bluuebunny/crossref_metadata_2025_split huggingface dataset:
ReCappable Seq: Comprehensive Determination of Transcription Start Sites derived from all RNA polymerases
Authors: Yan Bo , Tzertzinis George , Schildkraut Ira , Ettwiller Laurence 
Published: July 2019

AbstractDetermination of eukaryotic Transcription Start Sites (TSS) has been based on methods that require the cap structure at the 5’ end of transcripts derived from Pol-II RNA polymerase. Consequently, these methods do not reveal TSS derived from the other RNA polymerases which also play critical roles in various cell functions. To address this limitation, we developed ReCappable-seq which comprehensively identifies TSS for both Pol-lI and non-Pol-II transcripts at single-nucleotide resolution. The method relies on specific enzymatic exchange of 5’ m7G caps and 5’ triphosphates with a selectable tag. When applied to human transcriptomes, ReCappable-seq identifies Pol-II TSS that are in agreement with orthogonal methods such as CAGE. Additionally, ReCappable-seq reveals a rich landscape of TSS associated with Pol-III transcripts which have not previously been amenable to study at genome-wide scale. Novel TSS from non-Pol-II transcription can be located in the nuclear and mitochondrial genomes. ReCappable-seq interrogates the regulatory landscape of coding and non-coding RNA concurrently and enables the classification of epigenetic profiles associated with Pol-lI and non-Pol-II TSS.
Stochasticity of replication fork speed plays a key role in the dynamics of DNA replication
Authors: Yousefi Razie , Rowicka Maga 
Published: July 2019

AbstractEukaryotic DNA replication is elaborately orchestrated to duplicate the genome timely and faithfully. Replication initiates at multiple origins from which replication forks emanate and travel bi-directionally. The complex spatio-temporal regulation of DNA replication remains incompletely understood. To study it, computational models of DNA replication have been developed in S. cerevisiae. However, in spite of the experimental evidence of replication speed stochasticity, all models assumed that replication fork speed is constant or varies only with genomic coordinates. Here, we present the first model of DNA replication assuming stochastic speed of the replication fork. Utilizing data from both wild-type and hydroxyurea-treated yeast cells, we show that our model is more accurate than models assuming constant fork speed and reconstructs dynamics of DNA replication faithfully starting both from population-wide data and data reflecting fork movement in individual cells. Completion of replication in a timely manner is a challenge due to its stochasticity; we propose an empirically derived modification to replication speed based on the distance to the approaching fork, which promotes timely completion of replication. In summary, our work discovers a key role that stochasticity of the fork speed plays in the dynamics of DNA replication. We show that without including stochasticity of fork speed it is not possible to accurately reconstruct movement of individual replication forks, measured by DNA combing.Author summaryDNA replication in eukaryotes starts from multiple sites termed replication origins. Replication timing at individual sites is stochastic, but reproducible population-wide. Complex and not yet completely understood mechanisms ensure that genome is replicated exactly once and that replication is finished in time. This complex spatio-temporal organization of DNA replication makes computational modeling a useful tool to study replication mechanisms. For simplicity, all previous models assumed constant replication fork speed. Here, we show that such models are incapable of accurately reconstructing distances travelled by individual replication forks. Therefore, we propose a model with a stochastic replication fork speed. We show that such model reproduces faithfully distances travelled by individual replication forks. Moreover, our model is simpler than previous model and thus avoids over-learning (fitting noise). We also discover how replication speed may be attuned to timely complete replication. We propose that fork speed exponentially increases with diminishing distance to the approaching fork, which we show promotes timely completion of replication. Such speed up can be e.g. explained by a synergy effect of chromatin unwinding by both forks. Our model can be used to simulate phenomena beyond replication, e.g. DNA double-strand breaks resulting from broken replication forks.
Reconstructing temporal and spatial dynamics in single-cell experiments
Authors: Kuritz Karsten , Stöhr Daniela , Maichl Daniela , Pollak Nadine , Rehm Markus , Allgöwer Frank 
Published: July 2019

AbstractModern cytometry methods allow collecting complex, multi-dimensional data sets from heterogeneous cell populations at single-cell resolution. While methods exist to describe the progression and order of cellular processes from snapshots of such populations, these descriptions are limited to arbitrary pseudotime scales. Here we describe MAPiT, an universal transformation method that recovers real-time dynamics of cellular processes from pseudotime scales. As use cases, we applied MAPiT to two prominent problems in the flow-cytometric analysis of heterogeneous cell populations: (1) recovering the kinetics of cell cycle progression in unsynchronized and thus unperturbed cell populations, and (2) recovering the spatial arrangement of cells within multi-cellular spheroids prior to spheroid dissociation for cytometric analysis. Since MAPiT provides a theoretic basis for the relation of pseudotime values to real temporal and spatial scales, it can be used broadly in the analysis of cellular processes with snapshot data from heterogeneous cell populations.
Application of principles of supply chain management to the pharmaceutical good transportation practices
Authors: Kumar Nirmal , Jha Ajeya 
Published: July 2019

Purpose
Pharmaceuticals supply chain management (SCM) requires special expertise to transport the medicinal products because of weird features of their demand, supply and sensitivity towards quality. The purpose of this study is to establish the linkage of pharmaceutical quality system requirements with the SCM principles. The study enables the collaborative approach of technical, transport, logistics and supply chain teams within the pharmaceutical industry.

Design/methodology/approach
The methodology followed for this study is literature review and survey. The study is supplemented with data obtained through the structured questionnaire.

Findings
Through this study, an exclusive perspective for pharmaceutical good transportation practice (GTP) has been propagated in alignment with seven principles of SCM by Anderson. This study offers guidance to pharmaceutical industry for transportation of products by conceptualizing basic supply chain features such as segmentation, customization of requirement, market signals, differentiation, technology orientation and channel spanning performance.

Research limitations/implications
Here is limited information available about the transportation failures in the pharmaceutical industry. Application of supply chain principles to pharmaceutical transportation is sometimes affected by technical knowledge bias of the researcher.

Practical implications
The study has successfully expounded the practical aspects of pharmaceutical GTP for supply chain professionals.

Social implications
The study facilitates the patients and pharmaceutical consumers to get quality products in a timely manner across the globe.

Originality/value
The application of SCM principles to the pharmaceutical GTP is the result of novel research and has not been studied earlier.
Turnaround leaders’ shifting gears in chronos and kairos time
Authors: Yoon Irene H. , Barton Annie 
Published: July 2019

Purpose
In empirical research and practitioner guides, turnaround processes tend to be described in terms of discrete stages and strategies. Though necessary, this characterization belies the twists and turns of turnaround leadership. The purpose of this paper is to expand the assumptions of how turnaround proceeds in linear chronos time with the sensibilities of kairos time or the “right” time for turnaround leadership moves.

Design/methodology/approach
This study is an exploratory qualitative multi-case study with principals and their key supports (assistant principals, district leaders, teacher leaders) in four public turnaround schools. The grounded theory analysis conceptualizes the experiences of turnaround principals in flexible, complex ways.

Findings
The findings begin with a metaphor and definition of “shifting gears” at chronos and kairos times that emphasizes how turnaround principals make adaptive, agentic adjustments when moving forward through changing terrain. The second half of findings describes each principal’s experiences and reflections on their discernment of the right times for change within a chronological trajectory of turnaround. In addition, the leaders described shifting gears as strategic and responsive to contexts, sometimes taking a psychological toll.

Originality/value
Expanding notions of time in turnaround re-centers turnaround leaders as engaging in intellectually and emotionally demanding work. Such recognition challenges future research to address experiences and emotions in dynamic contexts. Hence, with this study, preparation programs and state and local systems may adjust holistic supports and leadership pipelines to sustain turnaround leaders.
Systematic review with meta‐analysis of over 90 000 patients. Does fast‐track review diagnose colorectal cancer earlier?
Authors: Mozdiak Ella , Weldeselassie Yonas , McFarlane Michael , Tabuso Maria , Widlak Monika M. , Dunlop Amber , Tsertsvadze Alexander , Arasaradnam Ramesh P. 
Published: July 2019

SummaryBackgroundNational UK data on colorectal cancer (CRC) stage at diagnosis is incomplete. Site‐specific fast‐track (2‐week wait) cancer data are not collected directly by NHS England. Policy making based on these data alone can lead to inaccuracy.AimsTo review available data on key outcomes (cancer conversion rate and stage at diagnosis) for the UK's lower gastrointestinal 2‐week wait pathway.MethodsA comprehensive literature search was conducted between 2000 and 2017. Primary outcomes were cancer conversion rate and cancer stage at diagnosis. Results were expressed as proportions with 95% CIs. A random effects model was used for meta‐analysis; heterogeneity was assessed by I2.ResultsOf 95 papers reviewed, 49 were included in analysis with a total study population of 93,655. Cancer conversion rate was 7.7% (95% CI: 6.9‐8.5). The proportion presenting at Dukes A = 11.2% (95% CI 7.4‐15.6), B = 36.7% (95% CI 30.8‐42.8), C = 35.7% (95% CI: 30.8‐40.8) and D = 11.1% (95% CI 7.3‐15.5). No colonic pathology was diagnosed in 54.6% (95% CI: 46.2‐62.8).ConclusionsOnly 7.7% of patients referred by the 2‐week wait pathway were found to have CRC. No beneficial effect on stage at diagnosis was found compared to non‐2‐week wait referral pathways. Over half of patients had no colonic pathology and detection of adenomas was very low. These results should prompt a reconsideration of the benefits of the 2‐week wait pathway in CRC diagnosis and outcomes, with more focus on strategies to improve patient selection.
Histological and histomorphometric analysis of bone tissue after guided bone regeneration with non‐resorbable membranes vs resorbable membranes and titanium mesh
Authors: Cucchi Alessandro , Sartori Maria , Parrilli Annapaola , Aldini Nicolò N. , Vignudelli Elisabetta , Corinaldesi Giuseppe 
Published: July 2019

AbstractBackgroundGuided bone regeneration (GBR) allows to achieve vertical ridge augmentation whether with nonresorbable membranes or resorbable membranes with Ti‐mesh, but till now no studies are published comparing histological and histomorphometrical outcomes of these two procedures.Materials and MethodsForty partially edentulous patients required vertical bone regeneration to place implants in the posterior mandible: 20 patients were randomly assigned to group A (Ti‐PTFE); while 20 patients to group B (Collagen plus Ti‐mesh). For both groups, graft material was a 50:50 mixture of autogenous bone and bone allograft. After 9 months, tissue biopsies were taken from augmented sites (regenerated bone ROI‐1; native bone ROI‐2) and undergone to histological and histomorphometric analysis. Percentages of bone tissue (B.Ar), biomaterial (Mat. Ar), and soft tissue (St.Ar) were measured; measurements of perimeters were calculated too. ROI‐1 values were also compared to ROI‐2 in both groups.ResultsTwenty‐five samples were collected and analyzed consecutively: 13 in group A and 12 in group B. The mean B.Ar, Mat.Ar, and St.Ar were 39.7%, 8.6%, and 52.1% in group A; similar results were obtained in group B, with mean values of 42.1%, 9.6%, and 48.3%, respectively. No significant statistically differences were observed. Differences were observed between ROI‐1 and ROI‐2 in both group. Finally, bone structure index of ROI‐1 and ROI‐2 showed statistical differences.ConclusionsThe preliminary results of this study suggest that GBR using nonresorbable membranes and Ti‐mesh with resorbable membranes in combination with autogenous bone and bone allograft provide similar histological and histomorphometric results.
Food Dependency in Sub‐Saharan Africa: Simply a Matter of ‘Vulnerability’, or Missed Development Opportunity?
Authors: Arment C. Jean 
Published: July 2019

ABSTRACTThis article seeks to refocus some of the attention devoted in the past several decades to the issue of food security in sub‐Saharan Africa to the broader context of food dependency. Using panel data for 44 countries over a period of 51 years (1961–2011), the article tests several hypotheses drawn from Lewis's classical model of development characterized by ‘unlimited supplies of labour’. The model requires either rising agricultural productivity (the closed model) or imports of global market foodstuffs (the open model) to ensure the low food prices and wages required for capital accumulation. Empirical results reject a positive association between food dependency, as represented by five decades of increasing per capita grain imports, and any measurable level of economic modernization with sufficient forward momentum to spur or justify such dependency. Results suggest instead a significant correlation between increasing food dependency and separate panel time periods associated with differing trade and policy regimes. More importantly, empirical results call for a re‐evaluation of Lewis's original development model, focusing on the pivotal role of a supported food subsistence sector in creating economic possibilities for development.
Measurement of mitral valve area in patients with mitral stenosis by 3D echocardiography: A comparison between direct planimetry on 3D zoom and 3D quantification
Authors: Sadeghian Hakimeh , Rezvanfard Mehrnaz , Jalali Arash 
Published: July 2019

AbstractBackgroundMeasurement of the mitral valve area (MVA) in patients with mitral stenosis (MS) by 3D echocardiography (3DE) is usually done via 3D quantification (3DQ). The present study on patients with severe MS sought to evaluate the agreement regarding the MVA measurement between 3DQ and direct planimetry on 3D zoom and also between 3DE and 2DE.MethodsTwenty‐six patients (22 female, mean age:34.5 ± 14.0 years) with severe MS diagnosed by 2D transthoracic echocardiography(2DTTE) underwent 3D transesophageal echocardiography (3DTEE). Direct planimetry, the pressure half‐time (PTH), and the continuity equation(CE) constituted 3 conventional 2DTTE methods, and 3DQ and direct planimetry on 3D zoom comprised two 3DTEE methods applied for the MVA measurement. Agreement between the 2D and 3D methods was assessed using the Bland–Altman plot and measuring the intra‐class correlation coefficient (ICC).ResultsThe mean MVA measured by 3DQ was significantly larger than that derived by direct planimetry on 3D zoom (0.935 ± 0.23 cm2 vs 0.846 ± 0.22 cm2, respectively; P = 0.026). The agreement between 3DQ and 3D zoom for the MVA measurement was moderate to good by the Bland–Altman plot (ICC = 0.67). The mean MVA measured by 2DE (all 3 methods of direct planimetry, the PTH, and the CE) was significantly larger than that derived by 3DE (both methods of 3DQ and direct planimetry on 3D zoom) (all Ps < 0.05). A moderate agreement between 3DQ and 2D planimetry (ICC = 0.43) was found by the Bland–Altman plot.ConclusionsThe MVA measurement by direct planimetry on 3D zoom showed a moderate‐to‐good agreement with 3DQ; it may, thus, be used in clinical practice as a simple method for the measurement of the MVA in patients with MS.
Intraoral confocal microscopy of suspicious oral lesions: a prospective case series
Authors: Contaldo Maria , Lauritano Dorina , Carinci Francesco , Romano Antonio , Di Stasio Dario , Lajolo Carlo , Della Vella Fedora , Serpico Rosario , Lucchese Alberta 
Published: July 2019

AbstractBackgroundOral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors.Materials and MethodsA series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated.ResultsTotally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive‐ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV).ConclusionRCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway.
Clinical performance evaluation of the new hematology analyzer Mindray BC‐6000
Authors: Shen Yimin , Cao Jun , Zhou Zhiying , Wang Yong , Shen Yili , He Jun 
Published: July 2019

AbstractIntroductionWith the progression of blood analysis technology, hematology analyzers become more complex and diverse. How to choose a superb instrument is a challenge for the laboratories. In the essay, we studied whether the newest BC‐6000 hematology analyzer meets the needs of a clinical hematology laboratory.MethodsMethods comparison was performed using 350 blood samples from patients between different measurement procedures; the basic analytical performance was also tested, including the throughput, carryover, precision, and linearity in different modes. The flagging performances for blasts, immature granulocytes, and NRBC were compared with manual microscopy.ResultsThere were minimal carryover (<0.30%) and excellent actual blood linearity for all routinely used parameters concerned by the clinicians (R2 ≥ 0.997). Repeatability and reproducibility were satisfactory at all testing levels. The functional sensitivity of leukocytes and platelets in the blood and leukocytes and erythrocytes in body fluid was excellent at the 20% CV level. BC‐6000 and XN displayed very high correlations for complete blood count (CBC) parameters and very high consistency for leukocyte differentials and NRBC compared with manual microscopy. BC‐6000 showed excellent sensitivity and specificity flagging ability on blasts (82.9% and 82.4%) and NRBC (80.0% and 96.9%). For immature granulocytes, BC‐6000 showed excellent sensitivity but common specificity flagging ability (91.7% and 65.6%).ConclusionThe clinical performance of BC‐6000 is excellent, and the analyzer can provide timely and accurate reporting for most of the small‐ to large‐scale laboratories.
Prevention of Lower Urinary Tract Symptoms Research Consortium focus group Study of Habits, Attitudes, Realities, and Experiences of Bladder health
Authors: Kane Low Lisa , Williams Beverly Rosa , Camenga Deepa R. , Hebert‐Beirne Jeni , Brady Sonya S. , Newman Diane K. , James Aimee S. , T. Hardacker Cecilia , Nodora Jesse , Linke Sarah E. , Burgio Kathryn L. 
Published: July 2019

AbstractAimThe study purpose is to explore adolescent and adult women's experiences, perceptions, beliefs, knowledge and behaviours related to bladder health across the life course using a socioecological perspective. Lower urinary tract symptoms affect between 20–40% of young adult to middle‐aged women, with symptoms increasing in incidence and severity with aging. There is limited evidence to address bladder health promotion and prevention of dysfunction. This first study of the Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium is designed to address gaps in existing qualitative research in this area.DesignThis focus group study will be implemented across seven geographically diverse United States research centres using a semi‐structured focus group guide informed by a conceptual framework based on the socioecological model.MethodsThe study was approved in July 2017. A total of 44 focus groups composed of 6–8 participants representing six different age categories (ranging from 11 to over 65 years) will be completed. We aim to recruit participants with diverse demographic and personal characteristics including race, ethnicity, education, socioeconomic status, urban/rural residence, physical/health conditions, and urinary symptom experience. Six of the focus groups will be conducted in Spanish and translated into English. Focus group transcripts will undergo content analysis and data interpretation to identify and classify themes and articulate emerging themes.DiscussionThis foundational qualitative study seeks to develop an evidence base to inform future research on bladder health promotion in adolescent and adult women.ImpactThis study has the potential to provide new insights and understanding into adolescent and adult women's lived experience of bladder health, the experience of lower urinary symptoms and knowledge and beliefs across the life course.