bluuebunny/crossref_metadata_2025 huggingface dataset:
Constriction rate modulation can drive cell size control and homeostasis inC. crescentus
Authors: Lambert Ambroise , Vanhecke Aster , Archetti Anna , Holden Seamus , Schaber Felix , Pincus Zachary , Laub Michael T. , Goley Erin , Manley Suliana
Published: February 2018

Rod-shaped bacteria typically grow first via sporadic and dispersed elongation along their lateral walls, then via a combination of zonal elongation and constriction at the division site to form the poles of daughter cells. Although constriction comprises up to half of the cell cycle, its impact on cell size control and homeostasis has rarely been considered. To reveal the roles of cell elongation and constriction in bacterial size regulation during cell division, we captured the shape dynamics ofCaulobacter crescentuswith time-lapse structured illumination microscopy and used molecular markers as cell-cycle landmarks. We perturbed constriction rate using a hyperconstriction mutant or fosfomycin inhibition. We report that constriction rate contributes to both size control and homeostasis, by determining elongation during constriction, and by compensating for variation in pre-constriction elongation on a single-cell basis.
Detection and Degradation of Nonsense-mediated mRNA Decay Substrates Involve Two Distinct Upf1-bound Complexes
Authors: Dehecq Marine , Decourty Laurence , Namane Abdelkader , Proux Caroline , Kanaan Joanne , Le Hir Hervé , Jacquier Alain , Saveanu Cosmin
Published: February 2018

Nonsense-mediated mRNA decay (NMD) is a translation-dependent RNA degradation pathway involved in many cellular pathways and crucial for telomere maintenance and embryo development. Core NMD factors Upf1, Upf2 and Upf3 are conserved from yeast to mammals, but a universal NMD model is lacking. We used affinity purification coupled with mass spectrometry and an improved data analysis protocol to obtain the first large-scale quantitative characterization of yeast NMD complexes in yeast (112 experiments). Unexpectedly, we identified two distinct complexes associated with Upf1: Detector (Upf1/2/3) and Effector. Effector contained the mRNA decapping enzyme, together with Nmd4 and Ebs1, two proteins that globally affected NMD and were critical for RNA degradation mediated by the Upf1 C-terminal helicase region. The fact that Nmd4 association to RNA was dependent on Detector components and the similarity between Nmd4/Ebs1 and mammalian Smg5-7 proteins suggest that in all eukaryotes NMD operates through successive Upf1-bound Detector and Effector complexes.
SETD3 protein is the actin-specific histidineN-methyltransferase
Authors: Kwiatkowski Sebastian , Seliga Agnieszka K. , Veiga-da-Cunha Maria , Vertommen Didier , Terreri Marianna , Ishikawa Takao , Grabowska Iwona , Jagielski Adam K , Drozak Jakub
Published: February 2018

Protein histidine methylation is rarely studied posttranslational modification of unknown biochemical importance. In vertebrates, only a few methylhistidne-containing proteins have been reported so far, including β-actin as an essential example. The evolutionary conserved methylation of β-actin H73 residue is catalyzed by a specific histidineN-methyltransferase that has never been identified molecularly. In the present investigation, we have purified actin-specific histidineN-methyltransferase from rat muscles about 1200-fold. Its activity was studied by the radiochemical assay employing either homogeneous recombinant human β-actin produced inE. colior its mutated form exhibiting substitution of H73 by Ala residue (H73A) as substrates. Three polypeptides of ≈65, 75 and 90 kDa coeluting with the enzyme activity were identified in the preparation. Mass spectrometry analysis of these polypeptides resulted in the identification of SETD3 methyltransferase as the only plausible candidate. Rat SETD3 and its human ortholog were expressed in COS-7 cells, purified to homogeneity and shown to catalyze methylation of β-actin at H73 residue as confirmed by mass spectrometry analysis. The SETD3 enzyme was active towards a synthetic peptide corresponding to residues 69-77 of β-actin, but not to its mutated form exhibiting His-to-Ala substitution. Finally, Setd3-deficient HAP1 cells were devoid of methylated H73 in β-actin and exhibited phenotypic changes, including a decrease in F-actin content and an increased glycolytic activity. We conclude that SETD3 is the actin-specific histidineN-methyltransferase. The data show for the first time the molecular identity of protein histidine N-methyltransferase in vertebrates and throw new light on the substrate specificity of SET-domain-containing enzymes.
Network analysis of ChIP-seq data by VULCAN identifies GRHL2 as a key co-regulator of ERa in luminal breast cancer
Authors: Holding Andrew N. , Giorgi Federico M. , Donnelly Amanda , Cullen Amy E. , Nagarajan Sankari , Selth Luke A , Markowetz Florian
Published: February 2018

VULCAN infers regulatory interactions of transcription factors by overlaying networks generated from tumor expression data onto ChIP-seq data. VULCAN analysis of estrogen receptor (ER) activation in breast cancer highlighted key components of the ER complex alongside a novel interaction with GRHL2. We demonstrate that GRHL2 is recruited to a subset of ER binding sites and regulates the transcriptional output of ER, as evidenced by: changes in ER-associated eRNA expression; and stronger ER binding at active enhancers (H3K27ac sites) after GRHL2 knockdown. Our findings provide new insight into ER signaling and demonstrate VULCAN, available from Bioconductor, as a powerful predictive tool.
Identification of the targets of T cell receptor therapeutic agents and cells by use of a high throughput genetic platform
Authors: Gejman Ron S. , Jones Heather F. , Klatt Martin G. , Chang Aaron Y. , Oh Claire Y. , Chandran Smita S. , Korontsvit Tatiana , Zakahleva Viktoriya , Dao Tao , Klebanoff Christopher A. , Scheinberg David A.
Published: February 2018

T cell receptor (TCR)-based therapeutic cells and agents have emerged as a new class of effective cancer therapeutics. These therapies work on cells that express intracellular cancer-associated proteins by targeting peptides displayed on major histocompatibility complex receptors. However, cross-reactivities of these agents to off-target cells and tissues have resulted in serious, sometimes fatal, adverse events. We have developed a high throughput genetic platform (termed “PresentER”) that encodes MHC-I peptide minigenes for functional immunological assays as well as for determining the reactivities of TCR-like therapeutic agents against large libraries of MHC-I ligands. In this report, we demonstrate that PresentER can be used to identify the on-and-off targets of T cells and TCR mimic antibodies usingin vitroco-culture assays or binding assays. We find dozens of MHC-I ligands that are cross-reactive with two TCR mimic antibodies and two native TCRs and that are not easily predictable by other methods.
DeepLoco: Fast 3D Localization Microscopy Using Neural Networks
Authors: Boyd Nicholas , Jonas Eric , Babcock Hazen , Recht Benjamin
Published: February 2018

Single-molecule localization super-resolution microscopy (SMLM) techniques like STORM and PALM have transformed cellular microscopy by substantially increasing spatial resolution. In this paper we introduce a new algorithm for a critical part of the SMLM process: estimating the number and locations of the fluorophores in a single frame. Our algorithm can analyze a 20000-frame experimental 3D SMLM dataset in about one second — substantially faster than real-time and existing algorithms. Our approach is straightforward but very different from existing algorithms: we train a neural network to minimize the Bayes’ risk under a generative model for single SMLM frames. The neural network maps a frame directly to a collection of fluorophore locations, which we compare to the ground truth using a novel loss function. While training the neural network takes several hours, it only has to be done once for a given experimental setup. After training, localizing fluorophores in new images is extremely fast — orders of magnitude faster than existing algorithms. Faster recovery opens the door to real-time calibration and accelerated acquisition, and future work could tackle more complicated optical systems and more realistic simulators.
Generation of tumorigenic porcine pancreatic ductal epithelial cells: toward a large animal model of pancreatic cancer
Authors: Remmers Neeley , Cox Jesse L. , Grunkemeyer James A. , Aravind Shruthi , Arkfeld Christopher K. , Hollingsworth Michael A. , Carlson Mark A.
Published: February 2018

Background. A large animal model of pancreatic cancer would permit development of diagnostic and interventional technologies not possible in murine models, and also would provide a more biologically-relevant platform for penultimate testing of novel therapies, prior to human testing. Here, we describe our initial studies in the development of an autochthonous, genetically-defined, large animal model of pancreatic cancer, using immunocompetent pigs.

Methods. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs; epithelial origin was confirmed with immunohistochemistry. Three transformed cell lines subsequently were generated from these primary cells using expression of oncogenic KRAS and dominant negative p53, with/without knockdown of p16 and SMAD4. We tested these cell lines using in vitro and in vivo assays of transformation and tumorigenesis.

Results. The transformed cell lines outperformed the primary cells in terms proliferation, population doubling time, soft agar growth, 2D migration, and Matrigel invasion, with the greatest differences observed when all four genes (KRAS, p53, p16, and SMAD4) were targeted. All three transformed cell lines grew tumors when injected subcutaneously in nude mice, demonstrating undifferentiated morphology, mild desmoplasia, and staining for both epithelial and mesenchymal markers. Injection into the pancreas of nude mice resulted in distant metastases, particularly when all four genes were targeted.

Conclusions. Tumorigenic porcine pancreatic cell lines were generated. Inclusion of four genetic “hits” (KRAS, p53, p16, and SMAD4) appeared to produce the best results in our in vitro and in vivo assays. The next step will be to perform autologous or syngeneic implantation of these cell lines into the pancreas of immunocompetent pigs. We believe that the resultant large animal model of pancreatic cancer could supplement existing murine models, thus improving preclinical research on diagnostic, interventional, and therapeutic technologies.
A fully automatic method yielding initial models from high-resolution electron cryo-microscopy maps
Authors: Terwilliger Thomas C. , Adams Paul D. , Afonine Pavel V. , Sobolev Oleg V.
Published: February 2018

A fully automated procedure for optimization and interpretation of reconstructions from cryo-EM is developed and applied to 476 datasets with resolution of 4.5 Å or better, including reconstructions of 47 ribosomes and 32 other protein-RNA complexes. The median fraction of residues in the deposited structures reproduced automatically was 71% for reconstructions determined at resolutions of 3 Å or better and 47% for those at lower resolution.
Atomic model of microtubule-bound tau
Authors: Kellogg Elizabeth H. , Hejab Nisreen M.A. , Poepsel Simon , Downing Kenneth H. , DiMaio Frank , Nogales Eva
Published: February 2018

Tau is a developmentally regulated protein found in axons, whose physiological role is to stabilize and bundle microtubules (MTs). Hyper-phosphorylation of tau is thought to cause its detachment from MTs and subsequent aggregation into pathological fibrils that have been implicated in Alzheimer’s disease pathogenesis. Despite its known MT binding role, there is no consensus regarding which tau residues are crucial for tau-MT interactions, where on the MT tau binds, and how binding results in MT stabilization. We have used cryo-EM to visualize the interaction of different tau constructs with MTs at high resolution (3.2-4.8 Å) and used computational approaches to generate atomic models of tau-tubulin interactions. Our work shows that the highly conserved tubulin-binding repeats within tau adopt very similar structures in their interactions with the MT. Each tau repeat binds the MT exterior and adopts an extended structure along the crest of the protofilament (PF), interacting with both α- and β-tubulin, thus stabilizing the interface between tubulin dimers. Our structures agree with and explain previous biochemical data concerning the effect of phosphorylation on MT affinity and lead to a model in which tau repeats bind in tandem along a PF, tethering together tubulin dimers and stabilizing longitudinal polymerization interfaces. These structural findings could establish a basis of future treatments aiming at the selective stabilization of tau-MT interactions.
Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival
Authors: Ramazzotti Daniele , Lal Avantika , Wang Bo , Batzoglou Serafim , Sidow Arend
Published: February 2018

Outcomes for cancer patients vary greatly even within the same tumor type, and characterization of molecular subtypes of cancer holds important promise for improving prognosis and personalized treatment. This promise has motivated recent efforts to produce large amounts of multidimensional genomic (‘multi-omic’) data, but current algorithms still face challenges in the integrated analysis of such data. Here we present Cancer Integration via Multikernel Learning (CIMLR), a new cancer subtyping method that integrates multi-omic data to reveal molecular subtypes of cancer. We apply CIMLR to multi-omic data from 36 cancer types and show significant improvements in both computational efficiency and ability to extract biologically meaningful cancer subtypes. The discovered subtypes exhibit significant differences in patient survival for 27 of 36 cancer types. Our analysis reveals integrated patterns of gene expression, methylation, point mutations and copy number changes in multiple cancers and highlights patterns specifically associated with poor patient outcomes.
Neural responses to naturalistic clips of behaving animals in two different task contexts
Authors: Nastase Samuel A. , Halchenko Yaroslav O. , Connolly Andrew C. , Gobbini M. Ida , Haxby James V.
Published: February 2018

Neuroimaging studies of object and action representation often use controlled stimuli and implicitly assume that the relevant neural representational spaces are fixed and context-invariant. Here we present functional MRI data measured while participants freely viewed brief naturalistic video clips of behaving animals in two different task contexts. Participants performed a 1-back category repetition detection task requiring them to attend to either animal taxonomy or animal behavior. The data and analysis code are freely available, and have been curated according to the Brain Imaging Data Structure (BIDS) standard. We thoroughly describe the data, provide quality control metrics, and perform a searchlight classification analysis to demonstrate the potential utility of the data. These data are intended to provide a test bed for investigating how task demands alter the neural representation of complex stimuli and their semantic qualities.
Inferring Cancer Progression from Single-cell Sequencing while Allowing Mutation Losses
Authors: Ciccolella Simone , Gomez Mauricio Soto , Patterson Murray , Vedova Gianluca Della , Hajirasouliha Iman , Bonizzoni Paola
Published: February 2018

Motivation

In recent years, the well-known Infinite Sites Assumption (ISA) has been a fundamental feature of computational methods devised for reconstructing tumor phylogenies and inferring cancer progressions seen as an accumulation of mutations. However, recent studies (Kuiperset al., 2017) leveraging Single-cell Sequencing (SCS) techniques have shown evidence of the widespread recurrence and, especially, loss of mutations in several tumor samples. Still, established methods that can infer phylogenies with mutation losses are however lacking.

Results

We present theSASC(Simulated Annealing Single-Cell inference) tool which is a new and robust approach based on simulated annealing for the inference of cancer progression from SCS data. More precisely, we introduce a simple extension of the model of evolution where mutations are only accumulated, by allowing also a limited amount of back mutations in the evolutionary history of the tumor: the Dollo-kmodel. We demonstrate thatSASCachieves high levels of accuracy when tested on both simulated and real data sets and in comparison with some other available methods.

Availability

The Simulated Annealing Single-cell inference (SASC) tool is open source and available athttps://github.com/sciccolella/sasc.

Contact

s.ciccolella@campus.unimib.it
Abstract concept learning in a simple neural network inspired by the insect brain
Authors: Cope Alex J. , Vasilaki Eleni , Minors Dorian , Sabo Chelsea , Marshall James A.R. , Barron Andrew B.
Published: February 2018

The capacity to learn abstract concepts such as ‘sameness’ and ‘difference’ is considered a higher-order cognitive function, typically thought to be dependent on top-down neocortical processing. It is therefore surprising that honey bees apparantly have this capacity. Here we report a model of the structures of the honey bee brain that can learn same-ness and difference, as well as a range of complex and simple associative learning tasks. Our model is constrained by the known connections and properties of the mushroom body, including the protocerebral tract, and provides a good fit to the learning rates and performances of real bees in all tasks, including learning sameness and difference. The model proposes a novel mechanism for learning the abstract concepts of ‘sameness’ and ‘difference’ that is compatible with the insect brain, and is not dependent on top-down or executive control processing.
Developing an automated iterative near-term forecasting system for an ecological study
Authors: White Ethan P. , Yenni Glenda M. , Taylor Shawn D. , Christensen Erica M. , Bledsoe Ellen K. , Simonis Juniper L. , Ernest S. K. Morgan
Published: February 2018

Most forecasts for the future state of ecological systems are conducted once and never updated or assessed. As a result, many available ecological forecasts are not based on the most up-to-date data, and the scientific progress of ecological forecasting models is slowed by a lack of feedback on how well the forecasts perform.

Iterative near-term ecological forecasting involves repeated daily to annual scale forecasts of an ecological system as new data becomes available and regular assessment of the resulting forecasts. We demonstrate how automated iterative near-term forecasting systems for ecology can be constructed by building one to conduct monthly forecasts of rodent abundances at the Portal Project, a long-term study with over 40 years of monthly data. This system automates most aspects of the six stages of converting raw data into new forecasts: data collection, data sharing, data manipulation, modeling and forecasting, archiving, and presentation of the forecasts.

The forecasting system uses R code for working with data, fitting models, making forecasts, and archiving and presenting these forecasts. The resulting pipeline is automated using continuous integration (a software development tool) to run the entire pipeline once a week. The cyberinfrastructure is designed for long-term maintainability and to allow the easy addition of new models. Constructing this forecasting system required a team with expertise ranging from field site experience to software development.

Automated near-term iterative forecasting systems will allow the science of ecological forecasting to advance more rapidly and provide the most up-to-date forecasts possible for conservation and management. These forecasting systems will also accelerate basic science by allowing new models of natural systems to be quickly implemented and compared to existing models. Using existing technology, and teams with diverse skill sets, it is possible for ecologists to build automated forecasting systems and use them to advance our understanding of natural systems.
CSR and consumer behavioral responses: the role of customer-company identification
Authors: Fatma Mobin , Khan Imran , Rahman Zillur
Published: February 2018

Purpose

The purpose of this paper is to examine the influence of perceived CSR and its influence on customer satisfaction and loyalty in the hotel industry.

Design/methodology/approach

Personal surveys of hotel guests were carried out in three metropolitan cities of India. The survey resulted in 327 valid responses which were further analyzed. To test the proposed model, structural equation modeling was applied.

Findings

The findings show that consumer perception of CSR activities positively influences consumer identification with the company, and identification positively results in customer satisfaction and loyalty.

Research limitations/implications

Findings of the study have important implications for hospitality companies as they suggest that hotel managers should invest more in socially responsible initiatives since consumers tend to support those firms that are perceived as socially responsible by developing a sense of loyalty towards them.

Originality/value

This study provides a comprehensive framework that integrates social identity and social exchange perspectives towards building customer satisfaction and loyalty.
Deconstructing the reinvention of operations management
Authors: Wilson James M.
Published: February 2018

Purpose

The purpose is to provide an intellectual history of Operations Management, particularly noting recent developments and its underlying continuity with earlier systems and thinking. Operations Management as a discipline identifies its “modern” incarnation as dating from the 1960s when it became more rigorous and managerially focused. This re-invention constructed a “narrative” that the profession still follows, yet a critical perspective reveals significant, though under-appreciated continuity with earlier theory and practice.

Design/methodology/approach

This paper presents a comprehensive literature review and comparative analysis of historic developments in management and academia.

Findings

In the early 1900s, F. W. Taylor’s Shop Management established Operation Management, but its main component, Scientific Management, had stagnated by the 1950s. At that point, the rise of Management Science both reinvigorated Operations Management and threatened it with a competing new discipline. To compete Operations Management then modernized by redefining itself, reasserting its interest in several areas and co-opting Operational Research tools for those. It also contracted, withdrawing from areas considered vocational, or more suited to Industrial Engineering.

Research limitations/implications

This historical overview shows the critical importance of drawing research agenda from practical managerial concerns.

Practical implications

Practitioners benefit from the intellectual rigor that academics provide and a historical perspective shows that the relationship has been mutually beneficial.

Social implications

The disciplines of Operations Management, Operations Research and Industrial Engineering are complementary and competitive in addressing many problems that transcend their boundaries, and use common ideas and techniques. The demands of “academic rigor” have had a deleterious effect on the practical managerial relevance of these disciplines.

Originality/value

A long-term, cross-disciplinary perspective provides a unique understanding of the research interests and practical orientations of these disciplines.
The Thatcher government and (de)regulation: modularisation of individual personal pensions
Authors: Burton Nicholas
Published: February 2018

Purpose

The (de)regulation agenda of the Conservative government, led by Margaret Thatcher, elected in 1979 is an important change point that has attracted only limited attention from management and historical research scholars. Thus, how (de)regulation in this era influenced the evolution of product design remains ripe for exploration. The purpose of this paper is to examine the UK individual personal pensions product market between the mid-1980s and mid-1990s to examine the relationship between (de)regulation – an industry-level factor – and its impact on architectural choices of product design – a product-level factor.

Design/methodology/approach

A retrospective, oral history research design with 31 senior managers in product development firms with first-hand experience of the change period was adopted.

Findings

Findings indicate that the (de)regulation reforms and the context of the financialisation of product markets came to define how products were then designed, evolving product design from non-modular to near-modular, a trajectory that arguably continues until the present day.

Originality/value

The main contribution lies in examining the role of (de)regulation and financialisation as modularisation processes. The increasing modularisation of individual personal pension product design between the mid-1980s and mid-1990s provides further support for the body of scholarly work on modularisation processes and their relationship with industry change.
The Free-Standing Company: a “zombie” theory of international business history?
Authors: Mollan Simon
Published: February 2018

Purpose

The purpose of this paper is to decompose the historical and conceptual basis of the Free-Standing Company (FSC) in international business history. This is used to critique the FSC concept. The paper then provides a new framework to explain the lifecycle of these firms in a theoretically sensitive way.

Design/methodology/approach

The paper is conceptual. The argument is developed through a critical reading of the existing literature.

Findings

The central argument presented is that the FSC concept is ahistorical and cannot fully explain the firms it considers over time. An alternative approach is proposed.

Research limitations/implications

The paper does not present new (archival) historical evidence.

Originality/value

The central contribution/ambition of the paper is to advance the theoretical understanding of international firms of considerable historical importance. The ambition of the paper is to help renew research into this important historical organizational form that speaks directly to the ability of historical research to help advance international business theory.
Shadow hybridity and the institutional logic of professional sport
Authors: Gillett Alex G. , Tennent Kevin D.
Published: February 2018

Purpose

Existing studies of the finance of English Association Football (soccer) have tended to focus on the sport’s early years, or on the post-1992 Premiership era. The authors examine a case from the turbulent 1980s charting the struggle for economic survival of one club in a rapidly changing financial, economic, political and demographic landscape. The purpose of this paper is to examine not only the financial management of a football club during this time, but also the interventionist role of the local authority during this turbulent period.

Design/methodology/approach

The authors investigate the financial difficulties of a sport business, Middlesbrough Football and Athletic Company Limited, examining the broader economic context, drawing on unseen archival sources dating from the 1980s to analyze the relationship between club, local and national government and the regional economy.

Findings

They not only examine the financial management of the football club but also analyse the interventionist role of the local authority in supporting the club which had symbolic value for the local community.

Practical implications

This paper is relevant to policymakers interested in the provision of local sports facilities and the links between elite sport and participation.

Originality/value

The authors show that professional sports clubs are driven by a different institutional logic to state organizations and the findings enable them to define these differences, thereby refining Thornton et al.’s (2012) typology of institutional orders. Furthermore, the case study highlights practices involving informal partnership between state and sport that the authors label as shadow hybridity.
Self-other agreement on transformational leadership and subordinates’ assessment of supervisor’s performance
Authors: Ertürk Alper , Van den Broeck Herman , Verbrigghe Jasmijn
Published: February 2018

Purpose

Given the importance of the extent to which supervisors and their subordinates agree in their assessment of supervisors’ leadership, the purpose of this paper is to investigate the possible relationship between self-other agreement on supervisors’ transformational leadership and subordinates’ perceptions of supervisors’ in-role and extra-role performance, through the mediating role of leader-member exchange.

Design/methodology/approach

Self-other agreement was conceptualized as the degree of congruence between supervisors’ self-assessment and subordinates’ assessment of supervisors’ transformational leadership. Data were collected from 36 supervisors and 189 of their subordinates. Cross-level polynomial regressions and surface response analysis were used to analyze the hypothesized relationships.

Findings

Statistical analyses revealed that self-other agreement on idealized influence and individual support are positively associated with subordinates’ perception of leader-member exchange, and in turn leader member fully mediates the relationship between self-other agreement and subordinates’ perceptions regarding their supervisors’ performance. Results from polynomial analyses indicate that subordinates’ ratings of leader-member exchange would be highest for underestimator, second for in-agreement/good supervisors, third for in-agreement/poor and lowest for overestimator supervisors both for the idealized influence and individual support.

Originality/value

This is one of the pioneer studies investigating the potential relationship between self-other agreement on supervisors’ transformational leadership and the subordinates’ perceptions on their supervisors’ performance through social exchange. Since researchers have paid scant attention to intervening mechanisms, this study aims to extend previous research in the literature by investigating those associations through the mediating effect of leader-member exchange.
Clinical guidelines for prevention and management of preterm birth: a systematic review
Authors: Medley N , Poljak B , Mammarella S , Alfirevic Z
Published: February 2018

Background

Clinical practice guidelines (CPG) endorse multiple strategies to prevent or manage preterm birth (PTB).

Objectives

To summarise CPG recommendations for PTB and identify areas of international consensus.

Search strategy

In May 2017 we searched for all CPG relevant to PTB without language restrictions.

Selection criteria

CPG were eligible if the following criteria were met: (1) the guideline was published or current from June 2013; (2) the guideline recommended practices for the prevention or management of PTB relevant to our prespecified clinical questions for screening, medications or surgery and other interventions; (3) publications on methods of guideline development for eligible CPG were included to enable quality assessment.

Data collection and analysis

Two authors classified CPG recommendations relevant to prespecified clinical questions. When more than 70% of CPGs reporting on a topic recommended or rejected an intervention, we regarded this as consensus. We summarised recommendations in tables.

Main results

We identified 49 guidelines from 16 guideline developers. We found consensus for several clinical practices: cervical length screening for high‐risk women; short‐term tocolysis; steroids for fetal lung maturation; and magnesium sulphate for fetal neuroprotection. We found discrepant recommendations for progesterone and fibronectin. No guideline identified an effective strategy for women with multiple pregnancy.

Conclusions

We identified interventions for which there is an international consensus on benefit for PTB. Systematic reviews of CPG using standardised methodology will help avoid duplication and target scarce resources for guideline developers globally.

Tweetable abstract

International clinical guidelines agree on the benefits and harmful effects of several important interventions to prevent preterm birth.
Attitudes of special education teachers towards using technology in inclusive classrooms: a mixed‐methods study
Authors: Mohamed Ahmed Hassan Hemdan
Published: February 2018

The purpose of this mixed‐methods study was to explore special education teachers’ attitudes towards using technology in inclusive classrooms in Oman. The sample consisted of 428 special education teachers working in Omani public schools (250 teachers of students with learning disabilities (LD), 90 teachers of students with intellectual disability and 88 teachers of students with hearing impairment). Participants responded to the attitudes towards computers questionnaire. For the qualitative section of this study, three semi‐structured group interviews were conducted with a group of special education teachers: 15 teachers of students with hearing impairment, 15 teachers of students with intellectual disabilities and 15 teachers of students with LD). Also, the teachers responded to a survey of educational technology which encompassed seven questions about computer technology. Results of the study indicated that the special education teachers’ attitudes towards using computers were generally positive. The most notable positive attitudes were in the following subscales: special education considerations, staff development considerations, computers use in society, and computers and quality of instruction issues. The analysis of variance results showed that experience and type of disability did not have a significant effect on teachers’ attitudes towards technology.
A Comparison Among Three Multiplex Y‐STR Profiling Kits for Sexual Assault Cases
Authors: Ferreira‐Silva Benedita , Fonseca‐Cardoso Margarida , Porto Maria João , Magalhães Teresa , Cainé Laura
Published: February 2018

Biological evidence of sexual assault is one of the most difficult sample types to analyze in forensic laboratories. Y‐STR markers are thus a valuable tool for analyzing these samples. The aim of this project was to compare three Y‐STR commercial kits by analyzing their amplification performance on casework samples. Overall, 247 trace samples were analyzed with a Yfiler® Plus PCR Amplification Kit (Applied Biosystems), PowerPlex® Y23 (Promega®) System and AmpFLSTR® Yfiler™ PCR Amplification Kit (Applied Biosystems). Comparing the amplification performance of the three kits, the first two were significantly more sensitive than the latter (p < 0.001). For samples, with a male DNA quantity less than 0.5 ng, the PowerPlex Y23® kit was the most sensitive and best performing kit, followed by the Yfiler® Plus kit (p = 0.009). In conclusion, the Yfiler® Plus and PowerPlex Y‐23® kits are viable alternatives to older kits for samples with low amounts of male DNA.
Dielectric properties for non‐invasive detection of normal, benign, and malignant breast tissues using microwave theories
Authors: Cheng Yiou , Fu Minghuan
Published: February 2018

Background

Despite the high incidence of breast cancer worldwide, methods for early non‐invasive diagnosis and sensitive and specific prognostic evaluation remain difficult. In this study, we investigated microwave parameters as a potential non‐invasive approach to detect breast cancer.

Methods

Samples of freshly excised breast tissues (n = 509) from 98 patients were identified as normal, benign tumor, or malignant cancer via histology. Further samples were prepared and the microwave effective dielectric permittivity and effective conductivity were measured every 0.0375 GHz from 0.5 GHz to 8 GHz. These parameters were compared among the breast tissue types.

Results

The effective relative permittivity and effective conductivity at each frequency was significantly higher in breast cancer tissues compared with benign tumors, which in turn was significantly higher than in normal breast tissue. The standard deviation of each parameter was narrowest at ~2.5 GHz in both normal and malignant breast tissues.

Conclusions

The effective dielectric permittivity and effective conductivity, measured via microwave technology, could differentiate breast cancer from normal and benign tumor tissues.
Auditors' Use of Formal Advice from Internal Firm Subject Matter Experts: The Impact of Advice Quality and Advice Awareness on Auditors' Judgments
Authors: Wright Nicole S. , Bhattacharjee Sudip
Published: February 2018

When subject matter experts are consulted during an audit, the quality of the expert's advice depends upon their ability to fully understand and incorporate client‐specific facts into their advice. Public Company Accounting Oversight Board (PCAOB) inspection reports suggest that auditors are neglecting to perform the required work to assess the quality of experts' recommendations. This study examines how characteristics of the audit, notably staffing decisions, can impede auditors' ability to discern advice quality. In an experiment, we examine how receiving advice of different levels of quality (lower or higher incorporation of relevant client facts) and awareness at the planning stage of the use of a subject matter expert (a priori aware or unaware) impacts auditors' effort, utilization of the advice, and judgment accuracy. We find that awareness of an expert being employed led to a social facilitation effect such that auditors who were a priori aware put forth more effort prior to receiving the expert advice and were initially in less agreement with management's aggressive revenue recognition position than auditors who were unaware. Upon receiving the expert advice, auditors who were a priori aware were more accurate than auditors who were unaware. These results should interest both audit regulators and practitioners by demonstrating how the timing and communication of consulting decisions affect auditors' assessments of advice received from subject matter experts.
Amyloid‐beta 1‐40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro
Authors: Schultz Nina , Brännström Kristoffer , Byman Elin , Moussaud Simon , Nielsen Henrietta M. ,   The Netherlands Brain Bank, Olofsson Anders , Wennström Malin
Published: February 2018

The population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amyloid‐beta (Aβ) has been suggested as a potential culprit. In the current study, we show reduced number of hippocampal NG2+ pericytes and an association between NG2+ pericyte numbers and Aβ1‐40 levels in AD patients. We further demonstrate, using in vitro studies, an aggregation‐dependent impact of Aβ1‐40 on human NG2+ pericytes. Fibril‐EP Aβ1‐40 exposure reduced pericyte viability and proliferation and increased caspase 3/7 activity. Monomer Aβ1‐40 had quite the opposite effect: increased pericyte viability and proliferation and reduced caspase 3/7 activity. Oligomer‐EP Aβ1‐40 had no impact on either of the cellular events. Our findings add to the growing number of studies suggesting a significant impact on pericytes in the brains of AD patients and suggest different aggregation forms of Aβ1‐40 as potential key regulators of the brain pericyte population size.
Formulating more consistent public health policies towards cannabis and tobacco
Authors: Hall Wayne , Kozlowski Lynn
Published: February 2018

Commentary to: The diverging trajectories of cannabis and tobacco policies in the United States: reasons and possible implications
Diversification Strategy, Ownership Structure, and Financial Crisis: Performance of Chinese Private Firms
Authors: Shen Na , Au Kevin , Yi Lan
Published: February 2018

The relationship between diversification and firm performance varies among institutions and over time. Less is known about the advantageousness of diversification in economy‐wide crises, which have occurred frequently in recent years. Using data on nearly 4000 Chinese private companies, we found that diversified firms performed better than focused firms during the recent global financial crisis. The diversification level was positively and linearly related to performance, that is, more diversified firms performed better. Moreover, we found that private firms that are totally owned by the founding owner and his/her family performed worse under crisis.
Innate lymphoid cells at the human maternal‐fetal interface in spontaneous preterm labor
Authors: Xu Yi , Romero Roberto , Miller Derek , Silva Pablo , Panaitescu Bogdan , Theis Kevin R. , Arif Afrah , Hassan Sonia S. , Gomez‐Lopez Nardhy
Published: February 2018

Problem

Pathological inflammation is causally linked to preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Our aims were to investigate whether (i) the newly described family of innate lymphoid cells (ILCs) was present at the human maternal‐fetal interface and (ii) ILC inflammatory subsets were associated with the pathological process of preterm labor.

Methods of study

Decidual leukocytes were isolated from women with preterm or term labor as well as from gestational age‐matched non‐labor controls. ILCs (CD15−CD14−CD3−CD19−CD56−CD11b−CD127+ cells) and their subsets (ILC1, T‐bet+ ILCs; ILC2, GATA3+ ILCs; and ILC3, RORγt+ ILCs) and cytokine expression were identified in the decidual tissues using immunophenotyping.

Results

(i) The proportion of total ILCs was increased in the decidua parietalis of women with preterm labor; (ii) ILC1s were a minor subset of decidual ILCs during preterm and term gestations; (iii) ILC2s were the most abundant ILC subset in the decidua during preterm and term gestations; (iv) the proportion of ILC2s was increased in the decidua basalis of women with preterm labor; (v) the proportion of ILC3s was increased in the decidua parietalis of women with preterm labor; and (vi) during preterm labor, ILC3s had higher expression of IL‐22, IL‐17A, IL‐13, and IFN‐γ compared to ILC2s in the decidua.

Conclusion

ILC2s were the most abundant ILC subset at the human maternal‐fetal interface during preterm and term gestations. Yet, during preterm labor, an increase in ILC2s and ILC3s was observed in the decidua basalis and decidua parietalis, respectively. These findings provide evidence demonstrating a role for ILCs at the maternal‐fetal interface during the pathological process of preterm labor.
Association between two common transitions of H2BFWT gene and male infertility: a case–control, meta, and structural analysis
Authors: Teimouri M. , Najaran H. , Hosseinzadeh A. , Mazoochi T.
Published: February 2018

H2BFWT is one of the testis‐specific histones that plays a fundamental role in spermatogenesis, and single nucleotide polymorphisms (SNPs) in this gene may result in male infertility. This study aimed to investigate the association between −9C>T and 368A>G transitions of H2BFWT gene and male infertility through a case–control, meta‐analysis, and a bioinformatics approach. In this case–control study, 490 subjects including 240 idiopathic infertile men and 250 healthy controls were included. The −9C>T and 368A>G SNPs genotyping were performed by a PCR–RFLP method. To find eligible studies for meta‐analysis, we searched valid scientific databases. The odds ratios with 95% confidence intervals were estimated to find the strength of these associations. Furthermore, the influences of two common transitions on the molecular features of H2BFWT were assessed by in silico tools. Our case–control data revealed that −9C>T is not associated with male infertility. But, there was a significant association between 368A>G and male infertility. In the meta‐analysis, five eligible studies were included. Our data revealed significant associations between −9C>T, 368A>G, and male infertility in overall and stratified analyses. Moreover, structural analysis showed that 368A>G could affect the protein structure (SNAP prediction: non‐neutral, score: 42, expected accuracy: 71%; SIFT prediction: deleterious, score: −2.55), while −9C>T may affect the binding nucleotide in the promoter region. Based on these findings, two aforementioned polymorphisms were associated with increased risk of male infertility. However, studies with larger sample size and different ethnicities are needed to obtain more accurate conclusions.
Endocrine and psychological aspects of sexual dysfunction in Klinefelter patients
Authors: Ferlin A. , Selice R. , Angelini S. , Di Grazia M. , Caretta N. , Cavalieri F. , Di Mambro A. , Foresta C.
Published: February 2018

Klinefelter syndrome is a frequent cause of hypogonadism, but despite hundreds of publications on different aspects of Klinefelter syndrome, only a few studies dealt with sexual dysfunction. In particular, testosterone is critical for various aspects of sexual response, but its role on sexuality in Klinefelter syndrome patients is debatable and no studies have evaluated the efficacy of testosterone treatment on sexual dysfunction in these subjects. Furthermore, the impact of psychological and relational aspects on sexual function of Klinefelter syndrome subjects is poorly defined. In this study, we aimed to determine the presence and type of sexual dysfunctions in Klinefelter syndrome subjects; to correlate them with testosterone levels and psychosexological and relational domains; and to evaluate the effects of testosterone therapy. We studied 62 non‐mosaic naïve Klinefelter syndrome patients and 60 age‐matched controls by means of medical history, psychosexological history, 15‐item International Index of Erectile Function questionnaire, endocrine assessment, and dynamic penile color Doppler ultrasound. Twenty‐five hypogonadal Klinefelter syndrome patients were studied after 6 months of testosterone replacement therapy. Klinefelter syndrome subjects have reduced 15‐item International Index of Erectile Function scores regarding sexual desire, intercourse satisfaction, and overall satisfaction with respect to controls, and these aspects were significantly associated with testosterone levels. Klinefelter syndrome subjects had also higher prevalence of erectile dysfunction, but no relation with testosterone levels was evident. A high prevalence of a range of psychological disturbances was present in Klinefelter syndrome subjects with erectile dysfunction with respect to those without erectile dysfunction. No statistical difference in the prevalence of premature and delayed ejaculation was observed between Klinefelter syndrome and control subjects. Testosterone replacement therapy improved sexual desire, intercourse satisfaction, and overall satisfaction scores, but had no effect on erectile function. Penile color Doppler ultrasound was normal in all subjects. This study shows that sexual dysfunction in Klinefelter syndrome is multifactorial and related only in part to hypogonadism and largely to psychological disturbances. Evaluation and therapy of sexual dysfunction should include a combined andrological and psychosexological approach.