bluuebunny/crossref_metadata_2025 huggingface dataset:
A Connectomic Atlas of the Human Cerebrum—Chapter 1: Introduction, Methods, and Significance
Authors: Baker Cordell M , Burks Joshua D , Briggs Robert G , Conner Andrew K , Glenn Chad A , Sali Goksel , McCoy Tressie M , Battiste James D , O’Donoghue Daniel L , Sughrue Michael E
Published: September 2018

BACKGROUND

As knowledge of the brain has increased, clinicians have learned that the cerebrum is composed of complex networks that interact to execute key functions. While neurosurgeons can typically predict and preserve primary cortical function through the primary visual and motor cortices, preservation of higher cognitive functions that are less well localized in regions previously deemed “silent” has proven more difficult. This suggests these silent cortical regions are more anatomically complex and redundant than our previous methods of inquiry can explain, and that progress in cerebral surgery will be made with an improved understanding of brain connectomics. Newly published parcellated cortex maps provide one avenue to study such connectomics in greater detail, and they provide a superior framework and nomenclature for studying cerebral function and anatomy.

OBJECTIVE

To describe the structural and functional aspects of the 180 distinct areas that comprise the human cortex model previously published under the Human Connectome Project (HCP).

METHODS

We divided the cerebrum into 8 macroregions: lateral frontal, motor/premotor, medial frontal, insular, temporal, lateral parietal, medial parietal, and occipital. These regions were further subdivided into their relevant parcellations based on the HCP cortical scheme. Connectome Workbench was used to localize parcellations anatomically and to demonstrate their functional connectivity. DSI studio was used to assess the structural connectivity for each parcellation.

RESULTS

The anatomy, functional connectivity, and structural connectivity of all 180 cortical parcellations identified in the HCP are compiled into a single atlas. Within each section of the atlas, we integrate this information, along with what is known about parcellation function to summarize the implications of these data on network connectivity.

CONCLUSION

This multipart supplement aims to build on the work of the HCP. We present this information in the hope that the complexity of cerebral connectomics will be conveyed in a more manageable format that will allow neurosurgeons and neuroscientists to accurately communicate and formulate hypotheses regarding cerebral anatomy and connectivity. We believe access to this information may provide a foundation for improving surgical outcomes by preserving lesser-known networks.
A Connectomic Atlas of the Human Cerebrum—Chapter 4: The Medial Frontal Lobe, Anterior Cingulate Gyrus, and Orbitofrontal Cortex
Authors: Baker Cordell M , Burks Joshua D , Briggs Robert G , Stafford Jordan , Conner Andrew K , Glenn Chad A , Sali Goksel , McCoy Tressie M , Battiste James D , O’Donoghue Daniel L , Sughrue Michael E
Published: September 2018

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 4, we specifically address regions relevant to the medial frontal lobe, anterior cingulate gyrus, and orbitofrontal cortex.
A Connectomic Atlas of the Human Cerebrum—Chapter 6: The Temporal Lobe
Authors: Baker Cordell M , Burks Joshua D , Briggs Robert G , Milton Camille K , Conner Andrew K , Glenn Chad A , Sali Goksel , McCoy Tressie M , Battiste James D , O’Donoghue Daniel L , Sughrue Michael E
Published: September 2018

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 6, we specifically address regions relevant to the temporal lobe.
A Connectomic Atlas of the Human Cerebrum—Chapter 7: The Lateral Parietal Lobe
Authors: Baker Cordell M , Burks Joshua D , Briggs Robert G , Conner Andrew K , Glenn Chad A , Taylor Kathleen N , Sali Goksel , McCoy Tressie M , Battiste James D , O’Donoghue Daniel L , Sughrue Michael E
Published: September 2018

In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we seek to show a comprehensive anatomic atlas of the human cerebrum demonstrating all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 7, we specifically address regions relevant to the lateral parietal lobe.
Genomic Dissection of Nonhost Resistance to Wheat Stem Rust in Brachypodium distachyon
Authors: Della Coletta Rafael , Hirsch Candice N. , Rouse Matthew N. , Lorenz Aaron , Garvin David F.
Published: September 2018

The emergence of new races of Puccinia graminis f. sp. tritici, the causal pathogen of wheat stem rust, has spurred interest in developing durable resistance to this disease in wheat. Nonhost resistance holds promise to help control this and other diseases because it is durable against nonadapted pathogens. However, the genetic and molecular basis of nonhost resistance to wheat stem rust is poorly understood. In this study, the model grass Brachypodium distachyon, a nonhost of P. graminis f. sp. tritici, was used to genetically dissect nonhost resistance to wheat stem rust. A recombinant inbred line (RIL) population segregating for response to wheat stem rust was evaluated for resistance. Evaluation of genome-wide cumulative single nucleotide polymorphism allele frequency differences between contrasting pools of resistant and susceptible RILs followed by molecular marker analysis identified six quantitative trait loci (QTL) that cumulatively explained 72.5% of the variation in stem rust resistance. Two of the QTLs explained 31.7% of the variation, and their interaction explained another 4.6%. Thus, nonhost resistance to wheat stem rust in B. distachyon is genetically complex, with both major and minor QTLs acting additively and, in some cases, interacting. These findings will guide future research to identify genes essential to nonhost resistance to wheat stem rust.
Evaluation of the Efficacy of Commercial Disinfectants Against Fusarium oxysporum f. sp. cubense Race 1 and Tropical Race 4 Propagules
Authors: Nguyen T. V. , Tran-Nguyen L. T. T. , Wright C. L. , Trevorrow P. , Grice K.
Published: September 2018

Panama disease caused by Fusarium oxysporum f. sp. cubense has devastated banana production worldwide. This work aimed to determine effective disinfectants against two races of F. oxysporum f. sp. cubense, race 1 and tropical race 4 (TR4), for implementation with on-farm biosecurity procedures against this disease following the outbreak of TR4 in North Queensland in 2015. A total of 32 commercial disinfectants were screened and their activity was assessed after ≤30 s, 5 min, 30 min, and 24 h of contact with an F. oxysporum f. sp. cubense suspension containing 105 chlamydospores/ml without and with soil added (0.05 g/ml). Of the disinfectants tested, the quaternary ammonium compounds containing ≥10% active ingredient were found to be the most effective against both F. oxysporum f. sp. cubense races. These products, when used at a 1:100 dilution, completely inhibited the survival of all F. oxysporum f. sp. cubense propagules across all the contact times regardless of the absence or presence of soil. The bioflavonoid product EvoTech 213 and bleach (10% sodium hypochlorite) used at a 1:10 dilution also eliminated all F. oxysporum f. sp. cubense propagules across all the contact times. None of the detergent-based or miscellaneous products tested were completely effective against both F. oxysporum f. sp. cubense races even used at a 1:10 dilution. Soil decreases the efficacy of disinfectants and therefore must be removed from contaminated items before treatments are applied.
Navigating the Murk: Ethical and Practical Considerations for the Surgical Treatment of the Sacroiliac Joint Syndrome
Authors: Bina Robert W. , Hurlbert R. John , Dang Alan
Published: September 2018

The field of spine surgery has many controversies. The surgical treatment of the sacroiliac (SI) joint is, too, fraught with debate. The diagnosis of painful SI joints is currently limited to relief following “diagnostic” injections and pain generated from a suite of clinical maneuvers. Diagnoses of SI joint dysfunction are dependent entirely on patient-reported responses to provocative maneuvers and invasive procedures. There is a glaring lack of objective radiographic and objective physical examination findings for this syndrome. The evidence for treatment, and specifically for the surgical treatment of the SI joint is reviewed and critiqued. Although the surgical techniques are simple, consensus is elusive for both indication and optimal technique. Ethical principles for surgical innovation and practical considerations for the treatment of the SI joint syndrome are discussed at length. Discussed as well are key points to consider when providing informed consent to a patient before proceeding with surgical intervention for this procedure and diagnosis. Spine surgery is a field with considerable regional variation in practice. Even today, the precise indications for arthrodesis, extent, and approach, remain frequently debated; however, as much conversation takes place surrounding lumbar surgery, even more confusion, bias, opinion, and deliberation exists when surgical treatment of the SI joint is considered. This chapter discusses the unique challenges associated with the SI joint and provides practical considerations for the treatment thereof.
Compassion
Authors: Sweeney Cynthia Divens
Published: September 2018

Delivering clinical nursing expertise enveloped with compassion should be the expectation for care. Ensuring this level of excellence happens when a critically ill patient is transferred from one hospital to another is challenging yet imperative to the patient’s and family’s experience. The DAISY Foundation recognizes nurses who provide compassionate and extraordinary nursing care, as demonstrated in the stories of 2 nurses, from different organizations, who cared for the same patient and family and were honored with The DAISY Award.
Cultural Competency Matters
Authors: Gergely Susan Williamson
Published: September 2018

Healthcare disparities for racial and ethnic minority patients are a serious issue in the United States. Although socioeconomic factors are a key contributor to these disparities, there are many other influences, related to the patient, system, and provider. A key strategy to address provider-related factors is to assess the cultural competence of caregivers. Utilizing a survey and interviews of AONE members, this study explored the influences affecting the ability of nurse leaders to lead their teams in providing culturally competent care. The study found that nurse leaders need a deeper understanding of the presence of healthcare disparities for racial and ethnic minority patients, more formalized training, and increased opportunities to reflect on their own abilities and potential for bias. Cultural competence must be a strategic priority, providing resources for training, and by holding leaders accountable to improve the level of cultural competence of their teams.
Predictors of Turnover Among Asian Foreign-Educated Nurses in Their 1st Year of US Employment
Authors: Geun Hyo Geun , Redman Richard W. , McCullagh Marjorie C.
Published: September 2018

OBJECTIVE:

The aim of this study was to investigate factors affecting turnover of Asian foreign-educated nurses (FENs), which may lead to improvements in retention strategies.

BACKGROUND:

Asian FENs working in the United States have considerable rates of turnover. Little is known about which factors are related.

METHODS:

A cross-sectional design was used. A convenience sample (n = 201) of Asian FENs completed surveys by regular mail and through a website. Backward multivariable logistic regression was performed to identify factors associated with turnover in their 1st year of employment.

RESULTS:

Most participants were from the Philippines and Korea. Perceived quality of orientation predicted organizational-level turnover and trended toward predicting unit-level turnover.

CONCLUSIONS:

Healthcare institutions may benefit from developing organizational programs for FENs that are sensitive to their unique needs, in the interest of reducing rapid or early turnover and accompanying negative effects on hospital finances and patient care.
Multisystem Balance Training Reduces Injurious Fall Risk in Parkinson Disease
Authors: Wong-Yu Irene S.K. , Mak Margaret K.Y.
Published: September 2018

Previous studies have shown that balance training could reduce falls in people with Parkinson disease. However, it remains unclear whether exercise can reduce injurious falls. The objective of present study was to determine whether multisystem balance training could reduce injurious falls and modify targeted fall risk factors in Parkinson disease nonfallers and single fallers. Participants were randomly assigned to an 8-wk balance group (experimental, n = 41) or an upper limbs group (control, n = 43). Outcomes examined at posttraining and 12-mo follow-up were: (1) injurious fall risk (ratio of noninjurious fallers to injurious fallers); (2) two potential fall risk factors based on Balance Evaluation Systems Test scores and dual-task timed-up-and-go times. At posttraining, results indicated that there were no injurious falls, and fewer experimental participants were found in high fall risk cohorts based on Balance Evaluation Systems Test scores and dual-task timed-up-and-go times (P < 0.05). At 12-mo follow-up, the number of injurious fallers was lower in experimental group (P < 0.05). There was also a marginally lower percentage of experimental group in the high fall risk cohort based on Balance Evaluation Systems Test scores (P = 0.059). The findings conclude that multisystem balance training potentially reduces injurious fall risk up to 12-mo posttraining and lowers balance-related fall risks in people with Parkinson disease.
Depression Characterization and Race Among Stroke Survivors Receiving Inpatient Rehabilitation
Authors: Pugh Terrence , Hirsch Mark A. , Nguyen Vu Q. C. , Rhoads Charles F. , Harris Gabrielle M. , Yang Qing , Thomas J. George , Guerrier Tami , Hamm Deanna , Pereira Carol , Yao Jia , Bettger Janet A. Prvu
Published: September 2018

Race and ethnicity play a significant role in poststroke outcomes. This brief report describes the presence of depression among stroke survivors who received inpatient rehabilitation and whether depression differs by race. Data from eRehabData and electronic medical records were analyzed for patients who received rehabilitation after an acute ischemic or hemorrhagic stroke. Of 1501 stroke patients, 61.3% were white, 33.9% were African American, and 4.8% were of other race/ethnic backgrounds. By retrospective clinical review, depression was documented for 29.7% of stroke patients. Premorbid versus new onset of poststroke depression was documented for 13.4% and 21.6% of whites, 7.5% and 11.5% of African American, and 0% and 16.7% of patients of other race/ethnic groups. Compared with whites, African American and people of other races had a lower odds of poststroke depression (African American adjusted odds ratio = 0.52, 95% confidence interval = 0.41–0.68; other races odds ratio = 0.37, 95% confidence interval = 0.19–0.71), after adjusting for all other significant risk factors identified in the bivariate analysis (sex, hyperlipidemia, cognitive deficit, neglect). Depression was documented for one in three stroke survivors who received inpatient rehabilitation and highest among whites especially for prestroke depression. Addressing depression in rehabilitation care needs to consider individual patient characteristics and prestroke health status.
Impact of Nursing Interventions on Medication Adherence During Hepatitis C Treatment
Authors: Williams Sheila
Published: September 2018

This article is a literature review to determine the state of the science regarding the impact of nursing interventions in the treatment of hepatitis C. Hepatitis C is a chronic disease impacting millions of people globally. Treatment is currently available that has the potential to cure the disease. Medication adherence is vital to the eradication of the disease. Nursing interventions could possibly assist in the improvement in medication adherence. By reviewing the literature, the factors influencing patient outcomes were identified. Four themes identified in the literature are influence of comorbidities, self-motivation, psychological factors, and provider support. The research studies are compared and contrasted within and across the themes. Identification of what is known and what is not known about nursing interventions in the treatment of hepatitis C is illustrated in the conclusion of the article. Finally, suggestions for future research are presented. Specific areas of study are identified for focus in the future research.
Use of an Educational Module to Improve Confidence and Knowledge of Celiac Disease Among Nurse Practitioners in Pennsylvania
Authors: Elkin Aleda , Grant Catherine , Coleman Timothy , Sereika Susan M.
Published: September 2018

Accurate and prompt diagnosis of celiac disease has proven difficult due to the myriad of presenting symptoms and a lack of a clear diagnostic protocol. This pilot study investigated the use of an evidence-based multimedia educational module on nurse practitioner confidence and knowledge of celiac disease. Thirteen nurse practitioners in Pennsylvania completed all study activities, which involved the use of an online pretest, learning component, an immediate post-test, along with 2 follow-up surveys. Results revealed that nurse practitioner confidence (p ≤ .05) and knowledge (p ≤ .05) levels significantly improved after participation in the educational intervention. Qualitative data also revealed that nurse practitioners are more aware of the various presentations and symptoms of celiac disease and stated that with this knowledge, their clinical practice has changed to include recognition of the various celiac disease presentations. Findings suggest that nurse practitioners are now more knowledgeable of the various presentations of celiac disease and may be more likely to consider celiac disease as a diagnosis if patients present with typical or atypical symptoms.
The Role of the Nurse Practitioner in the Management of Nonalcoholic Fatty Liver Disease
Authors: Hearn Chelsea , Ellington Betty J. , Jones Roberta
Published: September 2018

The incidence of nonalcoholic fatty liver disease (NAFLD) has increased over the past few decades because of the obesity epidemic and is also strongly associated with diabetes Type 2. Patients often present asymptomatically until the liver disease becomes advanced. Alternatively, persons with NAFLD can present with various stages of inflammation, hepatosis, or fibrosis, which can eventually result in cirrhosis and lead to hepatocellular carcinoma. Lifestyle modifications are the most important aspects of cirrhosis prevention. These changes are crucial because cirrhosis is a known cause of long-term liver disease. Nurse practitioners play an important role in the early detection of NAFLD and prevention of its potentially life-threatening complications.
Local epigenomic state cannot discriminate interacting and non-interacting enhancer–promoter pairs with high accuracy
Authors: Xi W. , Beer M.A.
Published: September 2018

We report an overfitting issue in recent machine learning formulations of the enhancer-promoter interaction problem arising from the fact that many enhancer-promoter pairs share features. Cross- fold validation schemes which do not correctly separate these feature sharing enhancer-promoter pairs into one test set report high accuracy, which is actually due to overfitting. Cross-fold validation schemes which properly segregate pairs with shared features show markedly reduced ability to predict enhancer-promoter interactions from epigenomic state. Parameter scans with multiple models indicate that local epigenomic features of individual pairs of enhancers and promoters cannot distinguish those pairs that interact from those which do with high accuracy, suggesting that additional information is required to predict enhancer-promoter interactions.
Atlas-CNV: a validated approach to call Single-Exon CNVs in the eMERGESeq gene panel
Authors: Chiang Theodore , Liu Xiuping , Wu Tsung-Jung , Hu Jianhong , Sedlazeck Fritz J. , White Simon , Schaid Daniel , de Andrade Mariza , Jarvik Gail P. , Crosslin David , Stanaway Ian , Carrell David S. , Connolly John J. , Hakonarson Hakon , Groopman Emily E. , Gharavi Ali G. , Fedotov Alexander , Bi Weimin , Leduc Magalie S. , Murdock David R. , Jiang Yunyun , Meng Linyan , Eng Christine M. , Wen Shu , Yang Yaping , Muzny Donna M. , Boerwinkle Eric , Salerno William , Venner Eric , Gibbs Richard A.
Published: September 2018

Purpose:

To provide a validated method to confidently identify exon-containing copy number variants (CNVs), with a low false discovery rate (FDR), in targeted sequencing data from a clinical laboratory with particular focus on single-exon CNVs.

Methods:

DNA sequence coverage data are normalized within each sample and subsequently exonic CNVs are identified in a batch of samples (midpool), when the target log2 ratio of the sample to the batch median exceeds defined thresholds. The quality of exonic CNV calls is assessed by C-scores (Z-like scores) using thresholds derived from gold standard samples and simulation studies. We integrate an ExonQC threshold to lower FDR and compare performance with alternate software (VisCap).

Results:

Thirteen CNVs were used as a truth set to validate Atlas-CNV and compared with VisCap. We demonstrated FDR reduction in validation, simulation and 10,926 eMERGESeq samples without sensitivity loss. Sixty-four multi-exon and 29 single-exon CNVs with high C-scores were assessed by MLPA.

Conclusions:

Atlas-CNV is validated as a method to identify exonic CNVs in targeted sequencing data generated in the clinical laboratory. The ExonQC and C-score assignment can reduce FDR (identification of targets with high variance) and improve calling accuracy of single-exon CNVs respectively. We proposed guidelines and criteria to identify high confidence single-exon CNVs.
Facilitating Patient and Public Involvement in basic and preclinical health research
Authors: Maccarthy James , Guerin Suzanne , Wilson Anthony G. , Dorris Emma R.
Published: September 2018

Involving patients in research broadens a researcher’s field of influence and may generate novel ideas. Preclinical research is integral to the progression of innovative healthcare. These are not patient-facing disciplines and implementing meaningful PPI can be a challenge. A discussion forum and thematic analysis identified key challenges of implementing PPI for preclinical researchers. In response we developed a “PPI Ready” planning canvas. For contemporaneous evaluation of PPI, a psychometric questionnaire and an open source tool for its evaluation were developed. The questionnaire measures information, procedural and quality assessment. Combined with the open source evaluation tool, researchers are notified if PPI is unsatisfactory in any of these areas. The tool is easy to use and adapts a psychometric test into a format familiar to preclinical scientists. Designed to be used iteratively across a research project, it provides a simple reporting grade to document satisfaction trend over the research lifecycle.
Using optically-pumped magnetometers to measure magnetoencephalographic signals in the human cerebellum
Authors: Lin Chin-Hsuan , Tierney Tim M , Holmes Niall , Boto Elena , Leggett James , Bestmann Sven , Bowtell Richard , Brookes Matthew J , Barnes Gareth R , Miall R Chris
Published: September 2018

We test the feasibility of an optically pumped magnetometer-magnetoencephalographic (OP-MEG) system for the measurement of human cerebellar activity. This is to our knowledge the first study investigating the human cerebellar electrophysiology using OPMs. As a proof of principle, we use an air-puff stimulus to the eyeball in order to elicit cerebellar activity that is well characterised in non-human models. In three subjects, we observe an evoked component at approx. 50ms post-stimulus, followed by a second component at approx. 85-115 ms post-stimulus. Source inversion localises both components in the cerebellum, while control experiments exclude potential sources elsewhere. We also assess the induced oscillations, with time-frequency decompositions, and identify the source in the occipital lobe, a region expected to be active in our paradigm. We conclude that the OP-MEG technology offers a promising way to advance the understanding of the information processing mechanisms in the human cerebellum.
Emergence and the spread of the F200Y benzimidazole resistance mutation in Haemonchus contortus and Haemonchus placei from buffalo and cattle
Authors: Ali Qasim , Rashid Imran , Shabbir Muhammad Zubair , Aziz-Ul-Rahman  , Shahzad Kashif , Ashraf Kamran , Sargison Neil D. , Chaudhry Umer
Published: September 2018

Benzimidazoles have been intensively used in the livestock sector, particularly in small ruminants for over 40 years. This has been led to the widespread emergence of resistance in a number of small ruminant parasite species, in particular Haemonchus contortus. In many counties benzimidazole resistance in the small ruminants H. contortus has become severely compromising its control; but there is a little information on benzimidazole resistance in H. contortus infecting buffalo and cattle. Resistance to benzimidazoles have also been reported in the large ruminant parasite, Haemonchus placei, but again there is relatively little information on its prevalence. Hence it is extremely important to understand how resistance-conferring mutations emerge and spread in both parasites in the buffalo and cattle host in order to develop the approaches for the recognition of the problem at an early stage of its development. The present study suggests that the F200Y (TAC) mutation is common in H. contortus, being detected in 5/7 populations at frequencies between 7 to 57%. Furthermore, 6/10 H. placei populations contained the F200Y (TAC) mutation, albeit at low frequencies of between 0.4 to 5%. The phylogenetic analysis suggests that the F200Y (TAC) mutation in H. contortus has emerged on multiple occasions in the region, with at least three independent emergence of resistance alleles across the populations. In contrast, the F200Y (TAC) resistance-conferring mutation in H. placei is only seen on a single haplotype. A high level of haplotype frequency of the susceptible alleles in the region, suggests that the unique resistance conferring-mutation has spread from a single emergence; likely by anthropogenic animal movement. Overall, these results provide the first clear genetic evidence for the spread of benzimidazoles resistance-conferring mutations to multiple different locations from a single emergence in H. placei; while supporting previous small ruminant-based observations of multiple emergence of resistance mutations in H. contortus.
Phospholipid-Cellulose Interactions: Insight from Atomistic Computer Simulations for Understanding the Impact of Cellulose-Based Materials on Plasma Membranes
Authors: Gurtovenko Andrey A. , Mukhamadiarov Evgenii I. , Kostritskii Andrei Yu. , Karttunen Mikko
Published: September 2018

Cellulose is an important biocompatible and nontoxic polymer widely used in numerous biomedical applications. The impact of cellulose-based materials on cells and, more specifically, on plasma membranes that surround cells, however, remains poorly understood. To this end, here we performed atomic-scale molecular dynamics (MD) simulations of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) bilayers interacting with the surface of a cellulose crystal. Both biased umbrella sampling and unbiased simulations clearly show the existence of strong attractive interactions between phospholipids and cellulose: the free energy of the cellulose-bilayer binding was found to be −1.89 and −1.96 kJ/mol per cellulose dimer for PC and PE bilayers, respectively. Although the values are similar, there is a pronounced difference between PC and PE bilayers. The driving force in both cases is the formation of hydrogen bonds. There are two distinct types of hydrogen bonds: 1) between the lipid head groups and the hydroxyl (hydroxymethyl) groups of cellulose, and 2) lipid-water and cellulose-water bonds. The former is the dominant component for PE systems whereas the latter dominates in PC systems. This suggests that achieving controlled binding via new cellulose modifications must pay close attention to the lipid head groups involved. The observed attractive phospholipid-cellulose interactions have a significant impact on bilayer properties: a cellulose crystal induces noticeable structural perturbations on the bilayer leaflet next to the crystal. Given that such perturbations can be undesirable when it comes to the interactions of cellulose-based materials with cell membranes, our computational studies suggest that the impact of cellulose could be reduced through chemical modification of the cellulose surface which prevents cellulose-phospholipid hydrogen bonding.
Lasting effects of repeated Δ9-tetrahydrocannabinol (THC) vapor inhalation during adolescence in male and female rats
Authors: Nguyen Jacques D. , Creehan K. M. , Kerr Tony M. , Taffe Michael A.
Published: September 2018

Adolescents are regularly exposed to Δ9-tetrahydrocannabinol (THC) via smoking, and, more recently, vaping, cannabis / extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behavior and lasting tolerance in response to THC. Male and female rats inhaled THC vapor, or that from the propylene glycol (PG) vehicle, twice daily for 30 minutes from postnatal day (PND) 35-39 and PND 42-45 using an e-cigarette system. Thermoregulatory responses to vapor inhalation were assessed by radio-telemetry during adolescence and from PND 86-94; chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after four days of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults. Female, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC with THC greater potency exhibited in females. Repeated-THC male rats consumed more food than their PG treated control group, in the absence of a significant bodyweight difference. Adolescent THC did not alter oxycodone self-administration in either sex, but increased fentanyl self-administration in females. Repeated THC vapor inhalation in adolescent rats results in lasting consequences observable in adulthood.

Abbreviations

PG, propylene glycol; THC, Δ9tetrahydrocannabinol;
Reduced representation characterization of genetic and epigenetic differentiation to oil pollution in the foundation plant Spartina alterniflora
Authors: Alvarez Mariano , Robertson Marta , van Gurp Thomas , Wagemaker Niels , Giraud Delphine , Ainouche Malika L. , Salmon Armel , Verhoeven Koen J. F. , Richards Christina L.
Published: September 2018

Theory predicts that environmental challenges can shape the composition of populations, which is manifest at the molecular level. Previously, we demonstrated that oil pollution affected gene expression patterns and altered genetic variation in natural populations of the foundation salt marsh grass, Spartina alterniflora. Here, we used a reduced representation bisulfite sequencing approach, epigenotyping by sequencing (epiGBS), to examine relationships among DNA sequence, DNA methylation, gene expression, and exposure to oil pollution. We documented genetic and methylation differentiation between oil-exposed and unexposed populations, suggesting that the Deepwater Horizon oil spill may have selected on genetic variation, and either selected on epigenetic variation or induced particular epigenotypes and expression patterns in exposed compared to unexposed populations. In support of the potential for differential response to the Deepwater Horizon oil spill, we demonstrate genotypic differences in response to oil under controlled conditions. Overall, these findings demonstrate genetic variation, epigenetic variation and gene expression are correlated to exposure to oil pollution, which may all contribute to the response to environmental stress.
ICTD: A semi-supervised cell type identification and deconvolution method for multi-omics data
Authors: Chang Wennan , Wan Changlin , Lu Xiaoyu , Tu Szu-wei , Sun Yifan , Zhang Xinna , Zang Yong , Zhang Anru , Huang Kun , Liu Yunlong , Lu Xiongbin , Cao Sha , Zhang Chi
Published: September 2018

We developed a novel deconvolution method, namely Inference of Cell Types and Deconvolution (ICTD) that addresses the fundamental issue of identifiability and robustness in current tissue data deconvolution problem. ICTD provides substantially new capabilities for omics data based characterization of a tissue microenvironment, including (1) maximizing the resolution in identifying resident cell and sub types that truly exists in a tissue, (2) identifying the most reliable marker genes for each cell type, which are tissue and data set specific, (3) handling the stability problem with co-linear cell types, (4) co-deconvoluting with available matched multi-omics data, and (5) inferring functional variations specific to one or several cell types. ICTD is empowered by (i) rigorously derived mathematical conditions of identifiable cell type and cell type specific functions in tissue transcriptomics data and (ii) a semi supervised approach to maximize the knowledge transfer of cell type and functional marker genes identified in single cell or bulk cell data in the analysis of tissue data, and (iii) a novel unsupervised approach to minimize the bias brought by training data. Application of ICTD on real and single cell simulated tissue data validated that the method has consistently good performance for tissue data coming from different species, tissue microenvironments, and experimental platforms. Other than the new capabilities, ICTD outperformed other state-of-the-art devolution methods on prediction accuracy, the resolution of identifiable cell, detection of unknown sub cell types, and assessment of cell type specific functions. The premise of ICTD also lies in characterizing cell-cell interactions and discovering cell types and prognostic markers that are predictive of clinical outcomes.
Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of adult major depressive episodes: A systematic review and network meta-analysis of 113 randomised clinical trials
Authors: Mutz Julian , Vipulananthan Vijeinika , Carter Ben , Hurlemann Rene , Fu Cynthia H Y , Young Allan H
Published: September 2018

Background: Non-surgical brain stimulation techniques have been applied as tertiary treatments in major depression. However, the relative efficacy and acceptability of individual protocols is uncertain. Our aim was to estimate the comparative clinical efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults. Methods: Embase, PubMed/MEDLINE and PsycINFO were searched up until May 8, 2018, supplemented by manual searches of bibliographies of recent reviews and included trials. We included clinical trials with random allocation to electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), accelerated TMS (aTMS), priming TMS (pTMS), deep TMS (dTMS), theta burst stimulation (TBS), synchronised TMS (sTMS), magnetic seizure therapy (MST) or transcranial direct current stimulation (tDCS) protocols or sham. Data were extracted from published reports and outcomes were synthesised using pairwise and network random-effects meta-analysis. Primary outcomes were response (efficacy) and all-cause discontinuation (acceptability). We computed odds ratios (OR) with 95% confidence intervals (CI). Remission and continuous post-treatment depression severity scores were also examined. Results: 113 trials (262 treatment arms) randomising 6,750 patients (mean age = 47.9 years; 59% female) with major depressive disorder or bipolar depression met our inclusion criteria. In terms of efficacy, 10 out of 18 treatment protocols were associated with higher response relative to sham in network meta-analysis: bitemporal ECT (OR=8.91, 95%CI 2.57-30.91), high-dose right-unilateral ECT (OR=7.27, 1.90-27.78), pTMS (OR=6.02, 2.21-16.38), MST (OR=5.55, 1.06-28.99), bilateral rTMS (OR=4.92, 2.93-8.25), bilateral TBS (OR=4.44, 1.47-13.41), low-frequency right rTMS (OR=3.65, 2.13-6.24), intermittent TBS (OR=3.20, 1.45-7.08), high-frequency left rTMS (OR=3.17, 2.29-4.37) and tDCS (OR=2.65, 1.55-4.55). Comparing active treatments, bitemporal ECT and high-dose right-unilateral ECT were associated with increased response. All treatment protocols were at least as acceptable as sham treatment. Conclusion: We found that non-surgical brain stimulation techniques constitute viable alternative or add-on treatments for adult patients with major depressive episodes. Our findings also highlight the need to consider other patient and treatment-related factors in addition to antidepressant efficacy and acceptability when making clinical decisions; and emphasize important research priorities in the field of brain stimulation.
Population-scale study of eRNA transcription reveals bipartite functional enhancer architecture
Authors: Kristjánsdóttir Katla , Kwak Yeonui , Tippens Nathaniel D. , Lis John T. , Min Kang Hyun , Kwak Hojoong
Published: September 2018

Enhancer RNAs (eRNA) are non-coding RNAs transcribed bidirectionally from active regulatory sequences. Their expression levels correlate with the activating potentials of the enhancers, but due to their instability, eRNAs have proven difficult to quantify in large scale. To overcome this, we use capped-nascent-RNA sequencing to efficiently capture the bidirectional initiation of eRNAs. We apply this in large scale to the human lymphoblastoid cell lines from the Yoruban population, and detected nearly 75,000 eRNA transcription sites with high sensitivity and specificity. We identify genetic variants significantly associated with overall eRNA initiation levels, as well as the transcription directionality between the two divergent eRNA pairs, namely the transcription initiation and directional initiation quantitative trait loci (tiQTLs and diQTLs) respectively. High-resolution analyses of these two types of eRNA QTLs reveal distinct positions of enrichment not only at the central transcription factor (TF) binding regions but also at the flanking eRNA initiation regions, both of which are equivalently associated with mRNA expression QTLs. These two regions - the central TF binding footprint and the eRNA initiation cores - define the bipartite architecture and the function of enhancers, and may provide further insights into interpreting the significance of non-coding regulatory variants.
Leveraging single cell RNA sequencing experiments to model intra-tumor heterogeneity
Authors: Ferrall-Fairbanks Meghan C. , Ball Markus , Padron Eric , Altrock Philipp M.
Published: September 2018

PURPOSE

Many cancers can be treated with targeted therapy. Almost inevitably, tumors develop resistance to targeted therapy, either from preexistence or by evolving new genotypes and traits. Intra-tumor heterogeneity serves as a reservoir for resistance, which often occurs due to selection of minor cellular sub-clones. On the level of gene expression, the ‘clonal’ heterogeneity can only be revealed by high-dimensional single cell methods. We propose to use a general diversity index (GDI) to quantify heterogeneity on multiple scales and relate it to disease evolution.

METHODS

We focused on individual patient samples probed with single cell RNA sequencing to describe heterogeneity. We developed a pipeline to analyze single cell data, via sample normalization, clustering and mathematical interpretation using a generalized diversity measure, and exemplify the utility of this platform using single cell data.

RESULTS

We focused on three sources of RNA sequencing data: two healthy bone marrow (BM) samples, two acute myeloid leukemia (AML) patients, each sampled before and after BM transplant (BMT), four samples of pre-sorted lineages, and six lung carcinoma patients with multi-region sampling. While healthy/normal samples scored low in diversity overall, GDI further quantified in which respect these samples differed. While a widely used Shannon diversity index sometimes reveals less differences, GDI exhibits differences in the number of potential key drivers or clonal richness. Comparing pre and post BMT AML samples did not reveal differences in heterogeneity, although they can be very different biologically.

CONCLUSION

GDI can quantify cellular heterogeneity changes across a wide spectrum, even when standard measures, such as the Shannon index, do not. Our approach offers wide applications to quantify heterogeneity across samples and conditions.
Mechanisms of integrin αVβ5 clustering in flat clathrin lattices
Authors: Zuidema Alba , Wang Wei , Kreft Maaike , Molder Lisa te , Hoekman Liesbeth , Bleijerveld Onno B. , Nahidiaza Leila , Janssen Hans , Sonnenberg Arnoud
Published: September 2018

Summary statement

This article highlights several molecular mechanisms that result in the assembly of integrin αVβ5-containing flat clathrin lattices in human keratinocytes.

The family of integrin transmembrane receptors is essential for the normal function of multicellular organisms by facilitating cell-extracellular matrix adhesion. The vitronectin-binding integrin αVβ5 localizes to focal adhesions (FAs) as well as poorly characterized flat clathrin lattices (FCLs). Here we show that in human keratinocytes αVβ5 is predominant found in FCLs and that formation of the αVβ5-containing FCLs requires the presence of vitronectin as ligand, calcium, and the clathrin adaptor proteins ARH, Numb, and EPS15/EPS15L1. Integrin chimeras, containing the extracellular and transmembrane domains of β5 and the cytoplasmic domains of β1 or β3, almost exclusively localize in FAs. Interestingly, lowering actomyosin-mediated contractility promotes integrin redistribution to FLCs in an integrin tail-dependent manner, while increasing cellular tension favors αVβ5 clustering in FAs. Our findings strongly indicate that clustering of integrin αVβ5 in FCLs is dictated by the β5 subunit cytoplasmic domain, cellular tension, and recruitment of specific adaptor proteins to the β5 subunit cytoplasmic domains.
Trait-based approach to bacterial growth efficiency
Authors: Muscarella Mario E. , Howey Xia Meng , Lennon Jay T.
Published: September 2018

Abstract

Bacterial growth efficiency (BGE) is the proportion of assimilated carbon that is converted into biomass and reflects the balance between growth and energetic demands. Often measured as an aggregate property of the community, BGE is highly variable within and across ecosystems. To understand this variation, we first identified how species identity and resource type affect BGE using 20 bacterial isolates belonging to the phylum Proteobacteria that were enriched from north temperate lakes. Using a trait-based approach that incorporated genomic and phenotypic information, we characterized the metabolism of each isolate and tested for predicted trade-offs between growth rate and efficiency. A substantial amount of variation in BGE could be explained at both broad (i.e., order, 20 %) and fine (i.e., strain, 58 %) taxonomic levels. While resource type was a relatively weak predictor across species, it explained > 60 % of the variation in BGE within a given species. Furthermore, a metabolic trade-off (between maximum growth rate and efficiency) and genomic features revealed that BGE is a predictable metabolic feature. Our study suggests that genomic and phylogenetic information may help predict aggregate microbial community functions like BGE and the fate of carbon in ecosystems.

Originality and Significance

Bacterial growth efficiency (BGE) is an important yet notoriously variable measure of metabolism that has proven difficult to predict. To better understand how assimilated carbon is allocated, we explored growth efficiency across a collection of bacteria strains using a trait-based approach. Specifically, we measured respiration and biomass formation rates for populations grown in minimal media containing one of three carbon resources. In addition, we collected a suite of physiological traits to describe each strain, and we sequenced the genome of each organism. Our results suggest that species identity and resource type may contribute to growth efficiency when measured as an aggregate property of a natural community. In addition, we identified genomic pathways that are associated with elevated BGE. The findings have implications for integrating microbial metabolism from the cellular to ecosystem scale.
Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage
Authors: Grendler Janelle , Lowgren Sara , Mills Monique , Losick Vicki P.
Published: September 2018

Tissue repair requires either polyploid cell growth or cell division, but the molecular mechanism promoting polyploidy and limiting proliferation remains poorly understood. Here we find that injury to the adultDrosophilaepithelium causes cells to enter the endocycle through the activation of Yorkie dependent genes (myc,e2f1, orcycE). Myc is even sufficient to induce the endocycle in the post-mitotic epithelium. As result, epithelial cells enter S phase but mitosis is blocked by inhibition of mitotic gene expression. The mitotic cell cycle program can be activated by simultaneously expressing the mitotic activator,Stg, while genetically depletingfzr. However, forcing cells to undergo mitosis is detrimental to wound repair as the adult fly epithelium accumulates DNA damage and mitotic errors ensue when cells are forced to proliferate. In conclusion, we find that wound-induced polyploidization enables tissue repair when cell division is not a viable option.