bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two cohorts of medically at-risk adolescents engaging in substance use (cancer survivors and asthmatics): Clinical predictors for monitoring care
Authors: Hollen Patricia J. , O'Laughlen Mary C. , Hellems Martha A. , Hinton Ivora D. , Xin Wenjun , Patrie James T.
Published: June 2019

Background and purpose:

Medically at-risk adolescents differ in their perception of severity and are vulnerable to substance use because of effects on their medical regimen. The intent in comparing two cohorts, adolescent survivors of cancer and teens with asthma, is to provide clinical predictors to help in monitoring those needing help with substance use decision making.

Methods:

Baseline data were obtained from two randomized controlled trials for a decision-making program of research for medically at-risk adolescents. Multivariate analyses were used to identify clinical predictors for poor decision making as well as lifetime and current substance use (smoking, alcohol use, and marijuana use).

Conclusions:

Predictors for both cohorts for lifetime and current substance use were increasing age and risk motivation. A significant predictor for both cohorts for poor decision making related to substance use was risk motivation, measured as a more positive attitude for engaging in substance use. Negative modeling by peers and family members had an impact on teen survivors' decision making; but, this was not clear for teens with asthma.

Implications for practice:

Research is needed comparing other medically at-risk adolescents to determine which cohorts on the substance use spectrum are less resilient to peer and parent modeling, have unrealistic views of their decision-making skills, and need close monitoring and guidance.
Altered Gray Matter Volume and White Matter Integrity in Sensorineural Hearing Loss Patients: A VBM and TBSS Study
Authors: Qi Rongmiao , Su Lianzi , Zou Liwei , Yang Jianming , Zheng Suisheng
Published: June 2019

Objective:

The purpose of the present study was to detect structural changes in the brains of patients with sensorineural hearing loss (SNHL) by combining voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS).

Methods:

Thirty-five patients with SNHL (mean age: 39.72 ± 1.81 yr) and 23 age-matched control subjects (mean age: 39.83 ± 1.96 yr) were assessed using three-dimensional, T1-weighted imaging, and diffusion tensor imaging. TBSS and VBM analyses were performed to evaluate grey matter (GM) volume changes and white matter (WM) alternations, as measured by mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD).

Results:

VBM showed decreased GM volume in patients with SNHL in the fusiform gyrus of the right temporal lobe and right middle occipital gyrus. TBSS revealed WM integrity changes, including decreased FA and RD and increased RD in several WM regions. However, MD showed no significant difference between patients with SNHL and age-matched controls.

Conclusion:

Patients with SNHL showed smaller GM volume and WM integrity changes in several regions.
Endoscopic-Assisted Repair of Spontaneous Temporomandibular Joint Herniation Through a Transcanal Approach
Authors: Xie Bingbin , Zhang Shaorong , Liu Yuehui
Published: June 2019

Objective:

To report of the presentation, diagnosis, and management of a spontaneous temporomandibular joint (TMJ) herniation.

Patients:

A 69-year-old man with a spontaneous TMJ herniation.

Interventions:

Diagnostic evaluation and surgical approaches.

Main Outcome Measures:

Imaging, and medical and surgical treatment outcomes.

Results:

At 14 months follow-up, the patient reported improved tinnitus and on examination there was no evidence of a hypertrophic scar or canal stenosis, no recurrence of TMJ herniation, no signs of otorrhea, otalgia; and with normal TMJ function.

Conclusions:

The advantages of repairing spontaneous TMJ herniation through a transcanal approach using oto-endoscopy include a high definition video of surgical field, minimal invasiveness, and good postoperative cosmetic outcome.
Insurance Loss in the Era of the Affordable Care Act
Authors: Mojtabai Ramin
Published: June 2019

Background:

Every year, millions of Americans lose their health insurance and remain uninsured for various reasons, potentially impacting access to medical services.

Objective:

To examine trends in health insurance loss in the periods shortly before and after implementation of Patient Protection and Affordable Care Act (ACA) and to assess the association of past-year health insurance loss with access to health services and medications.

Research Design and Subjects:

Trends in health insurance loss were examined in 176,961 nonelderly adult participants of the National Health Interview Survey 2011–2017—a representative cross-sectional annual survey of US general population. Multivariable logistic regression models were used to examine access to health services and medications.

Measures:

Loss of private insurance or Medicaid in the past year; use of emergency room services and hospitalizations; contact with medical providers; affording medical care or medications; cost-related medication nonadherence.

Results:

Private health insurance loss decreased from 3.9%–4.0% in 2011–2013 to 2.7% to 3.1% in 2014–2017 (P<0.001); Medicaid loss decreased from 8.5%–8.9% to 4.6%–6.4% in this period (P<0.001). Nevertheless, as late as 2017, ∼6 million uninsured adults reported having lost private insurance or Medicaid in the past year. Loss of either type of health insurance was associated with lower odds of accessing medical providers, but higher odds of not affording medical care and poor adherence to medication regimens to save costs.

Conclusions:

Implementation of ACA was associated with lower risk of health insurance loss. Nevertheless, health insurance loss remains a major barrier to accessing health services and prescribed medications.
Deep Learning to Classify Intraductal Papillary Mucinous Neoplasms Using Magnetic Resonance Imaging
Authors: Corral Juan E. , Hussein Sarfaraz , Kandel Pujan , Bolan Candice W. , Bagci Ulas , Wallace Michael B.
Published: June 2019

Objective

This study aimed to evaluate a deep learning protocol to identify neoplasia in intraductal papillary mucinous neoplasia (IPMN) in comparison to current radiographic criteria.

Methods

A computer-aided framework was designed using convolutional neural networks to classify IPMN. The protocol was applied to magnetic resonance images of the pancreas. Features of IPMN were classified according to American Gastroenterology Association guidelines, Fukuoka guidelines, and the new deep learning protocol. Sensitivity and specificity were calculated using surgically resected cystic lesions or healthy controls.

Results

Of 139 cases, 58 (42%) were male; mean (standard deviation) age was 65.3 (11.9) years. Twenty-two percent had normal pancreas; 34%, low-grade dysplasia; 14%, high-grade dysplasia; and 29%, adenocarcinoma. The deep learning protocol sensitivity and specificity to detect dysplasia were 92% and 52%, respectively. Sensitivity and specificity to identify high-grade dysplasia or cancer were 75% and 78%, respectively. Diagnostic performance was similar to radiologic criteria. Areas under the receiver operating curves (95% confidence interval) were 0.76 (0.70–0.84) for American Gastroenterology Association, 0.77 (0.70–0.85) for Fukuoka, and 0.78 (0.71–0.85) for the deep learning protocol (P = 0.90).

Conclusions

The deep learning protocol showed accuracy comparable to current radiographic criteria. Computer-aided frameworks could be implemented as aids for radiologists to identify high-risk IPMN.
Ki-67 Index of 5% is Better Than 2% in Stratifying G1 and G2 of the World Health Organization Grading System in Pancreatic Neuroendocrine Tumors
Authors: Gao Shao-Wei , Huang Chen-Song , Huang Xi-Tai , Chen Liu-Hua , Chen Wei , Cai Jian-Peng , Yin Xiao-Yu
Published: June 2019

Objective

The World Health Organization (WHO) grading system for the stratification of G1 and G2 pancreatic neuroendocrine tumors (pNETs) using an optimal Ki-67 index cutoff is still controversial. The present study aimed at finding one optimal Ki-67 cutoff value that distinguishes G1 and G2 tumors by analyzing the prognosis of patients with pNET in our center.

Methods

Data from 84 patients with pNET undergoing surgical resection in The First Affiliated Hospital of Sun Yat-sen University between March 2003 and October 2015 were retrospectively analyzed.

Results

The 5-year overall survival rate was 74.2%. Univariate analysis revealed that functional secretion, WHO grade, and TNM stage were significantly associated with long-term survival (all P < 0.05). Multivariate analysis demonstrated that WHO grade (P = 0.023) and TNM stage (P = 0.040) were independent prognostic factors. The receiver operating characteristic curve showed that the Ki-67 index of 5% had the best predictive ability (76.7%) for 5-year survival with a hazard ratio of 44.7. The hazard ratio was only 8.14 when the Ki-67 index cutoff was 2%.

Conclusions

TNM stage and WHO grade were independent prognostic factors of pNETs. A Ki-67 index of 5% is better than 2% in stratifying G1 and G2 pNET tumors.
The Impact of Cannabis Consumption on Mortality, Morbidity, and Cost in Acute Pancreatitis Patients in the United States
Authors: Simons-Linares Carlos Roberto , Barkin Jodie A. , Jang Sunguk , Bhatt Amit , Lopez Rocio , Stevens Tyler , Vargo John , Barkin Jamie S. , Chahal Prabhleen
Published: June 2019

Objectives

The aim of this study was to identify the prevalence of cannabis use among all patients admitted with acute pancreatitis (AP) in the United States and to investigate the impact of cannabis use on AP mortality, morbidity, and cost of care.

Methods

The National Inpatient Sample database from 2003 to 2013 was queried for all patients with AP and active exposure to cannabis. Outcomes included in-hospital mortality, length of stay, inflation adjusted charges, acute kidney injury, acute respiratory distress syndrome, and shock. Results were adjusted for age, sex, race, Charlson comorbidity index, median income quartile, and hospital characteristics.

Results

More than 2.8 million patients with AP patients were analyzed. Cannabis-exposed (CE) patients' prevalence was 0.3%. Patients exposed to cannabis were younger and mostly males compared with non–cannabis-exposed patients. After adjusting for these factors, the CE group had significantly lower inpatient mortality compared with the noncannabis group (odds ratio, 0.17; 95% confidence interval, 0.06–0.53). Cannabis-exposed patients also had decreased length of stay, inflation-adjusted charges, acute kidney injury, ileus, shock, acute respiratory distress syndrome, and parenteral nutrition requirement.

Conclusions

Cannabis-exposed hospitalized patients with AP had lower age-adjusted, mortality, morbidity, and hospitalization-cost than non–cannabis-exposed patients.
Liver Ultrasound Patterns in Children With Cystic Fibrosis Correlate With Noninvasive Tests of Liver Disease
Authors: Ling Simon C. , Ye Wen , Leung Daniel H. , Navarro Oscar M. , Weymann Alexander , Karnsakul Wikrom , Freeman A. Jay , Magee John C. , Narkewicz Michael R.
Published: June 2019

Objectives:

Early identification of children with cystic fibrosis (CF) at risk for severe liver disease (CFLD) would enable targeted study of preventative therapies. There is no gold standard test for CFLD. Ultrasonography (US) is used to identify CFLD, but with concerns for its diagnostic accuracy. We aim to determine if differences in standard blood tests, imaging variables and noninvasive liver fibrosis indices correlate with liver US patterns, and thus provide supportive evidence that a heterogeneous US liver pattern reflects clinically relevant liver disease.

Methods:

We studied baseline research abdominal US and bloodwork from 244 children with pancreatic insufficient CF, ages 3 to 12 years, enrolled in a prospective study of the ability of US to predict CF cirrhosis (PUSH study). Children with a heterogeneous (HTG) liver pattern on US (n = 62) were matched 1 : 2 in design with children with normal US (NL, n = 122). Analyses included children with nodular (NOD, n = 22) and homogeneous hyperechoic (HMG, n = 38) livers.

Results:

Univariate analysis showed significant differences between US groups for standard blood tests, spleen size, and noninvasive liver fibrosis indices. Multivariable models discriminated NOD versus NL with excellent accuracy (AUROC 0.96). Models also distinguish HTG versus NL (AUROC 0.76), NOD versus HTG (0.78), and HMG versus NL (0.79).

Conclusions:

Liver US patterns in children with CF correlate with platelet count, spleen size and indices of liver fibrosis. Multivariable models of these biomarkers have excellent discriminating ability for NL versus NOD, and good ability to distinguish other US patterns, suggesting that US patterns correlate with clinically relevant liver disease.
Correlates of Physical Activity in Colorectal Cancer Patients Based on Health Promotion Model
Authors: Kang Dong-Qin , Li Yu , Chen Zhi-Qi , Liu Qi , Su Chun-Xiang , Guo Hong , Yue Shu-Jin
Published: June 2019

Background

Increasing attention is being given to physical activity in colorectal cancer patients. Some studies have explored a few correlates of physical activity separately. A contemporary study based on the Health Promotion Model may systematically broaden the understanding of physical activity in colorectal cancer patients.

Objective

To understand the status of physical activity in Chinese colorectal cancer patients and to explore the correlated factors.

Methods

A total of 168 adults with colorectal cancer were recruited at 3 tertiary hospitals in China. Participant data were collected on demographics, physical activity, biological factors, anxiety and depression, benefits/barriers to physical activity, self-efficacy, and social support. SAS 8.2 was used for statistical analysis, including descriptive analysis, correlation analysis, single factor analysis, and multiple stepwise regression analysis.

Results

Only 25.60% of colorectal cancer survivors reached the requirements of the Colorectal Cancer Survivorship Care Guidelines. Employment states, number of complications, fatigue, body image, depression, perception of benefits/barriers, and self-efficacy were closely correlated with physical activity in Chinese colorectal cancer patients.

Conclusions

The physical activity status of patients with colorectal cancer is not optimal. The correlated factors that nurses can take measures to improve are fatigue, body image, depression, perception of benefits/barriers, and self-efficacy, which may improve physical activity in colorectal cancer patients in China. Additional research is needed to determine if improving factors correlated with physical activity will assist with directly increasing physical activity.

Implications for Practice

Nurses should evaluate physical activity of colorectal cancer patients timely and play an active role in health promotion programs to improve colorectal cancer patients’ physical activity.
Frameshift Mutations and Loss of Expression of CLCA4 Gene are Frequent in Colorectal Cancers With Microsatellite Instability
Authors: Mo Ha Yoon , Lee Ju Hwa , Kim Min Sung , Yoo Nam Jin , Lee Sug Hyung
Published: June 2019

Chloride channel calcium-activated (CLCA) genes encode regulators for chloride transport across the cell membrane. As for cancer development, some CLCA genes are considered putative tumor suppressor genes. The aim of this study was to explore whether CLCA4 gene would have mutations in its nucleotide repeats in colorectal cancer (CRC). In a public database, we found that CLCA4 gene had mononucleotide repeats in the coding sequences that might be mutational targets in the cancers with microsatellite instability. For this, the current study studied 146 CRCs for mutation and expression analyses by single-strand conformation polymorphism analysis, DNA sequencing, and immunohistochemistry. Overall, we found CLCA4 frameshift mutations in 12/101 (11.8%) CRCs with high-microsatellite instability (MSI-H), but none in microsatellite stable CRCs (0/45) (P<0.01). In addition, we analyzed intratumoral heterogeneity of the CLCA4 frameshift mutations and found that 1 CRC harbored regional intratumoral heterogeneity of the CLCA4 frameshift mutation. Loss of CLCA4 protein expression was identified in 50% of CRCs. Also, cancers with MSI-H harboring CLCA4 frameshift mutations showed lower CLCA4 immunostaining than those with the wild-type. Our data indicate that the CLCA4 gene harbors alterations both in somatic mutation and expression, suggesting their roles in tumorigenesis of CRC with MSI-H.
Sitting Matters! Differences Between Sitters and Nonsitters at 6 Months' Adjusted Age in Infants At-Risk and Born Preterm
Authors: Jensen-Willett Sandra , Pleasant Malinda , Jackson Barbara , Needelman Howard , Roberts Holly , McMorris Carol
Published: June 2019

Purpose:

Sitting delays in infants born preterm compound cognitive and language deficits. This retrospective study examines differences in prematurity-related risk and compares developmental outcomes between sitters and nonsitters at 6 months' adjusted age.

Methods:

A total of 105 graduates of the neonatal intensive care unit met inclusion criteria. Infant demographic and medical risk profiles and 6-month Bayley Scales of Infant Development-3rd edition (BSID-III) cognitive and language scores were retrieved. Infants who sat with hands free greater than 60 seconds were classified as “sitters.”

Results:

Sixty-nine percent of the sample were nonsitters and were born earlier, had lower birth weights, were chronologically older at follow-up, and spent more days with respiratory support. BSID-III scores were significantly higher in sitters but did not differ by gender, multiple birth, head ultrasound results, payment type, or race/ethnicity.

Conclusion:

Sitting abilities at 6 months' adjusted age are associated with prematurity risk factors. Cognitive and language scores differ significantly between sitters and nonsitters.
Low-grade Serous Carcinoma Arising in Inguinal Nodal Endosalpingiosis: Report of 2 Cases and Literature Review
Authors: Sah Shatrughan , Fulmali Rahul , McCluggage W. Glenn
Published: June 2019

We report 2 cases of low-grade serous carcinoma probably arising from endosalpingiosis within inguinal lymph nodes. The neoplasms occurred in 51- and 58-yr old women in the absence of tumor within the adnexa, peritoneum or elsewhere. These represent the first reported examples of low-grade serous carcinoma arising within and confined to inguinal nodes. We review the pertinent literature regarding primary nodal low-grade serous carcinoma.
An Assessment of Food Store Compliance With the Cook County Sweetened Beverage Tax
Authors: El-Sayed Osama M. , Pipito Andrea A. , Leider Julien , Chriqui Jamie F. , Powell Lisa M.
Published: June 2019

To examine the correct application of the $0.01/ounce Cook County, Illinois, Sweetened Beverage Tax on sugar-sweetened and artificially sweetened beverages, a total of 111 beverage products were purchased from 28 food stores in September and November 2017. Purchases were categorized by taxable (sugar-sweetened and artificially sweetened soda and juice drinks) and nontaxable (100% fruit juice and sparkling water) beverage type, store type (limited service vs supermarket/grocery), and area median household income (lower vs higher). Two-sample tests of proportions were conducted to compare correctly taxed purchases. The tax was correctly applied in 91.0% of cases. Correct tax application was found in 87.8% of taxable beverage purchases versus 97.3% of nontaxable beverage purchases (P = .10), 71.4% of juice drink purchases versus 95.6% of nonjuice drink purchases (P < .001), and 85.5% of limited service store purchases versus 100% of supermarket/grocery purchases (P = .01). No significant differences were found by area income.
Use of Person Locator Service to Facilitate Immunization Information System–Based Adolescent Reminder Project
Authors: Kuramoto Sydney , St. Martin Andrew , Muscoplat Miriam Halstead
Published: June 2019

Objective:

To determine the impact of using a person locator service to reduce undeliverable addresses for an immunization information system (IIS)–based reminder project.

Design:

Return mail was compared at address-difference levels between original IIS addresses and updated addresses.

Setting:

Minnesota residents were targeted for an immunization reminder postcard based on address.

Participants:

Both 11- and 12-year-olds with a Minnesota address in Minnesota's IIS.

Intervention:

An immunization reminder postcard was mailed to households of participants.

Main Outcome Measure(s):

Reminder postcard return rates were tracked for address-difference levels between original IIS addresses and updated addresses. Return mail rates were track at the ZIP Code Tabulation Area (ZCTA) level and analyzed for demographic characteristic associations.

Results:

Postcards had significantly lower odds of return when an address was confirmed (odds ratio [OR] = 0.09; 95% confidence interval [CI], 0.08-0.1; P < .001) or had major updates (OR = 0.47; 95% CI, 0.44-0.49; P < .001) than when no new address information was obtained. Significant, positive associations were found between return rate and both ZCTA-level poverty rate (γ = 0.235, P < .001) and ZCTA-level percentage of nonwhite residents (γ = 0.301, P < .001).

Conclusions:

Use of a person locator service is a promising method for reducing the barrier incorrect address information poses to successful reminder/recall notification. Implementation of person locator services could improve the data quality of address information in the IIS and success of outreach attempts by IIS users.
Relocation of macrophages maintains the barrier function of the urothelium and protects against persistent infection
Authors: Bottek Jenny , Soun Camille , Volke Julia K , Dixit Akanksha , Thiebes Stephanie , Beerlage Anna-Lena , Horstmann Marius , Urbanek Annett , Uszkoreit Julian , Eisenacher Martin , Bracht Thilo , Sitek Barbara , Hoffmann Franziska , Vijitha Nirojah , von Eggeling Ferdinand , Engel Daniel R
Published: June 2019

Macrophages perform essential functions during bacterial infections, such as phagocytosis of pathogens and elimination of neutrophils to reduce spreading of infection, inflammation and tissue damage. The spatial distribution of macrophages is critical to respond to tissue specific adaptations upon infections. Using a novel algorithm for correlative mass spectrometry imaging and state-of-the-art multiplex microscopy, we report here that macrophages within the urinary bladder are positioned in the connective tissue underneath the urothelium. Invading uropathogenicE.coliinduced an IL-6–dependent CX3CL1 expression by urothelial cells, facilitating relocation of macrophages from the connective tissue into the urothelium. These cells phagocytosed UPECs and eliminated neutrophils to maintain barrier function of the urothelium, preventing persistent and recurrent urinary tract infection.

GRAPHICAL ABSTRACT
RNA velocity and protein acceleration from single-cell multiomics experiments
Authors: Gorin Gennady , Svensson Valentine , Pachter Lior
Published: June 2019

The simultaneous quantification of protein and RNA makes possible the inference of past, present and future cell states from single experimental snapshots. To enable such temporal analysis from multimodal single-cell experiments, we introduce an extension of the RNA velocity method that leverages estimates of unprocessed transcript and protein abundances to extrapolate cell states. We apply the model to four datasets and demonstrate consistency among landscapes and phase portraits.
Multifaceted Hi-C benchmarking: what makes a difference in chromosome-scale genome scaffolding?
Authors: Kadota Mitsutaka , Nishimura Osamu , Miura Hisashi , Tanaka Kaori , Hiratani Ichiro , Kuraku Shigehiro
Published: June 2019

Background

Hi-C, a derivative of chromosome conformation capture (3C) targeting the whole genome, was originally developed as a means for characterizing chromatin conformation. More recently, this method has also been frequently employed in elongating nucleotide sequences obtained by de novo genome sequencing and assembly, in which the number of resultant sequences rarely converge into the chromosome number. Despite the prevailing and irreplaceable use, sample preparation methods for Hi-C have not been intensively discussed, especially from the standpoint of genome scaffolding.

Results

To gain insights into the best practice of Hi-C scaffolding, we performed a multifaceted methodological comparison using vertebrate samples and optimized various factors during sample preparation, sequencing, and computation. As a result, we have identified some key factors that help improve Hi-C scaffolding including the choice and preparation of tissues, library preparation conditions, and restriction enzyme(s), as well as the choice of scaffolding program and its usage.

Conclusions

This study provides the first comparison of multiple sample preparation kits/protocols and computational programs for Hi-C scaffolding, by an academic third party. We introduce a customized protocol designated the ‘inexpensive and controllable Hi-C (iconHi-C) protocol’, in which the optimal conditions revealed by this study have been incorporated, and release the resultant chromosome-scale genome assembly of the Chinese softshell turtle Pelodiscus sinensis.
Light-regulated collective contractility in a multicellular choanoflagellate
Authors: Brunet Thibaut , Larson Ben T. , Linden Tess A. , Vermeij Mark J. A. , McDonald Kent , King Nicole
Published: June 2019

Collective cell contractions that generate global tissue deformations are a signature feature of animal movement and morphogenesis. Nonetheless, the ancestry of collective contractility in animals remains mysterious. While surveying the Caribbean island of Curaçao for choanoflagellates, the closest living relatives of animals, we isolated a previously undescribed species (here namedChoanoeca flexasp. nov.), that forms multicellular cup-shaped colonies. The colonies rapidly invert their curvature in response to changing light levels, which they detect through a rhodopsin-cGMP pathway. Inversion requires actomyosin-mediated apical contractility and allows alternation between feeding and swimming behavior.C. flexathus rapidly converts sensory inputs directly into multicellular contractions. In this respect, it may inform reconstructions of hypothesized animal ancestors that existed before the evolution of specialized sensory and contractile cells.

One Sentence Summary

A newly described choanoflagellate species forms cup-shaped colonies that reversibly invert their curvature in response to light.
Impact of age-specific immunity on the timing and burden of the next Zika virus outbreak
Authors: Counotte Michel J. , Althaus Christian L. , Low Nicola , Riou Julien
Published: June 2019

The 2015–2017 epidemics of Zika virus (ZIKV) in the Americas caused widespread protective immunity. The timing and burden of the next Zika virus outbreak remains unclear. We used an agent-based model to simulate the dynamics of age-specific immunity to ZIKV, and predict the future age-specific risk using data from Managua, Nicaragua. We also investigated the potential impact of a ZIKV vaccine. Assuming lifelong immunity, the risk of a ZIKV outbreak will remain low until 2035 and rise above 50% in 2047. The imbalance in age-specific immunity implies that people in the 15–29 age range will be at highest risk of infection during the next ZIKV outbreak, increasing the expected number of congenital abnormalities. ZIKV vaccine development and licensure are urgent to attain the maximum benefit in reducing the population-level risk of infection and the risk of adverse congenital outcomes. This urgency increases if immunity is not lifelong.
Transcriptome dynamics predict thermotolerance in Caenorhabditis elegans
Authors: Jovic Katharina , Grilli Jacopo , Sterken Mark G. , Snoek Basten L. , Riksen Joost A. G. , Allesina Stefano , Kammenga Jan E.
Published: June 2019

Background

The detrimental effects of a short bout of stress can persist, and potentially turn lethal, long after the return to normal conditions. Thermotolerance, which is the capacity of an organism to withstand relatively extreme temperatures, is influenced by the response during stress exposure, as well as the recovery process afterwards. While heat-shock response mechanisms have been studied intensively, predicting thermal tolerance remains a challenge.

Results

Here, we use the nematode Caenorhabditis elegans to measure transcriptional resilience to heat stress and predict thermotolerance. Using high dimensionality reduction techniques in combination with genome-wide gene expression profiles collected in three high resolution time-series during control, heat stress and recovery conditions, we infer a quantitative scale capturing the extent of stress-induced transcriptome dynamics in a single value. This scale provides a basis for evaluating transcriptome resilience, defined here as the ability to depart from stress-expression dynamics during recovery. Independent replication across multiple highly divergent genotypes reveals that the transcriptional resilience parameter measured after a spike in temperature is quantitatively linked to long-term survival after heat stress.

Conclusion

Our findings imply that thermotolerance is an intrinsic property that pre-determines long term outcome of stress and can be predicted by the transcriptional resilience parameter. Inferring the transcriptional resilience parameters of higher organisms could aid in evaluating rehabilitation strategies after stresses such as disease and trauma.
The Role of Adaptation in Generating Monotonic Rate Codes in Auditory Cortex
Authors: Lee Jong Hoon , Wang Xiaoqin , Bendor Daniel
Published: June 2019

In primary auditory cortex, slowly repeated acoustic events are represented temporally by phase-locked activity of single neurons. Single-unit studies in awake marmosets (Callithrix jacchus) have shown that a sub-population of these neurons also monotonically increase or decrease their average discharge rate during stimulus presentation for higher repetition rates. Building on a computational single-neuron model that generates phase-locked responses with stimulus evoked excitation followed by strong inhibition, we find that stimulus-evoked short-term depression is sufficient to produce synchronized monotonic positive and negative responses to slowly repeated stimuli. By exploring model robustness and comparing it to other models for adaptation to such stimuli, we conclude that short-term depression best explains our observations in single-unit recordings in awake marmosets. Using this model, we emulated how single neurons could encode and decode multiple aspects of an acoustic stimuli with the monotonic positive and negative encoding of a given stimulus feature. Together, our results show that a simple biophysical mechanism in single neurons can allow a more complex encoding and decoding of acoustic stimuli.
Canonical Wnt pathway controls mESCs self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions
Authors: Aulicino Francesco , Sottile Francesco , Pedone Elisa , Lluis Frederic , Marucci Lucia , Cosma Maria Pia
Published: June 2019

The Wnt/β-catenin signalling pathway is a key regulator of embryonic stem cell self-renewal and differentiation. Constitutive activation of this pathway has been shown to significantly increase mouse embryonic stem cell (mESC) self-renewal and pluripotency marker expression. In this study, we generated a novel β-catenin knock-out model in mESCs by using CRISPR/Cas9 technology to delete putatively functional N-terminally truncated isoforms observed in previous knock-out models. While we showed that aberrant N-terminally truncated isoforms are not functional in mESCS, we observed that canonical Wnt signalling is not active in mESCs, as β-catenin ablation does not alter mESC transcriptional profile in LIF-enriched culture conditions; on the other hand, Wnt signalling activation represses mESC spontaneous differentiation. We also showed that transcriptionally silent β-catenin (ΔC) isoforms can rescue β-catenin knock-out self-renewal defects in mESCs, cooperating with TCF1 and LEF1 in the inhibition of mESC spontaneous differentiation in a Gsk3 dependent manner.
Effect of adiposity on leukocyte telomere length in US adults by race/ethnicity: The National Health and Nutrition Examination Survey
Authors: Davis Sharon K. , Xu Ruihua , Khan Rumana J. , Gaye Amadou , Liu Yie
Published: June 2019

Objective

Obesity is associated with telomere attrition – a marker of cellular and biological aging. The US has the highest proportion of obesity and is comprised of a racially/ethnic diverse population. Little is known about the relationship between obesity and telomere attrition according to race/ethnicity in the US. Our objective is to examine the differential association.

Design and setting

The effect of body mass index (BMI), % total body fat (TBF) and waist circumference (WC) on leukocyte telomere length (LTL) were examined as adiposity measures according to race/ethnicity and sex specific race/ethnicity using separate adjusted linear regressions on a sample of 4,919 respondents aged 20-84 years from cross-sectional 1999-2002 data using the US National Health and Nutrition Examination Survey. Mediation analyses assessed health behaviors associated with relationship between adiposity measures and LTL.

Main outcome measure

LTL

Results

African Americans (AA) experienced a 28% and 11% decrease in LTL associated with increasing BMI and WC, (p=.02 and .03) respectively. Mexican Americans (MA) experienced a 33% decrease in LTL associated with increasing %TBF (p=.04). Whites experienced a 19%, 23%, and .08% decrease in LTL associated with increasing BMI, %TBF, and WC, (p=.05, .003, .02) respectively. White men experienced a 26% decrease in LTL due to increasing BMI (p=.05). AA women experienced a 41%, 44%, and 16% decrease in LTL due to increasing BMI, %TBF, and WC, respectively (p=.007, .02, .04). White women experienced a 29% decrease in LTL associated with increasing %TBF (p=.006). Selected health behaviors were associated with the relationship between adiposity measures and LTL.

Conclusion

Overall, AA and Whites have worse cellular and biological aging related to collective adiposity measures. According to sex, AA women experienced more deleterious cellular and biological aging. Findings suggest tailored interventions to improve adverse behaviors that contribute to obesity may improve telomere attrition in US adults.
Decoding neural responses to motion-in-depth using EEG
Authors: Himmelberg Marc M. , Segala Federico G. , Maloney Ryan T. , Harris Julie M. , Wade Alex R.
Published: June 2019

Two stereoscopic cues that underlie the perception of motion-in-depth (MID) are changes in retinal disparity over time (CD) and interocular velocity differences (IOVD). These cues have independent spatiotemporal sensitivity profiles, depend upon different low-level stimulus properties, and are potentially processed along separate cortical pathways. Here, we ask whether these MID cues code for different motion directions: do they give rise to discriminable patterns of neural signals, and is there evidence for their convergence onto a single ‘motion-in-depth’ pathway? To answer this, we use a decoding algorithm to test whether, and when, patterns of electroencephalogram (EEG) signals measured from across the full scalp, generated in response to CD- and IOVD-isolating stimuli moving towards or away in depth can be distinguished. We find that both MID cue type and 3D-motion direction can be decoded at different points in the EEG timecourse and that direction decoding cannot be accounted for by static disparity information. Remarkably, we find evidence for late processing convergence: IOVD motion direction can be decoded relatively late in the timecourse based on a decoder trained on CD stimuli, and vice versa. We conclude that early CD and IOVD direction decoding performance is dependent upon fundamentally different low-level stimulus features, but that later stages of decoding performance may be driven by a central, shared pathway that is agnostic to these features. Overall, these data are the first to show that neural responses to CD and IOVD cues that move towards and away in depth can be decoded from EEG signals, and that different aspects of MID-cues contribute to decoding performance at different points along the EEG timecourse.
Functional characterization of RNase H1 proteins in Arabidopsis thaliana
Authors: Kuciński Jan , Kmera Aleksandra , Rowley M. Jordan , Khurana Pragya , Nowotny Marcin , Wierzbicki Andrzej T.
Published: June 2019

RNase H1 is an endonuclease specific towards RNA:DNA hybrids. Members of this protein family are present in most living organisms and are essential for removing RNA that base pairs with DNA. It prevents detrimental effects of RNA:DNA hybrids and is involved in several biological processes. We show that Arabidopsis thaliana contains four RNase H1-like proteins originating from two gene duplication events and alternative splicing. These proteins have the canonical RNase H1 activity, which requires at least four ribonucleotides for activity. Two of those proteins are nuclear, one is localized to mitochondria and one to plastids. While the nuclear RNases H1 are dispensable, the presence of at least one organellar RNase H1 is required for embryonic development. The plastid protein RNH1C affects plastid DNA copy number and sensitivity to hydroxyurea. This indicates that three genomes present in each plant cell are served by at least one specialized RNase H1 protein.
The conspicuousness of the toxicHeliconiusbutterflies across time and habitat
Authors: Dell’Aglio Denise Dalbosco , Troscianko Jolyon , Stevens Martin , McMillan W Owen , Jiggins Chris D
Published: June 2019

Forests are a mosaic of light spectra, and colour signal efficiency might change in different light environments. Local adaptation inHeliconiusbutterflies is linked to microhabitat use and the colourful wing colour patterns may be adapted for signalling in different light environments. These toxic butterflies exhibit conspicuous colours as a warning to predators that they should be avoided, but also find and choose potential mates based on colour signals. The two selection pressures of predation and mate preference are therefore acting together. Colour conspicuousness should show habitat-specific contrast for the butterflies, which would facilitate detection and species identification. On the other hand, selection for signal stability would be stronger in the avian visual system. In this study we analysed the contrast of twoHeliconiusmimicry rings in their natural habitats under varying degrees of forest fragmentation and light conditions. We used digital image analyses and mapped the bird and butterfly vision colour space in order to examine whether warning colours have greater contrast and if they transmit a consistent signal across time of the day and habitat in a tropical forest. We tested conspicuousness using opponent colour channels against a natural green background. For avian vision, colours are generally very stable through time and habitat. For butterfly vision, there is some evidence that species are more contrasting in their own habitats, where conspicuousness is higher for red and yellow bands in the border and for white in the forest. Light environment affectsHeliconiusbutterflies’ warning signal transmission to a higher degree through their own vision, but to a lesser degree through avian predator vision. This work provides insight into the use of colour signals in sexual and natural selection in the light of ecological adaptation.
Systematic Integration of Structural and Functional Data into Multi-Scale Models of Mouse Primary Visual Cortex
Authors: Billeh Yazan N. , Cai Binghuang , Gratiy Sergey L. , Dai Kael , Iyer Ramakrishnan , Gouwens Nathan W. , Abbasi-Asl Reza , Jia Xiaoxuan , Siegle Joshua H. , Olsen Shawn R. , Koch Christof , Mihalas Stefan , Arkhipov Anton
Published: June 2019

Abstract

Structural rules underlying functional properties of cortical circuits are poorly understood. To explore these rules systematically, we integrated information from extensive literature curation and large-scale experimental surveys into a data-driven, biologically realistic model of the mouse primary visual cortex. The model was constructed at two levels of granularity, using either biophysically-detailed or point-neurons, with identical network connectivity. Both variants were compared to each other and to experimental recordings of neural activity during presentation of visual stimuli to awake mice. While constructing and tuning these networks to recapitulate experimental data, we identified a set of rules governing cell-class specific connectivity and synaptic strengths. These structural constraints constitute hypotheses that can be tested experimentally. Despite their distinct single cell abstraction, spatially extended or point-models, both perform similarly at the level of firing rate distributions. All data and models are freely available as a resource for the community.
Comprehensive genomic analysis of dietary habits in UK Biobank identifies hundreds of genetic loci and establishes causal relationships between educational attainment and healthy eating
Authors: Cole Joanne B. , Florez Jose C. , Hirschhorn Joel N.
Published: June 2019

Unhealthy dietary habits are leading risk factors for life-altering diseases and mortality. Large-scale biobanks now enable genetic analysis of traits with modest heritability, such as diet. We performed genomewide association on 85 single food intake and 85 principal component-derived dietary patterns from food frequency questionnaires in UK Biobank. We identified 814 associated loci, including olfactory receptor associations with fruit and tea intake; 136 associations were only identified using dietary patterns. Mendelian randomization suggests a Western vs. prudent dietary pattern is causally influenced by factors correlated with education but is not strongly causal for coronary artery disease or type 2 diabetes.
The murine transcriptome reveals global aging nodes with organ-specific phase and amplitude
Authors: Schaum Nicholas , Lehallier Benoit , Hahn Oliver , Hosseinzadeh Shayan , Lee Song E. , Sit Rene , Lee Davis P. , Losada Patricia Morán , Zardeneta Macy E. , Pálovics Róbert , Fehlmann Tobias , Webber James , McGeever Aaron , Zhang Hui , Berdnik Daniela , Tan Weilun , Zee Alexander , Tan Michelle ,   The Tabula Muris Consortium, Pisco Angela , Karkanias Jim , Neff Norma F. , Keller Andreas , Darmanis Spyros , Quake Stephen R. , Wyss-Coray Tony
Published: June 2019

Aging is the single greatest cause of disease and death worldwide, and so understanding the associated processes could vastly improve quality of life. While the field has identified major categories of aging damage such as altered intercellular communication, loss of proteostasis, and eroded mitochondrial function1, these deleterious processes interact with extraordinary complexity within and between organs. Yet, a comprehensive analysis of aging dynamics organism-wide is lacking. Here we performed RNA-sequencing of 17 organs and plasma proteomics at 10 ages across the mouse lifespan. We uncover previously unknown linear and non-linear expression shifts during aging, which cluster in strikingly consistent trajectory groups with coherent biological functions, including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Remarkably, these gene sets are expressed similarly across tissues, differing merely in age of onset and amplitude. Especially pronounced is widespread immune cell activation, detectable first in white adipose depots in middle age. Single-cell RNA-sequencing confirms the accumulation of adipose T and B cells, including immunoglobulin J-expressing plasma cells, which also accrue concurrently across diverse organs. Finally, we show how expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to aging of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of aging, thereby providing a foundation to track systemic sources of declining health at old age.
Widespread immunogenic poly-epitope frameshift mutations in microsatellite unstable tumors
Authors: Roudko Vladimir , Bozkus Cansu Cimen , Orfanelli Theofano , Blank Stephanie V. , Greenbaum Benjamin , Bhardwaj Nina
Published: June 2019

Microsatellite instability-high (MSI-H) tumors are an important model system for evaluating neoantigen-based immunotherapies given their high tumor mutation burden and response to checkpoint blockade. We identified tumor-specific, frameshift peptides, encoding multiple epitopes that originated from indel mutations shared among patients with MSI-H endometrial, colorectal and stomach cancers. Epitopes derived from these shared frameshifts have high population occurrence rates, wide presence in many tumor subclones and are predicted to bind to the most frequent HLA alleles in the TCGA MSI-H patient cohorts. Neoantigens arising from these mutations are more dissimilar to both self and viral antigens, indicating the creation of peptides, that, when translated, can present truly novel antigens to the immune system. Finally, we validated the immunogenicity of common frameshift peptides from MSI-H endometrial patients in an array of T cell stimulation experiments, using peripheral blood mononuclear cells isolated from healthy donors. Our study describes for the first time the widespread occurrence and strong immunogenicity of tumor-specific antigens, derived from shared frameshift mutations in MSI-H cancer and Lynch syndrome patients, suitable for the design of common preventive “off-the-shelf” cancer vaccines.
Intertwined signatures of desiccation and drought tolerance in grasses
Authors: Pardo Jeremy , Wai Ching Man , Chay Hannah , Madden Christine F. , Hilhorst Henk W.M. , Farrant Jill M. , VanBuren Robert
Published: June 2019

Grasses are among the most resilient plants and some can survive prolonged desiccation in semi-arid regions with seasonal rainfall. This vegetative desiccation tolerance has arisen independently multiple times within the grass family, but the genetic elements that differentiate desiccation tolerant and sensitive grasses are largely unknown. Here we leveraged comparative genomic approaches with the resurrection grassEragrostis nindensisand the closely related desiccation sensitive cerealEragrostis tefto identify changes underlying desiccation tolerance. We extended the analyses to include the grasses maize, sorghum, rice, and the model desiccation tolerant grassOropetium thomaeumto identify broader evolutionary conservation and divergence. We identified changes in chromatin architecture and expression dynamics related to desiccation inE. nindensis. It was previously hypothesized that transcriptional re-wiring of seed desiccation pathways confers vegetative desiccation tolerance. We demonstrate that the majority of seed dehydration related genes show similar expression patterns in leaves of desiccation tolerant and sensitive species during dehydration. However, we discovered a small set of orthologs with expression specific to leaves of desiccation tolerant species, and seeds of sensitive species. This supports a nuanced role of seed-related genes where many overlap with typical drought responses but some crucial genes are desiccation specific in resurrection plants.