bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of miRNA‐141 in breast cancer cells is associated with cell migration and invasion: involvement of ANP32E targeting
Authors: Li Ping , Xu Tao , Zhou Xin , Liao Liangying , Pang Guolian , Luo Wan , Han Lu , Zhang Jiankun , Luo Xianyong , Xie Xiaobing , Zhu Kuichun 
Published: February 2017

AbstractMicroRNAs (miRNAs) regulate many cellular activities, including cancer development, progression, and metastasis. Some miRNAs are involved in breast cancer (BC) migration and invasion, thus affect patients’ prognosis. Microarray analysis was performed to compare miRNA expression in BC tissues, and results confirmed by qPCR. BC cell migration and invasion were studied in vitro with MDA‐MB‐231 cells using microplate transwell assays. miRNA targeting was investigated using luciferase assays, qPCR, and Western blot analysis in cells with overexpression of miRNA mimics. Knockdown of miRNA targets was performed using target siRNA lentiviral infection. Results show that microRNA‐141 (miR‐141) was downregulated in breast cancer tumor tissues compared with matched surrounding tissues. Downregulation of miR‐141 expression correlated with tumor stage, lymph node involvement, and expressions of PCNA, Ki67, and HER2. Overexpression of miR‐141 inhibited BC cell proliferation, migration, and invasion in vitro. ANP32E gene was selected as one putative target for further studies based on results from in silico analysis. Results from a dual‐luciferase reporter system suggested ANP32E as a direct target of miR‐141. Overexpression of miR‐141 downregulated ANP32E expression at both mRNA and protein levels in BC cells. Knockdown of ANP32E inhibited BC cell proliferation, migration, and invasion in vitro, mimicking the effect of the overexpression of miR‐141. Our study revealed important roles miR‐141 plays in BC growth and metastasis. Moreover, for the first time, we identified ANP32E as one of the miR‐141 targets, and demonstrated its involvement in the regulation of cell proliferation, migration, and invasion.
Diagnostic approach using ERCP‐guided transpapillary forceps biopsy or EUS‐guided fine‐needle aspiration biopsy according to the nature of stricture segment for patients with suspected malignant biliary stricture
Authors: Lee Yun Nah , Moon Jong Ho , Choi Hyun Jong , Kim Hee Kyung , Choi Seo‐Youn , Choi Moon Han , Lee Tae Hee , Lee Tae Hoon , Cha Sang‐Woo , Park Sang‐Heum 
Published: February 2017

AbstractIn malignant biliary stricture (MBS), the diagnostic accuracy of ERCP‐based tissue sampling is insufficient. EUS‐guided fine needle aspiration biopsy (EUS‐FNAB) is emerging as a reliable diagnostic procedure. This study aimed to evaluate the usefulness of a diagnostic approach using ERCP‐guided transpapillary forceps biopsy (TPB) or EUS‐FNAB according to the characteristics of suspected MBS. Consecutive patients diagnosed with suspected MBS with obstructive jaundice and/or cholangitis were enrolled prospectively. ERCP with intraductal ultrasonography (IDUS) and TPB were performed as initial diagnostic procedures. Based on the results of imaging studies and IDUS, all MBS were classified as extrinsic or intrinsic type. If the malignancy was not confirmed by TPB, EUS‐FNAB for extrinsic type or second TPB for intrinsic type was performed. Among a total of 178 patients, intrinsic and extrinsic types were detected in 88 and 90 patients, respectively. The diagnostic accuracy of first TPB was significantly higher in the intrinsic than in the extrinsic type (81.8% vs. 67.8, P = 0.023). In 33 patients with extrinsic type and negative for malignancy on first TPB, the diagnostic accuracy of EUS‐FNAB was 90.9%. In 19 patients with intrinsic type and negative for malignancy on first TPB, the diagnostic accuracy of second TPB was 84.2%. The diagnostic accuracies of the combination of initial TPB with EUS‐FNAB and second TPB were 96.7% and 96.6%, respectively. A diagnostic approach using EUS‐FNAB or TPB according to the origin of MBS is considered effective to improve the diagnostic accuracy of MBS with negative for malignancy on first TPB. (Clinical trial registration number: UMIN000016886).
Contextual Risk, Individualised Responses: An Assessment of Safeguarding Responses to Nine Cases of Peer‐on‐Peer Abuse
Authors: Firmin Carlene 
Published: February 2017

Practitioners, academics and policymakers are increasingly questioning the sufficiency of safeguarding practice in protecting young people from peer‐on‐peer abuse in England. Using the findings from an in‐depth analysis of nine cases where young people either raped or murdered their peers, this article explores approaches to assessing and intervening with those affected by peer‐on‐peer abuse. Building upon international calls for a contextual account of abuse between young people, the article identifies a professional struggle to address the interplay between young people's homes and the public and social spaces in which peer‐on‐peer abuse often manifests. Findings from this study are used to illuminate wider research into peer‐on‐peer abuse which has indicated a professional inability to: assess young people's behaviours with reference to the contexts in which they occur; change the environmental factors that influence abusive behaviours; and recognise the vulnerability of those who abuse their peers. The article concludes that to effectively respond to peer‐on‐peer abuse, multiagency partnerships are required which can identify, assess and intervene with the harmful norms in peer groups, schools and public spaces that can facilitate peer‐on‐peer abuse and undermine parental capacity to keep young people safe – thereby adopting a more contextual approach to safeguarding adolescents. Copyright © 2017 John Wiley & Sons, Ltd.‘Explores approaches to assessing and intervening with those affected by peer‐on‐peer abuse’Key Practitioner Messages

Social contexts such as peer groups, schools and neighbourhoods can make young people vulnerable to peer‐on‐peer abuse.
Assessing and intervening with young people and families affected by peer‐on‐peer abuse will not impact upon the social contexts associated with the phenomenon.
Multiagency partnerships need to intervene with social contexts that, albeit beyond the traditional remit of child protection, facilitate peer‐on‐peer abuse and undermine the capacity of parents to keep young people safe.
‘Social contexts such as peer groups, schools and neighbourhoods can make young people vulnerable to peer‐on‐peer abuse’
Diagnosis of myxedema coma complicated by renal failure: a case report
Authors: Takamura Akiteru , Sangen Ryusho , Furumura Yoshiki , Usuda Daisuke , Kasamaki Yuji , Kanda Tsugiyasu 
Published: February 2017

Key Clinical MessageMyxedema coma, caused by severe lack of thyroid hormone, is characterized by deterioration of mental status, hypothermia, hypotension, hyponatremia, and hypoventilation. We describe an 84‐year‐old woman who presented with renal failure and new onset severe hypothyroidism leading to challenges in the recognition of myxedema coma.
Crazy paving pattern
Authors: Verma Rajanshu , Abdoh Mamoun 
Published: February 2017

Key Clinical MessageCrazy paving pattern is the name given to characteristic polygonal pattern of interlobular thickening on computed tomography (CT scan) of the lung, which results from accumulation of collagen, interstitial fluid, cell, or other pathology and may be seen in multiple clinical conditions including metastatic cancer as described in this case.
Separating Thermodynamics from Kinetics—A New Understanding of the Transketolase Reaction
Authors: Marsden Stefan R. , Gjonaj Lorina , Eustace Stephen J. , Hanefeld Ulf 
Published: February 2017

AbstractTransketolase catalyzes asymmetric C−C bond formation of two highly polar compounds. Over the last 30 years, the reaction has unanimously been described in literature as irreversible because of the concomitant release of CO2 if using lithium hydroxypyruvate (LiHPA) as a substrate. Following the reaction over a longer period of time however, we have now found it to be initially kinetically controlled. Contrary to previous suggestions, for the non‐natural conversion of synthetically more interesting apolar substrates, the complete change of active‐site polarity is therefore not necessary. From docking studies it was revealed that water and hydrogen‐bond networks are essential for substrate binding, thus allowing aliphatic aldehydes to be converted in the charged active site of transketolase.
Enzyme‐Controlled Nanodevice for Acetylcholine‐Triggered Cargo Delivery Based on Janus Au–Mesoporous Silica Nanoparticles
Authors: Llopis‐Lorente Antoni , Díez Paula , de la Torre Cristina , Sánchez Alfredo , Sancenón Félix , Aznar Elena , Marcos María D. , Martínez‐Ruíz Paloma , Martínez‐Máñez Ramón , Villalonga Reynaldo 
Published: February 2017

AbstractThis work reports a new gated nanodevice for acetylcholine‐triggered cargo delivery. We prepared and characterized Janus Au–mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular β‐cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme‐mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies.
Novel Pieces for the Emerging Picture of Sulfoximines in Drug Discovery: Synthesis and Evaluation of Sulfoximine Analogues of Marketed Drugs and Advanced Clinical Candidates
Authors: Sirvent Juan Alberto , Lücking Ulrich 
Published: February 2017

AbstractSulfoximines have gained considerable recognition as an important structural motif in drug discovery of late. In particular, the clinical kinase inhibitors for the treatment of cancer, roniciclib (pan‐CDK inhibitor), BAY 1143572 (P‐TEFb inhibitor), and AZD 6738 (ATR inhibitor), have recently drawn considerable attention. Whilst the interest in this underrepresented functional group in drug discovery is clearly on the rise, there remains an incomplete understanding of the medicinal‐chemistry‐relevant properties of sulfoximines. Herein we report the synthesis and in vitro characterization of a variety of sulfoximine analogues of marketed drugs and advanced clinical candidates to gain a better understanding of this neglected functional group and its potential in drug discovery.
Prognostic methylation markers for overall survival in cytogenetically normal patients with acute myeloid leukemia treated on SWOG trials
Authors: Qu Xiaoyu , Othus Megan , Davison Jerry , Wu Yu , Yan Liying , Meshinchi Soheil , Ostronoff Fabiana , Estey Elihu H. , Radich Jerry P. , Erba Harry P. , Appelbaum Frederick R. , Fang Min 
Published: February 2017

BACKGROUNDAberrant DNA methylation is known to occur in patients with acute myeloid leukemia (AML), whereas methylation signatures and prognostic markers have been proposed. The objective of the current study was to evaluate all CpG sites of the genome and identify prognostic methylation markers for overall survival in patients with AML with normal karyotype (AML‐NK).METHODSAML‐NK samples from 7 SWOG trials were analyzed using a novel genome‐wide approach called “CHARMcox” (comprehensive high‐throughput array‐based relative methylation analysis combined with the Cox proportional hazards model) controlling for known clinical covariates. CHARMcox was applied to a phase 1 discovery cohort (72 patients) to identify survival‐associated methylation regions (SAMRs). Subsequently, using bisulfite pyrosequencing, SAMRs were studied in phase 2 model‐building (65 patients) and phase 3 validation (65 patients) cohorts. An independent external cohort from The Cancer Genome Atlas (TCGA) AML study (LAML) was used for further validation (93 patients).RESULTSTwo SAMRs, located at the CpG island shores of leucine zipper tumor suppressor 2 (LZTS2) and nuclear receptor subfamily 6 group a member 1 (NR6A1), respectively, were identified. Multivariable analyses demonstrated that hypomethylation of either LZTS2 or NR6A1 was associated with worse overall survival in the SWOG cohort (P<.001). The prognosis was validated in patients with AML‐NK from the TCGA‐LAML cohort. Methylation values below the median at both markers predicted worse overall survival (SWOG: hazard ratio, 1.89 [P<.001]; and TCGA‐LAML: hazard ratio, 2.08 [P=.006]). The C‐statistic was 0.71 for both cohorts, and the impact was independent of the Fms‐related tyrosine kinase 3 internal tandem duplication (FLT3‐ITD) status.CONCLUSIONSThe 2 methylation markers, measurable by clinically applicable assays such as bisulfite pyrosequencing, are promising for risk stratification among patients with AML‐NK. Cancer 2017;123:2472–81. © 2017 American Cancer Society.
Longitudinal follow‐up of adult survivors of Ewing sarcoma: A report from the Childhood Cancer Survivor Study
Authors: Marina Neyssa M. , Liu Qi , Donaldson Sarah S. , Sklar Charles A. , Armstrong Gregory T. , Oeffinger Kevin C. , Leisenring Wendy M. , Ginsberg Jill P. , Henderson Tara O. , Neglia Joseph P. , Stovall Marilyn A. , Yasui Yutaka , Randall R. Lor , Geller David S. , Robison Leslie L. , Ness Kirsten K. 
Published: February 2017

BACKGROUNDEwing sarcoma survivors (ESSs) are at increased risk for treatment‐related complications. The incidence of treatment‐related morbidity and late mortality with aging is unknown.METHODSThis study reports survival probabilities, estimated with the Kaplan‐Meier method, and the cumulative incidence of cause‐specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03).RESULTSAmong 404 5‐year ESSs (median age at last follow‐up, 34.8 years; range, 9.1‐54.8 years), the 35‐year survival rate was 70% (95% CI, 66%‐74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment‐related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1‐715.9) for osteosarcoma, 28.9 (95% CI, 3.2‐104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9‐25.5) for breast cancer, and 13.1 (95% CI, 4.8‐28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8‐25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4‐2.3). Thirty‐five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%‐88.8%) and 73.8% (95% CI, 67.8%‐79.9%), respectively.CONCLUSIONSWith extended follow‐up, ESSs' risk for late mortality and SNs does not plateau. Treatment‐related chronic conditions develop years after therapy, and this supports the need for lifelong follow‐up. Cancer 2017;123:2551–60. © 2017 American Cancer Society.
Breast cancer prevention strategies in lobular carcinoma in situ: A decision analysis
Authors: Wong Stephanie M. , Stout Natasha K. , Punglia Rinaa S. , Prakash Ipshita , Sagara Yasuaki , Golshan Mehra 
Published: February 2017

BACKGROUNDWomen diagnosed with lobular carcinoma in situ (LCIS) have a 3‐fold to 10‐fold increased risk of developing invasive breast cancer. The objective of this study was to evaluate the life expectancy (LE) and differences in survival offered by active surveillance, risk‐reducing chemoprevention, and bilateral prophylactic mastectomy among women with LCIS.METHODSA Markov simulation model was constructed to determine average LE and quality‐adjusted LE (QALE) gains for hypothetical cohorts of women diagnosed with LCIS at various ages under alternative risk‐reduction strategies. Probabilities for invasive breast cancer, breast cancer‐specific mortality, other‐cause mortality and the effectiveness of preventive strategies were derived from published studies and from the National Cancer Institute's Surveillance, Epidemiology, and End Results database.RESULTSAssuming a breast cancer incidence from 1.02% to 1.37% per year under active surveillance, a woman aged 50 years diagnosed with LCIS would have a total LE of 32.78 years and would gain 0.13 years (1.6 months) in LE by adding chemoprevention and 0.25 years (3.0 months) in LE by adding bilateral prophylactic mastectomy. After quality adjustment, chemoprevention resulted in the greatest QALE for women ages 40 to 60 years at LCIS diagnosis, whereas surveillance remained the preferred strategy for optimizing QALE among women diagnosed at age 65 years and older.CONCLUSIONSIn this model, among women with a diagnosis of LCIS, breast cancer prevention strategies only modestly affected overall survival, whereas chemoprevention was modeled as the preferred management strategy for optimizing invasive disease‐free survival while prolonging QALE form women younger than 65 years. Cancer 2017;123:2609‐17. © 2017 American Cancer Society.
The Role of Quality Management & Innovativeness on Green Performance
Authors: Pipatprapa Anirut , Huang Hsiang‐Hsi , Huang Ching‐Hsu 
Published: February 2017

AbstractRecently, many firms have been focusing on sustainable manufacturing. The manager has to understand the social requirement of concern for environmental protection. This study develops a model to enhance the understanding of how market orientation, quality management, and innovativeness assist Thailand's food industry in attaining its optimal green performance, and to assess the mediating effect of quality management and innovativeness on market orientation and green performance. A questionnaire was developed and employed to gather data from 178 managers in the food industry. Data analysis is performed using the structural equation modelling approach. The results indicate that market orientation, quality management, and innovativeness positively and significantly affect green performance, both directly and indirectly. Moreover, quality management and innovativeness have a partial mediator effect on market orientation and green performance. This finding illustrates that Thailand's food industry could achieve green performance by developing market‐driven, quality management capacity and innovation development. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Biological embedding of perinatal social relationships in infant stress reactivity
Authors: Thomas Jenna C. , Letourneau Nicole , Bryce Crystal I. , Campbell Tavis S. , Giesbrecht Gerald F. ,   The APrON Study Team
Published: February 2017

AbstractWhereas significant advances have been made in understanding how exposure to early adversity “gets under the skin” of children to result in long term changes in developmental outcomes, the processes by which positive social relationships become biologically embedded remain poorly understood. The aim of this study was to understand the pathways by which maternal and infant social environments become biologically embedded in infant cortisol reactivity. Two hundred seventy‐two pregnant women and their infants were prospectively assessed during pregnancy and at 6 months postpartum. In serial mediation analyses, higher perceived social support from partners during pregnancy was associated with lower infant cortisol reactivity or larger decreases in cortisol in response to a stressor at 6 months of age via lower self‐reported prenatal maternal depression and higher mother–infant interaction quality. The findings add to our understanding of how perinatal social relationships become biologically embedded in child development.
Fire history in a western Fennoscandian boreal forest as influenced by human land use and climate
Authors: Rolstad Jørund , Blanck Ylva‐li , Storaunet Ken Olaf 
Published: February 2017

AbstractKnowing the historical variation in fire regimes is instrumental in managing forests today and in predicting what may happen in the future. By cross‐dating 745 fire scars in 378 samples of remnant Scots pines, we delineated 254 individual forest fires during the past 700 years in a 74‐km2 section of Trillemarka‐Rollagsfjell Nature Reserve in south‐central Norway. Fire sizes, numbers, burn rates, and frequencies were compared with historical climate proxies, vegetation maps, and written sources. The results revealed patterns consistent with a predominantly climate‐driven fire regime up to 1625, followed by periods of strong anthropogenic influence that increased fire frequency during 1600–1700s and diminished fires during 1800–1900s. This was documented by an abrupt increase in number of small fires from the early 1600s that markedly shortened fire intervals from a median of 73 to 37 yr. This shift in fire frequency coincided with a sudden appearance of early‐season fires from 1625 and onward. Whereas late‐season burn rate increased with summer temperature, no such relationship was found for early‐season fires. These results were corroborated by written sources that describe anthropogenic forest fires and slash‐and‐burn cultivation expanding with the increasing population from the late 1500s and subsequently diminishing due to increasing timber values during 1700–1800s. Whereas human activity strongly influenced the fire regime at multidecadal to centennial scales, it was the interannual variability in climate that triggered large fire events, especially during the pre‐1625 period. Prior to 1625, the percentage of years with fire tripled from 7% during cold summers (10–12°C) to 21% during warm summers (14–16°C). Burn rate increased even more, from 0.01% to 1.3% for the same temperature intervals. Ecologically, the post‐1625 period is remarkable in such a way that human activity, first by greatly increasing fire frequency and subsequently almost eradicating fires, possibly influenced the fire regime to such an extent that it may be unprecedented for millennia.
The International Long Term Ecological Research Network: a platform for collaboration
Authors: Vanderbilt Kristin , Gaiser Evelyn 
Published: February 2017

AbstractMany scientists around the world became interested in the U.S. Long Term Ecological Research (U.S. LTER) Network's research model during the 1990s and began to develop LTER and Long Term Socio‐ecological Research networks in their own countries. These local networks, including the U.S. LTER Network, were loosely federated in 1993 to form the International Long Term Ecological Research (ILTER) Network, a “network of networks.” Although the first 10 yr of ILTER Network activities were largely supported by funds from the U.S. National Science Foundation, the ILTER Network had transformed into a robust, self‐sustaining entity by 2006 following a two‐year strategic planning process. The goal of the ILTER Network is to improve understanding of how pressures such as climate change and land use affect global ecosystems in order to inform solutions to current and future environmental problems. To fulfill this mission, the ILTER Network fosters collaborations among member scientists to extend the scope of their research across disciplinary boundaries and across more of the ILTER's 600+ research sites. The ILTER Network also has many long‐term data sets that are freely available for use by students, scientists, and policymakers all over the world. In this collection of papers, we consider how the ILTER Network has been, and will be, leveraged by U.S. researchers to advance understanding of ecological and socio‐ecological systems around the globe.