bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of RNA Extraction and Target Capture Methods on RNA Sequencing Using Formalin-Fixed, Paraffin Embedded Tissues
Authors: Hilker Christopher A. , Bhagwate Aditya V. , Jang Jin Sung , Meyer Jeffrey G , Nair Asha A. , Davila Jaime I. , McDonald Amber M. , Winters Jennifer L. , Wehrs Rebecca N. , Jackson Rory A. , Gorman Joshua A. , Cicek Mine S. , Oliveira Andre M. , Thompson E. Aubrey , Eckloff Bruce W. , Halling Kevin C. , Sun Zhifu A. , Jen Jin
Published: June 2019

Formalin fixed paraffin embedded (FFPE) tissues are commonly used biospecimen for clinical diagnosis. However, RNA degradation is extensive when isolated from FFPE blocks making it challenging for whole transcriptome profiling (RNA-seq). Here, we examined RNA isolation methods, quality metrics, and the performance of RNA-seq using different approaches with RNA isolated from FFPE and fresh frozen (FF) tissues. We evaluated FFPE RNA extraction methods using six different tissues and five different methods. The reproducibility and quality of the prepared libraries from these RNAs were assessed by RNA-seq. We next examined the performance and reproducibility of RNA-seq for gene expression profiling with FFPE and FF samples using targeted (Kinome capture) and whole transcriptome capture based sequencing. Finally, we assessed Agilent SureSelect All-Exon V6+UTR capture and the Illumina TruSeq RNA Access protocols for their ability to detect known gene fusions in FFPE RNA samples. Although the overall yield of RNA varied among extraction methods, gene expression profiles generated by RNA-seq were highly correlated (>90%) when the input RNA was of sufficient quality (≥DV200 30%) and quantity (≥ 100 ng). Using gene capture, we observed a linear relationship between gene expression levels for shared genes that were captured using either All-Exon or Kinome kits. Gene expression correlations between the two capture-based approaches were similar using RNA from FFPE and FF samples. However, TruSeq RNA Access protocol provided significantly higher exon and junction reads when compared to the SureSelect All-Exon capture kit and was more sensitive for fusion gene detection. Our study established pre and post library construction QC parameters that are essential to reproducible RNA-seq profiling using FFPE samples. We show that gene capture based NGS sequencing is an efficient and highly reproducible strategy for gene expression measurements as well as fusion gene detection.
Coordination of multiple joints increases bilateral connectivity with ipsilateral sensorimotor cortices
Authors: Wilkins Kevin B. , Yao Jun
Published: June 2019

Although most activities of daily life require simultaneous coordination of both proximal and distal joints, motor preparation during such movements has not been well studied. Previous results for motor preparation have focused on hand/finger movements. For simple hand/finger movements, results have found that such movements typically evoke activity primarily in the contralateral motor cortices. However, increasing the complexity of the finger movements, such as during a distal sequential finger-pressing task, leads to additional recruitment of ipsilateral resources. It has been suggested that this involvement of the ipsilateral hemisphere is critical for temporal coordination of distal joints. The goal of the current study was to examine whether increasing simultaneous coordination of multiple joints (both proximal and distal) leads to a similar increase in coupling with ipsilateral sensorimotor cortices during motor preparation compared to a simple distal movement such as hand opening. To test this possibility, 12 healthy individuals participated in a high-density EEG experiment in which they performed either hand opening or simultaneous hand opening while lifting at the shoulder on a robotic device. We quantified within- and cross-frequency cortical coupling across the sensorimotor cortex for the two tasks using dynamic causal modeling. Both hand opening and simultaneous hand opening while lifting at the shoulder elicited coupling from secondary motor areas to primary motor cortex within the contralateral hemisphere exclusively in the beta band, as well as from ipsilateral primary motor cortex. However increasing the task complexity by combining hand opening while lifting at the shoulder also led to an increase in coupling within the ipsilateral hemisphere as well as interhemispheric coupling between hemispheres that expanded to theta, mu, and gamma frequencies. These findings demonstrate that increasing the demand of joint coordination between proximal and distal joints leads to increases in communication with the ipsilateral hemisphere as previously observed in distal sequential finger tasks.
Armadillo repeat-containing protein 1 is a dual localization protein associated with mitochondrial intermembrane space bridging complex
Authors: Wagner Fabienne , Kunz Tobias C. , Chowdhury Suvagata R. , Thiede Bernd , Fraunholz Martin , Eger Debora , Kozjak-Pavlovic Vera
Published: June 2019

Cristae architecture is important for the function of mitochondria, the organelles that play the central role in many cellular processes. The mitochondrial contact site and cristae organizing system (MICOS) together with the sorting and assembly machinery (SAM) forms the mitochondrial intermembrane space bridging complex (MIB), a large protein complex present in mammalian mitochondria that partakes in the formation and maintenance of cristae. We report here a new subunit of the mammalian MICOS/MIB complex, an armadillo repeat-containing protein 1 (ArmC1). ArmC1 localizes both to cytosol and mitochondria, where it associates with the outer mitochondrial membrane through its carboxy-terminus. ArmC1 interacts with other constituents of the MICOS/MIB complex and its amounts are reduced upon MICOS/MIB complex depletion. Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility. ArmC1 represents therefore a peripheral MICOS/MIB component that appears to play a role in mitochondrial distribution in the cell.
Deconstructing hunting behavior reveals a tightly coupled stimulus-response loop
Authors: Mearns Duncan S. , Semmelhack Julia L. , Donovan Joseph C. , Baier Herwig
Published: June 2019

Animals build behavioral sequences out of simple stereotyped actions. A comprehensive characterization of these actions and the rules underlying their temporal organization is necessary to understand sensorimotor transformations performed by the brain. Here, we use unsupervised methods to study behavioral sequences in zebrafish larvae. Generating a map of swim bouts, we reveal that fish modulate their tail movements along a continuum. We cluster bouts that share common kinematic features and contribute to similar behavioral sequences into seven modules. Behavioral sequences comprising a subset of modules bring prey into the anterior dorsal visual field of the larvae. Fish then release a capture maneuver comprising a stereotyped jaw movement and fine-tuned stereotyped tail movements to capture prey at various distances. We demonstrate that changes to chaining dynamics, but not module production, underlie prey capture deficits in two visually impaired mutants. Our analysis thus reveals the temporal organization of a vertebrate hunting behavior, with the implication that different neural architectures underlie prey pursuit and capture.
Changes-of-mind in the absence of new post-decision evidence
Authors: Atiya Nadim A. A. , Zgonnikov Arkady , Schoemann Martin , Scherbaum Stefan , O’Hora Denis , Wong-Lin KongFatt
Published: June 2019

Decisions are occasionally accompanied by changes-of-mind. While considered a hallmark of cognitive flexibility, the mechanisms underlying changes-of-mind remain elusive. Previous studies on perceptual decision making have focused on changes-of-mind that are primarily driven by the accumulation of additional noisy sensory evidence after the initial decision. In a motion discrimination task, we demonstrate that changes-of-mind can occur even in the absence of additional evidence after the initial decision. Unlike previous studies of changes-of-mind, the majority of changes-of-mind in our experiment occurred in trials with prolonged initial response times. This suggests a distinct mechanism underlying such changes. Using a neural circuit model of decision uncertainty and change-of-mind behaviour, we demonstrate that this phenomenon is associated with top-down signals mediated by an uncertainty-monitoring neural population. Such a mechanism is consistent with recent neurophysiological evidence showing a link between changes-of-mind and elevated top-down neural activity. Our model explains the long response times associated with changes-of-mind through high decision uncertainty levels in such trials, and accounts for the observed motor response trajectories. Overall, our work provides a computational framework that explains changes-of-mind in the absence of new post-decision evidence.

Authors Summary

We used limited availability of sensory evidence during a standard motion discrimination task, and demonstrated that changes-of-mind could occur long after sensory information was no longer available. Unlike previous studies, our experiment further indicated that changes-of-mind were strongly linked to slow response time. We used a reduced version of a previously developed neural computational model of decision uncertainty and change-of-mind to account for these experimental observations. Importantly, our model showed that the replication of these experimental results required a strong link between change-of-mind and high decision uncertainty (i.e. low decision confidence), supporting the notion that change-of-mind are related to decision uncertainty or confidence.
The sensitivity of seabird populations to density‐dependence, environmental stochasticity and anthropogenic mortality
Authors: Miller Julie A. O. , Furness Robert W. , Trinder Mark , Matthiopoulos Jason
Published: June 2019

The balance between economic growth and wildlife conservation is a priority for many governments. Enhancing realism in assessment of population‐level impacts of anthropogenic mortality can help achieve this balance. Population Viability Analysis (PVA) is commonly applied to investigate population vulnerability, but outcomes of PVA are sensitive to formulations of density‐dependence, environmental stochasticity and life history. Current practice in marine assessments is to use precautionary models that assume no compensation from density‐dependence or rescue‐effects via “re‐seeding” from other colonies. However, if we could empirically quantify regulatory population processes, the responses of populations to additional anthropogenic mortality may be assessed with more realism in PVA.

Using Bayesian state‐space models fitted to population time series from three sympatric seabird populations, selected for varied life histories, we inferred the extent to which their dynamics are driven by environmental stochasticity and density‐dependence.

Based on these inferences, we conducted an exhaustive PVA across credible parameterizations for intrinsic and extrinsic population regulation, simulated as a closed and re‐seeded system. Scenarios of anthropogenic mortality, along a sliding scale of precaution, were applied both proportionally and as a fixed quota using Potential Biological Removal (PBR).

Baseline results from fitting revealed clear environmental regulation in two of our three species. Crucially, we found that for our empirically derived, realistic model parameterizations there are risks of decline to real populations even under very precautionary mortality scenarios. We find that PBR is dubious in application as a sustainable tool for population assessment when we account for regulation. Closed versus re‐seeded models showed a large divergence in outcomes, with sharper declines in closed simulations. Fixed‐quota mortality typically induced greater population declines comparative to proportional mortality, subject to regulation and re‐seeding.

Synthesis and applications. Practitioners using arbitrary formulations of population regulation risk over‐precaution (economic constraint) or under‐precaution (endangering populations). The demands of increased economic development and preservation of wildlife require that methodologies apply techniques that confer reality and rigour to assessment. The current practice of employing models lacking density‐dependence and empirical environmental information imposes limitations in the efficacy of estimating impacts. Here, we provide a method to quantify the conditions that predominantly regulate a population and exacerbate the risk of decline from anthropogenic mortality. It is in the interests of both developers and conservationists to apply methods in population impact assessments that capture realism in the processes driving population dynamics.
Invasion of Euryops floribundus in degraded South African communal grassland: Unpacking the invasion relationship with elevation, soil properties, the quality and quantity of the herbaceous layer
Authors: Masibonge Gxasheka , Tefera Solomon , Mota Lesoli
Published: June 2019

Shrub invasion is a recent occurrence in African grassland ecosystems. This study assessed the distribution of Euryops floribundus (a native shrub species) along an elevation and invasion intensity gradients, and its relationship with soil and herbaceous vegetation in a South African grassland. Shrub density increased (p < 0.05) from the uplands (2,301 plants/ha) to the bottomlands (4,888 plants/ha). Themeda triandra (a highly palatable grass) was dominant at the uplands and sloping sites, whereas Eragrostis plana and Sporobolus africanus (poorly palatable grasses) dominated the bottomlands. Upland soils had the highest organic carbon (OC), phosphorous (P), calcium and nitrogen (N) contents, but the lowest shrub density and herbaceous biomass. Canonical correspondence analysis indicated that elevation, soil OC and N contents determine important vegetation variables along the elevation gradient. In the shrub density gradient, soil P, OC and N responded positively to E. floribundus density. Grass biomass in the moderate and heavily invaded sites was high, but the abundance of palatable grasses declined, suggesting that E. floribundus invasion may be concomitant with a decrease in rangeland condition in terms of quality forage provision.
Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early‐onset lone atrial fibrillation
Authors: Seifert Mariam B. , Olesen Morten S. , Christophersen Ingrid E. , Nielsen Jonas B. , Carlson Jonas , Holmqvist Fredrik , Tveit Arnljot , Haunsø Stig , Svendsen Jesper H. , Platonov Pyotr G.
Published: June 2019

Background

Abnormal P‐wave morphology (PWM) has been associated with a history of atrial fibrillation (AF) in earlier studies. Although lone AF is believed to have substantial genetic basis, studies on associations between single nucleotide polymorphisms (SNP) linked to lone AF and PWM have not been reported. We aimed to assess whether SNPs previously associated with lone AF (rs2200733, rs13376333, rs3807989, and rs11047543) are also linked to P‐wave abnormalities.

Methods

Four SNPs were studied in 176 unrelated individuals with early‐onset lone AF (age at onset <50 years), median age 38 years (19–63 years), 149 men. Using sinus rhythm ECG, orthogonal PWM was classified as Type 1—positive in leads X and Y and negative in lead Z, Type 2—positive in leads X and Y and biphasic (−/+) in lead Z, Type 3—positive in lead X and biphasic in lead Y (+/−), and the remaining as atypical.

Results

Two SNPs were found to be significantly associated with altered P‐wave morphology distribution: rs3807989 near the gene CAV1/CAV2 and rs11047543 near the gene SOX5. Both SNPs were associated with a higher risk of non‐Type 1 P‐wave morphology (rs3807989: OR = 4.8, 95% CI = 2.3–10.2, p < 0.001; rs11047543: OR = 4.7, 95% CI = 1.1–20.5, p = 0.04). No association was observed for rs2200733 and rs13376333.

Conclusion

In this study, the two variants rs3807989 and rs11047543, previously associated with PR interval and lone AF, were associated with altered P‐wave morphology distribution in patients with early‐onset lone AF. These findings suggest that common genetic variants may modify atrial conduction properties.
Deregulation, workplace, and women: Nurses in private health care in India
Authors: Basu Hemantika
Published: June 2019

The paper examines the growth of private health care in India in the context of its regulatory provisions and questions the work and employment conditions of female care workers (nurses) employed there. Nurses constitute 80% of the total workers in each nursing home/hospital. In the wake of increased demand for private health care since mid‐1990s, insertion of technology and investment is inducing transformation of nursing homes into multi‐ and super‐speciality hospitals resulting in changes in work organization of nurses. This has led to demand for larger numbers of workers. Employers gain by the segmentation in the nursing labor market, paying low wages. Workers face widespread social discrimination, long working hours, and high work intensity. The deplorable situation of a significant section of workers employed in this sector indicates state failure to control the private health sector. Lack of effective standards of work impacts nature of work of the workforce employed in various levels in the healthcare system.
3‐Arylindanones and related compounds as antiproliferative agents against colorectal cancer
Authors: Srivastava Ankita , Ravi Kusumoori , Fatima Kaneez , Maheshwari Mayank , Ashraf Raghib , Hasanain Mohammad , Yadav Pankaj , Iqbal Hina , Kumar Yogesh , Luqman Suaib , Chanda Debabrata , Khan Feroz , Shanker Karuna , Sarkar Jayanta , Negi Arvind Singh
Published: June 2019

Diverse benzylidene indanones and their derivatives were synthesized as anticancer agents. Two of the analogues, that is 7 and 22, exhibited significant antiproliferative activity against several human cancer cell lines. Both the compounds possessed antimitotic activity and induced apoptosis in DLD1 colorectal adenocarcinoma cells through activation of caspase pathways. In cell cycle analysis, both the compounds induced predominantly G2/M phase arrest in DLD1 cells. Molecular docking studies revealed that compound 7 occupies colchicine binding pocket of β‐tubulin. Both the compounds were safe in acute oral toxicity in rodents. Both the compounds are further being optimized for better efficacy.
Susceptibility‐directed anticoagulation after pancreas transplantation: A single‐center retrospective study
Authors: Raveh Yehuda , Ciancio Gaetano , Burke George W. , Figueiro Jose , Chen Linda , Morsi Mahmoud , Namias Nicholas , Singh Bhavna P. , Lindsay Martine , Alfahel Waseem , Sleem Mahmoud S. , Nicolau‐Raducu Ramona
Published: June 2019

Pancreas transplant achieves consistent long‐term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous kidney‐pancreas or isolated pancreas transplanted between 1/1/2015 and 11/20/2018. Early postoperative anticoagulation regimens included the following: none, subcutaneous heparin/aspirin, with or without dextran, and heparin infusion. The regimens were empirically selected based on each surgeon's assessment of hemostasis of the operative field and personal preference. A sonographic‐based global scoring system of AT is presented. The 47‐month recipients and graft survival were 95% and 86%, respectively. Recipients with or without AT had similar survival. Five and four grafts were lost due to death and AT, respectively. Outcomes of prophylaxis regimens correlated with intensity of anticoagulation. Compared with no anticoagulation, an increase in hemorrhagic complications occurred exclusively with iv heparin. The higher arterial AT score found in regimens lacking antiplatelet therapy highlights the importance of early antiaggregants therapy. Abnormal fibrinolysis was associated with an increase in AT score. Platelet dysfunction, warm ischemia time, and enteric drainage were predictive of AT and, along with other known risk factors, were incorporated into an algorithm that matches intensity of early postoperative anticoagulation to the thrombotic risk.
The role of gene fusions in melanocytic neoplasms
Authors: Quan Victor L. , Panah Elnaz , Zhang Bin , Shi Katherine , Mohan Lauren S. , Gerami Pedram
Published: June 2019

Recent advances in next generation sequencing (NGS) have allowed for efficient whole transcriptome sequencing, leading to the identification of important kinase fusions as the primary driver in some melanocytic neoplasms. These fusions typically occur mutually exclusively of one another and other well‐known initiating mutations such as BRAF, NRAS, NF1, KIT, and GNAQ. Fusions are found in over 50% of Spitz neoplasms, including ALK, BRAF, NTRK1, NTRK3, ROS1, MET, MAP3K8, and RET. Familiarity with the typical morphologic features of certain fusion‐driven melanocytic neoplasms can help with classification, diagnosis, and identification of targeted molecular therapies in malignant cases. Spitz tumors with ALK, NTRK1, and NTRK3 fusions have characteristic morphologic features. BRAF and MAP3K8 fusions, in particular, tend to be epithelioid, high grade, and more frequent in Spitz melanoma than other fusion subtypes. Sporadic cases of pigmented epithelioid melanocytoma may have PRKCA fusions and sheets of monomorphic epithelioid melanocytes. Fusion events are also enriched among melanomas without the key mutations BRAF, NRAS, or NF1. Although NGS is the most reliable method to detect fusions, immunohistochemistry and fluorescence in situ hybridization are cost‐effective alternatives in some cases. We describe recent discoveries regarding the role of kinase fusions in melanocytic neoplasms and their associated morphologies.
A simple method to estimate the probable distribution of species
Authors: García‐Roselló Emilio , Guisande Cástor , González‐Vilas Luis , González‐Dacosta Jacinto , Heine Juergen , Pérez‐Costas Elisa , Lobo Jorge M.
Published: June 2019

Species distribution models (SDMs) are broadly used to predict species distributions from available presence data. However, SDMs results have been criticized for several reasons mainly related to two basic characteristics of most SDMs: 1) general lack of reliable species absence information, 2) the frequent use of an arbitrary geographical extent (GE) or accessible area of the species. These impediments have motivated us to generate a procedure called niche of occurrence (NOO). NOO provides the probable distribution of species (realized niche) relying solely on partial information about presence of species. It operates within a natural geographical extent delimited by available observations and avoids using misleading thresholds to obtain binary presence–absence estimations when the species prevalence is unknown. In this study the main characteristics of NOO are presented, comparing its performance with other recognized and more complex SDMs by using virtual species to avoid the omnipresent error sources of real data sets.
How does orofacial trauma in children affect the developing dentition? Long‐term treatment and associated complications
Authors: Flores Marie Therese , Onetto Juan Eduardo
Published: June 2019

Each year, millions of children are injured and live with the consequences of those injuries. Through infancy and childhood, orofacial trauma caused by falls or being struck by or against objects occurs in children. The long‐term implications on the developing permanent teeth are little known, even when the oral region is the second most frequently injured body area in children under 6 years of age. During this period, the developing permanent teeth may be directly involved after trauma, causing mild to severe hypoplasia, displacement, damage to the tooth germ, or an extended range of morphofunctional disturbances. In some cases, the effects of oral and dental injuries caused by trauma appear later with the eruption of the permanent incisors when ectopic eruption, malalignments, and other developmental disturbances become visible. Therefore, long‐term follow up of the patient in order to diagnose and treat associated complications becomes essential. Critical points for facing the consequences of orofacial trauma on the developing dentition are to recognize the impact of orofacial trauma in young children and the dentist's role in providing anticipatory guidance to parents and health care professionals, differentiate between mild and severe disturbances affecting the developing permanent teeth after oral injuries in early childhood, recognize the importance of follow‐up controls, and recognize the importance of early referral to a pediatric dentist and orthodontist for diagnosis and treatment planning.
MYCT1 represses apoptosis of laryngeal cancerous cells through the MAX/miR‐181a/NPM1 pathway
Authors: Wang He‐Tan , Tong Xue , Zhang Zhao‐Xiong , Sun Yuan‐Yuan , Yan Wei , Xu Zhen‐Ming , Fu Wei‐Neng
Published: June 2019

MYCT1 is an important gene known to regulate cell viability and apoptosis of laryngeal cancer cells. However, the underlying molecular mechanism remains unclear. Here, we show that MAX enhances the expression of miR‐181a by directly binding to its promoter, whereas miR‐181a targets NPM1 and suppresses its expression in laryngeal cancer cells. MYCT1 and miR‐181a decrease cell viability and colony formation through enhanced apoptosis, whereas NPM1 displays opposite effects in laryngeal cancer cells. Their opposing functions are further supported by the findings (a) that miR‐181a is down‐regulated, while NPM1 is up‐regulated in laryngeal cancer, and (b) that either inhibition of miR‐181a or overexpression of NPM1 can revert the pro‐apoptotic effects of MYCT1 on laryngeal cancer cells through extracellular and intracellular apoptotic pathways. Our data suggest that MYCT1 may synergistically interact with MAX as a co‐transcription factor or a component of MAX transcriptional complex, to transcriptionally regulate the expression of miR‐181a, which, in turn, decreases NPM1 expression at post‐transcriptional levels, leading to enhanced apoptosis in laryngeal cancer cells. These factors may serve as potential targets for early diagnosis and treatment of laryngeal cancer.
Flexible regions govern promiscuous binding of IL‐24 to receptors IL‐20R1 and IL‐22R1
Authors: Zahradník Jiří , Kolářová Lucie , Peleg Yoav , Kolenko Petr , Svidenská Silvie , Charnavets Tatsiana , Unger Tamar , Sussman Joel L. , Schneider Bohdan
Published: June 2019

Interleukin 24 (IL‐24) is a cytokine with the potential to be an effective treatment for autoimmune diseases and cancer. However, its instability and difficulties in its production have hampered detailed biological and biophysical studies. We approached the challenges of IL‐24 production by using the PROSS algorithm to design more stable variants of IL‐24. We used homology models built from the sequences and known structures of IL‐20 and IL‐19 and predicted and produced several extensively mutated IL‐24 variants that were highly stable and produced in large yields; one of them was crystallized (IL‐24B, PDB ID 6GG1; 3D Interactive at http://proteopedia.org/w/Journal: FEBS_Journal:1). The mutated variants, however, lost most of their binding capacity to the extracellular parts of cognate receptors. While the affinity to the receptor 2 (IL‐20R2) was preserved, the variants lost affinity to IL‐20R1 and IL‐22R1 (shared receptors 1). Back engineering of the variants revealed that reintroduction of a single IL‐24 wild‐type residue (T198) to the patch interacting with receptors 1 restored 80% of the binding affinity and signaling capacity, accompanied by an acceptable drop in the protein stability by 9 °C. Multiple sequence alignment explains the stabilizing effect of the mutated residues in the IL‐24 variants by their presence in the related and more stable cytokines IL‐20 and IL‐19. Our homology‐based approach can enhance existing methods for protein engineering and represents a viable alternative to study and produce difficult proteins for which only in silico structural information is available, estimated as >40% of all important drug targets.
Containment of Sources of Groundwater Contamination: Analysis of Mass Fluxes
Authors: Neville Christopher J. , Andrews Charles B.
Published: June 2019

Cutoff walls and liners are used frequently as barriers to isolate contaminants at both controlled and uncontrolled hazardous waste sites. Neville and Andrews (2006) presented a containment criterion for contaminant isolation by a barrier. The analysis of Neville and Andrews (2006) yields the inward Darcy flux that balances the diffusive mass flux from the source so that the net mass flux is zero. A requirement of zero net mass flux may not be achievable in all situations. The analysis developed by Neville and Andrews (2006) is extended to develop straightforward expressions for the long‐term mass fluxes across a barrier for any conditions. In cases where it may not be possible to satisfy a criterion of zero net mass flux, the results from an exact solution for transient solute transport are used to show how the mass fluxes evolve to their long‐term values.
Histomorphological and molecular profiling: friends not foes! Morpho‐molecular analysis reveals agreement between histological and molecular profiling
Authors: Hoberger Michael , von Laffert Maximilian , Heim Daniel , Klauschen Frederick
Published: June 2019

Aims

Whereas current cancer diagnosis largely relies on the well‐established organ and tissue typing of tumours, partially complemented by molecular properties, the comprehensive molecular profiling efforts of recent years have stimulated proposals for molecular reclassifications of tumours independently of anatomical origin. Proposals based only on mutational profiles show the least concordance with histotypes, whereas greater concordance is achieved when various genomic and proteomic data are included.

Methods and results

The most comprehensive molecular reclassification of tumours, by Hoadley et  al (Cell, 158, 2014; 929) and Hoadley et  al (Cell, 173, 2018; 291), integrated multi‐omics data, and proposes novel molecular tumour classes. To investigate the relationship between the proposed molecular classes and the original histological tumour types, we re‐examined the histomorphology of molecularly reclassified cases. Our results show that the claimed molecular reclassification is associated with and explainable by specific histological subtypes in 70% of the reclassified cases.

Conclusion

Therefore, in contrast to the proclaimed reclassification and independence of molecular and histological tumour types, our analysis demonstrates that comprehensive molecular profiling, which includes gene expression and methylation as well as proteomic profiling in addition to mutational analyses, is largely consistent with histomorphological tumour properties.
Knowledge, attitudes and behaviours of patients regarding interdental deplaquing devices: A mixed‐methods study
Authors: Smith Avie Jackie , Moretti Antonio J. , Brame Jennifer , Wilder Rebecca S.
Published: June 2019

Objectives

This mixed‐methods study assessed patients' oral health literacy, motivation level and barriers regarding interdental plaque control.

Methods

Participants (n = 49) from a study comparing the use of Glide® Pro‐Health Floss Original (F) or GUM® Curved Soft‐Picks® Advance (SP) completed daily diaries and questionnaires regarding motivation, tiredness, confidence and satisfaction for their deplaquing method. The Mantel‐Haenszel chi‐square test was utilized. Data were also collected from 19 participants who attended focus group discussions regarding their oral health habits, knowledge, motivators and barriers with interdental plaque control. Discussions were digitally recorded, transcribed and imported into ATLAS.ti 7.5.15 to identify themes.

Results

There were no statistically significant differences between the two groups in relation to age, sex or ethnicity. F users reported statistically significant higher agreement about ability to remove food/debris (P = 0.01), cleaning thoroughly (P = 0.02) and clean feeling of the mouth (P = 0.01). SP users reported higher ease/efficiency of use (P = 0.01), convenience (P = 0.003), easy to hold (P = 0.0001) and easy use away from home (P = 0.008). Daily diaries revealed higher motivation and compliance/ease of use (SP). During the focus groups, some reported that they did not feel clean unless they deplaqued interdentally; however, most reported that they lacked motivation due to constraints on time, no desire due to lack of immediate or tangible rewards, and lack of knowledge on proper use of interdental devices or the benefits of using them.

Conclusion

This study showed that the lack of compliance may be due to poor literacy and lack of motivation in patients due to gaps in patient education.
Influence of preparing conditions on the hot‐pressed sintering of transparent polycrystalline fluorite ceramics
Authors: Liu Zuodong , Gao Qi , Chang Fangfei , Jia Mengying , Wei Mengjun , Yi Guoqiang , Liu Peng , Jing Qiangshan
Published: June 2019

Transparent polycrystalline fluorite ceramics were manufactured from naturally occurring fluorite mineral by a hot‐pressed sintering method. Naturally occurring fluorite minerals were ball milled by a planetary milling equipment. The phase structures of powders were single cubic fluorite phase, and diameters of fluorite powders were decreased from 100 to 20 μm with increasing ball milling duration. Influence of ball milling duration and sintering temperatures on optical properties of polycrystalline fluorite ceramics were studied systematically to obtain the optimum manufacturing process. For the mineral powders after 1 hours ball‐milling, the polycrystalline ceramic hot‐pressed at 1050°C exhibited the highest optical transmission. For a 2.5 mm thickness polycrystalline ceramic, the highest optical transmission at 500 and 1500 nm were about 60.1% and 75.7%, respectively.
The relationship between geographic range extent, sea surface temperature and adult traits in coastal temperate fishes
Authors: Goodman Maurice Codespoti , Hannah Shawn Michelle , Ruttenberg Benjamin Isaac
Published: June 2019

Aim

We use publicly available data to assess the influence of ocean basin, various biological traits and sea surface temperature on biogeographic range extent for temperate, continental shelf fish species spanning 141 families.

Location

Coastal waters of the temperate Northern Hemisphere.

Taxon

Teleost Fishes (Infraclass Teleostei).

Methods

We assess the relationship between species range extent and depth range, maximum body length, schooling behaviour and use of multiple habitats for 1,251 species of northern, temperate, continental shelf fishes in different basins (Atlantic vs. Pacific) and margins (east vs. west) using linear mixed‐effect models with family and genus as nested random effects. We further assess the relationship between species range endpoint distribution and latitudinal temperature gradient using generalized linear models.

Results

We found strong positive relationships between the number of species northern range endpoints and the steepness of the latitudinal sea surface temperature gradient on the western margins of the Atlantic and Pacific Oceans, but no relationship on the eastern margins of these ocean basins. The strongest predictors of range extent in our global model are ocean basin/margin and depth range. Maximum body length, schooling behaviour and use of multiple habitats are also significant predictors of range extent in the global model. The factors influencing range extent differ by basin and margin.

Main conclusions

There are broad differences in patterns of species range extent and distribution of species ranges among basins/margins. These differences appear to be driven in part by variation in latitudinal water temperature gradient between basin margins. Our data suggest that sharp latitudinal temperature gradients may pose a barrier to dispersal and range expansion along the western margins of the Atlantic and Pacific Oceans, but not necessarily on the eastern margins. Our work also suggests that several post‐settlement traits may be associated with range extent either globally or in some temperate basins.
Characterization of macrophage polarization in periodontal disease
Authors: Garaicoa‐Pazmino Carlos , Fretwurst Tobias , Squarize Cristiane H. , Berglundh Tord , Giannobile William V. , Larsson Lena , Castilho Rogerio M.
Published: June 2019

Aim

To explore the M1/M2 status of macrophage polarization from healthy, gingivitis, and periodontitis patient samples.

Materials and methods

Gingival biopsies were collected from 42 individuals (14 gingivitis, 18 periodontitis, and 10 healthy samples) receiving periodontal therapy. Histomorphology analysis was performed with haematoxylin and eosin staining. Immunofluorescence was performed using a combination of CD68 (macrophages), iNOS (M1), and CD206 (M2) in order to acquire changes in macrophage polarization at a single‐cell resolution. Macrophages were quantified under microscopy using narrow wavelength filters to detect Alexa 488, Alexa 568, Alexa 633 fluorophores, and Hoechst 33342 to identify cellular DNA content.

Results

Gingivitis and periodontitis samples showed higher levels of macrophages compared with healthy samples. Unexpectedly, periodontitis samples displayed lower levels of macrophages dispersed in the stromal tissues compared with gingivitis samples; however, it remained higher than healthy tissues. The polarization of macrophages appears to be reduced in periodontitis and showed similar levels to those observed in healthy tissues.

Conclusions

Our study found that gingivitis and periodontitis differ from each other by the levels of macrophage infiltrate, but not by changes in macrophage polarization.
Heritabilities, social environment effects and genetic correlations of social behaviours in a cooperatively breeding vertebrate
Authors: Kasper Claudia , Schreier Tanja , Taborsky Barbara
Published: June 2019

Social animals interact frequently with conspecifics, and their behaviour is influenced by social context, environmental cues and the behaviours of interaction partners, allowing for adaptive, flexible adjustments to social encounters. This flexibility can be limited by part of the behavioural variation being genetically determined. Furthermore, behaviours can be genetically correlated, potentially constraining independent evolution. Understanding social behaviour thus requires carefully disentangling genetic, environmental, maternal and social sources of variations as well as the correlation structure between behaviours. Here, we assessed heritability, maternal, common environment and social effects of eight social behaviours inNeolamprologus pulcher, a cooperatively breeding cichlid. We bred wild‐caught fish in a paternal half‐sibling design and scored ability to defend a resource against conspecifics, to integrate into a group and the propensity to help defending the group territory (“helping behaviour”). We assessed genetic, social and phenotypic correlations within clusters of behaviours predicted to be functionally related, namely “competition,” “aggression,” “aggression‐sociability,” “integration” and “integration‐help.” Helping behaviour and two affiliative behaviours were heritable, whereas there was little evidence for a genetic basis in all other traits. Phenotypic social effects explained part of the variation in a sociable and a submissive behaviour, but there were no maternal or common environment effects. Genetic and phenotypic correlation within clusters was mostly positive. A group's social environment influenced covariances of social behaviours. Genetic correlations were similar in magnitude but usually exceeding the phenotypic ones, indicating that conclusions about the evolution of social behaviours in this species could be provisionally drawn from phenotypic data in cases where data for genetic analyses are unobtainable.
Use of an anteriorly based ventral tongue flap to reconstruct the lower vermilion following early‐stage cancer ablation
Authors: Yang Zhao‐hui , Zhou Bin , Zhong Jiang‐long , Chen Wei‐liang
Published: June 2019

Background

Reconstruction of lower vermilion defects is surgically challenging.

Aims

This study evaluated whether lower vermilion defects can be repaired using tongue flaps, and the reconstructive outcomes.

Materials and Methods

We evaluated 11 patients with early‐stage lower vermilion cancers who underwent lower vermilion reconstruction using anteriorly based ventral tongue flaps following cancer ablation. We treated eight males and three females aged 54‐67 years (median, 59.8 years). The defect/tongue flap dimensions ranged from 1.8 × 3.5 to 2.0 × 4.5 cm (median, 1.87 × 3.81 cm).

Results

No major complication developed in any patient. The postoperative esthetic results, orbicularis oris functions, and speech functions were excellent in six, eight, and nine patients, and satisfactory in five, three, and two, respectively. The patients were followed up for 13‐36 months (median, 21.7 months); two local recurrences developed, and these patients underwent salvage surgeries.

Conclusions

An anteriorly based ventral tongue flap is a safe and feasible option for reconstruction of lower vermilion defects.
Accidental epiphytism in the Harz Mountains, Central Europe
Authors: Hoeber Vincent , Weichgrebe Tizian , Zotz Gerhard
Published: June 2019

Questions

Vascular epiphytes make up about 9% of all vascular plants globally but are clearly underrepresented in the temperate zones. The accidental epiphytic occurrence of terrestrial species, in contrast, is common at these latitudes and can provide important insights in the evolution of obligate epiphytes. Here, we present the results of the first two annual censuses of a planned long‐term study on accidental epiphytes. We particularly aim to identify: (a) the abundance and species richness of accidental epiphytes; (b) the dynamics of accidental epiphytism; (c) occupied substrates and microsites; and (d) suitable host tree species.

Location

Harz Mountains, Germany, Central Europe.

Methods

We surveyed more than 1,200 trees in a low mountain range in two consecutive years for epiphytic individuals of vascular plants, considering host tree species and occupied microsites.

Results

About one quarter of the surveyed trees hosted epiphytic plants, totalling 1 450 (2016) and 1 350 (2017) individuals, respectively. These belonged to more than 100 species and 39 different families. The majority of epiphytic individuals newly emerged in 2017, whereas one‐third persisted since 2016 (or earlier) and a smaller proportion even reproduced in the epiphytic habitat. Accidental epiphytes were mostly restricted to host tree species providing water‐storing substrates such as extensive moss pads or arboreal soil accumulated in crotches. Compared to tropical epiphyte communities, accidental epiphytes in the temperate zones show a higher turnover, as they are less consistent in species abundance and composition in time.

Conclusion

For the majority of the observed species, epiphytism indeed is an accidental phenomenon. Undoubtedly, abiotic conditions limit the occurrence of obligate epiphytes at higher latitudes, but the presence and persistence of numerous epiphytic individuals illustrate that abiotic conditions do not per se preclude epiphytic occurrence of vascular plants in the north‐temperate zone. Besides water shortage, the availability of suitable host trees is a decisive environmental factor that contributes to limit epiphytism of vascular plants in Central Europe.
Prevalence and impact of sarcopenia in non‐cirrhotic portal hypertension
Authors: Lattanzi Barbara , Gioia Stefania , Di Cola Simone , D’Ambrosio Daria , Nardelli Silvia , Tavano Daniele , Farcomeni Alessio , Merli Manuela , Riggio Oliviero
Published: June 2019

Background & Aims

Little is known on nutritional parameters in patients with chronic portal vein thrombosis (PVT) and idiopathic non‐cirrhotic portal hypertension (INCPH). The study aims to assess the prevalence and the clinical impact of sarcopenia in patients with non‐cirrhotic portal hypertension (NCPH). A control group of cirrhotic patients was also studied. Both groups were followed up to establish the relationship between sarcopenia and clinical outcomes.

Methods

Sixty‐seven patients with NCPH (51 PVT and 16 INCPH) were included in the study group and 104 patients with liver cirrhosis in the control group. The axial plane passing through the intersomatic disk between L3 and L4 was evaluated for the quantitative analysis of muscle mass and the skeletal muscle index (SMI) was calculated. The presence of sarcopenia was established according to SMI validated cut off.

Results

Sarcopenia was present in the 38% of patients with INCPH, 35% of patients with chronic PVT, 32% of patients with compensated cirrhosis and 54% of decompensated cirrhotics. During a mean follow‐up of 51 ± 62 months, there was no difference in sarcopenic and non‐sarcopenic patients with NCPH for incidence of ascites, hepatic encephalopathy, esophageal varices, variceal bleeding and death. However, the incidence of refractory variceal bleeding requiring TIPS placement was significantly higher in comparison with the non‐sarcopenic ones (29% vs 7%, P = 0.01 at log‐rank test).

Conclusions

In patients with NCPH sarcopenia is similar to that observed in cirrhotic patients. Moreover, the rate of refractory variceal bleeding was higher in sarcopenic patients suggesting a clinical negative impact of muscle depletion.
Permanent indwelling peritoneal catheters for palliation of refractory ascites in end‐stage liver disease: A systematic review
Authors: Macken Lucia , Hashim Ahmed , Mason Louise , Verma Sumita
Published: June 2019

Background & Aims

The incidence and mortality from end‐stage liver disease is increasing, with a minority eligible for liver transplantation. Ascites is the commonest complication of end‐stage liver disease and large volume paracentesis (LVP) the accepted management strategy where refractory to medical treatment. In malignant ascites, permanent indwelling peritoneal catheters (PIPC) are an established palliative intervention. The aims are to describe available data using permanent indwelling peritoneal catheters in refractory ascites due to end‐stage liver disease.

Methods

Using systematic review methodology, databases were searched (MEDLINE, EMBASE, CINAHL [The Cumulative Index to Nursing and Allied Health Literature], Google Scholar and Cochrane Database of Systematic Reviews from inception‐March 2018), for studies combining ascites and palliative care. Inclusion and exclusion criteria were applied to results.

Results

Following initial and updated searches, 225 studies were identified for full text review, 18 were eligible for final analysis. The studies displayed heterogeneity in design, reported on different indwelling catheters and were overall of low quality. Only one pilot randomised controlled trial was identified, of PIPC versus LVP, recruiting one patient into each arm. Technical insertion success was 100%, with low rates of non‐infectious complications (<12%), none life threatening. Rates of bacterial peritonitis were not unacceptably high (12.7%), considering this was an end‐stage liver disease population and only a minority utilising long‐term prophylactic antibiotics. Only one study attempted quality‐of‐life assessments; none addressed potential health economic benefits.

Conclusions

Despite lack of well‐designed studies, preliminary data suggests low significant complication rates; however safety and efficacy of permanent indwelling peritoneal catheters in end‐stage liver disease remains to be confirmed. Further prospective randomised controlled trials are warranted, potentially translating permanent indwelling peritoneal catheters into improved palliative care in end‐stage liver disease.