bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antisense transcription-dependent chromatin signature modulates sense transcription and transcript dynamics
Authors: Brown Thomas , Howe Françoise S. , Murray Struan C. , Seward Emily , Rata Scott , Angel Andrew , Mellor Jane 
Published: September 2017

AbstractAntisense transcription is widespread in genomes. Despite large differences in gene size and architecture, we find that yeast and human genes share a unique, antisense transcription-associated chromatin signature. We asked whether this signature is related to a biological function for antisense transcription. Using quantitative RNA-FISH, we observed changes in sense transcript distributions in nuclei and cytoplasm as antisense transcript levels were altered. To determine the mechanistic differences underlying these distributions, we developed a mathematical framework describing transcription from initiation to transcript degradation. AtGAL1, high levels of antisense transcription alters sense transcription dynamics, reducing rates of transcript production and processing, while increasing transcript stability, which is also a genome-wide association. Establishing the antisense transcription-associated chromatin signature through disruption of the Set3C histone deacetylase activity is sufficient to similarly change these rates even in the absence of antisense transcription. Thus, antisense transcription alters sense transcription dynamics in a chromatin-dependent manner.Abstract FigureGraphical AbstractIn this work, Brown et al. provide a mechanistic understanding of the effect of antisense transcription on the production and fate of sense transcripts. Antisense transcription buffers genes against the action of the Set3 lysine deacetylase, thus altering rates of transcript production, processing and stability.Conserved antisense transcription-dependent chromatin architecture near promotersAntisense transcription alters sense transcription dynamics and transcript stabilityAntisense transcription functions in a chromatin-dependent mannerIncreased acetylation byset3Δmimics high antisense transcriptional dynamics
A genome-wide RNAi screen identifies MASK as a positive regulator of cytokine receptor stability
Authors: Fisher Katherine H , Fragiadaki Maria , Pugazhendhi Dhamayanthi , Bausek Nina , Brown Stephen , Zeidler Martin P 
Published: September 2017

AbstractIn order for cells to sense and thus respond to their environment, they require transmembrane receptors, which bind extracellular ligands and then transduce this signal within the cell. A subset of receptors, with single-pass transmembrane domains are known as cytokine receptors and act via the Janus Kinase and Signal Transducer and Activator of Transcription (JAK/STAT) pathway. These receptors are essential for processes such as haematopoiesis, immune responses and tissue homeostasis. In order to transduce ligand activation, cytokine receptors must dimerise. However, mechanisms regulating their dimerisation are largely unknown. In order to better understand the processes regulating cytokine receptor levels, activity and dimerisation, we used the highly conserved JAK/STAT pathway inDrosophila, which acts via a single receptor, known as Domeless. We have performed a genome-wide RNAi screen inDrosophilacells, identifying MASK as a positive regulator of Domeless dimerisation and protein levels. We show that MASK is able to regulate JAK/STAT signalling bothin vitroandin vivo. We go on to show that MASK is able to bind to Domeless via its Ankyrin repeat domains and alters the stability of the receptor. Finally, we extend our observations to the human homologue, ANKHD1, and demonstrate functional conservation, with ANKHD1 able to regulate JAK/STAT signalling and the levels of a subset of pathway receptors in human cells. Taken together, we have identified MASK as a conserved regulator of cytokine receptor levels, which may have implications for human health.
Intratumoral Heterogeneity of Tumor Infiltration of Glioblastoma Revealed by Joint Histogram Analysis of Diffusion Tensor Imaging
Authors: Li Chao , Wang Shuo , Yan Jiun-Lin , Piper Rory J. , Liu Hongxiang , Torheim Turid , Kim Hyunjin , Zou Jinjing , Boonzaier Natalie R. , Sinha Rohitashwa , Matys Tomasz , Markowetz Florian , Price Stephen J. 
Published: September 2017

AbstractIntroductionGlioblastoma exhibits profound tumor heterogeneity, which causes inconsistent treatment response. The aim of this study was to propose an interpretation method of diffusion tensor imaging (DTI) using joint histogram analysis of DTI-p and-q. With this method we explored the patterns of tumor infiltration which causes disruption of brain microstructure, and examined the prognostic value of tumor infiltrative patterns for patient survival.Materials and methodsA total of 115 primary glioblastoma patients (mean age 59.3 years, 87 males) were prospectively recruited from July 2010 to August 2015. Patients underwent preoperative MRI scans and maximal safe resection. DTI was processed and decomposed into p and q components. The univariate and joint histograms of DTI-p and-q were constructed using the voxels of contrast-enhancing and non-enhancing regions respectively. Eight joint histogram features were obtained and correlated with tumor progression and patient survival. Their prognostic values were compared with clinical factors using receiver operating characteristic curves.ResultsThe subregion of increased DTI-p and decreased DTI-q accounted for the largest proportion. Additional diffusion patterns can be identified via joint histogram analysis. Particularly, higher proportion of decreased DTI-p and increased DTI-q in non-enhancing region contributed to worse progression-free survival (hazard ratio = 1.08,p< 0.001) and overall survival (hazard ratio = 1.11, p < 0.001).ConclusionsJoint histogram analysis of DTI can provide a comprehensive measure of tumor infiltration and microstructure change, which showed prognostic values. The subregion of decreased DTI-p and increased DTI-q in non-enhancing regions may indicate a more invasive habitat.
Endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases
Authors: Pommier Arnaud , Anaparthy Naishitha , Memos Nicoletta , Kelley Z Larkin , Gouronnec Alizée , Albrengues Jean , Egeblad Mikala , Iacobuzio-Donahue Christine A. , Lyons Scott K. , Fearon Douglas T. 
Published: September 2017

AbstractPatients who have had their primary pancreatic ductal adenocarcinoma (PDA) surgically resected often develop metastatic disease, exemplifying the problem of latent metastases. Livers from patients and mice with PDA contained single, disseminated cancer cells (DCCs) with an unusual phenotype of being cytokeratin-19 (CK19)-and MHC class I (MHCI)-. We created a mouse model to determine how DCCs develop, their relationship to metastatic latency, and the role of immunity. Intra-portal injection of immunogenic PDA cells into pre-immunized mice seeded livers only with single, non-replicating DCCs lacking MHCI and CK19; naïve recipients had macro-metastases. Transcriptomic analysis of PDA cells with the DCC phenotype demonstrated an endoplasmic reticulum (ER) stress response. Relieving ER stress with a chemical chaperone, in combination with T cell-depletion, stimulated outgrowth of macro-metastatic lesions containing PDA cells expressing MHCI and CK19. The ER stress response is the cell-autonomous reaction that enables DCCs to escape immunity and establish latent metastases.One sentence summary:Latent pancreatic cancer metastases are created when T cells select disseminated cancer cells in which immune resistance and quiescence have been imposed by endoplasmic stress.
Inherited organizational performance? The perceptions of generation Y on the influence of leadership styles
Authors: Nazarian Alireza , Soares Anabela , Lottermoser Benjamin 
Published: September 2017

PurposeLeadership has a major impact on organizational performance (Agleet al., 2006; Felfe and Schyns, 2004; Petersonet al., 2003). However, results are still conflicting regarding these effects and research has yet to focus on the expectations and perceived impact from the point of view of young professionals (the future senior employees and managers). Therefore, the purpose of this paper is to investigate how leadership is perceived and how leadership styles influence performance from the perspective of young professionals.Design/methodology/approachA quantitative research strategy was implemented by using a self-completion online questionnaire and the data were analyzed using multivariate statistical analysis to demonstrate the impact of each leadership style on organizational performance. The Multifactor Leadership Questionnaire (Bass and Avolio, 1995) was used to measure leadership styles (passive/avoidant, transactional and transformational leadership) and organizational performance was measured based on the balanced scorecard performance dimensions (financial, learning and growth, customer orientation and organizational effectiveness) (Kaplan and Norton, 2005).FindingsThe main findings supported the literature suggesting a statistically significant positive impact of both transactional and transformational leadership on organizational performance. Conversely, the relationship between the passive/avoidant leadership style and organizational performance was statistically significant but negative. This suggests that leaders in organizations driven by German culture should reconsider their approaches and practices.Originality/valueThe present study has focused on the responses from young German professionals who represent future organizational success. Consequently, it is of major importance to know how these groups assess the leadership style of their leaders and how this has an influence on organizational performance.
Identifying the needs and usage habits of university study room users
Authors: Ruleman Alice B. , Kaiser Anthony 
Published: September 2017

Purpose
Study rooms are recognized as a popular feature in academic libraries. The purpose of this paper is to understand how students use the study rooms at the library of the University of Central Missouri.

Design/methodology/approach
A short survey was given to students who checked out study rooms keys. Students were asked how they used the rooms and what technology they used in the rooms. In total, 341 valid surveys were returned for analysis.

Findings
Students used the rooms mainly for academic reasons. In total, 73 percent of respondents frequently studied alone in the rooms while 56 percent frequently studied in groups. Use of the technology in the rooms, other than the computers (89 percent) was limited.

Research limitations/implications
Due to the voluntary nature of the surveys, results may not be applicable to all study room users. The researchers were particularly interested in the international students but demographic data from the survey indicated that the number of responses from this group may not be representative of the number that are actually using the rooms.

Practical implications
Students indicated they rarely used peripheral equipment, i.e. webcams and microphones, and the library removed them from the rooms and made them available at the circulation desk.

Originality/value
The authors found little research specific to the use of study rooms although available research of library space in general indicated study rooms are highly valued. The findings of this survey suggest that students may be more interested in individual/private spaces for academic work than “group” study rooms.
Software‐Related Recalls of Health Information Technology and Other Medical Devices: Implications for FDA Regulation of Digital Health
Authors: RONQUILLO JAY G. , ZUCKERMAN DIANA M. 
Published: September 2017

Policy Points:
Medical software has become an increasingly critical component of health care, yet the regulation of these devices is inconsistent and controversial.
No studies of medical devices and software assess the impact on patient safety of the FDA's current regulatory safeguards and new legislative changes to those standards.
Our analysis quantifies the impact of software problems in regulated medical devices and indicates that current regulations are necessary but not sufficient for ensuring patient safety by identifying and eliminating dangerous defects in software currently on the market.
New legislative changes will further deregulate health IT, reducing safeguards that facilitate the reporting and timely recall of flawed medical software that could harm patients.
ContextMedical software has become an increasingly critical component of health care, yet the regulatory landscape for digital health is inconsistent and controversial. To understand which policies might best protect patients, we examined the impact of the US Food and Drug Administration's (FDA's) regulatory safeguards on software‐related technologies in recent years and the implications for newly passed legislative changes in regulatory policy.MethodsUsing FDA databases, we identified all medical devices that were recalled from 2011 through 2015 primarily because of software defects. We counted all software‐related recalls for each FDA risk category and evaluated each high‐risk and moderate‐risk recall of electronic medical records to determine the manufacturer, device classification, submission type, number of units, and product details.FindingsA total of 627 software devices (1.4 million units) were subject to recalls, with 12 of these devices (190,596 units) subject to the highest‐risk recalls. Eleven of the devices recalled as high risk had entered the market through the FDA review process that does not require evidence of safety or effectiveness, and one device was completely exempt from regulatory review. The largest high‐risk recall categories were anesthesiology and general hospital, with one each in cardiovascular and neurology. Five electronic medical record systems (9,347 units) were recalled for software defects classified as posing a moderate risk to patient safety.ConclusionsSoftware problems in medical devices are not rare and have the potential to negatively influence medical care. Premarket regulation has not captured all the software issues that could harm patients, evidenced by the potentially large number of patients exposed to software products later subject to high‐risk and moderate‐risk recalls. Provisions of the 21st Century Cures Act that became law in late 2016 will reduce safeguards further. Absent stronger regulations and implementation to create robust risk assessment and adverse event reporting, physicians and their patients are likely to be at risk from medical errors caused by software‐related problems in medical devices.
Risk factors of post‐ endoscopic retrograde cholangiopancreatography pancreatitis in biliary type sphincter of Oddi dysfunction in Japanese patients
Authors: Miyatani Hiroyuki , Matsumoto Satohiro , Mashima Hirosato 
Published: September 2017

OBJECTIVESuspected sphincter of Oddi dysfunction (SOD) is a well‐known risk factor for post‐endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The indication of ERCP for suspected SOD patients was very low in Japan compared to other countries. Therefore, the risk of PEP may be different in Japanese SOD patients. The objective of this study was to evaluate the risk of PEP in suspected biliary type SOD in Japan.METHODSFrom December 1996 to January 2017, 72 patients were suspected as having biliary type SOD, by questionnaire, liver function tests, hepatobiliary scintigraphy, abdominal ultrasonography, upper gastrointestinal endoscopy, endoscopic ultrasonography and magnetic resonance cholangiopancreatography. Finally, 60 patients who underwent ERCP were included in this study, and the factors associated with PEP were evaluated.RESULTSThe overall PEP rate was 23.3% (n = 14). Diagnostic ERCP alone for SOD did not increase the risk of PEP. The correlation of PEP incidence with pancreatic duct guidewire (PGW) technique and endoscopic sphincterotomy (EST) was indicated in univariate and multivariate analysis. Pancreatic stent placement was a risk in univariate analysis but not in multivariate analysis.CONCLUSIONSPGW technique and EST for biliary type SOD were important risk factors for PEP. Pancreatic stenting was ineffective for prevention of PEP.
Prehospital Supraglottic Airway Was Associated With Good Neurologic Outcome in Cardiac Arrest Victims Especially Those Who Received Prolonged Cardiopulmonary Resuscitation
Authors: Park Min Ji , Kwon Woon Yong , Kim Kyuseok , Suh Gil Joon , Shin Jonghwan , Jo You Hwan , Kim Kyung Su , Lee Hui Jai , Kim Joonghee , Lee Se Jong , Kim Jeong Yeon , Cho Jun Hwi 
Published: September 2017

AbstractObjectivesWe performed this study to investigate the association of prehospital supraglottic airway (SGA) on neurologic outcome in cardiac arrest victims with adjustment of postresuscitation variables as well as prehospital and resuscitation variables.MethodsThis study was a retrospective study based on a multicenter prospective cohort registry from December 2013 to April 2016. According to the 28‐day cerebral performance categories (CPCs) scale, patients were divided into the good‐outcome group (CPC 1–2) and the poor‐outcome group (CPC 3–5). We compared the two groups with respect to demographic variables, prehospital and in‐hospital resuscitation variables, and postresuscitation variables.ResultsA total of 869 cardiac arrest victims who received in‐progress cardiopulmonary resuscitation (CPR) were delivered to the emergency department of three hospitals, and 310 patients were admitted to the intensive care unit. The use of a prehospital SGA was independently associated with 28‐day good neurologic outcome (odds ratio [OR] = 7.88; 95% confidence interval [CI] = 1.33–46.53; p = 0.023] when postresuscitation variables were adjusted, although there were no significant association with the acquisition of sustained return of spontaneous circulation (OR = 0.992; 95% CI = 0.591–1.666; p = 0.976). Furthermore, a prehospital SGA was significantly associated with good neurologic outcome, especially in patients who received prolonged CPR (low flow time > 15 minutes; OR = 3.41; 95% CI = 1.23–9.45; p = 0.018) rather than in patients with nonprolonged CPR (OR = 4.50; 95% CI = 0.75–27.13; p = 0.101).ConclusionsWhen postresuscitation variables were adjusted, the prehospital SGA was independently associated with 28‐day good neurologic outcome in cardiac arrest victims.
Physical activity may decrease the likelihood of children developing constipation
Authors: Seidenfaden Sandra , Ormarsson Orri Thor , Lund Sigrun H. , Bjornsson Einar S. 
Published: September 2017

AbstractAimChildhood constipation is common. We evaluated children diagnosed with constipation, who were referred to an Icelandic paediatric emergency department, and determined the effect of lifestyle factors on its aetiology.MethodsThe parents of children who were diagnosed with constipation and participated in a phase IIB clinical trial on laxative suppositories answered an online questionnaire about their children's lifestyle and constipation in March–April 2013. The parents of nonconstipated children that visited the paediatric department of Landspitali University Hospital or an Icelandic outpatient clinic answered the same questionnaire.ResultsWe analysed responses regarding 190 children aged one year to 18 years: 60 with constipation and 130 without. We found that 40% of the constipated children had recurrent symptoms, 27% had to seek medical attention more than once and 33% received medication per rectum. The 47 of 130 control group subjects aged 10‐18 were much more likely to exercise more than three times a week (72%) and for more than a hour (62%) than the 26 of 60 constipated children of the same age (42% and 35%, respectively).ConclusionConstipation risk factors varied with age and many children diagnosed with constipation had recurrent symptoms. Physical activity may affect the likelihood of developing constipation in older children.
Urinary prostaglandin D2 metabolite excretion during the first six months of life was significantly lower in breast‐fed than formula‐fed infants
Authors: Shoji Hiromichi , Ikeda Naho , Kitamura Tomohiro , Suganuma Hiroki , Ohba Mai , Okuno Toshiaki , Yokomizo Takehiko , Shimizu Toshiaki 
Published: September 2017

AbstractAimThe metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and breast milk is considered to provide the optimal source of infant nutrition. This pilot study from September 2013 to May 2015 examined the effect of breastfeeding on prostaglandin metabolism in healthy term infants.MethodsUrine samples were collected from 19 infants at one month of age in the Juntendo University Hospital, Tokyo, Japan. The 13 infants in the breast‐fed group received less than 540 mL/week of their intake from formula, and the other six were exclusively fed on formula. At six months, we sampled 14 infants: nine breast‐fed and five receiving formula. The infants were from normal single pregnancies and free from perinatal complications. We analysed urinary prostaglandin metabolites—tetranor prostaglandin E2 metabolite (t‐PGEM) and tetranor prostaglandin D2 metabolite (t‐PGDM)—using liquid chromatography tandem–mass spectrometry.ResultsUrinary t‐PGDM excretion at one and six months was significantly lower in breast‐fed infants than formula‐fed infants. However, urinary t‐PGEM excretion at one and six months was not significantly different between the groups.ConclusionOur study showed that the type of feeding in early infancy affected prostaglandin metabolism in healthy term infants.
Importance of the second extracellular loop for melatonin MT1 receptor function and absence of melatonin binding in GPR50
Authors: Clement Nathalie , Renault Nicolas , Guillaume Jean‐Luc , Cecon Erika , Journé Anne‐Sophie , Laurent Xavier , Tadagaki Kenjiro , Cogé Francis , Gohier Arnaud , Delagrange Philippe , Chavatte Philippe , Jockers Ralf 
Published: September 2017

Background and PurposeRecent crystal structures of GPCRs have emphasized the previously unappreciated role of the second extracellular (E2) loop in ligand binding and gating and receptor activation. Here, we have assessed the role of the E2 loop in the activation of the melatonin MT1 receptor and in the inactivation of the closely related orphan receptor GPR50.Experimental ApproachChimeric MT1‐GPR50 receptors were generated and functionally analysed in terms of 2‐[125I]iodomelatonin binding, Gi/cAMP signalling and β‐arrestin2 recruitment. We also used computational molecular dynamics (MD) simulations.Key ResultsMD simulations of 300 ns revealed (i) the tight hairpin structure of the E2 loop of the MT1 receptor (ii) the most suitable features for melatonin binding in MT1 receptors and (iii) major predicted rearrangements upon MT1 receptor activation, stabilizing interaction networks between Phe179 or Gln181 in the E2 loop and transmembrane helixes 5 and 6. Functional assays confirmed these predictions, because reciprocal replacement of MT1 and GPR50 residues/domains led to the predicted loss‐ and gain‐of‐melatonin action of MT1 receptors and GPR50 respectively.Conclusions and ImplicationsOur work demonstrated the crucial role of the E2 loop for MT1 receptor and GPR50 function by proposing a model in which the E2 loop is important in stabilizing active MT1 receptor conformations and by showing how evolutionary processes appear to have selected for modifications in the E2 loop in order to make GPR50 unresponsive to melatonin.Linked ArticlesThis article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc