cells. JS‐K caused a dose‐ and time‐dependent reduction in cell viability and increased in levels of LDH release. Meanwhile, JS‐K‐ induced apoptosis was characterized by mitochondrial membrane potential reduction, Hoechst 33342+/PI+ dual staining, release of cytochrome c (Cyt c), and activation of cleaved caspase‐9/3. Moreover, JS‐K‐treatment could lead to the activation of protein phosphatase 2A‐C (PP2A‐C), decrease of anti‐apoptotic Bcl‐2 family‐protein expression including p‐Bcl‐2 (Ser70), Bcl‐2, Bcl‐xL, and Mcl‐1 as well as the increase of pro‐apoptosis Bcl‐2 family‐protein including Bim, Bad, Bax, and Bak. Furthermore, JS‐K caused a marked increase of intracellular NO levels while pre‐treatment with Carboxy‐PTIO (a NO scavenger) reduced the cytotoxicity effects and the apoptosis rate. Meanwhile, pre‐treatment with Carboxy‐PTIO attenuated the JS‐K‐induced up‐regulation of PP2A, Cyt c, and cleaved‐caspase‐9/3 activation. The silencing PP2A‐C by siRNA could abolish the activation of PP2A‐C, down‐regulation of anti‐apoptotic Bcl‐2 family‐protein (p‐Bcl‐2, Bcl‐2, Bcl‐xL, and Mcl‐1), increase of pro‐apoptosis Bcl‐2 family‐protein (Bim, Bad, Bax, and Bak) and apoptotic‐related protein (Cyt c, cleaved caspase‐9/3) that were caused by JS‐K in HepG2 cells. In addition, pre‐treatment with OA (a PP2A inhibitor) also attenuated the above effects induced by JS‐K. In summary, NO release from JS‐K induces apoptosis through PP2A activation, which contributed to the regulation of Bcl‐2 family proteins.
Human APOBEC3B interacts with the heterogenous nuclear ribonucleoprotein A3 in cancer cells
Authors: Mishra Nawneet , Reddy K Sony , Timilsina Uddhav , Gaur Deepak , Gaur Ritu 
Published: April 2018

AbstractHuman APOBEC3B (A3B), like other APOBEC3 members, is a cytosine deaminase which causes hypermutation of single stranded genome. Recent studies have shown that A3B is predominantly elevated in multiple cancer tissues and cell lines such as the bladder, cervix, lung, head and neck, and breast. Upregulation and activation of A3B in developing tumors can cause an unexpected cluster of mutations which promote cancer development and progression. The cellular proteins which facilitate A3B function through direct or indirect interactions remain largely unknown. In this study, we performed LC‐MS‐based proteomics to identify cellular proteins which coimmunoprecipitated with A3B. Our results indicated a specific interaction of A3B with hnRNP A3 (heterogeneous nuclear ribonucleoprotein). This interaction was verified by co‐immunoprecipitation and was found to be RNA‐dependent. Furthermore, A3B and hnRNP A3 colocalized as evident from immunofluorescence analysis.
Retracted: MicroRNA‐339‐3p alleviates inflammation and edema and suppresses pulmonary microvascular endothelial cell apoptosis in mice with severe acute pancreatitis‐associated acute lung injury by regulating Anxa3 via the Akt/mTOR signaling pathway
Authors: Wu Xing‐Mao , Ji Kai‐Qiang , Wang Hai‐Yuan , Zhao Yang , Jia Jia , Gao Xiao‐Peng , Zang Bin 
Published: April 2018

AbstractSevere acute pancreatitis (SAP) is a disease with a high mortality. Patients with SAP may also be complicated with acute lung injury (ALI). So far the therapy for SAP‐ALI is still limited. Emerging evidences demonstrate that microRNAs (miRs) could play a role in SAP‐ALI. This study aims to define the role of miR‐339‐3p in SAP‐ALI via Anxa3 through the Akt/mTOR signaling pathway. Ten mice were selected as sham group and 36 mice as model group which further assigned into different groups. Relationship between miR‐339‐3p and Anxa3 was detected by dual luciferase reporter gene assay. Levels of TNF‐α, IL‐6, and serum amylase (AMS) and myeloperoxidase (MPO) in lung tissues were determined by ELISA. Expression of related genes in pulmonary vascular endothelial cells (PMVECs) and lungs tissues was determined by Western blot analysis and RT‐qPCR. Cell apoptosis was detected by flow cytometry and TUNEL. SAP‐ALI mice had decreased survival rate, increased levels of TNF‐α, IL‐6, AMS, MPO, and Schmidt scores. miR‐339‐3p was poorly expressed in lung tissue of SAP‐ALI mice while Anxa3 was reciprocal. Anxa3 was targeted by miR‐339‐3p. miR‐339‐3p inhibited the relative expression of the Akt/mTOR signaling pathway‐related proteins, alleviated inflammation and edema of SAP‐ALI mice, and suppressed apoptosis of PMVECs; Anxa3 exhibited opposite trends. In conclusion, overexpressed miR‐339‐3p could suppress Anxa3 to inhibit the Akt/mTOR signaling pathway, so as to decrease tissue edema, inflammation, and PMVEC apoptosis in SAP‐ALI mice.
Comparison of transabdominal and transvaginal sonography in the diagnosis of placenta previa
Authors: Petpichetchian Chusana , Pranpanus Savitree , Suntharasaj Thitima , Kor‐anantakul Ounjai , Hanprasertpong Tharangrut 
Published: April 2018

AbstractPurposeTo compare the accuracies of transabdominal sonography (TAS) and transvaginal sonography (TVS) in the diagnosis of placenta previa.MethodsA prospective, cross‐sectional study was conducted at a university hospital. Both TAS and TVS were performed on 81 pregnant women with a suspicion of placenta previa in the third trimester. The final diagnosis was confirmed at delivery. The agreement between the two ultrasound methods and the parameters of each method were calculated.ResultsFifty‐eight percent of the women had a placenta previa. The sensitivities of TAS and TVS were 86% (95% CI 78‐94%) and 95% (95% CI 91‐100%), respectively (p= 0.2). The specificity of both methods was 93% (95 CI 88‐99%), and the overall accuracies of TAS and TVS were 89% (95% CI 82‐96%) and 94% (95% CI 89‐100%), respectively. When TAS was followed by TVS, 23% of the previous diagnoses were changed. The agreement between both methods was good (Kappa value = 0.7, 95%CI 0.55‐0.86).ConclusionsFor the diagnosis of placenta previa, TAS showed a high sensitivity and specificity, which were comparable to those of TVS
Integrating dynamic contrast‐enhanced magnetic resonance imaging and diffusion kurtosis imaging for neoadjuvant chemotherapy assessment of nasopharyngeal carcinoma
Authors: Zheng Dechun , Lai Guojing , Chen Ying , Yue Qiuyuan , Liu Xiangyi , Chen Xiaodan , Chen Weibo , Chan Queenie , Chen Yunbin 
Published: April 2018

BackgroundSince neoadjuvant chemotherapy (NAC) has proven a benefit for locally advanced nasopharyngeal carcinoma (NPC), early response evaluation after chemotherapy is important to implement individualized therapy for NPC in the era of precision medicine.PurposeTo determine the combined and independent contribution between dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and diffusion kurtosis imaging (DKI) in the early monitoring of NAC response for NPC.Study TypeProspective.PopulationFifty‐three locally advanced NPC patients.Field Strength/SequenceFour examinations before and at 4, 20, and 40 days after NAC initiation were performed at 3T MRI including DCE‐MRI and DKI (b values = 0, 500, 1000, 1500 s/mm2).AssessmentDCE‐MRI parameters (Ktrans [the volume transfer constant of Gd‐DTPA], kep [rate constant], νe [the extracellular volume fraction of the imaged tissue], and νp [the blood volume fraction]) and DKI parameters (Dapp [apparent diffusion for non‐Gaussian distribution] and Kapp [apparent kurtosis coefficient]) were analyzed using dedicated software.Statistical TestsMRI parameters and their corresponding changes were compared between responders and nonresponders after one or two NAC cycles treatment using independent‐samples Student's t‐test or Mann–Whitney U‐test depending on the normality contribution test and then followed by logistic regression and receiver operating characteristic curve (ROC) analyses.ResultsThe responder group (RG) patients presented significantly higher mean Ktrans and Dapp values at baseline and larger
, Δvp(0‐4), and ΔDapp(0‐4) values after either one or two NAC cycles compared with the nonresponder group (NRG) patients (all P < 0.05). ROC analyses demonstrated the higher diagnostic accuracy of combined DCE‐MRI and DKI model to distinguish nonresponders from responders after two NAC cycles than using DCE‐MRI (0.987 vs. 0.872, P = 0.033) or DKI (0.987 vs. 0.898, P = 0.047) alone.Data ConclusionCombined DCE‐MRI and DKI models had higher diagnostic accuracy for NAC assessment compared with either model used independently.Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;47:1208–1216.
Impact of nitrogen availability upon the electron requirement for carbon fixation in Australian coastal phytoplankton communities
Authors: Hughes David J. , Varkey Deepa , Doblin Martina A. , Ingleton Tim , Mcinnes Allison , Ralph Peter J. , van Dongen‐Vogels Virginie , Suggett David J. 
Published: April 2018

AbstractNitrogen (N) availability affects phytoplankton photosynthetic performance and regulates marine primary production (MPP) across the global coast and oceans. Bio‐optical tools including Fast Repetition Rate fluorometry (FRRf) are particularly well suited to examine MPP variability in coastal regions subjected to dynamic spatio‐temporal fluctuations in nutrient availability. FRRf determines photosynthesis as an electron transport rate through Photosystem II (ETRPSII), requiring knowledge of an additional parameter, the electron requirement for carbon fixation (KC), to retrieve rates of CO2‐fixation. KC strongly depends upon environmental conditions regulating photosynthesis, yet the importance of N‐availability to this parameter has not been examined. Here, we use nutrient bioassays to isolate how N (relative to other macronutrients P, Si) regulates KC of phytoplankton communities from the Australian coast during summer, when N‐availability is often highly variable. KC consistently responded to N‐amendment, exhibiting up to a threefold reduction and hence an apparent increase in the efficiency with which electrons were used to drive C‐fixation. However, the process driving this consistent reduction was dependent upon initial conditions. When diatoms dominated assemblages and N was undetectable (e.g., post bloom), KC decreased predominantly via a physiological adjustment of the existing community to N‐amendment. Conversely, for mixed assemblages, N‐addition achieved a similar reduction in KC through a change in community structure toward diatom domination. We generate new understanding and parameterization of KC that is particularly critical to advance how FRRf can be applied to examine C‐uptake throughout the global ocean where nitrogen availability is highly variable and thus frequently limits primary productivity.
Dynamic processing of DOM: Insight from exometabolomics, fluorescence spectroscopy, and mass spectrometry
Authors: Smith H. J. , Tigges M. , D'Andrilli J. , Parker A. , Bothner B. , Foreman C. M. 
Published: April 2018

AbstractDissolved organic matter (DOM) in freshwater environments is an important source of organic carbon, supporting bacterial respiration. Frozen environments cover vast expanses of our planet, with glaciers and ice‐sheets storing upwards of 6 petagrams of organic carbon. It is generally believed that DOM liberated from ice stimulates downstream environments. If true, glacial DOM is an important component of global carbon cycling. However, coupling the release of DOM to microbial activity is challenging due to the molecular complexity of DOM and the metabolic connectivity within microbial communities. Using a single environmentally relevant organism, we demonstrate that processing of compositionally diverse DOM occurs, but, even though glacially derived DOM is chemically labile, it is unable to support sustained respiration. In view of projected changes in glacier DOM export, these findings imply that biogeochemical impacts on downstream environments will depend on the reactivity and heterogeneity of liberated DOM, as well as the timescale.
Involvement of a host Cathepsin L in symbiont‐induced cell death
Authors: Peyer Suzanne M. , Kremer Natacha , McFall‐Ngai Margaret J. 
Published: April 2018

AbstractThe cathepsin L gene of the host squid, Euprymna scolopes, is upregulated during the first hours of colonization by the symbiont Vibrio fischeri. At this time, the symbiotic organ begins cell death‐mediated morphogenesis in tissues functional only at the onset of symbiosis. The goal of this study was to determine whether Cathepsin L, a cysteine protease associated with apoptosis in other animals, plays a critical role in symbiont‐induced cell death in the host squid. Sequence analysis and biochemical characterization demonstrated that the protein has key residues and domains essential for Cathepsin L function and that it is active within the pH range typical of these proteases. With in situ hybridization and immunocytochemistry, we localized the transcript and protein, respectively, to cells interacting with V. fischeri. Activity of the protein occurred along the path of symbiont colonization. A specific Cathepsin L, nonspecific cysteine protease, and caspase inhibitor each independently attenuated activity and cell death to varying degrees. In addition, a specific antibody decreased cell death by ~50%. Together these data provide evidence that Cathepsin L is a critical component in the symbiont‐induced cell death that transforms the host tissues from a colonization morphology to one that promotes the mature association.
Recurrence quantification analysis of radiologists' scanpaths when interpreting mammograms
Authors: Gandomkar Ziba , Tay Kevin , Brennan Patrick C. , Mello‐Thoms Claudia 
Published: April 2018

PurposeThe purpose of this study was to Propose a classifier based on recurrence quantification analysis (RQA) metrics for distinguishing experts' scanpaths from those of less‐experienced readers and to explore the association of spatiotemporal dynamics of the mammographic scanpaths with the characteristics of cases and radiologists usingRQAmetrics.Materials and methodsEye movements were recorded from eight radiologists (two cohorts: four experienced and four less‐experienced) while reading 120 mammograms (59 cancer, 61 normal). TenRQAmeasures were extracted for each recorded scanpath. The measures described the temporal distribution of recurrent fixations as well as laminar and deterministic eye movements. Recurrent fixations are fixations that are located close to a previously fixated point in a scanpath. Deterministic eye movements represent looking back and forth between two locations, while laminar eye movements indicate detailed scanning of an area with consecutive fixations. TheRQAmetrics along with six conventional eye‐tracking parameters were used to construct a classifier for distinguishing experts' scanpaths from those of less‐experienced readers. Leave‐one‐out cross validation was used for evaluating the classifier. For each reader cohort, theANOVAanalysis was done to study the relationship ofRQAmeasures with breast density, case pathology, readers' expertise, and readers' decisions on the case. The proportions of laminar and deterministic movements involved fixations in the location of lesions were also compared for two reader cohorts using two proportion z‐tests.ResultsAllRQAmeasures differed significantly between scanpaths of experienced readers and those of less‐experienced readers. The classifier achieved an area under the receiver operating characteristic curve of 0.89 (0.87–0.91) for detecting experts' scanpaths. Proportionately more refixations and laminar and deterministic sequences were in the location of the lesion for the experienced cohort compared to the less‐experienced cohort (allP‐values < 0.001). Eight and fourRQAmeasures differed between normal and cancer cases for the experienced and less experienced readers, respectively. None of metrics differed between fatty and dense breasts for the less experienced readers, while two measures resulted into a significant difference for the experienced readers. For experts, six measures differed significantly between true negatives and false positives and nine were significantly different between true positives and false negatives. For the less‐experienced cohort, the corresponding figures were seven and one measures, respectively.ConclusionTheRQAmeasures can quantify the differences among experienced and less experienced radiologists. They also capture differences among experts' scanpaths related to case pathology and radiologists' decisions on the case.
Effect of radiation protraction in hypofractionated radiotherapy
Authors: Kuperman Vadim Y. 
Published: April 2018

PurposeTo evaluate how protracted delivery of radiation affects radiobiological properties of hypofractionated radiotherapy.MethodsThe utilized approach is based on the concept of biologically effective dose (BED). The linear‐quadratic model replete with a protraction factor is used to describe changes in biologically effective dose in normal tissue (BEDnt) caused by varying number of fractions under the condition of fixed BED in the treatment target (BEDtar). In the derivations, we study the influence of fraction time (T) and associated repair of sublethal damage of irradiated cells on BEDnt.ResultsWe have analytically derived conditions under which hypofractionation lowers BEDnt, in a parallel or serial organ at risk (OAR) in the presence of radiation protraction, as compared to standard fractionation. In the considered examples, maximum value of BEDnt in the spinal cord decreased with decreasing number of fraction when T was relatively short (e.g., T = 5 min). In contrast, in the case of long fraction times of 30 and 45 min, maximum BEDnt in the cord increased with decreasing number of fractions. In the case of lung cancer, the average BEDnt in the lung increased with decreasing number of fractions. The maximum increase in BEDnt varied between 4% for T = 1 min and 19% for T = 22 min.ConclusionIn the case when repair of sublethal damage occurs faster in the target than in the affected OAR, shortening fraction time helps lower BEDnt in hypofractionated regimen as compared to standard fractionation. In contrast, in the case when repair rate is higher in the OAR than in the target, long fraction times can be radiobiologically beneficial for hypofractionated radiotherapy. Consequently, comparison of different fractionation schemes should take into account both repair rates in the target and OAR, and fraction time.