bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of FOCUS‐GC: Framework for Outcomes of Clinical Communication Services in Genetic Counseling
Authors: Cragun Deborah , Zierhut Heather 
Published: October 2017

AbstractConceptual frameworks bring together existing theories and models in order to identify, consolidate, and fill in gaps between theory, practice, and evidence. Given the vast number of possible outcomes that could be studied in genetic counseling, a framework for organizing outcomes and postulating relationships between communication services and genetic counseling outcomes was sought. Through an iterative approach involving literature review, thematic analysis, and consolidation, outcomes and processes were categorized to create and define components of a conceptual framework. The final product, “Framework for Outcomes of Clinical commUnication Services” (FOCUS) contains the following domains: communication strategy; communication process measures; patient care experience, patient changes, patient health; and family changes. A website was created to allow easier access and ongoing modifications to the framework. In addition, a step‐by‐step guide and two examples were created to show flexibility in how the framework can be used. FOCUS may help in conceptualizing, organizing and summarizing outcomes research related to risk communication and counseling in genetic service delivery as well as other healthcare settings.
Prenatal Diagnosis of a 20 Mb Terminal Fetal 4q-Deletion in the Cytoband q33q35.2 Inherited from the Mother
Authors: Seneesh K. V. , Chandra Vipin , Balakrishnan Bijoy , Batra Meenu , Sreeja R. , Patil Swapneel , Kannoly Gopinathan 
Published: October 2017

AbstractThe authors present a case of prenatally diagnosed fetal terminal 4q deletion in the cytoband 4q33q35.2, inherited from the mother. The index pregnancy was referred at 28+2 weeks of gestation for polyhdramnios. Prior to performing the scan, distinctive facial features were noted in the mother. Target scan confirmed polyhdramnios, and revealed fetal retrognathia. The fetal karyotype reported a terminal 4q33>ter deletion, which was further delineated by chromosomal microarray analysis. Subsequently, maternal karyotype revealed identical deletion. Subtle fetal ultrasound abnormalities should receive meticulous assessment, and evaluation using the currently available wide range of cytogenetic and molecular gene tests.
Ribosome Profiling Reveals Genome-Wide Cellular Translational Regulation Upon Heat Stress in Escherichia Coli
Authors: Zhang Yanqing , Xiao Zhengtao , Zou Qin , Fang Jianhuo , Wang Qifan , Yang Xuerui , Gao Ning 
Published: October 2017

Abstract
Heat shock response is a classical stress-induced regulatory system in bacteria, characterized by extensive transcriptional reprogramming. To compare the impact of heat stress on the transcriptome and translatome in Escherichia coli, we conducted ribosome profiling in parallel with RNA-Seq to investigate the alterations in transcription and translation efficiency when E. coli cells were exposed to a mild heat stress (from 30 °C to 45 °C). While general changes in ribosome footprints correlate with the changes of mRNA transcripts upon heat stress, a number of genes show differential changes at the transcription and translation levels. Translation efficiency of a few genes that are related to environment stimulus response is up-regulated, and in contrast, some genes functioning in mRNA translation and amino acid biosynthesis are down-regulated at the translation level in response to heat stress. Moreover, our ribosome occupancy data suggest that in general ribosomes accumulate remarkably in the starting regions of ORFs upon heat stress. This study provides additional insights into bacterial gene expression in response to heat stress, and suggests the presence of stress-induced but yet-to-be characterized cellular regulatory mechanisms of gene expression at translation level.
The Relationship Between Sacral Slope and Symptomatic Isthmic Spondylolysis in a Cohort of High School Athletes: A Retrospective Analysis
Authors: Hanke Leigh F. , Tuakli‐Wosornu Yetsa A. , Harrison Julian R. , Moley Peter J. 
Published: October 2017

AbstractBackgroundSpondylolysis with and without anterolisthesis is the most common cause of structural back pain in children and adolescents, but few predictive factors have been confirmed. An association between abnormal sacropelvic orientation and both spondylolysis and spondylolisthesis has been supported in the literature. Sacral slope and other sacropelvic measurements are easily accessible variables that could aid clinicians in assessing active adolescents with low back pain, particularly when the diagnosis of spondylolysis is suspected.ObjectiveTo examine the relationship between sacral slope and symptomatic spondylolysis in a cohort of active adolescents.DesignCase‐control retrospective study.SettingAcademic outpatient physiatry practice.PatientsSeventy‐four patients of primarily adolescent age (between 12 and 22 years old) with a chief complaint of low back pain and presence of lateral radiographs of the lumbar spine were enrolled. Cases (n = 37) were defined as subjects with evidence of spondylolysis on both radiograph and magnetic resonance imaging of the lumbar spine. Controls (n = 37) were defined as subjects without spondylolysis.MethodsUsing a single sagittal radiograph, taken with the patient standing, a fellowship‐trained interventional spine physiatrist measured the sacral slope of each subject (angle between the superior plate of S1 and a horizontal reference on sagittal imaging of the lumbosacral spine). Ages and genders were collected from medical records.Main Outcome MeasurementsThe primary outcome was mean sacral slope. Mean sacral slope of cases was compared with mean sacral slope of controls with the Student t‐test.ResultsAges ranged from 12 to 22 for both groups, with no significant differences in age between the groups (cases: 16.8 ± 2.3 years; controls: 17.7 ± 2.7 years). The patients with spondylolysis (cases) consisted of 29 male and 8 female patients, whereas those without spondylolysis (controls) consisted of 15 male and 21 female patients (gender details for 1 patient were not available). The mean sacral slope among cases was 42.4°, whereas the mean sacral slope among controls was 37.4°. The difference achieved significance (P = .014).ConclusionsThe interdependence of positional parameters, such as sacral slope, with anatomic parameters, such as pelvic incidence, can affect lumbar lordosis and therefore upright positioning and loading of the spine. Sacral slope may be an important variable for clinicians to consider when caring for young athletes with low back pain, particularly when the index of suspicion for spondylolysis is high.Level of EvidenceIV
Consumption of kiwifruit capsules increasesFaecalibacterium prausnitziiabundance in functionally constipated individuals: a randomised controlled human trial
Authors: Blatchford Paul , Stoklosinski Halina , Eady Sarah , Wallace Alison , Butts Christine , Gearry Richard , Gibson Glenn , Ansell Juliet 
Published: October 2017

AbstractThis study investigated the impact of ACTAZIN™ green (2400 and 600 mg) and Livaux™ (2400 mg) gold kiwifruit supplements on faecal microbial composition and metabolites in healthy and functionally constipated (FC) participants. The participants were recruited into the healthy group (n20; one of whom did not complete the study) and the FC group (n9), each of whom consumed all the treatments and a placebo (isomalt) for 4 weeks in a randomised cross-over design interspersed with 2-week washout periods. Modification of faecal microbiota composition and metabolism was determined by 16S rRNA gene sequencing and GC, and colonic pH was calculated using SmartPill®wireless motility capsules. A total of thirty-two taxa were measured at greater than 1 % abundance in at least one sample, ten of which differed significantly between the baseline healthy and FC groups. Specifically, Bacteroidales andRoseburiaspp. were significantly more abundant (P< 0·05) in the healthy group and taxa including Ruminococcaceae,Doreaspp. andAkkermansiaspp. were significantly more abundant (P< 0·05) in the FC group. In the FC group,Faecalibacterium prausnitziiabundance significantly increased (P= 0·024) from 3·4 to 7·0 % following Livaux™ supplementation, with eight of the nine participants showing a net increase. Lower proportions ofF. prausnitziiare often associated with gastrointestinal disorders. The discovery that Livaux™ supplementation increasedF. prausnitziiabundance offers a potential strategy for improving gut microbiota composition, asF. prausnitziiis a butyrate producer and has also been shown to exert anti-inflammatory effects in many studies.
The level of caveolin-1 expression determines response to TGF-β as a tumour suppressor in hepatocellular carcinoma cells
Authors: Moreno-Càceres Joaquim , Caballero-Díaz Daniel , Nwosu Zeribe Chike , Meyer Christoph , López-Luque Judit , Malfettone Andrea , Lastra Raquel , Serrano Teresa , Ramos Emilio , Dooley Steven , Fabregat Isabel 
Published: October 2017

AbstractHepatocellular carcinoma (HCC) is a heterogeneous tumour associated with poor prognostic outcome. Caveolin-1 (CAV1), a membrane protein involved in the formation of caveolae, is frequently overexpressed in HCC. Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine having a dual role in hepatocarcinogenesis: inducer of apoptosis at early phases, but pro-tumourigenic once cells acquire mechanisms to overcome its suppressor effects. Apoptosis induced by TGF-β is mediated by upregulation of the NADPH oxidase NOX4, but counteracted by transactivation of the epidermal growth factor receptor (EGFR) pathway. Previous data suggested that CAV1 is required for the anti-apoptotic signals triggered by TGF-β in hepatocytes. Whether this mechanism is relevant in hepatocarcinogenesis has not been explored yet. Here we analysed the TGF-β response in HCC cell lines that express different levels of CAV1. Accordingly, stable CAV1 knockdown or overexpressing cell lines were generated. We demonstrate that CAV1 is protecting HCC cells from TGF-β-induced apoptosis, which attenuates its suppressive effect on clonogenic growth and increases its effects on cell migration. Downregulation of CAV1 in HLE cells promotes TGF-β-mediated induction of the pro-apoptotic BMF, which correlates with upregulation of NOX4, whereas CAV1 overexpression in Huh7 cells shows the opposite effect. CAV1 silenced HLE cells show attenuation in TGF-β-induced EGFR transactivation and activation of the PI3K/AKT pathway. On the contrary, Huh7 cells, which do not respond to TGF-β activating the EGFR pathway, acquire the capacity to do so when CAV1 is overexpressed. Analyses in samples from HCC patients revealed that tumour tissues presented higher expression levels of CAV1 compared with surrounding non-tumoural areas. Furthermore, a significant positive correlation among the expression of CAV1 and TGFB1 was observed. We conclude that CAV1 has an essential role in switching the response to TGF-β from cytostatic to tumourigenic, which could have clinical meaning in patient stratification.
DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway
Authors: Sun Xi , Li Bo , Xie Bingqian , Xu Zhijian , Chang Gaomei , Tao Yi , Zhang Yong , Chang Shuaikang , Wang Yingcong , Yu Dandan , Xie Yongsheng , Li Tingye , Wang Houcai , Chen Gege , Hu Liangning , Hou Jun , Zhang Yiwen , Xiao Wenqin , Gao Lu , Shi Jumei , Zhu Weiliang 
Published: October 2017

AbstractDiffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, characterized by a rapidly increasing painless mass. A novel compound, DCZ3301, was synthesized that exerted direct cytotoxicity against DLBCL cell lines. The effects of DCZ3301 on DLBCL cells in vitro and in vivo and the associated mechanisms were investigated. DCZ3301 inhibited the viability of DLBCL cell lines, even in the presence of protumorigenesis cytokines. Additionally, the compound induced apoptosis and cell cycle arrest at the G2/M phase by reducing mitochondrial membrane potential. DCZ3301 exerted an antitumor effect through modulation of Akt, extracellular signal-regulated kinases 1/2 (ERK1/2) and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. Furthermore, DCZ3301 downregulates STAT3 phosphorylation by inhibiting Lck/Yes-related novel protein tyrosine kinase (Lyn) activation in DLBCL. A synergistic cytotoxic effect on DLBCL cells was observed upon combination of DCZ3301 with panobinostat. In vivo, intraperitoneal injection of xenograft mice with DCZ3301 resulted in reduced tumor volume. Our preliminary results collectively support the utility of the small-molecule inhibitor DCZ3301 as an effective novel therapeutic option for DLBCL that requires further clinical evaluation.
The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinoma
Authors: Chen Shuo , Wu Dan-Dan , Sang Xiu-Bo , Wang Li-Li , Zong Zhi-Hong , Sun Kai-Xuan , Liu Bo-Liang , Zhao Yang 
Published: October 2017

AbstractHighly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA), which has recently been identified as a key regulator in the progression of hepatocellular carcinoma, gliomas and gastric cancer. However, its role in epithelial ovarian carcinoma (EOC) remains unknown. In this study, HULC expression was examined in EOC, borderline and benign ovarian tumors, and normal ovarian tissues by RT-PCR. Ovarian cancer cell phenotypes, as well as autophagy-associated proteins were examined after HULC overexpression or downregulation by plasmid or small interfering RNA (siRNA) transfection, respectively. LncRNA–protein interactions were examined by ribonucleoprotein immunoprecipitation (RIP) assays. We found that HULC expression levels were higher in EOC tissues than normal samples. HULC overexpression induced cell proliferation, migration, invasion, whereas reduced cell apoptosis in vitro and induced tumor growth in vivo. In contrast, downregulation of HULC by siRNA transfection reduced cell proliferation, migration and invasion, and induced cell apoptosis and autophagy. Our results showed that HULC overexpression reduced ATG7, LC3-II and LAMP1 expression, while inducing SQSTM1 (P62) and ITGB1 expression. HULC downregulation had the opposite effects. Furthermore, RIP indicated that ATG7 interacted with HULC; ATG7 downregulation also induced cell proliferation, reduced apoptosis and inhibited autophagy in vitro by reducing LC3-II and LAMP1 expression, while inducing SQSTM1 expression. Furthermore, ATG7 co-transfection with HULC reversed the oncogenic effects of HULC both in vitro and in vivo; however, downregulating ATG7 did not affect cell migration and invasive ability. We found that ITGB1 siRNA co-transfection with HULC reversed the function of HULC in inducing ovarian cancer cell migration and invasive ability. Taken together, our results show that HULC may promote ovarian carcinoma tumorigenesis by inhibiting ATG7 and inducing progression by regulating ITGB1.
miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14
Authors: Ji Quanbo , Xu Xiaojie , Li Ling , Goodman Stuart B , Bi Wenzhi , Xu Meng , Xu Yameng , Fan Zhongyi , Maloney William J , Ye Qinong , Wang Yan 
Published: October 2017

AbstractOsteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3′-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan–Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.
Differential regulation of spermatogenic process by Lkb1 isoforms in mouse testis
Authors: Kong Feifei , Wang Mei , Huang Xiaojing , Yue Qiuling , Wei Xiang , Dou Xiaowei , Peng Xiaoxu , Jia Yuanyuan , Zheng Ke , Wu Tinghe , Yan Jun , Li Jing 
Published: October 2017

AbstractLiver serine/threonine kinase B1 (LKB1) is a tumor suppressor associated with the pathogenesis of Peutz-Jeghers syndrome. Affected males are at increased risk of developing Sertoli cell tumors and display defective spermatogenesis. Male mice lacking the short isoform (Lkb1S) of Lkb1 were sterile and exhibited abnormal spermiogenesis. In addition to the short isoform, the long isoform of Lkb1 (Lkb1L) is also expressed in testis; however, the requirement of the long isoform for fertility and the functional difference between the isoforms remain unknown. Herein, different from the spermiation failure reported in Lkb1S knockout mice, conditional deletion (cKO) of both isoforms of Lkb1 in germ cells resulted in male sterility stemming from defects in acrosome formation, as well as nuclear elongation and condensation during spermatid differentiation. Additionally, cKO mice showed a progressive germ cell loss that was never reported in mice with Lkb1S deletion. Further experiments revealed that the defect resulted from the failure of spermatogonial stem/progenitor cells (SPCs) maintenance. Although increased mTORC1 activity in postnatal cKO testes was consistent with a tendency toward germline stem cell differentiation, in vivo inhibition of the pathway by rapamycin treatment failed to rescue the phenotype. Concurrently, we detected a significant reduction of mitochondrial activity in Lkb1deficient SPCs. The results suggest that the regulation of LKB1 on SPCs’ maintenance is associated with mitochondrial functions but not through the mTOR signaling pathway. In summary, our study supports different roles of Lkb1 isoforms in spermatogenesis with Lkb1L directing SPCs maintenance, and Lkb1L and Lkb1S coordinately regulating spermatid differentiation.
Wind loads and competition for light sculpt trees into self-similar structures
Authors: Eloy Christophe , Fournier Meriem , Lacointe André , Moulia Bruno 
Published: October 2017

AbstractTrees are self-similar structures: their branch lengths and diameters vary allometrically within the tree architecture, with longer and thicker branches near the ground. These tree allometries are often attributed to optimisation of hydraulic sap transport and safety against elastic buckling. Here, we show that these allometries also emerge from a model that includes competition for light, wind biomechanics and no hydraulics. We have developed MECHATREE, a numerical model of trees growing and evolving on a virtual island. With this model, we identify the fittest growth strategy when trees compete for light and allocate their photosynthates to grow seeds, create new branches or reinforce existing ones in response to wind-induced loads. Strikingly, we find that selected trees species are self-similar and follow allometric scalings similar to those observed on dicots and conifers. This result suggests that resistance to wind and competition for light play an essential role in determining tree allometries.
Triparental plants provide direct evidence for polyspermy induced polyploidy
Authors: Nakel Thomas , Tekleyohans Dawit G. , Mao Yanbo , Fuchert Golo , Vo Dieu , Groß-Hardt Rita 
Published: October 2017

AbstractIt is considered an inviolable principle that sexually reproducing organisms have no more than two parents and fertilization of an egg by multiple sperm (polyspermy) is lethal in many eukaryotes. In flowering plants polyspermy has remained a hypothetical concept, due to the lack of tools to unambiguously identify and trace this event. We established a high-throughput polyspermy detection assay, which uncovered that supernumerary sperm fusion does occur in planta and can generate viable polyploid offspring. Moreover, polyspermy can give rise to seedlings with one mother and two fathers, challenging the bi-organismal concept of parentage. The polyspermy derived triploids are taller and produce bigger organs than plants resulting from a regular monospermic fertilization. In addition, we demonstrate the hybridization potential of polyspermy by instantly combining three differentArabidopsisaccessions in one zygote. Our results provide direct evidence for polyspermy as a route towards polyploidy, which is considered a major plant speciation mechanism.
OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF in mouse ESCs
Authors: Sheinboim Danna , Maza Itay , Dror Iris , Parikh Shivang , Krupalnik Vladislav , Bell Rachel E. , Zviran Asaf , Suita Yusuke , Hakim Ofir , Mandel-Gutfreund Yael , Khaled Mehdi , Hanna Jacob H. , Levy Carmit 
Published: October 2017

AbstractEctopic expression of lineage master regulators induces transdifferentiation. Whether cell fate transitions can be induced during various developmental stages has not been systemically examined. Here we discover that amongst different developmental stages, mouse embryonic stem cells (mESCs) are resistant to cell fate conversion induced by the melanocyte lineage master regulator MITF. By generating a transgenic system we exhibit that in mESCs, the pluripotency master regulator Oct4, counteracts pro-differentiation induced by Mitf by physical interference with MITF transcriptional activity. We further demonstrate that mESCs must be released from Oct4-maintained pluripotency prior to ectopically induced differentiation. Moreover, Oct4 induction in various differentiated cells represses their lineage identity in vivo. Alongside, chromatin architecture combined with ChIP-seq analysis suggest that Oct4 competes with various lineage master regulators for binding promoters and enhancers. Our analysis reveals pluripotency and transdifferentiation regulatory principles and could open new opportunities in the field of regenerative medicine.